Botulism

Semin Neurol, 2003 Sep, 23(3), 277 - 84
Case studies in movement disorders; Evidente VG et al.; Six cases representing the most commonly encountered movement disorders-restless legs syndrome with periodic limb movements, tics, myoclonus, chorea, essential tremor, and cervical dystonia-are presented . Discussion of each case focuses on a practical approach to recognizing the important clinical features of each movement disorder as well as the current therapeutic options . A detailed discussion of botulinum toxin follows the case on cervical dystonia, focusing on its mechanism of action, clinical indications, side effects, and dosing.

Anesthesiol Clin North America, 2003 Dec, 21(4), 715 - 31
Botulinum toxin therapy in pain management; Raj PP; BTs seem to be a useful treatment in refractory MPS and headache . Presumably BTs work by breaking the spasm or pain cycle giving the patient a "window of opportunity" for traditional conservative measures to have a greater beneficial impact, but several studies suggest that a direct antinociceptive effect distinct from any reduction in muscle spasm may be at play . The major benefit of BTs compared with standard therapies is duration of response . We do not advocate that BTs be used as a first line treatment for MPS or headache . However, in refractory cases where nothing else has worked, it may offer a chance for improvement or cure not otherwise available . For now, it remains an off label, but increasingly accepted, approach in-patients with refractory myofascial pain and headache, who despite multidisciplinary approaches, continue to suffer.

Neurology, 2004 Jan 13, 62(1), 37 - 40
A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson's disease; Ondo WG et al.; BACKGROUND: Injections of botulinum toxin A are an effective treatment for sialorrhea in Parkinson's disease (PD) . Based on the relatively high rates of dry mouth seen with botulinum toxin B, there is reason to suspect that it may also improve sialorrhea . OBJECTIVE: To determine whether botulinum toxin B (Myobloc; Elan Pharmaceuticals, New York, NY) is a safe and effective treatment for sialorrhea in patients with PD . METHODS: Demographics, PD treatments, head posture, the Unified Parkinson's Disease Rating Scale (UPDRS), two questionnaires regarding drooling, Visual Analogue Scale, global impressions, salivary gland imaging, and a dysphagia questionnaire were assessed in 16 PD subjects with problematic sialorrhea . Patients were then randomized to receive either botulinum toxin B (1,000 units into each parotid gland and 250 units into each submandibular gland) or a pH-matched placebo, using only anatomic landmarks . Patients returned 1 month later to undergo an identical assessment . RESULTS: Compared with placebo, those randomized to drug reported improvement on the Visual Analogue Scale (p < 0.001), global impressions of change (p < 0.005), Drooling Rating Scale (p < 0.05), and Drooling Severity and Frequency Scale (p < 0.001) . There was no change in UPDRS, head posture, or Dysphagia Scale . Adverse events were mild and included dry mouth (three patients), worsened gait (two), diarrhea (one), and neck pain (one) in the botulinum toxin B group . CONCLUSION: Anatomically guided injections of botulinum toxin B into the parotid and submandibular glands appear to effectively improve sialorrhea without compromising dysphagia in patients with PD.

Biochemistry, 2004 Jan 20, 43(2), 526 - 32
Uptake of botulinum neurotoxin into cultured neurons; Keller JE et al.; Botulinum neurotoxins (BoNTs) act within the synaptic terminal to block neurotransmitter release . The toxin enters the neuron by binding to neuronal membrane receptor(s), being taken up into an endosome-like compartment, and penetrating the endosome membrane via a pH-dependent translocation process . Once within the synaptic cytoplasm, BoNT serotypes A and E cleave separate sites on the C-terminus of the neuronal protein SNAP-25, one of the SNARE proteins required for synaptic vesicle fusion . In this study, we measured the effect of brief toxin exposure on SNAP-25 proteolysis in neuronal cell cultures as an indicator of toxin translocation . The results indicate that (1) uptake of both BoNT-A and -E is enhanced with synaptic activity induced by K+ depolarization in the presence of Ca2+ and (2) translocation of BoNT-A from the acidic endosomal compartment is slow relative to that of BoNT-E . Polyclonal antisera against each toxin protect cells when applied with the toxin during stimulation but has no effect when added immediately after toxin exposure, indicating that toxin endocytosis occurs with synaptic activity . Both serotypes cleave SNAP-25 at concentrations between 50 pM and 4 nM . IC50 values for SNAP-25 cleavage are approximately 0.5 nM for both serotypes . Inhibition of the pH-dependent translocation process by pretreating cultures with concanamycin A (Con A) prevents cleavage of SNAP-25 with IC50 values of approximately 25 nM . Addition of Con A at times up to 15 min after toxin exposure abrogated BoNT-A action; however, addition of Con A after 40 min was no longer protective . In contrast, Con A inhibited, but did not prevent, translocation of BoNT-E even when added immediately after toxin exposure, indicating that pH-dependent translocation of BoNT-E is rapid relative to that of BoNT-A . This study demonstrates that uptake of both BoNT-A and -E is enhanced with synaptic activity and that translocation of the toxin catalytic moiety into the cytosol occurs at different rates for these two serotypes.

J Urol, 2004 Feb, 171(2 Pt 1), 845 - 8; discussion 848
Botulinum-A toxin injection into the detrusor: a safe alternative in the treatment of children with myelomeningocele with detrusor hyperreflexia; Riccabona M et al.; PURPOSE: We prospectively evaluated the efficacy and durability of botulinum-A toxin in the treatment of detrusor hyperreflexia in children with myelomeningocele (MMC) . MATERIALS AND METHODS: This study involved 15 patients with MMC (10 male and 5 female, mean age 5.8 years), all nonresponders to orally and intravesically administered anticholinergic medication and all on clean intermittent catheterization . Pretreatment assessment included a videourodynamic evaluation, an incontinence score and a mercaptoacetyltriglycine-3 renal scan . We injected 10 U/kg to a maximum of 360 U of botulinum-A toxin into the detrusor at 25 to 40 sites, sparing the trigone . Followup lasted between 12 and 30 months . All children underwent a urodynamic reevaluation, an assessment of the bladder capacity and an incontinence score at 3, 9 and 12 months after the first injection . A second intravesical injection was administered after 12 months and followup repeated as in the first year . RESULTS: After the first injection treatment mean bladder reflex volume increased from 72.00 +/- 28.12 ml to 298 +/- 32.45 ml (mean +/- SD, p <0.001) . Maximum detrusor pressure decreased from 78.76 +/- 23.14 cm H2O to 42.76 +/- 24.34 cm H2O (p <0.001) . Maximum bladder capacity increased from 136.34 +/- 45.71 ml to 297.02 +/- 87.17 ml (p <0.001) . Detrusor compliance increased from 18.29 +/- 27.19 ml/cm H2O to 51.17 +/- 38.17 ml/cm H2O (p <0.001) . Of the 15 patients 13 became completely dry with CIC . The remaining 2 patients improved from score 3 to 1 . Results after 9 months were similar to those obtained after 3 months . Mean durability of the effect of the drug was 10.5 months after the first as well as after the second intravesical injection . CONCLUSIONS: Botulinum-A toxin is a safe alternative in the management of detrusor hyperreflexia in children with MMC . The preliminary results regarding urodynamic parameters and continence have been promising.

Acta Otolaryngol, 2003 Dec, 123(9), 1060 - 3
Effect of botulinum toxin type A on nasal symptoms in patients with allergic rhinitis: a double-blind, placebo-controlled clinical trial; Unal M et al.; OBJECTIVE: To investigate the possible beneficial effects of botulinum toxin type A (BTX-A) on nasal symptoms in patients with allergic rhinitis (AR) . MATERIAL AND METHODS: Thirty-four patients (21 females, 13 males; mean age 28 years) were included in the study . AR was diagnosed by means of history, clinical examination and skin prick test . Patients were randomly divided into 3 subgroups a follows: in Group A, 20 units of BTX-A was injected into each nasal cavity (total 40 units); in Group B, 30 units of BTX-A was injected into each nasal cavity (total 60 units); and in Group C, 2 ml of isotonic saline was injected as placebo . The symptoms of AR (rhinorrhea, nasal obstruction, sneezing, itching) were scored by the patient on a six-point scale (from 0 to 5) . All of the patients were followed up at Weeks 1, 2, 4, 6 and 8; at each visit an anterior rhinoscopic examination was done and symptom scores were recorded . RESULTS: There was no statistically significant difference between Groups A and B in terms of average symptom scores . Rhinorrhea, nasal obstruction and sneezing scores in Groups A and B were significantly better than those in Group C at all time points . Although itching scores were significantly lower at Weeks 1 and 2, there was no difference in the Week 4, 6 and 8 scores in Groups A and B . When total symptom scores were evaluated, the results for Groups A and B were similar but significantly better than those for Group C . CONCLUSION: In selected cases, injection of 40 units of BTX-A into the turbinates, as a single agent, may help the symptomatic control of AR for up to 8 weeks.

Am J Phys Med Rehabil, 2004 Jan, 83(1), 42 - 50; quiz 51-3
Botulinum neurotoxin type B and physical therapy in the treatment of piriformis syndrome: a dose-finding study; Fishman LM et al.; OBJECTIVE: To measure dosage effects of botulinum neurotoxin type B with physical therapy in piriformis syndrome . DESIGN: Prospective study of consecutive patients complaining of buttock pain and sciatica, measuring serial H-reflex tests in flexion, adduction, and internal rotation; visual analog scale; and adverse effects at 0, 2, 4, 8, and 12 wks . We used an electrophysiologic criterion for piriformis syndrome: a 1.86-msec prolongation of the H-reflex with the flexion, adduction, and internal rotation test . Four piriformis syndrome groups were identified . Serial groups were injected once with either 5000, 7500, 10,000, or 12,500 units of botulinum neurotoxin type B in successive months under electromyographic guidance in four separate locations of the affected piriformis muscle, with a 1-mo safety observation period between groups . Patients received physical therapy twice weekly for 3 mos . RESULTS: The flexion, adduction, and internal rotation test and visual analog scale declined significantly, correlating at 72% sensitivity and 77% specificity . A total of 24 of 27 study patients had >/=50% pain relief . Mean visual analog scale score declined from 6.7 to 2.3 . A volume of 12,500 units of botulinum neurotoxin type B was superior to 10,000 units at 2 wks postinjection . The most severe adverse effects were dry mouth and dysphagia, approaching 50% of patients at 2 and 4 wks . CONCLUSION: Physical therapy and 12,500 units of botulinum neurotoxin type B seem to be safe and effective treatment for piriformis syndrome . In addition, the flexion, adduction, and internal rotation test seems to be an effective means of diagnosing piriformis syndrome and assessing its clinical improvement . Injection may benefit patients for >3 mos.

J Neurol Sci, 2004 Feb 15, 217(2), 229 - 32
Severe bruxism following basal ganglia infarcts: insights into pathophysiology; Tan EK et al.; Bruxism characterized by clenching and grinding of teeth can lead to toothwear, headaches and depression . While bruxism has been associated with a number of neurological diseases, it has not been highlighted following cerebral infarction.An elderly man presented with an acute onset of tooth grinding and jaw clenching associated with dysarthria . His bruxism was worse during the day and resolved during sleep . He had frequent jaw aches, headaches and swallowing difficulty . Examination demonstrated the presence of dysarthria with jaw clenching and tooth grinding, producing persistent high pitch and loud squeaky sounds . A magnetic resonance imaging and angiography examination revealed a recent infarct in the right thalamus . In addition, chronic lacunar infarcts were present in the bilateral caudate nuclei with severe basilar artery stenosis . He was successfully treated with botulinum toxin.We discuss the pathophysiologic mechanisms of bruxism associated with basal ganglia infarcts . Dysfunction of the efferent and/or afferent thalamic or striatopallidal tracts may play a role in bruxism . Early recognition of bruxism following stroke could reduce unnecessary suffering since the condition can be effectively treated.

Am J Ophthalmol, 2004 Jan, 137(1), 201 - 2
Retinal detachment from inadvertent intraocular injection of botulinum toxin A; Liu M et al.; PURPOSE: To report a case of inadvertent intraocular injection of botulinum toxin A (Botox, BTA) resulting in a retinal tear and bullous retinal detachment . The retinal detachment resolved spontaneously, and the tear was treated with laser demarcation with good visual outcome . DESIGN: Interventional case report . METHODS: A 36-year-old woman underwent Botox injections for paralytic esotropia and developed ocular perforation . Dilated fundus examination showed a slit-like retinal tear infranasally with a bullous retinal detachment nasally . RESULTS: The retinal detachment spontaneously resolved, and the patient was treated with laser demarcation on the following day . After 2 more days, her vision returned to baseline . CONCLUSIONS: Botox did not appear toxic to human intraocular tissues . Close observation may be indicated in the event of an inadvertent intraocular Botox injection.

J Am Acad Dermatol, 2004 Jan, 50(1), 61 - 2
Does wrist nerve block influence the result of botulinum toxin A treatment in palmar hyperhidrosis?
Hund M, Rickert S, Kinkelin I, Naumann M, Hamm H.
Treatment of palmar hyperhidrosis with intracutaneous injections of botulinum toxin type A is painful, making anesthesia desirable . However, nerve blocks may be associated with reduced efficacy . In 20 patients with idiopathic palmar hyperhidrosis both palms were treated with intracutaneous injections of botulinum toxin type A after having randomly chosen one hand for anesthesia by median und ulnar nerve block and the other hand for cooling . There was no difference in efficacy of botulinum toxin A treatment between both palms but significantly greater injection pain after cooling compared with nerve block.

J Med Assoc Thai, 2003 Nov, 86(11), 1051 - 4
Botulinum toxin treatment for upper lid retraction of dysthyroidism; Chuenkongkaew W; Six patients with upper eyelid retraction due to dysthyroidism at Siriraj Hospital received subcutaneous botulinum toxin treatment at a dosage of 5-20 units per injection . Five patients experienced an improvement in the lid retraction lasting at least 40 months and 3 patients required more than one injection . Botulinum toxin injection is an alternative treatment for the upper eyelid retraction of dysthyroidism, which is effective and causes minimal side effects, particularly in patients with euthyroid status.

Bioessays, 2004 Jan, 26(1), 73 - 9
Cross-strand disulphides in cell entry proteins: poised to act; Wouters MA et al.; Cross-strand disulphides (CSDs) are unusual bonds that link adjacent strands in the same beta-sheet . Their peculiarity relates to the high potential energy stored in these bonds, both as torsional energy in the highly strained disulphide linkage and as deformation energy stored in the sheet itself . CSDs are relatively rare in protein structures but are conspicuous by their presence in proteins that are involved in cell entry . The finding that entry of botulinum neurotoxin and HIV into mammalian cells involves cleavage of CSDs suggests that the activity of other cell entry proteins may likewise involve cleavage of these bonds . We examine emerging evidence of the involvement of these unusual disulphides in cell entry events .

Dermatol Surg, 2004 Jan, 30(1), 102 - 4
Botulinum toxin for the treatment of facial flushing; Yuraitis M et al.; BACKGROUND: Facial flushing is a common problem that is encountered by fair-skinned patients of Celtic and Northern European descent . Although usually transient in nature, some patients display a persistent reddened skin tone, with periods of increased erythema . Treatment of this condition is limited . OBJECTIVE: To describe a novel method for the treatment of persistent facial flushing . METHOD: We report a case of persistent facial flushing that was resistant to multiple pulsed dye laser treatments and was successfully treated with botulinum toxin A . RESULTS: The posttreatment appearance was dramatic, and the patient was highly satisfied with the cosmetic outcome . CONCLUSION: Botulinum toxin A can be used in small quantities to decrease persistent facial flushing temporarily.

Cephalalgia, 2004 Jan, 24(1), 60 - 5
Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study; Ondo WG et al.; Sixty patients with headaches of more than 15 days per month were recruited for this double-blind, placebo-controlled, parallel study of botulinum toxin type A (BTX) for chronic tension type and chronic migraine headaches . The primary efficacy point was the number of headache-free days as assessed by diary for 12 weeks after BTX injection . Secondary efficacy points included global impressions, the use of abortive headache medications, and palpation . After recruitment, subjects kept diaries for 4 weeks prior to randomization, at which time they received either 200 U of BTX or matching placebo and were followed . After the week-12 evaluation, patients were offered 200 U of BTX (open label), and were similarly followed for another 12 weeks . The mean days with headache of the 60 subjects (49 female, mean age 47 +/- 11 years) was 23 +/- 7 out of 30 . Both groups were demographically similar (58 completed) . Over a 12-week period after injections, headache-free days had improved in the BTX group from week 8 to 12 (P < 0.05), and strongly tended to improve over the entire 12-week period, 33 +/- 23 vs . 24 +/- 16 days without headache (P = 0.07), but did not meet the a priori significance criteria . The subject global impressions (P < 0.05), subject change in headache impressions (P < 0.005), and investigator global impressions (P < 0.001) all improved in the BTX group compared with placebo . Adverse events were mild and did not differ between groups . At week 24 (open label), headache-free days were less in the twice BTX injected group compared with the once injected group, 40 +/- 26 vs . 26 +/- 19 (P < 0.05) . BTX may help chronic daily headache and appears to have a cumulative effect with subsequent injections . The treatment was very well tolerated.

Protein Expr Purif, 2003 Nov, 32(1), 1 - 9
Scale-up of the fermentation and purification of the recombinant heavy chain fragment C of botulinum neurotoxin serotype F, expressed in Pichia pastoris; Johnson SK et al.; A recombinant heavy chain fragment C of botulinum neurotoxin serotype F (BoNTF(Hc)) has been expressed in Pichia pastoris for use as an antigen in a proposed human vaccine . P . pastoris cells were grown using glycerol batch, glycerol fed-batch, and methanol fed-batch methods to achieve high cell densities . The total cellular protein recovered after homogenization was 72 mg/g of cell paste . BoNTF(Hc) was purified from soluble Pichia cell lysate employing ion-exchange chromatographic (IEC) and hydrophobic interaction chromatographic (HIC) methods developed at the bench scale using 10-100 mL columns . The process was performed at the pilot scale using 1-4L columns for evaluation of scale up . The purification process resulted in greater than 98% pure product consisting of at least three forms of BoNTF(Hc) based on mass spectrometry and yielded up to 205 mg/kg cells at the bench scale and 170 mg/kg cells at the pilot scale . Full-length BoNTF(Hc) is present based on mass spectrometry and SDS-PAGE, however is postulated to be N-terminally blocked by acetylation . N-terminal sequencing showed that two of the three forms are missing the first 11 (80%) and 14 (20%) amino acids of the N-terminus from the full-length form . The ratios of the two clipped forms were consistent from the bench to pilot scales . Purified BoNTF(Hc) at the pilot scale was found to sufficiently protect mice against a high dose of BoNTF neurotoxin.

Hybrid Hybridomics, 2003 Oct, 22(5), 277 - 83
Recombinant anti-botulinum neurotoxin A single-chain variable fragment antibody generated using a phage display system; Mah DC et al.; A recombinant single-chain fragment variable antibody (scFv) to botulinum A neurotoxin (BoNT/A) was developed . BALB/C mice were immunized with BoNT/A . Splenomic RNA was isolated from the hyperimmune mice and used to prepare a cDNA library, from which the variable regions of the heavy and light chain antibody genes were generated and connected by a DNA linker . The resulting scFv genes were cloned into the phagemid vector pCANTAB5 in order to construct phage display scFv libraries . Individual anti-BoNT/A phage clones were isolated from the phage display libraries by immunoaffinity selection using immobilized BoNT/A and further evaluated by enzyme-linked immunosorbant assay, immunoprecipitation and Western blotting . Forty-eight clones were found to be BoNT/A-reactive . The most reactive clone, designated D12, was selected for further study . The scFv gene of D12 was subcloned into a Pichia pastoris vector, and expression in yeast was evaluated.

Int Urogynecol J Pelvic Floor Dysfunct, 2003 Dec, 14(6), 424 - 6 Epub 2003 Nov 25.
Treatment of overactive bladder with botulinum toxin type B: a pilot study; Dykstra D et al.; The purpose of this study was to determine the efficacy and safety of botulinum toxin type B (BTX-B/Myobloc) in the treatment of patients with overactive bladder . This open-label dose-escalation study enrolled 15 female patients with urinary frequency with or without incontinence . The BTX-B doses used in this study were 2500, 3750, 5000, 10 000 and 15 000 units . Response was defined as a subjective improvement in frequency, urgency and incontinence symptoms . A paired t-test of the pre/post frequency difference indicates that these 15 patients experienced an average of 5.27 fewer frequency episodes per day after treatment with BTX-B . The p value for the paired t-test was <0.001 . The longest duration effect was 3 months using 10 000-15 000 units of BTX-B . The correlation between dose and duration was very significant, with a correlation coefficient = 0.96, p<0.001 . Based on these findings, we feel the use of botulinum toxin to treat patients with overactive bladder warrants further study.

J Invest Dermatol, 2003 Dec, 121(6), 1312 - 6
Botulinum toxin type B blocks sudomotor function effectively: a 6 month follow up; Birklein F et al.; This study analyzes the suppression of sweat gland activity by botulinum toxin type B . We injected botulinum toxin type B (between 2 and 1000 mouse units subcutaneously) in the lateral side of both lower legs in 15 healthy volunteers . Sweat tests were carried out before botulinum toxin type B injections, and at 3 wk, 3 mo, and 6 mo . We studied focal anhidrosis by iodine-starch staining and by capacitance hygrometry after carbachol iontophoresis, according to the quantitative sudomotor axon reflex test (QSART) . Iodine starch staining indicated that a threshold dose of 8 mouse units botulinum toxin type B leads to anhidrotic skin spots (>4 cm2) after 3 wk . Duration of anhidrosis was prolonged for 3 mo when 15 mouse units and for 6 mo when 125 mouse units botulinum toxin type B were injected . The size of the anhidrotic area decreased with time (p<0.001), indicating partial recovery at the edges . After 3 wk, the QSART score had significantly decreased to 18% of baseline and had decreased to zero in most subjects with doses of 62.5 mouse units or more . After 3 mo, the QSART had returned to 91% of baseline in all but one subject and, after 6 mo, recovery of sudomotor function was complete . Analysis by iodine-starch staining and QSART indicated that botulinum toxin type B suppresses sudomotor function effectively, in a concentration-dependent manner.

J Neurochem, 2004 Jan, 88(1), 124 - 35
Small peptides patterned after the N-terminus domain of SNAP25 inhibit SNARE complex assembly and regulated exocytosis; Blanes-Mira C et al.; Synthetic peptides patterned after the C-terminus of synaptosomal associated protein of 25 kDa (SNAP25) efficiently abrogate regulated exocytosis . In contrast, the use of SNAP25 N-terminal-derived peptides to modulate SNAP receptors (SNARE) complex assembly and neurosecretion has not been explored . Here, we show that the N-terminus of SNAP25, specially the segment that encompasses 22Ala-44Ile, is essential for the formation of the SNARE complex . Peptides patterned after this protein domain are potent inhibitors of SNARE complex formation . The inhibitory activity correlated with their propensity to adopt an alpha-helical secondary structure . These peptides abrogated SNARE complex formation only when added previous to the onset of aggregate assembly . Analysis of the mechanism of action revealed that these peptides disrupted the binary complex formed by SNAP25 and syntaxin . The identified peptides inhibited Ca2+-dependent exocytosis from detergent-permeabilized excitable cells . Noteworthy, these amino acid sequences markedly protected intact hippocampal neurones against hypoglycaemia-induced, glutamate-mediated excitotoxicity with a potency that rivalled that displayed by botulinum neurotoxins . Our findings indicate that peptides patterned after the N-terminus of SNAP25 are potent inhibitors of SNARE complex formation and neuronal exocytosis . Because of their activity in intact neurones, these cell permeable peptides may be hits for antispasmodic and analgesic drug development.

Mov Disord, 2003 Dec, 18(12), 1522 - 6
Auditory startle response in cervical dystonia; Muller J et al.; The excitability of brainstem neurons is abnormally enhanced in patients with cervical dystonia (CD), but the extend of such abnormality is not known . We examined whether patients with CD showed abnormalities in the auditory startle response (ASR), a brainstem reflex elicited by an unexpected loud stimulus . Thirteen patients with CD were investigated 3 months after botulinum toxin treatment . Thirteen healthy volunteers served as controls . ASRs were elicited by binaural high-intensity auditory stimuli . Reflex electromyographic (EMG) activity was recorded simultaneously with surface electrodes bilaterally from masseter, orbicularis oculi, sternocleidomastoid, and biceps brachii muscles . We found that ASR onset latencies were similar for patients and controls . CD patients had significantly lower ASR probabilities than controls (P = 0.007) . ASR area under the curve was significantly smaller in CD patients (P = 0.017) . Similar to controls, patients showed a significant habituation of ASR (P < 0.001, each); however, CD patients showed a prolonged tonic or phasic EMG activity after the initial ASR that was not observed in controls . Normal latencies and recruitment pattern indicate a preserved organization of intrinsic neural pathways mediating ASR in CD . Reduced ASR probability and magnitude as well as prolonged EMG activity after the proper startle response corroborate and extend previous findings on brainstem dysfunction in CD .

Mov Disord, 2003 Dec, 18(12), 1424 - 35
Movement disorders in patients with peripheral facial palsy; Valls-Sole J et al.; Acute unilateral facial paralysis is usually a benign neurological condition that resolves in a few weeks . However, it can also be the source of a transient or long-lasting severe motor dysfunction, featuring disorders of automatic and voluntary movement . This review is organized according to the two most easily recognizable phases in the evolution of facial paralysis: (1) . Just after presentation of facial palsy, patients may exhibit an increase in their spontaneous blinking rate as well as a sustained low-level contraction of the muscles of the nonparalyzed side, occasionally leading to blepharospasm-like muscle activity . This finding may be due to an increase in the excitability of facial motoneurons and brainstem interneurons mediating trigeminofacial reflexes . (2) . If axonal damage has occurred, axonal regeneration beginning at approximately 3 months after the lesion leads inevitably to clinically evident or subclinical hyperactivity of the previously paralyzed hemifacial muscles . The full-blown postparalytic facial syndrome consists of synkinesis, myokymia, and unwanted hemifacial mass contractions accompanying normal facial movements . The syndrome has probably multiple pathophysiological mechanisms, including abnormal axonal branching after aberrant axonal regeneration and enhanced facial motoneuronal excitability . Although the syndrome is relieved with local injections of botulinum toxin, fear of such uncomfortable contractions may lead the patients to avoid certain facial movements, with the implications that this behavior might have on their emotional expressions .

Skinmed, 2003 Jul-Aug, 2(4), 209 - 11
Botulinum toxin in the treatment of axillary hyperhidrosis; Galadari I et al.; INTRODUCTION: Axillary hyperhidrosis can be a source of social isolation and embarrassment . The available treatments are either ineffective or have intolerable side effects . The search for a simple, long-lasting, and safe treatment has led to the use of botulinum-A toxin injections in those with excessive axillary hyperhidrosis . MATERIALS AND METHODS: Fifteen patients participated in this study . All had a history of axillary hyperhidrosis of 1-6 years duration and were using different types of therapies without any benefit . Each patient was injected intradermally with 125 units of botulinum-A toxin (Dysport, Spenywood Pharmaceutical) in 5-6 points over an elliptical area on each side . Patient follow-up was performed using the iodine-starch test . RESULTS: A total of 14 out of the 15 patients had complete anhidrosis 1 week after the injection . This result lasted for periods ranging from 1-6 months . No side effects were encountered . CONCLUSION: Intradermal injection of botulinum-A toxin seems to be a safe, rapid, and effective method of treatment in axillary hyperhidrosis.

Arch Phys Med Rehabil, 2003 Dec, 84(12), 1808 - 12
Spasticity in adults living in a developmental center; Pfister AA et al.; OBJECTIVES: To ascertain the prevalence of spasticity among adults living in a developmental center and to document the development of spasticity treatment plans for this population . DESIGN: Descriptions of the clinical features of medical disorders and a prevalence survey . SETTING: Residential developmental center . PARTICIPANTS: One hundred three adults . INTERVENTIONS: Not applicable . MAIN OUTCOME MEASURES: Characteristics described included the prevalence of spasticity in this population, the specific spasticity diagnosis, functional goals for spasticity treatment identified by the participants' multidisciplinary teams, and the specific treatment indicated by the neurologist . RESULTS: Of the 103 people diagnosed by the neurologist, 24 had diplegic spasticity, 4 had hemiplegic spasticity, 44 had quadriplegic spasticity, and 31 had no spasticity . Functional goals identified by multidisciplinary teams were undergarment change (46.3% of the persons for whom goals were identified), splinting hands (11%), dressing (57.4%), hygiene (20.4%), wheelchair positioning (25.9%), ambulation improvement (14.8%), and transfers (9.3%) . After physical and occupational therapy, the first invasive treatments indicated for people with spasticity included botulinum toxin injections (60%), intrathecal baclofen (26.4%), orthopedic surgery (5.6%), and medication (1.4%) . No treatment was recommended for 25% of the spasticity patients . CONCLUSIONS: The prevalence of spasticity was 35% in this developmental center population of 205 individuals . A multidisciplinary team approach to the evaluation of adults with spasticity who live in a developmental center makes it possible to identify functional goals that are amenable to spasticity treatment and minimizes treatment that does not target specific functional goals.

Dev Med Child Neurol, 2003 Dec, 45(12), 829 - 32
Ultrasound-guided botulinum toxin injection technique for the iliopsoas muscle; Westhoff B et al.; Intramuscular botulinum toxin A injections are beneficial for the treatment of functional shortening of the iliopsoas muscle, but it is difficult to achieve precise needle positioning and injection . As a solution to this we present an ultrasound-guided injection technique for the iliopsoas muscle using an anterior approach from the groin . The procedure was performed 26 times in 13 patients (seven males, six females; mean age 11 years, SD 9 years 8 months; age range 4 to 31 years), 10 times bilaterally . Indications were functional iliopsoas shortening due to cerebral palsy (17 hips), hereditary spastic paraplegia (four hips), and Perthes disease (five hips) . In all cases the iliopsoas muscle was identified easily by ultrasound; the placement of the injection needle and injection into the site of interest were observed during real time . No complications were encountered . Botulinum toxin A (BTX-A) injections have become established as a standard procedure for the treatment of functional shortening of different muscles in persons with spasticity or dystonia (Kessler et al . 1999, Bakheit et al . 2001, Kirschner et al . 2001) . Optimal needle placement is essential to avoid severe side effects and to assess lack of response to the drug or incorrect region of injection . While injection into superficial, very palpable muscles is quite easy, the approach to other muscles such as the iliopsoas muscle may be more difficult and the placement of the needle for an optimal injection site is harder to control . As a solution to this, we present an ultrasound-guided injection technique . The main indications for BTX-A injections in the iliopsoas muscle are dynamic hip flexion deformities mostly due to spastic conditions which may compromise walking (increased anterior pelvic tilt during the whole gait cycle, decreased hip extension at terminal stance, increased peak hip flexion during swing; Molenaers et al . 1999 . Another indication might be decentration of the femoral head (as part of an injection programme which also includes other muscles like the adductors and the medial hamstrings) for pain relief, reducing care difficulties and, possibly, prevention of further decentration (Porta 2000, Foster et al . 2001, Deleplanque et al . 2002, Lubik et al . 2002) . In Perthes disease, BTX-A injections in the iliopsoas muscle and the adductors may prevent a fixed deformity, which is a negative prognostic factor.

Neurology, 2003 Dec 9, 61(11), 1546 - 50
Effects of botulinum toxin on motor system excitability in patients with writer's cramp; Boroojerdi B et al.; OBJECTIVE: To investigate botulinum toxin (BTX) effects on central and peripheral motor excitability in writer's cramp . METHODS: Using transcranial magnetic stimulation over the motor cortex and brainstem and peripheral electrical stimulation, the authors investigated measures of motor cortical and peripheral motor excitability on the affected and unaffected side before and 2 to 4 weeks after BTX A injection into the affected muscles in six patients with writer's cramp . The following motor excitability measures were studied: resting and active motor threshold, cortical silent period, intracortical inhibition and facilitation using the double-pulse technique, recruitment curves, motor evoked potentials following magnetic brainstem stimulation, and maximum M-response amplitude following supramaximal peripheral nerve stimulation . RESULTS: BTX injection improved function and reduced the M response . No other measures of motor system excitability showed significant changes following BTX injection, and there was no difference in these measures between sides . CONCLUSIONS: BTX A effects on motor system excitability seem to be based mainly on its peripheral mechanisms of action . There was no difference in the motor system excitability between the clinically affected and unaffected sides in this group of patients.

Urology, 2003 Nov, 62(5 Suppl 2), 20 - 7
Diagnosis and treatment of the overactive bladder; Wein AJ; Overactive bladder syndrome (OAB) is a symptomatic diagnosis based on the presence of urgency, with or without urge incontinence, and usually accompanied by frequency and nocturia, in the absence of obvious pathologic or metabolic disease . Initial management of OAB requires an integrated approach using behavioral and pharmacologic methods . Patients should be educated about the functioning of the lower urinary tract system, fluid and dietary management, timed or prophylactic voiding and bladder training regimens, the keeping of micturition charts or bladder diaries, and pelvic floor exercises . Although the effectiveness of muscarinic receptor antagonists for the treatment of OAB has been shown, adverse effects, such as dry mouth, constipation, and blurred vision have somewhat limited their usefulness . Newer agents that are more bladder selective have been and continue to be developed . The concept of clinical effectiveness-a combination of efficacy, tolerability, and compliance-can be used to evaluate not only how well a drug works, but also the side-effect profile and bothersomeness and how likely patients are to continue treatment . Patients who do not respond to antimuscarinic treatment of OAB may do so because of a variety of nonpharmacologic and pharmacologic reasons . Most cases of OAB are not cured, but rather the symptoms are reduced, with an associated improvement in the patients' quality of life . Patients who have failed behavioral and pharmacologic intervention may respond to neuromodulation and augmentation cystoplasty . Future approaches may include (1) other types of systemic pharmacologic therapy; (2) intravesical administration of drugs, including blockers of afferent input; (3) intradetrusor injection of botulinum toxin; (4) the use of tissue engineering to simplify augmentation cystoplasty; (5) genetic interventions to reverse neuroplasticity changes; and (6) combinations of these approaches.

CNS Drugs, 2003, 17(15), 1093 - 107
Poststroke motor dysfunction and spasticity: novel pharmacological and physical treatment strategies; Hesse S et al.; Following stroke, approximately 90% of patients experience persistent neurological motor deficits that lead to disability and handicap . Both pharmacological and physical treatment strategies for motor rehabilitation may be considered . In terms of pharmacological treatment, drugs that may potentially promote motor recovery when added to a regimen of physical therapy include the stimulants amphetamine and methylphenidate, as well as levodopa and fluoxetine . Botulinum toxin A has proven effective and well tolerated in several placebo-controlled trials for the treatment of focal upper and lower limb spasticity, although it has not been shown to improve motor function . The focal injection of botulinum toxin A inhibits the release of acetylcholine into the synaptic cleft, resulting in a reversible paresis of the muscles relevant for the spastic deformity . Other drugs, such as benzodiazepines, antiepileptic drugs and antipsychotics, may have detrimental effects on motor function and should be avoided, if possible . With respect to physical strategies, modern concepts of motor learning favour a task-specific repetitive approach that induces skill-acquisition relevant to the patient's daily life . Constrained-induced movement therapy based on the concept of learned non-use, electromyography-triggered electrical stimulation of the wrist muscles, robot-assisted motor rehabilitation to increase therapy intensity and bilateral practice to facilitate the movement of the paretic extremity are examples in upper limb rehabilitation . Lower limb rehabilitation has been enriched by treadmill training with partial bodyweight support, enabling the practice of up to 1000 steps per session; automated gait rehabilitation to relieve the strenuous effort required of the therapist; and rhythmic auditory stimulation, applying individually adjusted music to improve walking speed and symmetry.

Laryngoscope, 2003 Dec, 113(12), 2192 - 5
Laryngeal dystonia causing inspiratory stridor in children with cerebral palsy; Worley G et al.; SUMMARY: OBJECTIVE To present three cases of inspiratory stridor caused by laryngeal dystonia (LD) in children with cerebral palsy (CP), one of whom is being treated by periodic botulinum toxin type A (BTX) injection into a vocalis muscle, thereby avoiding tracheostomy.STUDY DESIGN Case series.RESULTS AND CONCLUSIONS Laryngeal dystonia was diagnosed in three children with CP who presented with inspiratory stridor associated with generalized dystonia, all of whom were thought previously to have had laryngomalacia . The inspiratory stridor was severe enough in one patient that a tracheostomy was planned . In common with the movement disorder of generalized dystonia, the inspiratory stridor caused by LD was present in our patients when they were awake, worse when they were excited or agitated, diminished when they were awake and calm, and absent when they were asleep . Although there is overlap between the symptoms of LD and laryngomalacia (and other structural causes of upper airway obstruction) in children with CP, structural causes result in inspiratory stridor that is often persistent when patients are awake and relaxed or when they are asleep . Fiberoptic laryngoscopy in an awake patient with LD reveals vocal cord adduction in inspiration causing inspiratory stridor in association with generalized dystonia . Baclofen and gabapentin used together relieved the inspiratory stridor and improved the generalized dystonia of two patients, confirming the clinical diagnosis of LD, but for the last 2 years the third patient (the one with the most severe inspiratory stridor) also has required a periodic BTX injection into a vocalis muscle (the major vocal cord adductor) to relieve her inspiratory stridor, alternating the side of injection . Her mother considers this is a small price to pay to avoid tracheostomy . This is the first report of LD causing inspiratory stridor in patients with CP and the first reported use of BTX injection into a vocalis muscle for relief of inspiratory stridor due to LD in a child.

Brain Inj, 2004 Jan, 18(1), 57 - 63
Functional outcome following Botulinum toxin A injection to reduce spastic equinus in adults with traumatic brain injury; Fock J et al.; PRIMARY OBJECTIVE: The aim of this study was to assess the effect of Botulinum toxin A in the management of spastic equinus resulting from traumatic brain injury . RESEARCH DESIGN: A before-after intervention design was used without controls . METHODS AND PROCEDURES: Subjects were seven patients suffering from traumatic brain injury of average duration 14 (4-38) months as a result of motor vehicle trauma, who had spastic equinus interfering with gait . EXPERIMENTAL INTERVENTION: The patients were treated with injections of Botulinum toxin A into the spastic calf muscles: gastrocnemius, soleus and tibialis posterior . Assessments were made pre-injection and at 2 weeks and 3 months post-injection . MAIN OUTCOME AND RESULTS: At the end of the 3-month period, all patients showed a significant improvement in gait velocity, cadence and stride length . CONCLUSIONS: The findings suggest that Botulinum toxin A may be useful in the management of spastic equinus following traumatic brain injury.

Arch Soc Esp Oftalmol, 2003 Nov, 78(11), 631 - 5
{Strabismus surgery of the myopic patient under topical anaesthesia}; Morales Bertrand J et al.; PURPOSE: To study the epidemiological characteristics and the results of strabismus surgery of high myopic patients under topical anaesthesia . METHOD: Retrospective study of nine high myopic patients with restrictive myopic myopathy (RMM) that underwent surgery in the last year and with a minimum follow-up of at least 6 months following surgery . Clinical findings, alteration of the extrinsic ocular motility (EOM) and response to surgical treatment were evaluated in each case . RESULTS: RMM was more frequent in women, average age was 46 years and average refractive error was 14 diopters . Diplopia was the most frequent reason for consultation, followed by the wish to undergo surgery because of an aesthetically unacceptable strabismus . High myopia was the most frequent etiology . One case was secondary to decompensated fourth cranial nerve palsy . The alteration of the EOM more frequently observed was endotropia associated with hypotropia . The recurrence rate of the deviation was 44%, occurring generally in the immediate postoperative period . In these cases botulinum toxin is a valid treatment option . CONCLUSIONS: Topical anaesthesia offers undoubted advantages for a better adjustment of diplopia in RMM surgery . During the intraoperative adjustment it is convenient to overcorrect the horizontal deviation and to undercorrect the vertical deviation.

Schmerz, 2003 Dec, 17(6), 450 - 8
{Use of botulinum toxin the the treatment of muscle pain}; Benecke R et al.; The analgesic effects of botulinum toxin (BTX) have been discussed controversially due to substantial placebo effects and flaws in the study designs used . Additionally, pathophysiological concepts of pain and the specific analgesic mechanisms of BTX remain largely unclear . Apart from pain reduction through the well-documented effects of BTX at the neuromuscular endplate, additional analgesic mechanisms, including other synaptic and local effects, have been suggested . Currently, BTX can be recommended for pain treatment in dystonia and spasticity . In myofascial pain syndromes, pain relief by BTX injections has been reported, but definite proof according to evidence-based medicinal criteria is still lacking . In fibromyalgia, there seems to be no analgesic effect . The role of BTX in pain therapy is likely to increase in the future.

Nervenarzt, 2003 Dec, 74(12), 1098 - 104
{Antibody-induced failure of botulinum toxin therapy}; Dressler D; Botulinum toxin (BT) has been used with great success in a large number of medical specialities . In some patients, however, formation of antibodies against BT (BTAB), with therapy failure (ABTF) occurs . Risk factors for ABTF are the amount of BT given at each injection series and the duration of the intervals between injection series . Treatment time and cumulative BT dose as well as patient age and gender are not independent risk factors . BTAB titres drop spontaneously after cessation of BT therapy, but latencies are too long to be compatible with a clinically effective therapy . Once these titres have dropped, BT therapy can be restarted using improved parameters and improved BT preparations with lower antigenicity . Increasing the BT dosage can be successful for overcoming ABTF when BTAB titres are low and target muscle responses are only moderately reduced . The use of alternative BT type A preparations fails to overcome ABTF . Alternative BT types such as types B and F are initially successful in ABTF but stimulate the formation of antibodies against the alternative BT types after few applications . When type B is used, substantial systemic anticholinergic side effects can occur . Prevention of BTAB formation is of paramount importance . Risk factors for BTAB formation have to be taken into account when planning BT therapy . The most interesting perspective, however, seems to be the development of new BT preparations with improved specific potency and reduced antigenicity.

Pediatr Neurol, 2003 Oct, 29(4), 299 - 301
The use of botulinum toxin type A treatment in children with spasticity; Sarioglu B et al.; The current modalities in managing spastic children have some limitations; thus, alternative therapeutic agents are in need . The purpose of this study is to investigate whether intramuscular botulinum toxin type A administration may be an alternative agent in the treatment of children with cerebral palsy . Eighteen children who were aged between 3 and 17 years and manifested cerebral palsy were administered intramuscular botulinum toxin type A with a total dose of 6 U/kg body weight . Outcome measurements were determined with four methods, including Ashworth Spasticity Scale, standardized videotape assessments, observational gait analysis, and walking velocity . Ashworth Spasticity Scale and videotape assessments were statistically significant before and after treatment in all muscles (P < 0.001) . The best improvement in video gait analysis was evident at week 8 . The botulinum toxin type A injections yielded an improved walking velocity at all visits . The observational gait analysis and walking velocity demonstrated an improvement after treatment in the gastrocnemius-injected group (P < 0.001) . In conclusion, intramuscular botulinum toxin type A administration may be effective in children with cerebral palsy, especially at week 4 and when injected in gastrocnemius.

Dis Esophagus, 2003, 16(3), 204 - 9
Treatment of patients with achalasia with botulinum toxin: a multicenter prospective cohort study; Martinek J et al.; Botulinum toxin (BT) injection is an alternative treatment of achalasia . The aim of the study was to examine outcomes of patients treated with BT in the Czech Republic . Since 1997, 49 patients with achalasia have been treated with BT . We prospectively evaluated the effect of BT injection on 41 patients during a median follow-up of 24 months (range 9-62) . Esophageal manometry was performed before and at 3-5 months after the injection . In 16 patients, BT was injected from the antegrade angle only (subgroup A), in 15 patients, BT was injected from both retrograde and antegrade angles (subgroup B) and, in 10 patients, BT injection was combined with subsequent balloon dilatation (subgroup C) . Immediate clinical response was achieved in 93% of patients . Clinical remission was sustained beyond 3 months in 83% of patients (responders) . Fourteen responders (41%) did not experience a relapse during the median of 22 months . Twenty responders (59%) experienced symptomatic relapse approximately 8 months after the injection . Ten relapsers underwent BT reinjection, five (50%) of them were asymptomatic for another 14 months . The remaining five (50%) patients reported a second relapse approximately 6 months after the reinjection . Median duration of the symptom-free period was 11.5 months after the first BT injection, and 10.5 months after the second (P = 0.21) . We did not find any significant predictor of a favorable outcome; responders tended to be older and to have a lower basal lower-esophageal-sphincter pressure . Patients in subgroup C were more likely to be in remission at 1 and 2 years as compared with patients in subgroup A . BT injection is an effective treatment of achalasia in the short term . However, almost 70% of patients experience a relapse within 2 years . BT injection should therefore be reserved for patients at risk for more invasive procedures or for patients who prefer this treatment.

Expert Opin Pharmacother, 2003 Dec, 4(12), 2229 - 37
New developments in the pharmacotherapy of tension-type headaches; Zhao C et al.; The first International Headache Society classification defined tension-type headaches (TTHs) by itemising those characteristics of migraines TTHs did not possess {1} . As a result, TTHs, both episodic and chronic, remain the most nonspecific of all the commonly observed primary headaches . Until recently, there has been little impetus on the part of the pharmaceutical industry to investigate TTHs; many of the potentially useful drugs are now generic and unprofitable . In addition, few investigators have pursued the study of TTHs in lieu of its more glamorous neighbour, migraine . As a result, there are few well-designed studies on the pharmacotherapy of TTHs . The few studies that exist support the use of age-old standard drug classes, the tricyclic antidepressants and the NSAIDs . New research is now emerging that points to the potential utility of botulinum toxin type A, NMDA-receptor antagonists including Mg(2+) and nitric oxide synthase inhibitors . More scientifically rigorous clinical studies are needed.

J Biol Chem, 2004 Feb 6, 279(6), 4234 - 40 Epub 2003 Nov 25.
Syntaxin-1A binds the nucleotide-binding folds of sulphonylurea receptor 1 to regulate the KATP channel; Pasyk EA et al.; ATP-sensitive potassium (KATP) channels in neuron and neuroendocrine cells consist of a pore-forming Kir6.2 and regulatory sulfonylurea receptor (SUR1) subunits, which are regulated by ATP and ADP . SNARE protein syntaxin 1A (Syn-1A) is known to mediate exocytic fusion, and more recently, to also bind and modulate membrane-repolarizing voltage-gated K+ channels . Here we show that Syn-1A acts as an endogenous regulator of KATP channels capable of closing these channels when cytosolic ATP concentrations were lowered . Botulinum neurotoxin C1 cleavage of endogenous Syn-1A in insulinoma HIT-T15 cells resulted in the increase in KATP currents, which could be subsequently inhibited by recombinant Syn-1A . Whereas Syn-1A binds both nucleotide-binding folds (NBF-1 and NBF-2) of SUR1, the functional inhibition of KATP channels in rat islet beta-cells by Syn-1A seems to be mediated primarily by its interactions with NBF-1 . These inhibitory actions of Syn-1A can be reversed by physiologic concentrations of ADP and by diazoxide . Syn-1A therefore acts to fine-tune the regulation of KATP channels during dynamic changes in cytosolic ATP and ADP concentrations . These actions of Syn-1A on KATP channels contribute to the role of Syn-1A in coordinating the sequence of ionic and exocytic events leading to secretion.

Eur J Neurol, 2003 Nov, 10(6), 695 - 9
Reduced jaw opening from paradoxical activity of mandibular elevator muscles treated with botulinum toxin; Bakke M et al.; The aim of the study was the effect of injections with botulinum toxin A (BTX-A) on reduced jaw opening, caused by paradoxical, antagonistic activity of jaw elevator muscles after brain stem lesions . The study included a male (51 years) and a female (69 years) patient . Subjective assessment, clinical recordings, muscle blocks and electromyography (EMG) were used to diagnose paradoxical activity, and to plan, guide and evaluate the treatment . The paradoxical innervation pattern was unilateral in the male and bilateral in the female . The paradoxical activity during jaw opening amounted to 24-109% of the level during maximum biting, and bursts of paradoxical activity were also present during chewing . EMG-guided blocks and later BTX-A injections of the affected muscles increased the opening by 9-23 mm from pre-treatment values of 15-18 mm, and normalized chewing . The study proved BTX-A to be an effective treatment for reduced jaw opening caused by paradoxical activity . Treatment was optimized by EMG evaluation of the current activity of the jaw elevator muscles, permitting individual treatment plans with longer intervals between BTX-A injections and lower doses than with conventional treatment for oromandibular dystonia . Thus the treatment only had to be repeated one to two times per year to maintain acceptable jaw mobility.

Mov Disord, 2003 Nov, 18(11), 1381 - 2
Severe cervical dystonia in pathologically proven Parkinson's disease and dementia; Cohen O et al.; We describe and present a videotape of a patient with parkinsonism and dementia who developed severe cervical dystonia, despite treatment with levodopa and botulinum toxin . The clinical diagnosis of Parkinson's disease and dementia (PDD) was confirmed at autopsy.

Muscle Nerve, 2003 Dec, 28(6), 767 - 72
Laryngeal electromyography: an evidence-based review; Sataloff RT et al.; This article reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders . The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders . Thirty-three of the 584 articles met the predefined inclusion criteria . The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial . A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the two techniques and no significant treatment benefit . Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia . There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them . There is an urgent need for evidence-based research addressing the use of laryngeal EMG for other applications.

Health Technol Assess, 2003, 7(40), iii, ix - x, 1-111
Treatments for spasticity and pain in multiple sclerosis: a systematic review; Beard S et al.; OBJECTIVES: To identify the drug treatments currently available for the management of spasticity and pain in multiple sclerosis (MS), and to evaluate their clinical and cost-effectiveness . DATA SOURCES: Electronic bibliographic databases, National Research Register, MRC Clinical Trials Register and the US National Institutes of Health Clinical Trials Register . REVIEW METHODS: Systematic searches identified 15 interventions for the treatment of spasticity and 15 interventions for treatment of pain . The quality and outcomes of the studies were evaluated . Reviews of the treatment of spasticity and pain when due to other aetiologies were also sought . RESULTS: There is limited evidence of the effectiveness of four oral drugs for spasticity: baclofen, dantrolene, diazepam and tizanidine . Tizanidine appears to be no more effective than comparator drugs such as baclofen and has a slightly different side-effects profile . Despite claims that it causes less muscle weakness, there was very little evidence that tizanidine performed any better in this respect than other drugs, although it is more expensive . The findings of this review are consistent with reviews of the same treatments for spasticity derived from other aetiologies . There is good evidence that both botulinum toxin (BT) and intrathecal baclofen are effective in reducing spasticity, and both are associated with functional benefit . However, they are invasive, and substantially more expensive . None of the studies included in the review of pain were designed specifically to evaluate the alleviation of pain in patients with MS and there was no consistency regarding the use of validated outcome measures . It was suggested that, although expensive, the use of intrathecal baclofen may be associated with significant savings in hospitalisation costs in relation to bed-bound patients who are at risk of developing pressure sores, thus enhancing its cost-effectiveness . No studies of cost-effectiveness were identified in the review of pain . There is evidence, albeit limited, of the clinical effectiveness of baclofen, dantrolene, diazepam, tizanidine, intrathecal baclofen and BT and of the potential cost-effectiveness of intrathecal baclofen in the treatment of spasticity in MS . CONCLUSIONS: Many of the interventions identified are not licensed for the alleviation of pain or spasticity in MS and the lack of evidence relating to their effectiveness may also limit their widespread use . Indeed, forthcoming information relating to the use of cannabinoids in MS may result in there being better evidence of the effectiveness of new treatments than of any of the currently used drugs . It may therefore be of value to carry out double-blind randomised controlled trials of interventions used in current practice, where outcomes could include functional benefit and impact on quality of life . Further research into the development and validation of outcomes measures for pain and spasticity may also be useful, as perhaps would cost-utility studies.

Tenn Med, 2003 Nov, 96(11), 511 - 3
Successful treatment of childhood spasticity secondary to cerebral palsy using Botox; Gill C et al.; Spasticity resulting from cerebral palsy can reduce the quality of life in affected children and can eventually cause more severe impairments, such as joint dislocation and scoliosis . Botulinum toxin type A (Botox) is widely used to temporarily alleviate the increased muscle tone associated with spasticity, and when combined with a comprehensive physical therapy regimen can result in permanent improvement . This report documents the successful use of Botox over a two-year period to treat spasticity secondary to cerebral palsy in a preschool-age child . Botox was used in conjunction with a specific physical therapy regimen in order to reach a functional goal of independent ambulation.

Br J Dermatol, 2003 Nov, 149(5), 1041 - 5
A double-blind, randomized, comparative study of Dysport vs . Botox in primary palmar hyperhidrosis; Simonetta Moreau M et al.; BACKGROUND: Intradermal injections of type A botulinum toxin have been reported to reduce excessive sweating in patients with primary palmar hyperhidrosis . Two preparations are commercially available in Europe: Botox (Allergan; 100 U per vial) and Dysport (Beaufour Ipsen Biotech; 500 U per vial), which are not bioequivalent . A few studies have tried to find an appropriate conversion factor between the two preparations in dystonic patients but results remain controversial . OBJECTIVES: To compare the efficacy of Botox and Dysport in palmar hyperhidrosis using a conversion factor of 1 : 4 . METHODS: In a double-blind, randomized study, eight patients with severe primary palmar hyperhidrosis received in the same session intradermal injections of Dysport in one palm and Botox in the other, after regional median and ulnar nerve blocks . Quantification of sweat production was performed by Minor's iodine starch test at baseline, 1, 3 and 6 months after the treatment . Subjective assessment of sweat production was performed using a visual analogue scale . RESULTS: The mean +/- SD number of injection sites (28 +/- 1), mean volume of reconstituted solution injected (2.8 mL) and mean sweating area at baseline (BSA) were similar in each palm group . The mean +/- SD dose injected was 69.3 +/- 3.1 U for the Botox-treated palms and 283.7 +/- 11.3 U for the Dysport-treated palms (1 : 4) . At 1 month, Minor's test revealed significant decreases in mean sweating area for each preparation (Dysport palms: -78.6% vs . BSA, P = 0.0002; Botox palms: -56.6% vs . BSA, P = 0.003) . The percentage of decrease was more pronounced in Dysport palms compared with Botox palms but the difference did not reach statistical significance . At 3 months, the decrease in sweating area remained significant for Dysport palms (-69.4% vs . BSA, P = 0.008) but not for Botox palms (-48.8% vs . BSA) . Self-evaluation showed a similar amount of improvement in both palm groups at 1 and 3 months (77% and 75% for Dysport; 68% and 72% for Botox) . Local side-effects were more frequent in Dysport palms (weakness of thumb-index pinch in four cases, lasting 8-30 days) than in Botox palms (weakness of thumb-index pinch in two cases, lasting 15-21 days) . The mean duration of positive effect was similar: 17 weeks in Dysport (range 8-32) and 18 weeks in Botox palms (range 8-32) . CONCLUSIONS: Using a conversion factor of 1 : 4, the efficacy of Botox and Dysport injections was similar . However, there was a trend towards a larger improvement after Dysport treatment but with a higher incidence of adverse effects.

Headache, 2003 Nov-Dec, 43(10), 1085 - 9
Single-site botulinum toxin type a injection for elimination of migraine trigger points; Behmand RA et al.; BACKGROUND: Botulinum toxin may be effective in suppressing migraine . Most injection regimens utilized have involved multiple sites . PURPOSE: To evaluate prospectively the effect of botulinum toxin type A injections into the corrugator supercilii muscles alone on the frequency and severity of migraine . METHODS: Twenty-nine patients (24 women, 5 men) with migraine were enrolled in the study . Average age was 45 years (range, 24 to 63) . The frequency (number of migraines per month) and intensity (recorded on an analog scale of 1 to 10, 10 being most severe) of headache were recorded before and after treatment . Twenty-five units of botulinum toxin type A was injected into each corrugator supercilii muscle, for a total of 50 units . RESULTS: At 2 months, 24 (83%) of 29 patients reported a positive response to the injection of botulinum toxin type A (P <.001) . Sixteen patients (55%) reported complete elimination of headache (P <.001), 8 (28%) experienced significant improvement (at least 50% reduction in frequency or intensity) (P <.04), and 5 (17%) did not notice a change in headache . The duration of efficacy of the botulinum toxin type A injections ranged from 6 to 12 weeks, with an average of 8 weeks . In patients who had improvement in migraine but not complete elimination, the headache frequency decreased from 6.4 to 2.1 per month on average (P <.04), and the intensity decreased from 8.6 to 6.1 (P <.04) . CONCLUSION: These results support the hypothesis that focal injection of botulinum toxin type A may be an effective therapy for migraine.

Acta Pharmacol Sin, 2003 Nov, 24(11), 1070 - 6
Low molecular weight G-proteins of rho-family mediate relaxations to bradykinin in porcine coronary arteries; Shibano T et al.; AIM: To determine whether or not low molecular G-proteins are involved in the endothelium-dependent relaxations to bradykinin . METHODS: The effects of botulinum ADP-ribosyltranferase C3 were studied in porcine coronary arteries and endothelial cells . RESULTS: Incubation of membrane fractions isolated from endothelial cells with the enzyme and 32P-NAD resulted in the ribosylation of the proteins with molecular weight of 24-25 kDa . Radio labelling of these proteins was suppressed in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP-gammaS), a hydrolysis-resistant analog of GTP . In the isolated arteries, ADP-ribosyltransferase C3 attenuated the relaxations to bradykinin during contractions with prostaglandin F2alpha in the presence of tween 80 (non ionic detergent), but not in the absence of tween 80 . CONCLUSION: Low molecular weight G-proteins of the Rho family contribute to the mechanism of relaxation induced by bradykinin.

Neuroreport, 2003 Dec 2, 14(17), 2177 - 81
Mechanisms of secretion of ATP from cortical astrocytes triggered by uridine triphosphate; Abdipranoto A et al.; The mechanisms involved in autocrine ATP release from cultured astrocytes isolated from the rat cortex were investigated using an online bioluminescence technique . Astrocytes released ATP in response to application of 10 microM uridine triphosphate, which was blocked by the non-specific purinergic receptor antagonist suramin . Intracellular pathways of the uridine triphosphate-stimulated ATP release were seen to involve inositol triphosphate and calcium with the assistance of the Golgi-complex and cytoskeleton as the release was inhibited by phospholipase C antagonist lithium, endoplasmic reticulum calcium-dependent ATPase inhibitor thapsigargin, F-actin interruptor cytochalasin D and Golgi-complex interruptor brefeldin A . The uridine triphosphate-stimulated ATP release was also potently blocked by exocytosis inhibitor botulinum toxin A and anion transporter blockers furosemide and glibenclamide . These results suggest that calcium-dependent exocytosis and transportation via anion transporters are the predominant secretion mechanisms for uridine triphosphate-stimulated ATP release from cortical astrocytes.

Biologicals, 2003 Dec, 31(4), 265 - 76
Role for standards in assays of botulinum toxins: international collaborative study of three preparations of botulinum type A toxin; Sesardic D et al.; The biological activity of therapeutic preparations of botulinum type A toxin is currently expressed in units defined on the basis of the median lethal intraperitoneal dose of that preparation in mice at 72 h, the LD50 dose . In this study we describe the comparison, by ten laboratories in five countries, of three different formulations of botulinum type A toxin using the mouse lethality test, and also using the relative activities of the preparations . The results of this study show that use of a standard preparation and expression of relative potency gives substantially greater consistency between and within laboratories than when mouse LD50 unit is used to define activity of botulinum toxin.

J Pain, 2002 Feb, 3(1), 21 - 7
The use of botulinum toxin for the treatment of chronic facial pain; Borodic GE et al.; An open label pilot study was conducted to evaluate efficacy of botulinum toxin injections for the treatment of patients with chronic facial pain seeking tertiary care at a pain clinic . Diagnoses included temporomandibular joint syndrome, postsurgical pain syndromes, essential headache, and idiopathic trigeminal neuralgia . Thirty-three (75%) of 44 patients favorably responded, including 8 of 11 patients with trigeminal neuralgia . The duration of beneficial effect ranged from 2 to 4 months, and all responding patients desired further injections . Complications were mild and included temporary facial asymmetry and weakness secondary to neuromuscular effects of botulinum toxin . Doses ranged from 25 to 75 LD 50 units with Hall strain-derived botulinum toxin type A . A small degree of facial edema during pain or erythema seemed to have predictive value when categorically evaluated against response.

J Pain, 2003 Apr, 4(3), 159 - 65
Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A; Freund B et al.; Botulinum toxin A has demonstrated efficacy in relieving pain in spastic and nonspastic muscle conditions . This analgesic property has generally been attributed to muscular relaxation . This study demonstrates initial muscular relaxation and concomitant pain relief in a masticatory muscle model . However, as muscle power returns to normal, pain relief is still very evident . This result suggests that the analgesic effect attributed to botulinum toxin is more complex than simple muscular relaxation.

Eur J Neurosci, 2003 Oct, 18(8), 2403 - 7
Molecular scaffold reorganization at the transmitter release site with vesicle exocytosis or botulinum toxin C1; Stanley EF et al.; Neurotransmitter release sites at the freeze-fractured frog neuromuscular junction are composed of inner and outer paired rows of large membrane particles, the putative calcium channels, anchored by the ribs of an underlying protein scaffold . We analysed the locations of the release site particles as a reflection of the scaffold structure, comparing particle distributions in secreting terminals with those where secretion was blocked with botulinum toxin A, which cleaves a small segment off SNAP-25, or botulinum toxin C1, which cleaves the cytoplasmic domain of syntaxin . In the idle terminal the inner and outer paired rows were located approximately 25 and approximately 44 nm, respectively, from the release site midline . However, adjacent to vesicular fusion sites both particle rows were displaced towards the midline by approximately 25% . The intervals between the particles along each row were examined by a nearest-neighbour approach . In control terminals the peak interval along the inner row was approximately 17 nm, consistent with previous reports and the spacing of the scaffold ribs . While the average distance between particles in the outer row was also approximately 17 nm, a detailed analysis revealed short 'linear clusters' with a approximately 14 nm interval . These clusters were enriched at vesicle fusion sites, suggesting an association with the docking sites, and were eliminated by botulinum C1, but not A . Our findings suggest, first, that the release site scaffold ribs undergo a predictable, and possibly active, shortening during exocytosis and, second, that at the vesicle docking site syntaxin plays a role in the cross-linking of the rib tips to form the vesicle docking sites.

Dig Liver Dis, 2003 Oct, 35(10), 735 - 7
Spontaneous perforation of an oesophageal diverticulum in achalasia; Cantu P et al.; Spontaneous perforation of the oesophagus is a rare occurrence that is usually due to vomiting and is seldom associated with an oesophageal lesion . We report a case of the spontaneous perforation of a large oesophageal diverticulum not preceded by any precipitating event in a 75-year-old male who was not known to have achalasia . The diverticulum was repaired by emergency surgery . Achalasia was later diagnosed and successfully treated with botulin toxin injection . Surgery decision-making and the treatment of achalasia are discussed.

J Pharmacol Exp Ther, 2004 Mar, 308(3), 857 - 64 Epub 2003 Nov 14.
The role of the interchain disulfide bond in governing the pharmacological actions of botulinum toxin; Simpson LL et al.; All serotypes of botulinum toxin possess a disulfide bond that links the heavy chain and light chain components of the holotoxin . Experiments were done to assess the functional significance of this covalent bond, and the work was facilitated by use of mercurial compounds that modify residues in the vicinity of the catalytic site . The data indicated that reduction of the interchain disulfide bond had two major effects: 1) . changing conformation or orientation of the two chains, which diminished toxicity against intact cells, and 2) . loosening or relocating a heavy chain belt segment that encircles the light chain and occludes the catalytic site . Interestingly, disulfide bond reduction of all serotypes produced conformational changes that diminished toxicity against intact cells, but it produced conformational changes that led to exposure of the catalytic site in only three serotypes . For the other serotypes, the catalytic site was accessible even before disulfide bond reduction . Neither of the major structural effects was dependent upon separation of the heavy chain and light chain components of the toxin, nor were they dependent on toxin substrate . Depending on the initial state of the toxin molecule, the combination of disulfide bond reduction and treatment with a mercurial compound could abolish toxicity . Therefore, this combination of treatments was used to convert active toxin into a parenteral vaccine . Administration of the modified toxin evoked a substantial IgG response, and it produced complete protection against a large dose of native toxin.

Colorectal Dis, 2003 Nov, 5(6), 552 - 7
Botulinum toxin injection inhibits myogenic tone and sympathetic nerve function in the porcine internal anal sphincter; Jones OM et al.; OBJECTIVE: Botulinum toxin is an effective treatment for anal fissure, though there is a lack of agreement over the optimal site for its injection . This reflects our current ignorance of its mechanism, and whether it has any action on the nerves of the internal anal sphincter (IAS) . This study set out to resolve this issue through use of a pig model . MATERIALS AND METHODS: Eight pigs were studied in pairs: one of each pair received a botulinum toxin injection into the anal sphincter, whilst the other acted as its control . Manometry was performed every two weeks under anaesthesia . Pigs were slaughtered at between four and six weeks after injection and the properties of the IAS compared in vitro . RESULTS: Whilst maximum anal resting pressure (MARP) increased slowly in control pigs during the experimental period, reflecting weight gain, a fall was observed in treated pigs . In vitro, IAS strips from control pigs generated 400 mg of spontaneous tone per gram of tissue (+/- 45; standard error), compared to 250 (+/- 25) mg/g tissue from treated pigs (P < 0.01) . Electric Field Stimulation at 50 Hz produced 150 (+/- 22) mg contraction/gram tissue in IAS strips from control pigs compared to 53 (+/- 13) mg/g tissue in treated pigs (P < 0.0005) . This contractile response was blocked by guanethidine . CONCLUSION: Botulinum toxin has a significant action on the IAS . It reduces myogenic tone and contractile responses of this tissue to sympathetic nerve stimulation . Further studies are required to clarify its mechanism of action more precisely.

Plant J, 2003 Dec, 36(5), 589 - 601
Functional analysis of barley RAC/ROP G-protein family members in susceptibility to the powdery mildew fungus; Schultheiss H et al.; Small monomeric G-proteins of the plant ras (rat sarcome oncogene product) related C3 botulinum toxin substrate (RAC)/Rho of plants (ROP) family are molecular switches in signal transduction of many cellular processes . RAC/ROPs regulate hormone effects, subcellular gradients of Ca2+, the organisation of the actin cytoskeleton and the production of reactive oxygen intermediates . Therefore, we followed a genetic bottom-up strategy to study the role of these proteins during the interaction of barley (Hordeum vulgare L.) with the fungal biotrophic pathogen Blumeria graminis f.sp . hordei (Bgh) . We identified six barley RAC/ROP proteins and studied their gene expression . Five out of six Rac/Rop genes were expressed constitutively in the leaf epidermis, which is the site of interaction with Bgh . None of the genes showed enhancement of mRNA abundance after inoculation with Bgh . After microprojectile mediated transformation of single barley epidermal cells with constitutively activated mutant RAC/ROP proteins, we found an RAC/ROP-specific enhancement of pathogen accessibility, tagging HvRACB, HvRAC3 and HvROP6 as host proteins potentially involved in the establishment of susceptibility to Bgh . Confocal laser scanning microscopy (CLSM) of green fluorescent protein (GFP):HvRAC/ROP-transformed cells revealed varying strengths of plasma membrane association of barley RAC/ROPs . The C-terminal CAAX motif for presumable prenylation or the C-terminal hypervariable region (HVR), respectively, were required for membrane association of the RAC/ROPs . Proper intracellular localisation was essential for HvRACB and HvRAC3 function . Together, our data support the view that different paths of host signal transduction via RAC/ROP G-proteins are involved in processes supporting parasitic entry into epidermal host cells.

Clin Exp Dermatol, 2003 Nov, 28(6), 592 - 4
Successful use of Botulinum toxin-A for the treatment of neck and anterior chest wall flushing; Sterodimas A et al.; Neck and anterior chest wall flushing can be a social handicap to the sufferer and current treatment options are often unsatisfactory . We report the case of a 48-year-old woman with severe flushing of the anterior neck and anterior chest wall which resolved after three treatments of intracutaneous botulinum toxin A injections . We believe that this treatment method for skin flushing is simple, effective and free of significant side effects at these sites . Further studies are needed to evaluate the duration of the therapeutic effect.

Rev Neurol (Paris), 2003 Oct, 159(10 Pt 1), 928 - 31
{Parkinsonian dystonia}; Dowsey-Limousin P; Dystonias are frequently observed in Parkinson's disease or other parkinsonian syndromes . They can occur during off-periods, either in the morning (early morning dystonia) or during daily off-periods, and during on-periods . Dystonia involves more frequently the upper and lower limbs, the neck or the face . Dystonia can be painful in particular off-period feet dystonia . The mechanisms underlying dystonia are not fully understood, basal ganglia activity and levodopa levels seems to play an important role . There are several medical options to try and improve those dystonias, adjustment of levodopa doses, adding a dopamine agonist drug, anticholinergics, lithium, baclofene or clonazepam . Those options are not always very effective . Botulinum toxin injections are an alternative treatment for focal dystonia . Muscles have to be selected by observation of the dystonia . Deep muscles in particular in the legs can be injected under EMG guidance . Botulinum toxin injections are particularly helpful and safe for lower limb dystonia . They can be used also for other forms of dystonia . Upper limb dystonia can be injected, allowing more comfort and easier hygiene but not necessarily better function, weakness is the main side effect . Cervical dystonia, blepharospam and oromandibular dystonia can be managed the same way as idiopathic dystonia . The dose might be lower since the muscles are usually not as hypertrophic . Side effects are as expected dysphagia and neck weakness in case of cervical dystonia, ptosis, inocclusion and diplopia in case of blepharospasm, jaw opening difficulty with oromandibular dystonia . Basal ganglia surgery can also help dystonia in a selected population of parkinsonian patients.

Rev Neurol (Paris), 2003 Oct, 159(10 Pt 1), 923 - 7
{Problems of treating writer's cramp with botulinum toxin injections: results from 10 years of experience}; Marion MH et al.; We studied the efficacy of botulinum toxin (BTX-A) injections in 167 patients, from a large cohort of 259 patients, presenting with writer's cramp (WC) and followed up to 10 years . The selection of the muscle was based on a careful physical examination, using up to 6 manoeuvres whilst attempting to write in order to bring out the original dystonic posture . The injection technique had to be precise, under EMG guidance, with a hollow recording needle to detect muscle or finger fascicle . The results showed a good efficacy and tolerance of this treatment in the long term with recovery of normal writing in 46 per cent, partial benefit in 10 per cent, failure in 21 per cent, and loss to follow-up after the first injection in 23 per cent . Among the responders, 27 per cent carried on the treatment every 9 months on average, with a duration of benefit of 6 months with follow-up between 3 and 9 years . Mirror dystonia had no prognostic value . Secondary dystonia, tremulous WC, long duration WC and progressive WC were associated with poor outcome.

Rev Neurol (Paris), 2003 Oct, 159(10 Pt 1), 916 - 22
{Laryngeal dystonia}; Klap P et al.; Laryngeal dystonia alters phonatory and respiratory functions in ways that may differ according to the various clinical forms . Spasmodic dysphonia, however, is the most usual clinical consequence; it is characterized either and most often by an raucous, strained, jerky voice and dotted by vocal short stops, or, more rarely, by a breathed, murmured hardly audible voice . Laryngeal dystonia may also express itself by a permanent inspiratory dyspnea witch will increase with effort . The authors describe the principal diagnostic data with are provided essentially by laryngeo-video-fibroscopy and laryngeal electromyography . Treatment of laryngeal dystonia by botulinium toxin is spectacularly efficient, with 66.7 to 100p.100 of good results in literature . Injection techniques are described as well as combined surgical treatments . In adductor spasmodic dysphonia and permanent inspiratory dyspnea, each thyro-arytenoids muscles are injected with 20 to 40 Dysport units or 5 to 10 Botox units, bilaterally; in abductor spasmodic dysphonia, we inject uni or bilaterally, 60 to 80 Dysport units or 15 to 20 Botox units in each posterior crico-arytenoids muscles . Endoscopic or external laryngeal surgery is proposed to improve functional results when the effects of botulinium toxin injection are disappointing.

Ann Gen Hosp Psychiatry . 2003 Oct 17;2(1):9.
Treatment of severe neuroleptic-induced tardive torticollis; Havaki-Kontaxaki BJ et al.; BACKGROUND: The aim of this paper is to describe a case of severe neuroleptic-induced tardive torticollis successfully treated with a combination of clozapine, clonazepam and botulinum toxin-A . CASE REPORT: The patient, a 30-year old man with a seven-year history of delusional disorder experienced severe right torticollis with painful tightness of the neck and elevation of the shoulder . At this time he was receiving haloperidol 20 mg, trifluoperazine 5 mg, zuclopenthixol 20 mg and biperidine 4 mg daily . The combination therapy with clozapine and clonazepam and the long-term use of botulinum toxin-A resulted in a complete remission of dystonic movements . CONCLUSIONS: The present observations provide evidence indicating that this combination therapy may be of benefit in patients with severe neuroleptic-induced tardive torticollis.

Skin Therapy Lett, 2003 Nov-Dec, 8(7), 1 - 4
Treatment of hyperhidrosis with botulinum toxin A; Lauchli S et al.; Focal hyperhidrosis of axillae, palms or soles is a frequent, socially debilitating condition triggered by various emotional stimuli . There are several treatment options such as local application of metal sales (aluminum chloride) or tap water iontophoresis, which provide temporary relief for some patients . More recently, local intradermal injections of botulinum toxin A (BTX-A), a neurotoxin blocking the cholinergic stimulus of eccrine sweat glands, offers an effective treatment option with few side-effects . Patient satisfaction rates are high, although treatment effects only last a few months . For definite care, surgical procedures have to be considered.

Neurology, 2003 Nov 11, 61(9), 1279 - 81
A randomized trial of botulinum toxin A for treatment of drooling; Lipp A et al.; The authors compared the efficacy of three different doses (18.75, 37.5, and 75 MU per parotid gland) of botulinum toxin A (BTX-A; Dysport, Ipsen Pharma, Germany) injections vs vehicle in patients with sialorrhea (n = 32) using a single-center, prospective, double-blind, placebo-controlled dose-finding study . The primary endpoint was achieved with 75 MU BTX-A without treatment-related adverse events, suggesting BTX-A is a safe and effective treatment for patients with sialorrhea.

Tech Coloproctol, 2003 Jul, 7(2), 85 - 8; comment 88
Botulinum toxin for the treatment of secondary chronic anal fissure; Madalinski MH; BACKGROUND: Botulinum toxin A (BT-A) injection into internal or external anal sphincter causes relaxation of the anal sphincters, enhancing microcirculation at the fissure site and promoting fissure healing . There are no such observations in patients with secondary anal fissure . METHODS: Six patients with fissures after surgical or nonsurgical treatment of hemorrhoids and four patients with ulcerative colitis received injections of BT-A on both edges of the fissure (total dose, 25 U Botox) . RESULTS: In the week following BTA injection, patients with fissure after hemorrhoids treatment had relief of fissure symptoms, but one month later the fissures still existed . They then received an additional 25 U Botox . One month after the second BT-A injection, all fissures were healed . The patients with ulcerative colitis had only symptomatic improvement after BT-A injection . CONCLUSION: BT-A therapy seems effective for the treatment of chronic anal fissure after surgical or nonsurgical treatment of hemorrhoids.

Laryngoscope, 2003 Nov, 113(11), 1973 - 6
Three-dimensional reconstruction of immunolabeled neuromuscular junctions in the human thyroarytenoid muscle; Sheppert AD et al.; OBJECTIVES/HYPOTHESIS: The objective was to reveal the location of the neuromuscular junctions in a three-dimensional reconstruction of the human thyroarytenoid muscle within the true vocal fold . STUDY DESIGN: Immunohistochemical analysis of serially sectioned human true vocal folds was performed, followed by reconstruction in three dimensions using computer imaging software . METHODS: Six fresh human larynges from autopsy were harvested, fixed in formalin, and embedded in paraffin . Eight vocal cords were studied from these six larynges . Five-micron serial sections were collected throughout the entire vocal cord in an axial plane at 500-microm intervals . Immunohistochemical analysis was performed with anti-synaptophysin antibody . A computer-controlled imaging and reconstruction system was used to create a three-dimensional reconstruction from the serial sections and to represent the location of the clustered band of neuromuscular junctions within each true vocal fold . The vocal cord was divided into equal thirds from anterior to posterior for statistical analysis . RESULTS: The most neuromuscular junctions (74%) were located in the middle third, and the least (7%) were found in the anterior third . The difference in anterior-to-posterior distribution was statistically significant in all eight specimens by chi2 analysis (P <.001) . CONCLUSION: The distribution of neuromuscular junctions is not random within the human thyroarytenoid muscle . Because neuromuscular junctions are most highly concentrated in a band within the mid belly of the muscle, botulinum toxin type A (Botox) injection in patients with spasmodic dysphonia should be targeted to this region.

Dis Esophagus, 2000, 13(2), 96 - 101; discussion 102-3
Long-term follow-up of achalasic patients treated with botulinum toxin; D'Onofrio V et al.; Botulinum toxin A (BoTx), a potent inhibitor of acetylcholine release from nerve endings both within the myenteric plexus and at the nerve-muscle junction, has been shown to decrease the lower esophageal sphincter (LES) pressure in patients with achalasia . Because of this property, the esophageal injection of BoTx has been suggested as an alternative treatment in achalasia . The objective of this study was to determine the long-term efficacy and safety of intrasphincteric injection of BoTx in a group of achalasic patients . Nineteen patients (mean age 56.1 +/- 19.2 years) were enrolled in the study . All of them were injected endoscopically with 100 U of BoTx by sclerotherapy needle at different sites of the LES . Symptom score (dysphagia, regurgitation and chest pain, each on a 0-3 scale), esophageal manometer and esophageal radionuclide emptying were assessed before the treatment and at 4 weeks, 3 months and 1 year after BoTx injection . In case of failure or relapse (symptom score > 2), the treatment was repeated . All but five patients (74%) were in clinical remission at 1 month . Mean symptom score after 1 month of BoTx decreased from 7.1 +/- 0.9 to 2.2 +/- 2.5 (p < 0.05) . LES pressure decreased from 38.4 +/- 13.7 to 27.4 +/- 13.5 mmHg (p < 0.05) and 10-min radionuclide retention decreased from 70.9 +/- 20.7% to 33.8 +/- 27.0% (p < 0.05) . Side-effects (transient chest pain) were mild and infrequent . At 12 months, the clinical score was 0.9 +/- 0.5 (p < 0.05 vs . basal); mean LES pressure was 22.0 +/- 7.1 (p < 0.05 vs . basal) and 10-min radionuclide retention was 15.8 +/- 6.0% (p < 0.05 vs . basal) . The efficacy of the first injection of BoTx lasted for a mean period of 9 months (range 2-14 months) . At the time of writing (follow-up period mean 17.6 months, range 2-31), 14 patients (10 with one injection) were still in remission (74%) . Our results showed that one or two intrasphincteric injections of BoTx resulted in clinical and objective improvement in about 74% of achalasic patients and are not associated with serious adverse effects; the efficacy of BoTx treatment was long lasting; this procedure could be considered an attractive treatment, especially in elderly patients who are poor candidates for more invasive procedures.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Nov, 96(5), 544 - 9
Treatment of perioral dystonia with botulinum toxin in 4 cases of Meige's syndrome; Moller E et al.; OBJECTIVE: We describe the treatment of 4 patients (median age, 53.5 years) with incapacitating perioral dystonia and insufficient response to peroral medication . Their general treatment with clonazepam and anticholinergics was supplemented by intramuscular injections with botulinum toxin A (20-40 U) in the orbicularis oris muscle, guided by electromyography (EMG) . STUDY DESIGN: Perioral dystonia and treatment effect were assessed by using subjective global and visual analog scales, examiner-based video movement counts and rating scales, and quantitative EMG . t Tests were used for statistical analysis . RESULTS: The result of the intramuscular botulinum toxin A injections was characterized by the patients as "much improved"; correspondingly, dystonia was significantly reduced in visual analog scale scores, on examiner-based assessments, and in recordings of EMG . The side effects were few and short-lasting . CONCLUSION: Incapacitating perioral dystonia in Meige's syndrome may be safely controlled by recurrent EMG-guided botulinum toxin A injections in the orbicularis oris muscle, in combination with general medication.

Neuroreport, 2003 Nov 14, 14(16), 2079 - 83
ATP secretion from nerve trunks and Schwann cells mediated by glutamate; Liu GJ et al.; ATP release from rat sciatic nerves and from cultured Schwann cells isolated from the nerves was investigated using an online bioluminescence technique . ATP was released in relatively large amounts from rat sciatic nerve trunks during electrical stimulation . This release was blocked by the sodium channel inhibitor tetrodotoxin and the non-NMDA glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) . Schwann cells isolated from the nerve trunks did not release ATP when electrically stimulated but did in response to glutamate in a concentration-dependent manner . Glutamate-stimulated ATP release was inhibited by specific non-competitive AMPA receptor antagonist GYKI 52466 and competitive non-NMDA receptor antagonist CNQX . Glutamate-stimulated ATP release was decreased by inhibition of anion transporter inhibitors by furosemide, cystic fibrosis transmembrane conductance regulator by glibenclamide and exocytosis by botulinum toxin A, indicating that anion transporters and exocytosis provide the main secretion mechanisms for ATP release from the Schwann cells.

Ann Chir Plast Esthet, 2003 Oct, 48(5), 346 - 9
{The plastic surgeon and the prevention of facial aging process}; Le Louarn C; The fight against aging is carried out on several levels: a healthy life, anti-aging medicine as well as fight against aging symptoms . In our days, plastic surgeons anxious to find answers to the specific demands of their patients must invest themselves in other areas, to at least, acquire the knowledge or, to enable them to practice the necessary skills to meet those needs . Once it is agreed upon that a healthy life is the forerunner of any meaningful anti-aging program, the forceful demands of patients for anti-aging treatments must be treated with great care . This specialty is presently at an embryonic stage . Today the research is focused on providing the best well being while aging rather than stopping it . In addition, to date, certain hormonal treatments have not proven their efficacy and safety . As for the prevention of facial aging, the injection of botulinum toxin A presents the most advanced technique known . It acts on aging resulting from muscular hyperkinetics . Furthermore, because of increased hydration of the skin it delays actinic aging . This technique has lots of room for improvement: on the physician side by developing a better understanding of functional anatomy to target the injections to suit each patient's case, and on the supplier side by improvement of the product.

Biol Cell, 2003 Oct, 95(7), 459 - 64
Calmodulin-dependent regulation of a lipid binding domain in the v-SNARE synaptobrevin and its role in vesicular fusion; De Haro L et al.; Trans SNARE complex assembly is an essential step in Ca2+-dependent membrane fusion, although the SNARE proteins do not bind Ca2+ ions . Studies to evaluate how the Ca2+sensor protein calmodulin might regulate this process led to the identification of a consensus calmodulin binding motif in the v-SNARE VAMP2 . This sequence (residues 77-90) is situated precisely C-terminal to the tetanus toxin (TeNT) and botulinum B toxin cleavage site (76Q-F77) close to the transmembrane anchor . The same domain also binds acidic phospholipids and Ca2+/calmodulin or lipid binding are mutually exclusive . Directed mutagenesis of basic or hydrophobic residues within this motif reduced interactions with both Ca2+/calmodulin and phospholipids to a similar extent . The effects of these mutations on Ca2+-dependent exocytosis was explored using an hGH release assay in permeabilized pheochromocytoma PC12 cells . Treatment of cells with tetanus toxin (TeNT), which cleaves endogenous VAMP, abolished secretion . Secretion could be re-established by transfecting TeNT-resistant VAMP with mutations (Q76V,F77W) in the cleavage site . However rescue of exocytosis was abolished when additional mutations (K83A,K87V or W89A,W90A) were introduced that inhibited calmodulin and phospholipid binding to VAMP . Thus calmodulin and/or phospholipid binding to the membrane proximal region of VAMP is required for Ca2+-dependent exocytosis . We speculate that interactions between cis phospholipids at the vesicle surface and the membrane proximal region of VAMP inhibits SNARE complex assembly . Displacement of these interactions by Ca2+/calmodulin may promote SNARE complex assembly and lead to trans interactions between the membrane proximal region of VAMP and phospholipids in the plasma membrane.

Hand Clin, 2003 Nov, 19(4), 591 - 600
Botulinum toxin A in the management of upper limb spasticity in cerebral palsy; Chin TY et al.; Clinical experience thus far has shown BoNT-A to be a safe and efficacious method in the short to medium term management of spasticity of the upper limb in cerebral palsy . The relaxation of hypertonic musculature allows for improvement in function and posture, reduction of pain, and in some patients, improvement in cosmesis . It is also a valuable tool in predicting response to and guiding contemplated muscle-tendon surgery . Careful patient selection, detailed clinical assessment of deformity and disability, and a clear outline of treatment goals are essential to good outcomes . Further work needs to be done to determine optimum doses of BoNT-A for individual muscles and to evaluate the long-term outcome of repeated injections.

Prof Nurse, 2003 Oct, 19(2), 85 - 7
Botulinum toxin: a deadly substance with great therapeutic effect; Holmes S; Injections of botulinum toxin are commonly associated with cosmetic improvements . However, BTX is also used therapeutically to treat patients with neuromuscular and neurological disorders . Therapy is primarily carried out in outpatients as part of a wider management regimen, so it is vital for nurses to not only be aware of how BTX works but also of its deadly toxic properties.

Spine J, 2001 Jan-Feb, 1(1), 31 - 46
Cervicogenic headaches: a critical review; Haldeman S et al.; BACKGROUND CONTEXT: The notion that headaches may originate from disorders of the cervical spine and can be relieved by treatments directed at the neck is gaining recognition among headache clinicians but is often neglected in the spine literature . PURPOSE: To review and summarize the literature on cervicogenic headaches in the following areas: historical perspective, diagnostic criteria, epidemiology, pathogenesis, differential diagnosis, and treatment . STUDY DESIGN/SETTING: A systematic literature review of cervicogenic headache was performed . METHODS: Three computerized medical databases (Medline, Cumulative Index to Nursing and Allied Health Literature {CINAHL}, Mantis) were searched for the terms "cervicogenic" and "headache." After cross-referencing, we retrieved 164 unique citations; 48 citations were added from other sources, for a total of 212 citations, although all were not used . RESULTS: Hilton described the concept of headaches originating from the cervical spine in 1860 . In 1983 Sjaastad introduced the term "cervicogenic headache" (CGH) . Diagnostic criteria have been established by several expert groups, with agreement that these headaches start in the neck or occipital region and are associated with tenderness of cervical paraspinal tissues . Prevalence estimates range from 0.4% to 2.5% of the general population to 15% to 20% of patients with chronic headaches . CGH affects patients with a mean age of 42.9 years, has a 4:1 female disposition, and tends to be chronic . Almost any pathology affecting the cervical spine has been implicated in the genesis of CGH as a result of convergence of sensory input from the cervical structures within the spinal nucleus of the trigeminal nerve . The main differential diagnoses are tension type headache and migraine headache, with considerable overlap in symptoms and findings between these conditions . No specific pathology has been noted on imaging or diagnostic studies which correlates with CGH . CGH seems unresponsive to common headache medication . Small, noncontrolled case series have reported moderate success with surgery and injections . A few randomized controlled trials and a number of case series support the use of cervical manipulation, transcutaneous electrical nerve stimulation, and botulinum toxin injection . CONCLUSIONS: There remains considerable controversy and confusion on all matters pertaining to the topic of CGH . However, the amount of interest in the topic is growing, and it is anticipated that further research will help to clarify the theory, diagnosis, and treatment options for patients with CGH . Until then, it is essential that clinicians maintain an open, cautious, and critical approach to the literature on cervicogenic headaches.

J Neurosci, 2003 Oct 29, 23(30), 9697 - 709
Vesicular localization and activity-dependent trafficking of presynaptic choline transporters; Ferguson SM et al.; Presynaptic synthesis of acetylcholine (ACh) requires a steady supply of choline, acquired by a plasma membrane, hemicholinium-3-sensitive (HC-3) choline transporter (CHT) . A significant fraction of synaptic choline is recovered from ACh hydrolyzed by acetylcholinesterase (AChE) after vesicular release . Although antecedent neuronal activity is known to dictate presynaptic CHT activity, the mechanisms supporting this regulation are unknown . We observe an exclusive localization of CHT to cholinergic neurons and demonstrate that the majority of CHTs reside on small vesicles within cholinergic presynaptic terminals in the rat and mouse brain . Furthermore, immunoisolation of presynaptic vesicles with multiple antibodies reveals that CHT-positive vesicles carry the vesicular acetylcholine transporter (VAChT) and synaptic vesicle markers such as synaptophysin and Rab3A and also contain acetylcholine . Depolarization of synaptosomes evokes a Ca2+-dependent botulinum neurotoxin C-sensitive increase in the Vmax for HC-3-sensitive choline uptake that is accompanied by an increase in the density of CHTs in the synaptic plasma membrane . Our study leads to the novel hypothesis that CHTs reside on a subpopulation of synaptic vesicles in cholinergic terminals that can transit to the plasma membrane in response to neuronal activity to couple levels of choline re-uptake to the rate of ACh release.

Cochrane Database Syst Rev . 2003;(4):CD003431.
Non surgical therapy for anal fissure; Nelson R; BACKGROUND: Because of the disability associated with surgery for anal fissure and the risk of incontinence, medical alternatives for surgery have been sought . Most recently, pharmacologic methods that relax the anal smooth muscle, to accomplish reversibly what occurs in surgery, have been used to obtain fissure healing . OBJECTIVES: To assess the efficacy and morbidity of various medical therapies for anal fissure . SEARCH STRATEGY: Search terms include "anal fissure randomized" . SELECTION CRITERIA: Studies in which participants were randomized to a non-surgical therapy for anal fissure . Comparison groups may include an operative procedure, an alternate medical therapy or placebo . Chronic fissure, acute fissure and fissure in children are included in the review . Atypical fissures associated with inflammatory bowel disease or cancer or anal infection are excluded . DATA COLLECTION AND ANALYSIS: Data were abstracted from published reports and meeting abstracts, assessing method of randomization, blinding, "intention to treat" and drop-outs, therapies, supportive measures (applied to both groups), dosing and frequency and cross-overs . Dichotomous outcome measures included Non-healing of the fissure (a combination of persistence and recurrence), and Adverse events (including incontinence, headache, infection, anaphylaxis) . Continuous outcome measures included measures of pain relief and anorectal manometry . MAIN RESULTS: 21 different comparisons of the ability of medical therapies to heal anal fissure have been reported in 31 RCTs . Nine agents were used (nitroglycerin ointment (GTN), isosorbide dinitrate, Botulinum toxin (Botox), diltiazem, nifedipine (Calcium channel blockers or Cachablos), hydrocortisone, lignocaine, bran, placebo) as well as anal dilators and surgical sphincterotomy . When two studies are excluded from analysis due to quality concerns, the significance disappears in the three main analyses: GTN vs . placebo group (0.78; 0.56-1.08), in children (0.96; 0.48-1.92) and adults (0.73; 0.50-1.07) . That is, GTN was, in this modified analysis, not significantly better than placebo in curing anal fissure . Cachablos were not tested against placebo, but in a comparison to GTN, Cachablo was equivalent in its ability to cure fissure (odds ratio 0.66; 0.22-2.01) . Botox, in a meta-analysis of two studies compared to placebo, showed no significant advantage in efficacy (0.75; 0.32-1.77), and in a comparison to GTN analyzing two studies, was also not significantly better than GTN (0.48; 0.21-1.10) . REVIEWER'S CONCLUSIONS: Medical therapy for chronic anal fissure, acute fissure and fissure in children may be applied with a chance of cure that is only marginally better than placebo, and, for chronic fissure in adults, far less effective than surgery.

Cochrane Database Syst Rev . 2003;(4):CD001332.
Anti-spasticity agents for multiple sclerosis; Shakespeare DT et al.; BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care . A variety of oral and parenteral medications are available . OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients . SEARCH STRATEGY: We searched the Cochrane MS Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (January 1966 to June 2003), EMBASE (January 1988 to June 2003), bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies . SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration . DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised . Missing data were collected by correspondence with principal investigators . A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed . MAIN RESULTS: Twenty-six placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam, threonine and cannabinoids) and thirteen comparative studies met the selection criteria and were included in this review . Only fifteen of these studies used the Ashworth scale, of which only three of the eight placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs . Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive . REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing . The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.

Biochemistry, 2003 Nov 4, 42(43), 12539 - 49
Autocatalytically fragmented light chain of botulinum a neurotoxin is enzymatically active; Ahmed SA et al.; The zinc-endopeptidase light chain of botulinum A neurotoxin undergoes autocatalytic fragmentation that is accelerated by the presence of the metal cofactor, zinc {Ahmed, S . A . et al . (2001) J . Protein Chem . 20, 221-231} . We show in this paper that >95% fragmented light chain obtained in the absence of added zinc retained 100% of its original catalytic activity against a SNAP-25-derived synthetic peptide substrate . In the presence of zinc chloride, when >95% of the light chain had undergone autocatalytic fragmentation, the preparation retained 35% of its original catalytic activity . On the other hand, in the presence of glycerol, the light chain did not display autocatalysis and retained 100% of the original activity . These results suggest that the activity loss by incubation with zinc was not a direct consequence of autocatalysis and that the environment of the active site was not affected significantly by the fragmentation . The optimum pH 4.2-4.6 for autocatalysis was different than that (pH 7.3) for intrinsic catalytic activity . Inhibition of autocatalysis at low pH by a competitive inhibitor of catalytic activity rules out the presence of a contaminating protease but suggests a rate-limiting step of low pH-induced conformational change suitable for autocatalysis . Our results of LC concentration dependence of the fragmentation reaction indicate that the autocatalysis occurs by both intramolecular and intermolecular mechanisms.

Dev Med Child Neurol, 2003 Nov, 45(11), 758 - 62
Botulinum toxin with and without casting in ambulant children with spastic diplegia: a clinical and functional assessment; Bottos M et al.; This study compared clinical and functional outcomes after treatment with botulinum toxin A (BTX-A) and BTX-A with casting in children with dynamic equinus foot . Ten children (seven males, three females; mean age 6 years 4 months, SD 2 years 7 months; range 4 to 11 years) with mild spastic diplegia and independent walking were divided into two groups: group 1, BTX-A and group 2, BTX-A plus casting . BTX-A was injected in the triceps surae bilaterally at multiple sites while the children were sedated with mask anaesthesia . Dysport toxin was used, 15 to 20 IU/kg in each muscle . Immediately after injection an ankle-foot orthosis was applied to children in group 1 and a cast to children in group 2 . Clinical assessment using the Ashworth scale, Gross Motor Function Measure (GMFM), range of movement measurement, and gait analysis was performed before treatment and 1, 4, and 12 months after treatment . Spasticity decreased significantly at 1-month examination in both groups (p = 0.002), at 4-month examinations (Wilcoxon test p = 0.003), and 12 month (p = 0.052) examinations in group 2 . GMFM highlighted a significant improvement in group 2 at the 4-month examination (p = 0.052 for standing,p = 0.007 for walking) . Gait analysis showed a significant increase in the walking speed in group 2 (p = 0.04) . No change was detected in ankle kinematics and kinetics or in muscular activity during the gait cycle . We confirmed that BTX-A reduces spasticity and improves functional performance in standing and walking; association with casting provides more marked and enduring results.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 901 - 10
Spinal cord injury and use of botulinum toxin in reducing spasticity; Fried GW et al.; Spasticity is commonly seen after spinal cord injury, and a large percentage of patients with spinal cord injury will need treatment to control it . Although oral medications do a fair job of controlling spasticity in most patients, some patients will need additional forms of treatment . In many cases, oral medications alone do not adequately control spasticity or the patient cannot tolerate the side effects . In these instances, botulinum toxin may help control the spasticity for approximately 3 months after injection . The amount of botulinum toxin and the injection sites can be tailored to meet individual patient needs . Botulinum toxins can reduce spasticity, improve function, and reduce the amount of needed assistance.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 885 - 99
Botulinum toxins in the treatment of migraine and tension-type headaches; Winner P; Botulinum toxins are promising preventive treatments for patients with moderate to severe episodic and chronic migraine and chronic daily headache . The recommended indications for botulinum toxins as preventive therapy lend themselves to the following patient types: those who demonstrate a lack of improvement from preventive (prophylactic) pharmacotherapy; those who experience severe and intolerable adverse events from preventive medications; those who refuse to use daily medications; those who have contraindications to acute migraine therapy, and elderly patients with chronic migraine . Both open-label and double-blind placebo-controlled studies using fixed-site, "follow the pain." or a combination approach have demonstrated significant reduction in migraine frequency, severity, and duration, as well as decreased use of acute medications . The most prominent reductions have been noted in those with reportedly the most severe migraine headaches . Large, well-designed, double-blind, placebo-controlled studies are recommended to further clarify optimum dosage and location of injection, reduce treatment frequency and duration, and address other primary headache disorders that may benefit from this therapy.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 837 - 54
Treatment of hyperhidrosis and drooling with botulinum exotoxin; Odderson IR; The treatment of focal hyperhidrosis and drooling with neurolysis of the neuroglandular junction is a relatively new and useful technique for managing such obvious conditions and improving the patient's quality of life . The treatment is safe, minimally invasive, and an effective alternative to other treatment modalities.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 821 - 35
Use of botulinum toxin type A and type B for spasticity in upper and lower limbs; Bell KR et al.; BT is likely effective in controlling spasticity in the smaller muscles of the arm and hand, although there has been only one large controlled trial . For lower limb spasticity, the outcomes are more mixed . No large randomized, controlled trials have been done, and the larger size of the muscles results in a decreased ability to treat widespread spasticity . For more focal treatment in the legs and feet, however, and when combined with other denervating agents or physical modalities, BT is probably effective . Careful analysis is warranted before performing any chemodenervation on a limb muscle or muscles.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 805 - 20
Botulinum toxins in pain management; Royal MA; BTs are a useful treatment in refractory MPS and have shown promise in various superficial neuropathic pain syndromes . Presumably BTs work by breaking the spasm/pain cycle, giving the patient a "window of opportunity" for traditional conservative measures to have a greater beneficial impact, but several studies suggest that a direct antinociceptive effect distinct from any reduction in muscle spasm may be at play . The major benefit of BTs compared with standard therapies is duration of response . BTs cannot be considered a "first line" treatment for any pain application; however, in refractory cases in which nothing else has helped, BTs may offer the patient and physician a chance for improvement and perhaps even cure.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 793 - 804, vi
Botulinum toxin in the management of bowel and bladder function in spinal cord injury and other neurologic disorders; Dykstra DD; Botulinum toxin inhibits release of acetylcholine and other neurotransmitters . It has been used successfully to treat pain and abnormal skeletal and smooth muscle activity in patients . This article discusses its use in patients with bladder and bowel disorders.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 781 - 92
The importance of electromyographic guidance and electrical stimulation for injection of botulinum toxin; Childers MK; The importance of EMG or electrical stimulation for guiding injections of botulinum toxin in limb muscles to treat dystonia or spasticity is based more on theoretical and preclinical data than on controlled clinical trials . Questions remain about the preferred administration of botulinum toxin for these conditions . Future clinical research is necessary to show clearly functional benefit of any particular injection localization method.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 767 - 79
Botulinum toxin for spasmodic dysphonia; Rodriquez AA; Botulinum toxin is the accepted method of managing SD and has given most patients with adductor SD the ability to develop satisfactory vocal function . Results have been less satisfactory in abductor SD . Management is accomplished best with a team approach . The physiatrist with experience in EMG and botulinum toxin usage can be a prominent member of this team.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 749 - 66, vi
Botulinum toxin therapy for cervical dystonia; Walker FO; Botulinum toxin revolutionized the treatment of cervical dystonia . In contrast to systemically active medications, the effect of botulinum toxin results from selective administration to weaken muscles involved in the dystonic posturing of the head . This article reviews the pathophysiologic basis of symptoms in cervical dystonia and how botulinum toxin alleviates them . Other therapeutic options are reviewed for comparison . This article discusses strategies for maximizing the clinical benefit of botulinum toxin in this disorder and reviews muscle selection and identification with electromyography.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 727 - 48
The management of oromandibular motor disorders and facial spasms with injections of botulinum toxin; Clark GT; Although much work is yet to be done in this area, nine general conclusions can be derived: 1 . Local site-of-injection side effects from botulinum toxin injections are rare, assuming proper technique is used . 2 . The two most common medication-related side effects from botulinum toxin orofacial injections are alterations in salivary consistency and inadvertent weakness of the swallowing, speech, and facial muscles . These complications are injection site-specific (eg, more common with lateral pterygoid injections and palatal and tongue muscle injections) and dose-dependent problems . These problems are bothersome but are not contraindications for the therapy if it is needed . 3 . The data presented in this article are mostly case series-based and open trial-based information that is promising, but randomized, blinded, controlled trials are needed to establish the true efficacy of this method for the orofacial motor and pain disorders . 4 . The novice should begin with injection of muscles he or she can inject with low risk of incorrect placement . The hard-to-find muscles should be avoided when starting out . The novice clinician should inject and dissect a few cadavers to improve injection technique . 5 . The general latency for botulinum toxin type A is 1 week, its duration is 2 to 3 months, and it is recommended that injection be done no more than once every 12 weeks to avoid development of antibodies against the toxin . 6 . Depending on the target muscle, injection dose is 10 to 50 U of Botox type A per site with a total dose of 200 U in the masticatory system . More than this can be used (400 U maximum) if other sites in the head and neck are included in the injection protocol . 7 . Regarding injecting painful muscles that do not exhibit palpable muscle hardness or EMG-determined spasticity or observable involuntary movements but have chronic myofascial trigger points or the patient localizes them as the site of their chronic daily headache pain, botulinum toxin injections might be helpful used in this manner, but conclusive data for this controversial application of botulinum toxin are still missing . 8 . Hemifacial spasm has the largest number of open-label, clinical trials, some of which have a 10-year follow-up . The conclusions reached by all of these reports is that treatment of hemifacial spasm with repeated injections of botulinum toxin has been highly successful and that the dose and relative effect of the injections are stable over time . 9 . Although EMG-guided injection may be useful, EMG is neither practical nor needed in most situations for orofacial injections because most of the orofacial muscles are easily palpable muscles or have definitive bony landmarks to help with the localization process.

Phys Med Rehabil Clin N Am, 2003 Nov, 14(4), 703 - 25
The use of botulinum toxin in pediatric disorders; Gaebler-Spira D et al.; Botulinum toxins have an exciting and important role in treating the child with hypertonia . The guidelines presented in this article are those that have been published representing the safe use of botulinum toxins in children . Experience and a decade of research have provided the framework for using botulinum toxins in decreasing deformity and promoting function . In children, a window of opportunity exists with botulinum toxin that allows improved motor control and elongation of shortened muscles . Although 3 to 4 months in an adult life is short, for a child it is a relatively greater proportion of their life experience and may be long enough for skill development . The improvement noted in function after botulinum toxin use is facilitated by comprehensive rehabilitation . The pediatric physiatrist has a unique role in the management of children with cerebral palsy and other conditions with hypertonia . Their knowledge and training reflect an understanding of anatomy and development that allows accurate evaluation of specific functional problems in children related to hypertonia . The pediatric physiatrist has experience in localization of muscles by EMG, nerve stimulation, and surface anatomy . Although many other physicians inject botulinum toxins, goal-directed management is the cornerstone to the physiatrist's thinking and treatment plan . Orthopedic surgery ultimately may be the intervention of choice if persistent contracture or progression of contractures occurs . Working in collaboration with an orthopedist identifies the timing of optimal surgical intervention for alignment . For persistent and severe hypertonia, the treatment team includes a neurosurgeon . All options for spasticity, such as selective posterior rhizotomy and intrathecal baclofen, should be considered . Re-evaluation of the child after selective dorsal rhizotomy or intrathecal baclofen is appropriate and should be discussed with therapists for focal intervention . Communication between members of the team and the family is desirable and frequently is one of the major contributions of the pediatric physiatrist . For children with focal hypertonia, botulinum toxins offer a dramatic but temporary repeatable change that affects rehabilitation . Research rapidly has captured the positive effect of the toxins on impairment and functional limitations . Not to be overlooked are outcomes related to quality of life . The long-term use of botulinum toxins and the role the toxins play throughout the life span of the person with a childhood hypertonic disorder are yet to be determined.

Urol Res, 2003 Oct, 31(5), 352 - 4 Epub 2003 Sep 04.
Effect of botulinum-A toxin to cremaster muscle: an experimental study; Cakmak M et al.; OBJECTIVE: A controversy exists on the definition, etiology and treatment of the retractile testes . In the present experimental study, we aimed to show the effect of botulinum-A toxin (Botox) on cremasteric muscle of a rat, and whether it may be an alternative to surgical treatment of retractile testis . METHODS: Ten Wistar rats were used in the study . By stimulating cremasteric reflex, five compound muscle action potentials (CMAP) of the right and left cremasteric muscles of each rat were recorded using surface electrodes . Intramuscular injection of botulinum-A toxin was done to the right side . Saline was injected to the left cremasteric muscles, and the left side also served as control . CMAP of the cremasteric muscles were recorded 45 days after the injection . Statistical analysis was done using Wilcoxon Signed rank test . RESULTS: Mean CMAP of the right side was 3.25+/-1.39 microV before the injection and 0.44+/-0.25 microV after botulinum-A toxin injection . The difference was statistically significant (p<0.05) . Mean CMAP on the left side was 3.48+/-0.32 microV and 3.14+/-1.12 microV at baseline and the end of the study, respectively . The difference was not statistically significant (p>0.05) . CONCLUSION: The botulinum-A toxin paralyzes the cremasteric muscles of the rats . As cremasteric hypertonicity is accepted as one of the reasons for retractile testes, botulinum-A toxin injection to cremasteric muscles may be helpful in diagnosis and may be an alternative to surgical treatment of this pathology in repeated dosages . Long-term evaluation of this paralysis is necessary.

Proc Natl Acad Sci U S A, 2003 Nov 11, 100(23), 13621 - 5 Epub 2003 Oct 22.
Botulinum toxin type B micromechanosensor; Liu W et al.; Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to humans; early and rapid detection is essential for adequate medical treatment . Presently available tests for detection of BoNTs, although sensitive, require hours to days . We report a BoNT-B sensor whose properties allow detection of BoNT-B within minutes . The technique relies on the detection of an agarose bead detachment from the tip of a micromachined cantilever resulting from BoNT-B action on its substratum, the synaptic protein synaptobrevin 2, attached to the beads . The mechanical resonance frequency of the cantilever is monitored for the detection . To suspend the bead off the cantilever we use synaptobrevin's molecular interaction with another synaptic protein, syntaxin 1A, that was deposited onto the cantilever tip . Additionally, this bead detachment technique is general and can be used in any displacement reaction, such as in receptor-ligand pairs, where the introduction of one chemical leads to the displacement of another . The technique is of broad interest and will find uses outside toxicology.

Free Radic Biol Med, 2003 Nov 1, 35(9), 1037 - 50
Rho A negatively regulates cytokine-mediated inducible nitric oxide synthase expression in brain-derived transformed cell lines: negative regulation of IKKalpha; Rattan R et al.; The present study describes the role of RhoA as a negative regulator of iNOS expression via the inactivation of NF-kappaB in transformed brain cell lines {C(6) glioma, human astrocytoma (T98G, A172), neuroblastoma (NEB), and immortal rat astrocytes} . Treatment with lovastatin resulted in the induction of LPS/IFN-gamma-mediated iNOS mRNA and increased nitric oxide (NO) production . The addition of mevalonate and geranylgeranylpyrophosphate (GGPP) reversed the lovastatin-mediated effect, whereas FPP had no effect . An inhibitor of geranylgeranyltransferase inhibitor (GGTI 298) further induced the cytokine and lovastatin-mediated iNOS expression, suggesting the involvement of geranylgeranylated proteins in the regulation of iNOS . Bacterial toxin B (inactivates RhoA, B, and C; CDC42; Rac proteins), C3 ADP-ribosyltransferase (C3) toxin from C . botulinum (inactivates RhoA, B, and C proteins), and Y-27632 (selective inhibitor of Rho-associated kinases) increased the LPS/IFN-gamma-mediated iNOS expression . Lovastatin treatment induced NO by increasing NF-kappaB translocation and its association with the CREB-binding protein (CBP/p300) via the downregulation of RhoA . Inhibition of RhoA resulted in increased activation of IKKalpha . Cotransfection studies with dominant-negative form of RhoA and iNOS-luciferase or NF-kappaB-luciferase reporter constructs further support these observations . Taken together, these studies show that downregulation of RhoA by lovastatin resulted in increased iNOS expression via the activation of NF-kappaB-CBP/p300 pathway in transformed brain cells.

Brain Res, 2003 Nov 14, 990(1-2), 165 - 71
Agmatine induces glutamate release and cell death in cultured rat cerebellar granule neurons; Abe K et al.; We investigated the effect of agmatine on cell viability of rat cerebellar granule neurons in a high-K+ (27.5 mM) medium . Exposure of cultured rat cerebellar granule neurons to agmatine (200-800 microM) resulted in a significant decrease in cell viability . Agmatine-induced neuronal death began to occur 6-12 h after addition, and gradually progressed . The agmatine neurotoxicity was attenuated by N-methyl-D-aspartate (NMDA) receptor antagonists and by enzymatic degradation of L-glutamate with glutamic pyruvic transaminase . Furthermore, a significant increase in extracellular L-glutamate concentration was detected before cell death occurred . In addition, agmatine-induced glutamate release and cell death were both blocked by pretreatment with botulinum toxin C, which is known to specifically inhibit the exocytosis . The agmatine neurotoxicity was not observed when extracellular K+ concentration was lower (10 mM) . These results suggest that agmatine induces glutamate release through the exocytosis and thereby causes NMDA receptor-mediated neuronal death in conditions in which extracellular K+ concentrations are elevated.

J AAPOS, 2003 Oct, 7(5), 339 - 44
Congenital absence of the inferior rectus muscle--diagnosis and management; Astle WF et al.; BACKGROUND: Congenital absence of the inferior rectus muscle is a rare cause of apparent inferior rectus palsy especially in the absence of associated cranial facial anomalies . METHODS: We report three cases of isolated congenital absence of the inferior rectus muscle and its successful surgical management . RESULTS: Failure of the normal embryologic development of the mesodermal complex around the eye can lead to agenesis of the extraocular muscles . In apparent palsies of the inferior rectus muscle and no definite cause, a high index of suspicion and orbital imaging can confirm the diagnosis of congenitally absent inferior rectus preoperatively . Surgical correction may involve inferior transposition of the horizontal rectus muscles . CONCLUSIONS: Although rare, congenital absence of the inferior rectus muscle is a possible cause of apparent inferior rectus muscle palsy particularly in the absence of another identifiable cause . Strabismus surgery in conjunction with intramuscular botulinum toxin injection can offer significant improvement in function and cosmesis of these patients.

J Pediatr Ophthalmol Strabismus, 2003 Sep-Oct, 40(5), 288 - 92
Incidence of stereopsis after treatment of infantile esotropia with botulinum toxin A; McNeer KW et al.; PURPOSE: The incidence of stereoscopic vision following surgery for infantile esotropia has been reported, but not from patients treated with simultaneous bimedial injection of botulinum toxin A . We previously reported other findings from 41 patients treated with botulinum toxin A before the age of 12 months . The purpose of this study was to report the incidence of stereopsis in these patients after long-term follow-up . PATIENTS AND METHODS: Data were acquired by recording the response to subjective stereoscopic testing during the postinjection follow-up period when reliable subjective responses could be obtained . At least 5 years had passed following injection, and the mean age of the patients was 8 years . RESULTS: Of the 41 patients, 11 were lost to follow-up, 10 had no stereopsis, 9 had gross stereopsis (according to Titmus fly tests), 1 had 800 seconds of stereoscopic vision, 2 had 400 seconds, 2 had 200 seconds, 1 had 60 seconds, and 5 had 40 seconds . CONCLUSIONS: In this study, two-thirds of the patients acquired stereopsis following simultaneous bimedial injection of botulinum toxin A for infantile esotropia . Stereopsis acquisition following injection of botulinum toxin A had a success rate comparable with that reported for surgically corrected infantile esotropia . Bimedial injection of botulinum toxin A accompanied by alternate patching prior to injection and diligent attention at ages ranging from 4 to 12 months is a simple and efficacious method for the management of infantile esotropia.

Neurology, 2003 Oct 14, 61(7), 940 - 4
A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A; Voller B et al.; OBJECTIVE: Botulinum toxin type A (BTXA) is used to treat neurologic disorders associated with increased muscle tone . Its use is often associated with pain relief . METHODS: A possible direct analgesic effect of BTXA on C and Adelta fibers was studied on 16 healthy volunteers receiving 30 U BTXA into one forearm and pure saline into the other . To exclude the secondary effect due to muscular tone reduction, BTXA was injected intradermally . Thermal sensory testing of heat pain (threshold and tolerance) and neuroselective current sensory testing of current pain threshold/tolerance were performed at baseline and 3, 14, and 28 days after treatment . Thereafter, on day 28, capsaicin was administered simultaneously into both forearms to evaluate a possible peripheral effect and central effect on pain processing and on the axon reflex flare . RESULTS: The authors observed no significant difference in any of the perception outcome measures between BTXA and placebo pretreated areas . Flare areas as a result of the release of neuropeptides after capsaicin application showed no differences . CONCLUSIONS: The results suggest that pain reduction after BTXA treatment is mediated through its effect on muscle tone rather than a direct analgesic effect.

Endoscopy, 2003 Oct, 35(10), 841 - 4
A modified method of botulinum toxin injection in patients with achalasia: a pilot trial; Martinek J et al.; BACKGROUND AND AIMS: Injection of botulinum toxin (BT) from direct vision into the lower esophageal sphincter (LES) lowers its basal tone and improves symptomatology in most of the patients with achalasia . We hypothesized that the effect could be improved by better degree of LES infiltration by toxin administered from both prograde and retrograde views . The aim of the study was to investigate the feasibility, safety and efficacy of this modified method of intrasphincteric BT injection in patients with achalasia . PATIENTS AND METHOD: Sixteen patients with achalasia were treated with BT injection . Hundred units of BT (Botox) were diluted with 4 ml of normal saline . Aliquots of 0.5 ml were injected into four quadrants of the LES from retrovision and then into each quadrant from direct vision . The patients were followed up for a median of 25.5 months (range 19-31) . RESULTS: No serious adverse events were noted . All patients responded well to the injection within one week and 3 patients (18.7 %) experienced an early relapse . The remaining 13 patients were classified as responders . After a single BT injection, 11 responders reported a relapse and 2 patients remained asymptomatic . The median symptom-free interval was 17 months (8-28) . Five patients with a relapse underwent BT reinjection . Three of them remained asymptomatic and two experienced the second relapse . After BT reinjection, the median symptom-free interval was 16 months (10-19) . All other patients with a relapse and without BT reinjection were treated with either balloon dilatation or surgery and are currently asymptomatic . CONCLUSION: Combining injection of BT into the LES from both direct vision and retrovision was feasible, safe and produced a rapid response which was sustained for more than 1 year in the majority of patients . This method of BT administration might be superior to the traditional injection from direct view only, and a randomized and prospective study comparing those techniques of administration should be performed.

J Biol Chem, 2004 Jan 2, 279(1), 644 - 51 Epub 2003 Oct 09.
High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E; Rickman C et al.; The release of hormones and neurotransmitters requires the fusion of cargo-containing vesicles with the plasma membrane . This process of exocytosis relies on three SNARE proteins, namely syntaxin and SNAP-25 on the target plasma membrane and synaptobrevin on the vesicular membrane . In this study we examined the molecular assembly pathway that leads to formation of the fusogenic SNARE complex . We now show that the plasma membrane syntaxin and SNAP-25 interact with high affinity and equimolar stoichiometry to form a stable dimer on the pathway to the ternary SNARE complex . In bovine chromaffin cells, syntaxin and SNAP-25 colocalize in defined clusters that average 700 nm in diameter and cover 10% of the plasma membrane . Removal of the C terminus of SNAP-25 by botulinum neurotoxin E, a known neuroparalytic agent, dissociates the target SNARE dimer in vitro and disrupts the SNARE clustering in vivo . Together, our data uncover formation of stable syntaxin/SNAP-25 dimers as a central principle of the SNARE assembly pathway underlying regulated exocytosis.

Pediatr Rehabil, 2003 Apr-Jun, 6(2), 85 - 96
Evidence-based approach of the use of Botulinum toxin type A (BTX) in cerebral palsy; Wong V; A systematic review with the Sachett model of evidence-based medicine of the use of Botulinum toxin type A (BTX) for intervention in children with Cerebral Palsy (CP) is highlighted . Currently, the evidence showed that BTX is useful for treating pes equinus due to spasticity of the gastrocnemius-soleus muscles . However, careful patient selection and goals of treatment have to be addressed . More multi-centre clinical trials with standardized protocols are needed before widespread recommendation of the use of BTX in treating spasticity in CP can be made.

J Urol, 2003 Nov, 170(5), 1908 - 12
Botulinum A toxin urethral injection for the treatment of lower urinary tract dysfunction; Kuo HC; PURPOSE: This study investigates the effectiveness of botulinum A toxin in the treatment of various types of lower urinary tract dysfunction and determines the predictive factors for a successful outcome . MATERIALS AND METHODS: A total of 103 patients with chronic urinary retention (45) or severely difficult urination (58) received urethral injection of botulinum A toxin . The dose was 50 units in 48 patients and 100 units in 55 . Clinical effects and urodynamic parameters were compared at baseline and after treatment . RESULTS: The 48 men and 55 women (age range 14 to 86 years) had various types of lower urinary tract dysfunction including detrusor sphincter dyssynergia in 29, dysfunctional voiding in 20, nonrelaxing urethral sphincter in 19, cauda equina lesion in 8, peripheral neuropathy in 14 and idiopathic detrusor underactivity in 13 . A total of 40 (39%) patients had an excellent result and 47 (46%) had significant improvement as assessed by the patients . The total success rate was 84.5% . Among these patients mean maximum voiding pressure decreased significantly (62 +/- 40 vs 43 +/- 31 cm H2O, p = 0.000), as did maximal urethral closure pressure (65 +/- 36 vs 48 +/- 31 cm H2O, p = 0.000) and post-void residual (226 +/- 165 vs 89 +/- 112 ml, p = 0.000) at 2 to 4 weeks after treatment . Among 45 patients with urinary retention the indwelling catheters were removed or clean intermittent catheterization was discontinued in 39 (87%) . CONCLUSIONS: Botulinum A toxin urethral injections at doses of 50 or 100 units were effective in decreasing urethral sphincter resistance in patients with various types of lower urinary tract dysfunction.

Eur Neurol, 2003, 50(3), 165 - 71
Is the reduction of spasticity by botulinum toxin a beneficial for the recovery of motor function of arm and hand in stroke patients?
Woldag H, Hummelsheim H.
To determine the functional benefit of botulinum toxin A (BtxA) in spasticity of arm flexors, we conducted an open-label study with 10 stroke patients . 480 mouse units BtxA (Dysport((R))) were injected into flexor muscles . Outcome measures were done by the Modified Ashworth Scale, Rivermead Motor Assessment (arm section), active and passive ranges of motion (ROM), grip strength and a 3-dimensional motion analysis . The functional capacity of the entire arm, even of the shoulder, and the ROM of fingers and wrist increased . Despite a diminution of muscle tone, grip strength remained unchanged or increased . An improvement of forearm extension was only observed in cases of preserved voluntary extensor motricity . Injection of BtxA into spastic distal flexor muscles may lead to a functional improvement of the entire arm . Grip strength is not necessarily reduced .

Toxicon, 2003 Oct, 42(5), 461 - 9
Intramuscular injection of 125I-botulinum neurotoxin-complex versus 125I-botulinum-free neurotoxin: time course of tissue distribution; Tang-Liu DD et al.; The diffusion from the site of intramuscular injection of 900 kDa botulinum neurotoxin-hemagglutinin complex (BoNT/A-complex) and 150 kDa free-botulinum neurotoxin (free-BoNT/A) was compared . Radioiodinated compounds were injected into the gastrocnemius muscle of rats (70Units (U) 125I-BoNT/A-complex, 67 or 344 U free-125I-BoNT/A, or free-125I-iodide) and the eyelids of rabbits (24 U 125I-BoNT/A-complex or 108 U free-125I-BoNT/A), and measured in various tissues at different time points . There were no detectable systemic effects or generalized botulinum neurotoxin toxicity in either rats or rabbits, indicating that most of the toxin, whether as 125I-BoNT/A-complex or free-125I-BoNT/A, remained at the injection site . In rats, 125I-BoNT/A-complex and free-125I-BoNT/A diffused in a pattern that was grossly similar . Almost no radioactivity was recovered from the brain . Radioactivity recovered from distant tissues (thyroid, skin, and contralateral muscle) was primarily attributable to either low molecular weight 125I-containing peptides or 125I-iodide . After injection into rabbit eyelids, neither 125I-BoNT/A-complex nor free-125I-BoNT/A spread to distant structures, including the eye . The results indicate that most of the neurotoxin does not diffuse from the injection site, whether in free or complexed form, and this may reduce the potential for systemic effects.

Neuropharmacology, 2003 Nov, 45(6), 857 - 62
SNAP-25 Ser187 does not mediate phorbol ester enhancement of hippocampal synaptic transmission; Finley MF et al.; Phorbol esters, activators of protein kinase C (PKC), have been shown to enhance synaptic transmission . One potential downstream target of PKC in the presynaptic terminal is the soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptor (SNARE) SNAP-25, which has a PKC phosphorylation site in its C-terminal coil centered at serine 187 (S187/Ser187) . We examined the role of S187 in hippocampal synaptic transmission . After proteolytic cleavage of native SNAP-25 by botulinum neurotoxin E (BoNT/E), synaptic transmission was restored in a subset of transfected CA3 pyramidal cells with a toxin-resistant form of SNAP-25 containing unaltered S187 (Swt), S187 mutated to alanine (SA) or S187 mutated to glutamate (SE) . We observed that phorbol-12,13-diacetate (PDAc, 10 microM) induced potentiation of neurotransmission to a similar degree for both Swt and SA (2.4-fold and 3.1-fold increase, respectively) . Furthermore, basal levels of transmission mediated by SE were reduced relative to that of Swt (failure rates of 72% and 41%, respectively) . Together, these data suggest that phosphorylation of SNAP-25 S187 does not mediate the observed enhancement of neurotransmission by phorbol esters at hippocampal synapses.

Pharmacotherapy, 2003 Sep, 23(9), 1105 - 22
Essential tremor: diagnosis and treatment; Chen JJ et al.; Essential tremor is a common movement disorder in adults that interferes with the performance of functional and social activities . Differentiation of essential tremor from other tremor syndromes is important in order to provide appropriate patient education and therapy . The mainstays of pharmacotherapy are propranolol and primidone; however, in selected patients, agents such as alcohol, benzodiazepines, botulinum toxin, and gabapentin may provide symptomatic benefits . Advances in surgical interventions, such as stereotactic thalamotomy and thalamic deep brain stimulation, offer patients an alternative treatment modality when pharmacotherapy is inadequate . A treatment algorithm is provided to guide clinicians in the management of patients with essential tremor.

Top Stroke Rehabil, 2001 Spring, 8(1), 47 - 55
Effective use of chemodenervation and chemical neurolysis in the management of poststroke spasticity; McGuire JR; Chemodenervation with botulinum toxin (BTX) and chemical neurolysis with phenol can be used alone or in combination to effectively manage focal spasticity after a stroke . As with other treatments, these interventions must be done the right way, at the right time, in the right patient, and for the right reason . The proper use of these treatments requires careful patient assessment and realistic goals, knowledge of the peripheral functional anatomy, and an understanding of how these treatments work and how to best to administer them . This article reviews how BTX and phenol can be used in the management of poststroke spasticity.

Top Stroke Rehabil, 2001 Spring, 8(1), 36 - 46
Intrathecal baclofen therapy for stroke-related spasticity; Francisco GE; Intrathecal baclofen (ITB) therapy is a widely recognized management technique for severe, disabling spasticity in individuals with cerebral palsy and spinal and brain injuries . Its utility in the stroke population has only been recognized recently . Unlike the aforementioned patient populations, many stroke survivors are ambulatory and are able to maintain a certain degree of functional independence through compensatory use of the uninvolved limbs . Clinicians often fail to recognize the potential enhancement in the function of these individuals if they gain better control of their spastic limbs . Other spasticity treatments, such as oral medications and neurolytic procedures, offer the advantage of being nonsurgical; however, not every stroke patient will respond well to them . Some patients may not tolerate the systemic side effects of oral medications, such as drowsiness and sedation . In patients with severe multilimb spasticity, phenol and even high doses of botulinum toxin may not adequately control spasticity . ITB therapy offers the advantage of effectively decreasing severe, diffuse spasticity without causing untoward effects on arousal and cognition . This article will review the efficacy of ITB therapy in treating spasticity and enhancing function in stroke survivors.

Acta Neurochir Suppl, 2003, 87, 129 - 31
Neurosurgical treatment for writer's cramp; Taira T et al.; BACKGROUND: Writer's cramp is a type of focal dystonia due to dysfunction of the pallido-thalamo-cortical circuit . The symptom is refractory to most conservative treatment, though botulinum toxin injection is generally used for symptomatic relief . As a surgical treatment of dystonia we performed stereotactic nucleus ventrooralis (Vo) thalamotomy for dystonic cramp of the hand . METHOD: Eight patients (5 men, 3 women, age 26-40 yrs, mean 32.1 yrs) with medically intractable task-specific focal dystonia of the hand underwent Vo thalamotomy . Stereotactic target was chosen at the junction of the anterior and posterior Vo nuclei . FINDINGS: The mean duration of the symptom ranged from 3 to 6 years (mean, 4.0 yrs) . All patients had complained of difficulty in writing . Six patients were professional workers, such as comic artist, guitarist, and barber, and, because of the dystonic symptoms at their professional work, they had stopped pursuing their profession . All patients showed immediate postoperative disappearance of dystonic symptoms, and the effect was sustained during the follow up period (3-29 months, mean 13.1 mo) except in one case . One patient showed partial recurrence of the symptom and underwent second thalamotomy 5 months after the initial surgery with satisfactory results . The score of the writer's cramp rating scale significantly (p < 0.001) decreased after Vo thalamotomy . There was no permanent operative complication . There was no mortality or permanent morbidity . INTERPRETATION: Although a longer follow-up is needed, stereotactic Vo thalamotomy is a useful and safe therapeutic option for writer's cramp.

Acta Neurochir Suppl, 2003, 87, 43 - 7
New development of functional neurorehabilitation in neurosurgery; von Wild KR; OBJECTIVES: Today, increasingly more patients with severe brain and spinal cord lesions mainly secondary to accidents, violence, stroke, and tumours survive their injuries, in many cases, however, suffering from severe functional impairments of functioning as described by the WHO-ICF criteria . New developments of functional neurorehabilitation in neurosurgery could significantly improve the patients' quality of life (QoL) in terms of brain and body functioning and certain health-related components of well-being (such as social activities and leisure) . METHODS: Functional rehabilitation is an original task of neurosurgery from the very outset . Advances in biotechnology regarding both basic research and clinical application have opened up a new and very promising field to restore or compensate impaired or definitively lost organic functions in addition to the conservative rehabilitation methods . RESULTS: Along with the scientific progress in biotechnology and functional MRI and PET, neurosurgeons have become increasingly interested and actively involved in rehabilitation science and neurosurgical re-engineering of the damaged brain and spinal cord . Some of them have developed new specially designed institutions for early (acute) and subacute neurorehabilitation . Attached to the acute services, neurosurgeons thus become responsible for neurorehabilitation and at the same time for the management of all kinds of complications, which significantly improves the early and late functional outcome . At the same time microelectronics, biotechnology, and genetic engineering are being introduced into the field of neurosurgical rehabilitation in a step-by-step manner . DISCUSSION: Progress in the fields of microelectronics, computer technology, and genetic engineering along with rehabilitation science is opening up a new field of unknown chances to partially restore lost body functions and to help improve the quality of life of disabled patients in the sense of ICF . Functional neurosurgery plays a major role in neurosurgical rehabilitation . e.g . functional electrostimulation, brain-stem implants, pain and epilepsy control, restoration of locomotion and grasp faculties, and the use of potent substances such as botulinum toxin (Btx) . This demands the capacity of time work and the realization of the necessity to draw up a detailed plan for the restoration of impaired functions prior to enacting a neurosurgical intervention in the sense of a complex neurorehabilitation, and consequently to assume the responsibility for the patient's outcome . From the beginning of neurological surgery, the preservation and restoration of impaired brain and spinal-cord functions as an original task for neurosurgeons demand their involvement with issues of functional neurorehabilitation including neurosurgical re-engineering of the damaged brain and spinal cord . In this connection the close and trusting cooperation with the clinical neuropsychologist from the very outset is an indispensible factor.

Curr Treat Options Neurol, 2003 Nov, 5(6), 483 - 492
The Use of Botulinum Toxins for Chronic Pain and Headaches; Argoff CE; The use of botulinum toxin in the management of various neurologic and non-neurologic disorders has grown considerably over the past decade . At the same time, new information regarding the mechanism of action of these toxins has evolved allowing for a greater understanding of the versatility of these agents . Although two types of botulinum toxin (type A Botox and type B Myobloc ) are commercially available in the US, most studies of the use of these toxins for the management of chronic pain and headache have been completed with type A . Data from open-label and retrospective studies as well as clinical practice suggest as strongly as possible that there is a role for these agents, especially Botox, in the management of several chronic headache disorders, including chronic migraine, chronic tension-type, cervicogenic, and cluster headache . Emerging data regarding the use of these agents for so-called "analgesic-rebound" headache also appear impressive; however, as of yet, no multicenter, randomized, controlled studies for any headache type have been published that confirm the results seen in noncontrolled studies . Nevertheless, the benefit that some patients experience from this agent is impressive, and this drug appears for many to modify the disorder in a very positive manner . In a similar fashion, data for other pain states are often restricted to open-label and case study approaches; however, clinical experience and some of the available studies (even small controlled studies) suggest a role for the toxins in the management of various chronic pain states, such as myofascial pain, low back pain, and neuropathic pain . One of the greatest challenges ahead for all interested in this area is confirming the benefit seen clinically through appropriately designed multicenter, randomized, controlled studies.

Dev Med Child Neurol, 2003 Oct, 45(10), 664 - 70
Measures of muscle and joint performance in the lower limb of children with cerebral palsy; Fosang AL et al.; The aim of this study was to determine the reliability and magnitude of error of three lower-limb clinical measures for children with cerebral palsy (CP): the Modified Ashworth Scale of Spasticity (MAS), passive range of movement (PROM) and the modified Tardieu scale (MTS) . Six physiotherapists measured 11 females and seven males (mean age 6 years 4 months, SD 2 years 4 months; age range 2 years 4 months to 10 years) on two occasions using a repeated measures design, collecting all data over 6 days . The severity of CP spanned all five levels of the Gross Motor Function Classification System and all children demonstrated varying degrees of spasticity . Exclusion criteria included botulinum toxin injections, inhibitory plasters, and orthopaedic surgery within the 6 months before study entry . For PROM and the MTS interrater reliability was acceptable with an intraclass correlation coefficient of 0.7, but results for MAS were lower . Standard error of measurement for repeated measures of PROM and MTS was about five degrees, but 95% confidence interval ranges were considerably higher . Test-retest results varied widely, particularly for the MAS . These measurement tools should be used with caution when evaluating changes in young children with CP.

J Voice, 2003 Sep, 17(3), 434 - 41
Permanent medialization of the paralyzed vocal fold utilizing botulinum toxin and Gelfoam; Rontal E et al.; The clinical picture of a paralyzed vocal fold often has the same appearance as a subluxated arytenoid, with anterior and medial displacement of the arytenoid and a foreshortened and lax vocal fold . Previous work by the authors has shown that a subluxated arytenoid may be permanently repositioned by reduction and selective injection of the intrinsic laryngeal musculature with botulinum toxin . The injection changes the forces within the larynx, allowing the arytenoid to be brought back to proper position on the cricoid cartilage . This concept has been extended to the paralyzed vocal fold . It has been noted that even a clinically paralyzed vocal fold has voluntary motor units that may still act on the arytenoid through residual action from the interarytenoid and synkinesis . These forces are significant enough to manipulate the arytenoid and, thus, the vocal fold, into its correct, adducted position . In this paper, the arytenoid is mobilized to free any fibrosis . The thyroarytenoid and lateral cricoarytenoid muscles are then injected to prevent any forward synkinetic pull on the arytenoid . Next, a Gelfoam injection medializes the vocal fold to create glottic closure . This rebalancing sufficiently positions the arytenoid, so that valvular function is permanently restored . In the ten patients studied for over 1 year, there was a 90% success rate as measured by videostroboscopy, phonation time, and V-RQOL analysis . There were no untoward complications . All the materials used are nonpermanent . The procedure does not limit other techniques from being performed at a later time.

No Shinkei Geka, 2003 Sep, 31(9), 1015 - 20
{Peri-operative treatment with botulinum A toxin prior to posterior cervical decompression in a case with cervical spondylosis caused by spasmodic torticollis secondary to cerebral palsy}; Iwamuro H et al.; Patients with spasmodic torticollis secondary to athetoid cerebral palsy may develop symptomatic degenerative cervical disc disease or spondylosis . In these cases, peri-operative stabilization of the cervical spine is considered to be difficult and recurrence occurs frequently . We reported a case with cervical spondylosis induced by athetoid cerebral palsy . A 44-year-old female with athetoid cerebral palsy had suffered from secondary spasmodic torticollis . 7 years previously, she had been admitted to our hospital for the first time with complaints of gait disturbance, dysesthesia and hypesthesia in all extremities . CT-myelography and MRI showed disc degeneration and spondylosis at the level of C4/5 and C5/6, compressing the spinal cord . She underwent C5 vertebrectomy and C4-6 anterior fusion . However, due to cervical dystonia, it was difficult for her to wear a Philadelphia collar, so she had to under go complete bed rest for postoperative neck stabilization . Her symptoms improved after the operation . 5 years after the first operation, she complained of gait disturbance and sensory disturbance, again . MRI showed compression of the spinal cord at C2-C4, rostral to the level of the previous surgical area . So we planned the second operation . Prior to the operation, we used botulinum A toxin to reduce the athetoid movement of the neck . And we performed C3-6 expansive laminoplasty and partial laminectomy of C2 and C7 laminae . After the second operation, she was able to wear the Philadelphia collar without trouble and her neurological condition improved again . Botulinum A toxin was very effective to control the spasmodic torticollis peri-operatively in this case with cervical dystonia.

Arq Neuropsiquiatr, 2003 Sep, 61(3A), 607 - 10 Epub 2003 Sep 16.
{Botulinum toxin type B in the management of dystonia non-responsive to botulinum toxin type A}; Cardoso F; BACKGROUND: Botulinum toxin (BTX) injection is the first choice treatment for focal dystonias . However 10% or more of patients who receive repetitive injections of BTX type A (BTX-A) lose response (secondary non-responders) . One of the strategies to manage such patients is to treat them with another serotype . The aim of this article is to describe my experience with BTX type B (BTX-B) in the management of patients with focal dystonia who became secondary non-responders to BTX-A . METHOD: Open-label non-controlled use of BTX-B injections to treat dystonia patients who developed secondary nonresponse to BTX-A Response to treatment was rated on a 0-4 scale (Jankovic) . RESULTS: Four patients entered the study . Pacient 1- At age 48 this man developed idiopathic cervical dystonia . Five years later he also presented with blepharospasm and idiopathic oromandibular dystonia . He was treated with 7604U of BTX-A along 23 sessions separated by a mean interval of 18.8 weeks (range 6-39) . Loss of response was noticed after the seventh session . First treatment with BTX-B consisted of injection of 20000U with response rated 3 but duration of 3 weeks . Second session, 23500U, resulted in score 4 with response lasting 12 weeks . Patient 2- This man, with Tourette syndrome since age 8 years, developed tardive blepharospasm at age 51 . On 8 sessions of BTX-A injections he received a cumulative dosage of 550U with a mean interval between sessions of 8.8 weeks (range 6-12) . Decline of response was noticed after the fifth session . First treatment with BTX-B, 3000U, had a response rated 3 with duration of 12 weeks . Second session, 6000U, resulted in score 4 . Patient 3- This woman noticed onset of blepharospasm at age 58 and developed oromandibular and laryngeal dystonia as well as cervical dystonia, respectively, at ages 59 and 65 . In other institutions she received 6 sessions of BTX-A . In my service she received a dosage of 1404U along 8 sessions with a mean interval between sessions of 17.4 weeks (range 16-18) . She became secondary non-responder after the ninth session . First treatment with BTX-B, 6000U, was rated 0 . Second session, 12000U, was rated 4 . Patient 4- At age 69 this man developed idiopathic cranial dystonia . Prior to follow up with me, he received 6 sessions of BTX-A in other services . In my institution he was treated with a cumulative dosage of 730U along 4 sessions with a mean interval between sessions of 16.3 weeks (range 15-18) . He developed loss of response on the sixth session . Treatment with BTX-B, 12000U, was rated 4 and lasted 20 weeks . Side-effects: local pain (all patients) and dryness of mouth and ptosis (one patient each) . CONCLUSION: My findings confirm that BTX-B injections are a safe and effective option for the management of dystonia patients who become secondary non-responders to BTX-A . The results also underscore the need of individualizing dosage regimens before optimum results are achieved.

Clin Ther, 2003 Aug, 25(8), 2268 - 78
A preliminary comparison of the efficacy and tolerability of botulinum toxin serotypes A and B in the treatment of myofascial pain syndrome: a retrospective, open-label chart review; Lang AM; BACKGROUND: Myofascial pain syndrome (MPS) is characterized by acute or chronic regional muscle pain associated with single or multiple trigger points within taut bands of muscle . Botulinum toxins have clinical utility when sustained focal muscle relaxation is required and may be a useful addition to the treatment armamentarium for MPS . OBJECTIVE: The purpose of the present article was to compare the efficacy and tolerability of botulinum toxin serotypes A and B (BTX-A and BTX-B) in the treatment of MPS . METHODS: This was a retrospective, open-label, single-center chart review . Charts of all patients who received either BTX-A or BTX-B for MPS between January and November 2001 were included in the review . Patients rated the intensity of their pain on a visual analog scale (VAS) from 0 = no pain to 10 = worst pain imaginable before and after receiving BTX-A or BTX-B . RESULTS: The charts of 91 patients (74.7% female, 25.3% male; mean {SD} age, 47 {10.2} years) who received BTX-A (n = 56; mean dose, 256.9 U; range, 100-600 U) or BTX-B (n = 35; mean dose, 9000 U; range, 2500-20,000 U) were included in this retrospective review . Patients who received BTX-A had significantly greater mean reductions in VAS pain scores compared with those who received BTX-B (mean reduction, 2.7 vs 1.8, respectively; P < 0.001) . Patients who received BTX-A also reported significantly longer durations of pain relief compared with those who received BTX-B (4.5 vs 2.7) months; P < 0.001) . Eight of 56 patients (14.3%) in the group that received BTX-A reported mild adverse events that included flulike symptoms, injection-site pain, and weakness of the neck muscles . Seven of 35 patients (20.0%) in the group that received BTX-B reported adverse events that included mild flulike symptoms, dry eyes, severe visual disturbances, and severe dry mouth . CONCLUSION: Patients with MPS who received BTX-A reported significantly greater reductions in pain for longer durations compared with those who received BTX-B . No patients who received BTX-A experienced severe systemic adverse events, compared with 4 patients who received BTX-B . The results of this comparison are consistent with the US Food and Drug Administration-approved labeling indicating that BTX-A is not interchangeable with any other botulinum toxin in terms of biological activity.

Biochem Biophys Res Commun, 2003 Oct 10, 310(1), 84 - 93
Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity; Burnett JC et al.; Botulinum neurotoxins (BoNTs) are among the most lethal biological substances to have been weaponized and are listed as biodefense category A agents . Currently, no small molecule (non-peptidic) therapeutics exist to counter this threat; hence, identifying and developing compounds that inhibit BoNTs is a high priority . In the present study, a high-throughput assay was used to identify small molecules that inhibit the metalloprotease activity of BoNT serotype A light chain (BoNT/A LC) . All inhibitors were further verified using a HPLC-based assay . Conformational analyses of these compounds, in conjunction with molecular docking studies, were used to predict structural features that contribute to inhibitor binding and potency . Based on these results, a common pharmacophore for BoNT/A LC inhibitors is proposed . This is the first study to report small molecules (non-peptidics) that inhibit BoNT/A LC metalloprotease activity in the low microM range.

Br J Dermatol, 2003 Sep, 149(3), 447 - 51
A review of peripheral nerve blockade as local anaesthesia in the treatment of palmar hyperhidrosis; Hayton MJ et al.; Injection of botulinum toxin type A (BTX-A) is an effective method of controlling palmar hyperhidrosis . It is, however, an uncomfortable procedure without adequate anaesthesia . We outline the techniques used, the reasons for them and potential pitfalls that can be avoided, with an outline of the neural anatomy relevant to the palmar injection of BTX-A . We have been using peripheral nerve blockade as local anaesthesia during BTX-A treatment of palmar hyperhidrosis for the last few years, and have found it an effective method of providing pain relief during the procedure, giving greater anaesthesia than that given by topical anaesthetic cream under occlusion and ice . It has been our experience that patients prefer wrist blockade to topical anaesthesia and ice when receiving BTX-A injections for treatment of palmar hyperhidrosis.

Ophthalmic Surg Lasers Imaging, 2003 Sep-Oct, 34(5), 391 - 5
Botulinum toxin A in the treatment of adherence syndrome; Ozkan SB et al.; The effect of botulinum toxin A is investigated in the treatment of adherence syndrome related to strabismus surgery . An 18-year-old boy with decompensated right congenital fourth nerve palsy underwent ipsilateral superior rectus muscle recession and inferior oblique muscle disinsertion . During the early postoperative period, a right hypotropia with limitation of elevation developed and the result of the forced duction test was positive for passive elevation of the right eye . Botulinum toxin A was injected into the right inferior rectus muscle on the 15th postoperative day and orthophoria was achieved 1 week later . A repeat injection of botulinum toxin A was performed 6 months later . On follow-up 2 1/2 years later, his eyes remained orthophoric with limitation of elevation in the right eye and the patient was satisfied with the result . This case demonstrated that adherence syndrome can be treated successfully by botulinum toxin A injection if it is administered during the acute phase, before the development of fibrous scar tissue.

Am J Clin Dermatol, 2003, 4(10), 709 - 25
Botulinum toxin A (Botox Cosmetic): a review of its use in the treatment of glabellar frown lines; Frampton JE et al.; Botox Cosmetic (Botox) is a formulation of the neuromuscular blocking agent botulinum toxin type A (BTX-A) . When injected into hyperactive corrugator superciliaris and/or procerus muscles of the face that predominantly control frowning, Botox produces a transient (3- to 6-month), dose-dependent localized muscle weakness, resulting in a temporary improvement in glabellar frown lines ('brow furrows') . After a decade of successful 'off-label' use, the efficacy and tolerability of Botox (total dose 20 biological units) in the treatment of glabellar frown lines have been demonstrated in two identical, large, multicenter, randomized, double-blind, placebo-controlled pivotal trials in a total of 537 subjects, mostly women, with moderate or severe glabellar lines during facial animation . Based both on subjects' and physicians' assessments, the improvement in glabellar lines with Botox was superior to that with placebo at each visit during the 120-day post-injection follow-up period, beginning on day 7 post-injection . The peak effect was seen on day 30 post-injection when 80% of subjects in the two studies combined had the severity of their lines at maximum frown reduced to mild or none, as assessed by their physician, and 89% had at least a moderate (> or =50%) improvement in the appearance of their glabellar lines, as rated by themselves . In a noncomparative extension of these trials, there was a tendency for a higher proportion of subjects to respond to Botox injections after a second and third treatment session . Botox injections for glabellar lines are well tolerated . Headache, the most common adverse event, occurred with a similar frequency to placebo in the two pivotal studies (13% vs 18%) . Temporary blepharoptosis occurred in 3.2% of Botox recipients; however, the incidence of this adverse event tended to decrease with repeated treatment sessions . In summary, Botox injections offer a convenient, effective, and well tolerated treatment for improving glabellar frown lines . Repeated injections are necessary to maintain a long-term effect; however, this technique clearly represents an attractive option for individuals who wish to avoid a more major procedure.

Am J Clin Dermatol, 2003, 4(10), 681 - 97
Management of primary hyperhidrosis: a summary of the different treatment modalities; Connolly M et al.; Hyperhidrosis is a common and distressing condition involving increased production of sweat . A variety of treatment modalities are used to try to control or reduce sweating . Sweat is secreted by eccrine glands innervated by cholinergic fibers from the sympathetic nervous system . Primary hyperhidrosis most commonly affects palms, axillae and soles . Secondary hyperhidrosis is caused by an underlying condition, and treatment involves the removal or control of this condition . The treatment options for primary hyperhidrosis involve a range of topical or systemic medications, psychotherapy and surgical or non-surgical invasive techniques . Topical antiperspirants are quick and easy to apply but they can cause skin irritation and have a short half life . Systemic medications, in particular anticholinergics, reduce sweating but the dose required to control sweating can cause significant adverse effects, thus, limiting the medications' effectiveness . Iontophoresis is a simple and well tolerated method for the treatment of hyperhidrosis without long-term adverse effects; however, long-term maintenance treatments are required to keep patients symptom free . Botulinum toxin A has emerged as a treatment for hyperhidrosis over the past 5-6 years with studies showing good results . Unfortunately, botulinum toxin A is not a permanent solution, and patients require repeat injections every 6-8 months to maintain benefits . Psychotherapy has been beneficial in a small number of cases . Percutaneous computed tomography-guided phenol sympathicolysis achieved good results but has a high long-term failure rate . Surgery has also been shown to successfully reduce hyperhidrosis but, like other therapies, has several complications and patients need to be informed of these prior to undergoing surgery . The excision of axillary sweat glands can cause unsightly scarring and transthoracic sympathectomy (either open or endoscopic) can be associated with complications of compensatory and gustatory hyperhidrosis, Horner syndrome and neuralgia, some of which patients may find worse than the condition itself.

Vaccine, 2003 Oct 1, 21(27-30), 4335 - 47
Phase II safety and immunogenicity study of type F botulinum toxoid in adult volunteers; Edelman R et al.; An aluminum hydroxide (alum)-adsorbed, purified, botulinum F toxoid (Bot F) vaccine was manufactured to be administered as a stand-alone monovalent vaccine or to be added to the current botulinum pentavalent toxoid vaccine to make a hexavalent vaccine . We conducted a phase II trial of the Bot F vaccine over 3 years in 144 healthy adult volunteers to identify one of three vaccination schedules that was safe and maximally immunogenic for adult volunteers . We vaccinated 116 volunteers 1-3 times with Bot vaccine, and 28 volunteers 1-3 times with a licensed, alum-adsorbed hepatitis B vaccine (Engerix-B) as a reaction control group . After 1 year, 42 Bot volunteers with low, mouse anti-toxin titers (<0.10 IU/ml) received a booster injection and were followed for an additional year . The Bot vaccine inoculated three times over 28-42 days was generally well tolerated and safe, whether injected by the subcutaneous (s.c.) or intramuscular (i.m.) route, although it caused significantly more local reactions than did the HBV vaccine . Two vaccination schedules of three primary injections over 42 days (days 0, 14 and 42 or days 0, 21 and 42) provided significantly better protective immunity (anti-toxin levels >0.02 IU/ml) than did vaccinations given over 28 days (days 0, 7 and 28) . Vaccine reactogenicity and immunogenicity were similar over 42 days whether administered subcutaneously or intramuscularly . However, even the most immunogenic schedule left 7-16% of volunteers unprotected at day 56 and 33-42% of vaccinees unprotected at 1 year . The booster dose administered at 1 year induced high levels of protective serum anti-toxin in all persons assayed which persisted for at least one additional year . A more potent vaccine formulation will be required to protect more individuals after primary immunization.

Plast Reconstr Surg, 2003 Oct, 112(5 Suppl), 88S - 93S; discussion 94S-97S
The role of botulinum toxin type B (Myobloc) in the treatment of hyperkinetic facial lines; Kim EJ et al.; Botulinum toxin type B was studied for the management of hyperkinetic facial lines . It showed clinical longevity of up to 12 weeks on subjective rating scales and 8 weeks on objective rating scales . Botulinum toxin type B has shown relative safety but can have autonomic side effects at higher total doses, which limits the possibility of continued dose escalation . Although these findings may preclude its use as a primary modality for the use in hyperkinetic facial lines, botulinum toxin type B still has a role in the treatment of the aesthetic patient and is yet another tool in the armamentarium of aesthetic practitioners.

Plast Reconstr Surg, 2003 Oct, 112(5 Suppl), 66S - 72S; discussion 73S-74S
The effect of botulinum toxin injections on the nasolabial fold; Kane MA; The use of botulinum toxin A (Botox; Allergan, Irvine, Calif.) for cosmetic purposes was first described in the medical literature in 1992 . The author has been using botulinum toxin A in his practice for cosmetic purposes since 1991 . In May of 1992, he began using Botox for improvement of the nasolabial folds . An experience of over 1000 injections to the nasolabial folds in more than 200 unique patients is presented . Technique and selection criteria have changed greatly during the past 10 years, and this evolution is discussed . The keys to achieving adequate correction and satisfied patients when treating the nasolabial fold are proper diagnosis of what is causing the fold and careful patient selection.

Plast Reconstr Surg, 2003 Oct, 112(5 Suppl), 33S - 39S
Classification of crow's feet patterns among Caucasian women: the key to individualizing treatment; Kane MA; One of the most common complaints of aging patients is the appearance of crow's feet lines in the lateral canthal region . Many different treatment methods, including chemical peels, surgical procedures, filler material injections, botulinum toxin injections, and laser resurfacing, have been used for effacement of these lines among aging patients and patients with sun damage . Despite the fact that many scientific articles have been written regarding the treatment of crow's feet lines, the actual patterns of these lines have not been adequately studied or classified . Several different patterns of animation in this area have been observed . These different patterns and their frequencies are described . All crow's feet patterns are not the same, and it follows that treatment of different patterns of crow's feet lines should be adapted to the particular patterns.

Plast Reconstr Surg, 2003 Oct, 112(5 Suppl), 6S - 18S; discussion 19S-20S
Botulinum toxin type A for facial aesthetic enhancement: role in facial shaping; Fagien S; The application of injectable chemodenervation with botulinum toxin type A has become a useful and significant tool for facial rejuvenation . Since its original discovery and descriptions of its use for improvement of dynamic facial lines and furrows, botulinum toxin type A has been shown to be effective in a host of other applications . Because of its synergistic effects, it is used as an adjunctive agent for a variety of procedures, from injectable facial soft-tissue augmentation to brow lifts . The art of using botulinum toxin type A, or Botox (Allergan, Irvine, Calif.), has evolved from a technical procedure to one that is influenced by aesthetic judgment and applications that extend beyond line eradication to improve facial form and shape.

Mov Disord, 2003 Sep, 18(9), 1059 - 61
Botulinum toxin B reduces sialorrhea in parkinsonism; Racette BA et al.; We report on our open-label experience with botulinum toxin B for the treatment of severe sialorrhea associated with parkinsonism . Nine adult patients with parkinsonism and medically intractable sialorrhea were treated with botulinum toxin B (1,000 units into each parotid gland using superficial landmarks) . After treatment, patients experienced a 61% mean subjective improvement and a 42% mean reduction of quantitative saliva production . There were no adverse effects seen in any subjects . Mean peak benefit from injections lasted 14 weeks . We conclude that denervation of salivary glands with botulinum toxin B produces excellent reduction of excessive salivation associated with parkinsonism .

Curr Opin Ophthalmol, 2003 Oct, 14(5), 241 - 5
Chemodenervation for facial dystonias and wrinkles; Harrison AR; PURPOSE OF REVIEW: Chemodenervation has evolved greatly over the past 30 years since botulinum toxin was first introduced as a therapeutic injection for managing strabismus . RECENT FINDINGS: Botulinum toxins are now accepted as a first-line treatment for patients suffering from spasms secondary to facial dystonias . These treatments are extremely effective and well tolerated by most patients . New agents including doxorubicin, Doxil, and ricin mab35 are being developed to create a longer-lasting treatment option for patients with facial dystonias . Recently the use of chemodenervation for managing facial wrinkles has expanded the use of these agents . The botulinum toxins have been found to be extremely efficacious in managing facial wrinkles, especially in the upper half of the face . The federal drug administration approved the use of Botox (Allergan, Irvine, CA) for glabellar furrows . Periocular crow's feet lines and horizontal forehead lines are also amenable to treatment with the botulinum toxins . Further uses including chemical browlift, as well as lower face and neck line treatments have also been described . SUMMARY: The use of the botulinum toxins has revolutionized the treatment of a broad array of diseases from benign essential blepharospasm to facial wrinkles.

Otol Neurotol, 2003 Sep, 24(5), 714 - 6
Treatment for severe palatoclonus by occlusion of the eustachian tube; Ensink RJ et al.; PURPOSE: Surgical blocking of the eustachian tube is presented as an ultimate treatment option in a 11-year-old suicidal boy with a therapy-resistant, persistent clicking tinnitus caused by myoclonus of the levator veli palatini . PATIENT: An 11-year-old boy decompensated psychologically as a result of loud and objective tinnitus . The tinnitus could be heard easily by an examiner by bringing his own ear at a distance of approximately 20 to 30 cm to the left ear of the patient . No neurologic etiology for the tinnitus could be traced . Pediatric psychiatric evaluation resulted in a recommendation to perform, as a last resort, an experimental surgical option like blockage of the eustachian tube . INTERVENTION: Treatment with Tegretol (Novartis, The Netherlands) had no effect . Treatment with Dysport (Ipsen) botulin toxin with 30 to 60 U was temporarily effective . Finally, 60 U were not effective anymore . As last refugium, a surgical blockage of the eustachian tube has been performed, first with bone cement and later by a more conventional surgical blockage of that bony tube . OUTCOME: After surgical blockage of the bony part of the eustachian tube, the objective tinnitus disappeared . Blockage of the protympanum by bone cement resulted in only 1 year of successful blocking . After recurrence of the tinnitus combined with aeration of the middle ear, a second surgical transcanal approach was successful in blocking the eustachian tube . With a grommet, the hearing level remained within 10 dB for 0.5 to 8.0 kHz.

J Physiol, 2003 Dec 1, 553(Pt 2), 497 - 509 Epub 2003 Sep 18.
Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones; Tyler WJ et al.; The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood . We show here that brain-derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in organotypic slice cultures prepared from postnatal rat hippocampal slices . This effect was observed also in the absence of action potentials, and even when miniature synaptic transmission was inhibited with botulinum neurotoxin C (BoNT/C) . There were, however, marked differences in the morphology of individual spines induced by BDNF across these different levels of spontaneous ongoing synaptic activity . During both normal synaptic transmission, and when action potentials were blocked with TTX, BDNF increased the proportion of stubby, type-I spines . However, when SNARE-dependent vesicular release was inhibited with BoNT/C, BDNF increased the proportion of thin, type-III spines . Our results indicate that BDNF increases spine density irrespective of the levels of synaptic transmission . In addition, miniature synaptic transmission provides sufficient activity for the functional translation of BDNF-triggered spinogenesis into clearly defined morphological spine types, favouring those spines potentially responsible for coordinated Ca2+ transients thought to mediate synaptic plasticity . We propose that BDNF/TrkB signalling represents a mechanism of expression of both morphological and physiological homeostatic plasticity in the hippocampus, leading to a more efficient synaptic information transfer across widespread levels of synaptic activity.

Arch Phys Med Rehabil, 2003 Sep, 84(9), 1399 - 400
Use of botulinum toxin type B for the treatment of detrusor hyperreflexia in a patient with multiple sclerosis: a case report; Dykstra DD et al.; We describe a patient with multiple sclerosis (MS) who had detrusor hyperreflexia that was not responsive to oral medications or clean intermittent catheterization . This patient was successfully treated with 2 separate injections of botulinum toxin type B into the bladder . The results of the treatment lasted 4 months and there were no side effects . A cystometrogram (CMG) done before the botulinum toxin type B injections showed significant detrusor instability . A repeat CMG months later showed no detrusor instability . To our knowledge, this is the first reported successful use of botulinum toxin type B in a patient with detrusor hyperreflexia from MS.

J Child Neurol, 2003 Sep, 18 Suppl 1, S67 - 78
Neurosurgical treatment of spasticity and other pediatric movement disorders; Albright AL; For children whose spasticity and movement disorders are inadequately treated by oral medications and botulinum toxins, neurosurgical procedures are now available to effectively treat spasticity, tremor, and many cases of dystonia . Spastic diplegia can be treated with selective lumbar rhizotomies, which significantly decrease spasticity, increase range of motion, and improve Gross Motor Function Measure scores . Children with spastic quadriparesis and those with secondary dystonia can be treated with intrathecal baclofen, which diminishes both spasticity and dystonia and is associated with improved function and quality of life . Children with primary dystonia and those with tremor can be treated with deep brain stimulation of the internal globus pallidus and thalamus, respectively . Some children with chorea respond to deep brain stimulation . There are no effective neurosurgical treatments for athetosis or ataxia . The effectiveness of neurosurgical treatments of pediatric movement disorders has increased significantly in the past 15 years.

Dermatol Surg, 2003 Oct, 29(10), 1057 - 9; discussion 1060
Cryoanalgesia with dichlorotetrafluoroethane lessens the pain of botulinum toxin injections for the treatment of palmar hyperhidrosis; Baumann L et al.; BACKGROUND: Hyperhidrosis is a troublesome problem that can be embarrassing in both social and professional situations . Botulinum toxin injections have proven efficacious in the treatment of hyperhidrosis . However, when treating palmar hyperhidrosis, pain at the injection site limits this therapy . We describe a method of cryoanalgesia using dichlorotetrafluoroethane to lessen the pain of botulinum toxin injections during the treatment of palmar hyperhidrosis . OBJECTIVE: To show the successful use of dichlorotetrafluoroethane or Frigiderm in the treatment of palmar hyperhidrosis . METHODS: This is a case report of a patient with a 20-year history of palmar hyperhidrosis who had previously tried several unsuccessful techniques to control pain during botulinum toxin injections to his palms . The left hand of the patient was pretreated with a spray of Frigiderm for 5 seconds before each of the botulinum injections . Two to 3 seconds of dichlorotetrafluoroethane at a distance of 2 to 4 inches were sprayed before each palmar injection . There was 1 to 2 seconds of frosting on the skin before the botulinum toxin was administered . After the botulinum toxin injection was administered, the patient was subjectively asked about pain during injection . RESULTS: The patient subjectively reported a 75% decrease in the intensity of pain with the Frigiderm application, which he said made the injections much more tolerable . No epidermal changes were noted at the time of treatment or at the telephone follow-up visit . The patient presented for follow-up 3 months later . He stated that the sweating had minimally returned but that he had not yet returned to baseline . CONCLUSION: The use of botulinum toxin for the treatment of palmar hyperhidrosis is often limited because of the pain of multiple injections . In this case report, we describe the successful use of cryoanalgesia with dichlorotetrafluoroethane or Frigiderm to lessen the pain of botulinum toxin injections during the treatment of palmar hyperhidrosis.

J Assoc Physicians India, 2003 May, 51, 447 - 53
Botulinum toxin in the treatment of dystonias--a hospital based study; Gupta M et al.; BACKGROUND: Dystonia is a neurological disorder usually of idiopathic etiology with a wide spectrum of clinical manifestations . The advent of botulinum toxin has revolutionized the treatment of focal dystonias . This study was a prospective long term study to see the efficacy of botulinum toxin in the treatment of dystonias . MATERIAL AND METHODS: There were a total of 215 injection sessions of botulinum toxin during a period of 4 years and 8 months . Patients were evaluated in detail and their severity of dystonias was graded on objective scales . Botulinum toxin injection were administered depending on the type and severity of dystonias . The response to treatment was gauged in terms of latency, and the degree and duration of improvement . The dosages were repeated as and when required, with minimal interval of 3 months . RESULTS: We had a total number of 215 injection sessions, with maximum patient sessions with blepharospasm and hemifacial spasm (59 and 61, respectively) . The lowest dosages of botulinum toxin were required for writer's cramps and blepharospasm (92.5 +/- 5.3; and 122 +/- 5.1) while highest dosages were required for generalized and cervical dystonias (512 +/- 10.5; and 452.5 +/- 8.5) . The best response in terms of different parameters assessed was seen with blepharospasm and hemifacial spasm while it was lowest for the generalized dystonia group . We did not observe any declining responsiveness to botulinum toxin with repeated injections . The side effects were minimal and self-limiting . CONCLUSION: Botulinum toxin injection is an effective and safe modality for the treatment of disabling dystonias . Cost is one of the major hinderances to its widespread use.

Plast Reconstr Surg, 2003 Sep 15, 112(4), 1089 - 98
Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines; Carruthers JD et al.; The objective of this study was to evaluate the efficacy and safety of botulinum toxin type A for the treatment of glabellar lines . Patients with moderate or severe glabellar lines at maximal frown received intramuscular injections of placebo or 20 U of botulinum toxin type A (Botox; Allergan, Inc., Irvine, Calif.) distributed among five injection sites (one in the procerus muscle and two in each corrugator supercilii) . Follow-up assessments were performed at 7, 30, 60, 90, and 120 days after injections . Efficacy measures were the physician's rating of glabellar line severity at maximal frown and at rest (none, mild, moderate, or severe) and the patient's global assessment of changes in glabellar lines, from +4 (100 percent better) to -4 (100 percent worse) . A total of 273 patients were enrolled (botulinum toxin, 202 patients; placebo, 71 patients) . All except five patients (botulinum toxin, two patients; placebo, three patients) completed the study . For the physician's rating at maximal frown, the responder rate (percentage of patients with severity ratings of none or mild in follow-up evaluations) for the botulinum toxin group peaked at 77 percent at day 30 and was significantly greater than that for the placebo group at every follow-up visit (p < 0.001) . For the patient's assessment, the responder rate (percentage of patients with scores of +2 or more) for the botulinum toxin group peaked at 89 percent at day 30 and was significantly greater than that for the placebo group at every follow-up visit (p < 0.001) . Rates of adverse events were similar for the two groups . The only adverse event with an incidence of >/=5 percent was headache (botulinum toxin, 11 percent; placebo, 20 percent) . The incidence of blepharoptosis was 1 percent for the botulinum toxin group . Botulinum toxin type A was remarkably safe and effective in reducing glabellar lines.

Laryngoscope, 2003 Sep, 113(9), 1479 - 82
Botulinum neurotoxin for pharyngeal constrictor muscle spasm in tracheoesophageal voice restoration; Hamaker RC et al.; OBJECTIVES/HYPOTHESIS: The purpose of the study was to evaluate the effectiveness of Botulinum neurotoxin (Botox) for elimination of pharyngeal constrictor muscle spasm in tracheoesophageal voice restoration . STUDY DESIGN: A retrospective review was made of 62 patients between 1991 and 2002 who had Botox as the initial treatment for pharyngeal constrictor muscle spasm . METHODS: One hundred units of Botox properly diluted in 3 mL saline was instilled unilaterally under electromyographic guidance after fluoroscopic identification and marking of the contracted pharyngeal constrictor muscles . The patients were divided into three groups based on their response to the first Botox injection: group I, complete relaxation of the pharyngeal constrictors resulting in fluent voice, intratracheal phonation pressure of 20 to 40 cm H2O, and the ability to say 15 to 20 uninterrupted syllables; group II, hypertonic or incomplete relaxation of the pharyngeal constrictors resulting in intratracheal phonation pressure of 45 to 70 cm H2O and the ability to say 7 or 8 syllables; and group III, failure to produce relaxation of the pharyngeal constrictors . RESULTS: After the first injection of Botox, 49 (79%) patients were in group I or II (41 in group I and 8 in group II) and group III consisted of 13 patients . Thirty-four patients (55%) had group I (28) or II (6) responses for greater than 6 months . A second Botox injection enabled 6 of the 13 failures to move into group I . In all, 8 pharyngeal constrictor muscle myotomies (13%) were ultimately required in the 62 patients . The group I speaker for the longest period has enjoyed 11 years of fluency and successful daily use of a tracheostoma valve after two Botox injections . CONCLUSION: Botox relaxation of the pharyngeal constrictor muscles has proven to be effective, has replaced secondary pharyngeal myotomy for the initial treatment of pharyngeal muscle spasm, and is the only treatment in patients who are not candidates for elective surgery . Radiographic assessment, electromyographically monitored injection, and the number of Botox units appear to be important to successful outcomes.

BMC Gastroenterol . 2003 Sep 10;3(1):26.
Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats; Runfola M et al.; BACKGROUND: Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions . The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl . METHODS: Sixty-four rats were randomized in two groups and laparotomized . One group was treated with botulinum toxin-A 10 U by multiple submucosal gastric injections, while the second group was injected with saline . Two weeks later, acid secretion was stimulated by pyloric ligation and acid output was measured . Body weight, food and water intake were also recorded daily . RESULTS: HCl production after pyloric ligation was found to be significantly lower in botulinum toxin-treated rats (657 +/- 90.25 micromol HCl vs . 1247 +/- 152 . P = 0.0017) . Botulinum toxin-treated rats also showed significantly lower food intake and weight gain . CONCLUSIONS: Botulinum toxin type A reduces stimulated gastric acidity . This is likely due either to inhibition of the cholinergic stimulation of gastric parietal cells, or to an action on the myenteric nervous plexuses . Reduction of growth and food intake may reflect both impaired digestion and decreased gastric motility.

Surg Laparosc Endosc Percutan Tech, 2003 Aug, 13(4), 227 - 40
Achalasia: a comprehensive review; St Peter SD et al.; Achalasia is a rare neurologic deficit of the esophagus, producing a syndrome of impaired relaxation of the lower esophageal sphincter and decreased motility of the esophageal body for which the cause is unknown . The resultant chronic esophageal stasis produces discomforting symptoms that can be managed with medication, chemical paralysis of the lower esophageal sphincter, mechanical dilation, or surgical esophagomyotomy . Chemical paralysis by injection of the esophagus with botulinum toxin and dilation with an inflatable balloon offers good short-term relief of symptoms; however, the best long-term results are produced by surgery, and advancing minimally invasive techniques continually reduce the morbidity of these operations . The type of surgical procedure, the necessity for fundoplication, and the order of treatment continue to be unresolved issues, but prospective evaluation with objective followup should allow us to provide the optimal treatment regimen to our patients.

Hosp Med, 2003 Aug, 64(8), 464 - 7
Botulinum toxin and the eye; Marsh IB; Botulinum toxin in ophthalmology is used to reduce the function of the eyelid muscles in spasms or therapeutically . Therapeutic and diagnostic use in strabismus is also discussed, along with the controversial treatment of nystagmus.

Hosp Med, 2003 Aug, 64(8), 460 - 3
The use of botulinum toxin in head and neck disorders; Hawthorne MR; Not only can botulinum toxin be used for cervical and laryngeal dystonia but in this article its use and complications in the management of oromandibular dystonia, Frey's syndrome, crocodile tears and drooling is described.

Hosp Med, 2003 Aug, 64(8), 452 - 9
Movement, visceral and autonomic disorders: use of botulinum toxin; Moore AP; This article reviews the development of botulinum toxin treatment, how it works, the range of conditions it can treat and the benefits and side effects . It sets out how it is used in practice in specialist units.

Urol Res . 2003 Sep 4; {Epub ahead of print}
Effect of botulinum-A toxin to cremaster muscle: an experimental study; Cakmak M et al.; Objective: A controversy exists on the definition, etiology and treatment of the retractile testes . In the present experimental study, we aimed to show the effect of botulinum-A toxin (Botox) on cremasteric muscle of a rat, and whether it may be an alternative to surgical treatment of retractile testis . Methods: Ten Wistar rats were used in the study . By stimulating cremasteric reflex, five compound muscle action potentials (CMAP) of the right and left cremasteric muscles of each rat were recorded using surface electrodes . Intramuscular injection of botulinum-A toxin was done to the right side . Saline was injected to the left cremasteric muscles, and the left side also served as control . CMAP of the cremasteric muscles were recorded 45 days after the injection . Statistical analysis was done using Wilcoxon Signed rank test . Results: Mean CMAP of the right side was 3.25+/-1.39 micro V before the injection and 0.44+/-0.25 micro V after botulinum-A toxin injection . The difference was statistically significant ( p<0.05) . Mean CMAP on the left side was 3.48+/-0.32 micro V and 3.14+/-1.12 micro V at baseline and the end of the study, respectively . The difference was not statistically significant ( p>0.05) . Conclusion: The botulinum-A toxin paralyzes the cremasteric muscles of the rats . As cremasteric hypertonicity is accepted as one of the reasons for retractile testes, botulinum-A toxin injection to cremasteric muscles may be helpful in diagnosis and may be an alternative to surgical treatment of this pathology in repeated dosages . Long-term evaluation of this paralysis is necessary.

Yonsei Med J, 2003 Aug 30, 44(4), 579 - 82
Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate; Kim WO et al.; Gustatory hyperhidrosis is facial sweating usually associated with the eating of hot spicy food or even smelling this food . Current options of treatment include oral anticholinergic drugs, the topical application of anticholinergics or aluminum chloride, and the injection of botulinum toxin . Thirteen patients have been treated to date with 1.5% or 2% topical glycopyrrolate . All patients had gustatory hyperhidrosis, which interfered with their social activities, after transthroacic endoscopic sympathectomy, and which was associated with compensatory focal hyperhidrosis . After applying topical glycopyrrolate, the subjective effect was excellent (no sweating after eating hot spicy food) in 10 patients (77%), and fair (clearly reduced sweating) in 3 patients (23%) . All had reported incidents of being very embarrassed whilst eating hot spicy foods . Adverse effects included a mildly dry mouth and a sore throat in 2 patients (2% glycopyrrolate), a light headache in 1 patient (1.5% glycopyrrolate) . The topical application of a glycopyrrolate pad appeared to be safe, efficacious, well tolerated, and a convenient method of treatment for moderate to severe symptoms of gustatory hyperhidrosis in post transthoracic endoscopic sympathectomy or sympathicotomy patients, with few side effects.

Eur Neurol, 2003, 50(2), 91 - 3
Treatment of pain and limited movement of the shoulder in hemiplegic patients with botulinum toxin a in the subscapular muscle; Yelnik AP et al.; Three poststroke hemiplegic patients were treated by injecting Botulinum toxin A (BtxA) into the subscapularis muscle, to reduce pain and increase the range of motion in the shoulder . According to the described procedure, 250 units of Dysport toxin were injected through a 0.8-mm diameter needle with electrostimulation guidance . In the 3 cases, injection of BtxA reduced pain and improved the range of motion, especially abduction and external rotation, of the hemiplegic shoulder . This result confirms the role of spasticity in hemiplegic shoulder pain and the beneficial effects of Botulinum toxin injection into the subscapularis muscle deserve to be confirmed in further series .

Headache, 2003 Sep, 43(8), 853 - 60
Botulinum toxin type A as an effective prophylactic treatment in primary headache disorders; Blumenfeld A; OBJECTIVE: To measure the effect of botulinum toxin type A (Botox, Allergan, Inc, Irvine, CA) treatment in 271 patients diagnosed with headache in accordance with International Headache Society (IHS) criteria . BACKGROUND: Botulinum toxin type A has shown promise for the treatment of headache in several clinical trials, but uncertainty remains as to how botulinum toxin type A optimally should be used for treating headache and which patients are best suited for this treatment . METHODS: This was a retrospective chart review of all patients who received botulinum toxin type A for the treatment of headache from January 1999 to February 2002 . Patients were injected with an average dose of 63.2 U (SD, 14.5) of botulinum toxin type A on 2 or more visits, with treatments involving a "fixed-site" or a "follow-the-pain" (or a combination of both) approach . In the fixed-site approach, botulinum toxin type A was injected into the procerus, corrugator, frontalis, and temporalis muscles . In the follow-the-pain approach, botulinum toxin type A was injected into a combination of the procerus, corrugator, frontalis, temporalis, occipitalis, trapezius, and/or semispinalis capitis muscles . The primary outcomes for the trial were the reduction in headache days per month or headache intensity (0 to 3 scale) (or both) from baseline . Patients were diagnosed according to IHS criteria and subsequently classified into the following categories: chronic daily headache (more than 15 headache days per month), episodic tension-type headache, episodic migraine, and "mixed" HA (less than 15 headache days per month, combination of migraine and tension-type headache) . RESULTS: Treatment period was an average of 8.6 months (SD, 6.4); patients received an average of 3.4 doses (SD, 1.6) 3 months apart . Of the 271 patients, 29 (10.7%) had episodic migraine, 17 (6.3%) had episodic tension-type headache, 71 (26.2%) had mixed headache, and 154 (56.8%) had chronic daily headache . Two-hundred fifty-six patients had data for the number of headache days per month, 117 had data for headache intensity, and all 271 had data for headache days or headache intensity . Botulinum toxin type A treatment significantly reduced the number of headache days per month from 18.9 (SD, 10.3) to 8.3 (SD, 8.9) (n=256, P<.001)--a 56% reduction . Headache intensity decreased from 2.4 points (SD, 0.6) to 1.8 points (SD, 0.8) (n=117, P<.001)--a 25% reduction . Of 263 patients surveyed, 225 (85.6%) reported improvement in headache frequency and intensity . There was no correlation of effect/lack of effect with reason for treatment, duration/number of treatments, injection technique, mean/total dose, age, gender, or comorbidity . Approximately 95% of patients did not experience medication side effects . CONCLUSION: These results suggest that botulinum toxin type A may be an effective and safe prophylactic treatment for a variety of moderate to severe chronic headache types.

Ann Otol Rhinol Laryngol, 2003 Aug, 112(8), 704 - 11
Effect of tensor veli palatini muscle paralysis on eustachian tube mechanics; Ghadiali SN et al.; Several physiological functions, such as regulating middle ear (ME) pressure and clearing ME fluid into the nasopharynx, require an opening of the collapsed eustachian tube (ET) . The ability to perform these functions has been related to several mechanical properties of the ET: opening pressure (Popen), compliance (ETC), and hysteresis (eta) . These global properties may be influenced by the mechanics of the surrounding tissue and/or the mucosa-air interface . In this study, we investigated the influence of tissue mechanics by paralyzing the right tensor veli palatini (TVP) muscle in 12 cynomolgus monkeys via botulinum toxin injection . A previously developed modified forced-response protocol was used to measure Popen, ETC, and eta under normal conditions and after muscle paralysis . The loss of muscle tone and/or stiffness resulted in a significant decrease in Popen (p < .01) and a significant increase in ETC (p < .01) . In addition, muscle paralysis reduced the viscoelastic properties of the TVP muscle and therefore resulted in a significant decrease in eta (p < .05) . A comparison with previous measurements on the influence of surface tension mechanics indicates that the ET's compliance is primarily determined by tissue elastic properties . The ET hysteresis, however, is equally affected by viscoelastic tissue properties and surface tension hysteretic properties . Knowledge of how these physical components affect the global mechanical environment may lead to improved treatments for ET dysfunction that target the underlying mechanical abnormality.

Invest Ophthalmol Vis Sci, 2003 Sep, 44(9), 3866 - 72
Increasing extraocular muscle strength with insulin-like growth factor II; McLoon LK et al.; PURPOSE: Botulinum toxin type A and, more recently, the immunotoxin ricin-mAb35 have been effective as means of pharmacologically weakening the extraocular muscle . However, currently there are no drug treatments to strengthen an underacting extraocular muscle . In limb muscle, treatment with insulin-like growth factor causes myofiber hypertrophy . In this study, the short-term effects of insulin-like growth factor II (IGF-II) on extraocular muscle morphometry and force generation were examined . METHODS: One superior rectus muscle in normal adult rabbits received a single injection of 10 micro g IGF-II, and the contralateral muscle received an injection of saline only . One week after injection, muscle morphology and muscle force were compared between the IGF-treated and control muscles . RESULTS: In the treated muscle, there was no significant change in the mean cross-sectional area of myofibers compared with the control . However, there was an increase in the heterogeneity of myofiber cross-sectional area, with increases in both small and very large myofibers . Mean single-twitch force generation was 0.48 +/- 0.12 mN/cm(3) compared with 0.27 +/- 0.04 mN/cm(3) (P = 0.0473) in control samples . Mean tetanic force generation was increased significantly at all stimulation frequencies . Treatment had no effect on muscle fatigability . CONCLUSIONS: Extraocular muscle is very responsive to direct injection of IGF-II . Although no difference was seen in mean myofiber cross-sectional area, overall there was sufficient alteration in myofiber heterogeneity to result in increased force generation . If a sustained treatment effect can be achieved with IGF-II and, potentially, other growth factors, the pharmacological treatment of strabismus could be advanced by simultaneous injection of agonist-antagonist pairs with agents that weaken and strengthen the treated extraocular muscle.

Br J Dermatol, 2003 Aug, 149(2), 306 - 10
Reproducibility of a four-point clinical severity score for glabellar frown lines; Honeck P et al.; BACKGROUND: Focal injections of botulinum toxin A are used successfully for the treatment of hyperkinetic facial wrinkles . Efficacy can be measured by several methods . However, so far none has been investigated for its reproducibility . Objectives To investigate the reproducibility of a clinical 0-3 score for glabellar frown lines . METHODS: In the first part of the study, a standardized photographic documentation of glabellar frown lines was produced . Based on the results of this phase, a consensus atlas of glabellar frown lines was developed and participants were trained using this atlas . In the main study, 50 standardized photographs were shown on two consecutive days to 28 dermatologists . The reproducibility of the score was investigated by conventional kappa statistics . RESULTS: In the main study, we found an unweighted kappa according to Fleiss of 0.62 for interobserver reproducibility . Intraobserver reproducibility showed an unweighted kappa according to Cohen of between 0.57 and 0.91 for each observer, and a weighted kappa according to Cicchetti and Allison of between 0.68 and 0.94 . CONCLUSIONS: The clinical 0-3 score for glabellar frown lines shows a good inter- and intraobserver reproducibility.

Nippon Jibiinkoka Gakkai Kaiho, 2003 Jul, 106(7), 754 - 7
{Botulinum toxin injection into the cricopharyngeal muscle for dysphagia: report of 2 successful cases}; Yokoyama T et al.; Dysphagia is frequently observed in patients with sequelae after multiple cerebral infarctions and those with neuromyopathy . Dysphagia in these patients can be successfully treated by laryngeal suspension and cricopharyngeal myotomy . Surgery is not indicated in senile patients with serious complications, where conservative treatment is performed . We injected botulinum toxin into the right cricopharyngeal muscle with excellent results in two dysphagic patients with multiple cerebral infarction who refused surgery . There two cases developed dysphasia after multiple cerebral infarction, where surgical therapy was not indicated . Dysphagia is successfully treated by 5 units of botulinum toxin injected into the cricopharyngeal muscle . Botulinum toxin injection is considered useful for dysphagia in patients in whom surgery is not indicated . The effect of botulinum toxin lasts for 3 to 4 months . Injection of botulinum toxin is useful for patients with temporary dysphasia after cerebral infarction and soon improves swallowing with the assistance of rehabilitation.

Dermatol Surg, 2003 Sep, 29(9), 943 - 50; discussion 950-1
Botulinum A toxin (BOTOX) in the lower eyelid: dose-finding study; Flynn TC et al.; BACKGROUND: Botulinum toxin type A (BTX-A, BOTOX) is an excellent therapeutic option for hyperkinetic facial lines . It improves wrinkles by relaxing the muscles of facial expression, which underlie the rhytids . Periocular wrinkles such as lateral orbital rhytids respond well to treatment . BOTOX can be used in the lower eyelid to improve wrinkles and widen the eye . OBJECTIVE: To determine whether there is additional benefit in using more than 2 U of BTX-A to improve infraorbital wrinkles and widen the eye . METHODS: Nineteen women had BTX-A injected into the orbicularis oculi muscle . Eleven women had 4 U injected into the lower eyelid bilaterally, 3 mm below the ciliary margin, and 12 U of BTX-A injected into one lateral orbital (crow's feet) area . Eight patients had 8 U injected bilaterally into the lower eyelid and 12 U placed unilaterally into the crow's feet . Physicians and patients independently evaluated the degree of improvement (grade 3=dramatic improvement, grade 2=moderate improvement, grade 1=mild improvement, and grade 0=no improvement) . Single investigator analysis was used to measure, in actual millimeters, the amount of increase in palpebral aperture . Side effects were noted . RESULTS: Improvement was noted in lower eyelid wrinkles by both physicians and patients at both dose groups . When only the lower lid was injected, patients reported an improvement of 1.18 with 4 U and a grade of 1.63 with 8 U . When both the lower eyelid the lateral orbital area were treated, an improvement of 1.73 was reported with 4 U and a grade of 2.25 reported with 8 U in the lower eyelid . Physician evaluations had grades of 1.85 for 4 U alone and 1.85 with 8 U alone . Grades of 2.35 and 2.25 were obtained for 4 U plus 12 U and 8 U plus 12 U, respectively . An increase in palpebral aperture (IPA) occurred in all subjects . Subjects who received 4 U in the lower eyelid alone had a 1.8-mm IPA at rest and a 2.6-mm increase at full smile . Subjects who received 8 U of BTX-A alone in the lower lid had an IPA of 2.2 mm at rest and 2.9 mm at full smile . Eyes treated with 12 U in the bilateral orbital area plus 4 U in the lower eyelid had an IPA of 2.2 at rest and 4.5 mm at full smile . Those treated with 8 U in the lower lid plus the crow's feet had an IPA of 1.5 at rest and 4.0 at full smile . Side effects increased with dosage, with eight of eight subjects in the 8-U dose groups reporting bothersome side effects such as lower eyelid edema and incomplete sphincter function . CONCLUSION: A dose-response curve is seen with increasing doses of BTX-A used in the lower eyelid . Treatment of the lateral orbital area in combination with the lower lid produces a synergistic response at lower doses, but at higher doses, a plateau effect is suggested . Although increasing doses of BTX-A increases eye widening, unattractive results and side effects are seen at higher doses . The authors recommend that lower 2- or 4-U doses of BTX-A be used in the lower eyelid and specifically discuss techniques.

J Neurol, 2003 Aug, 250(8), 967 - 9
Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure; Dressler D et al.; Recently, it was reported that botulinum toxin type B complex (BoNT/B) (NeuroBloc(R), Elan Pharmaceuticals) can produce an adequate therapeutic response in patients with antibody induced failure of botulinum toxin type A complex (BoNT/A) therapy . We wanted to study whether this effect is transient or sustained . For this, 10 consecutive patients (6 males, 4 females, age 54.6 +/- 14.3 years, duration of illness 15.8 +/- 7.0 years) with complete BoNT/A therapy failure and BoNT/A antibody titres in excess of 10mU/ml in the mouse diaphragm assay (MDA) received BoNT/B in an initial dose of 12370 +/- 1804MU . After the first BoNT/B application the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) improved from 20.1 +/- 3.0 to 11.9 +/- 3.4 . In all patients systemic anticholinergic side effects occurred . Three patients had stable continuous responses to two, three and five subsequent BoNT/B applications . Six patients showed complete secondary therapy failure to the second or third subsequent BoNT/B applications . Side effects did no longer occur . In four of them the BoNT/B doses were doubled without producing any therapeutic benefit or any side effects . In five of them MDA testing was performed and revealed BoNT/B antibody titres in excess of 1mU/ml . One patient lost half of her initial BoNT/B responsiveness indicating partial secondary BoNT/B therapy failure . This partial therapy failure was seen on two consecutive application series and has not proceeded to complete therapy failure so far . BoNT/B seems to be only temporarily effective in the majority of patients with BoNT/A antibody induced therapy failure . Whether the formation of BoNT/B antibody points to a high antigenic potency of BoNT/B, to an increased immunoreactivity in BoNT/A antibody carriers or whether it is due to the large amount of protein applied in BoNT/B therapy needs to be studied.

Eye, 2003 Aug, 17(6), 739 - 42
Strabismus surgery: adjustable sutures-good for all?
Tripathi A, Haslett R, Marsh IB.
AIMS: The role of adjustable sutures in strabismus surgery has mainly been limited to conditions like dysthyroid restrictive myopathy, blow-out fractures of orbit, aberrant regeneration of nerves, and certain other long-standing and complicated squints . In this clinical study, an attempt has been made to analyse the efficacy of adjustable sutures in squint surgery as a routine procedure . We also studied patients' acceptability and satisfaction following this procedure and analysed various factors that may influence the surgical outcome (age, sex, previous surgeries, injections of botulinum toxin, etc) . METHODS: A total number of 443 patients, aged between 13 and 78 years, who underwent strabismus surgery in our department, from January 1996 to January 2000, were included in this study . Of these patients, 141 had surgery with adjustable sutures and 302 patients without adjustable sutures . Surgical results were followed up for a period ranging from 12 to 50 months . The main outcome measure was a need for a reoperation in the two groups . In addition, we also studied patients' satisfaction with regard to final cosmetic appearance or relief of diplopia; percentage change in angle of deviation in two groups, and influence of various factors such as age, sex, previous surgeries, and injection of botulinum toxin on the final surgical outcome . The results were statistically analysed using Levene's test for equality of variances, t-test for equality of means, and statistical significance of the results was analysed by calculating P-values . RESULTS: In total, 8.51% of the patients in the adjustable group and 27.15% in the nonadjustable group needed a reoperation . Surgical results were found to be significantly better in patients who had adjustable sutures in comparison to those who did not have adjustable sutures (P<0.005) . Patients' satisfaction and percentage change in angle of deviation was also much higher in adjustable sutures group . Age, sex, number of previous surgeries, previous injections of botulinum toxin, and type and amount of deviation had no statistically significant influence on the surgical outcome . CONCLUSIONS: Strabismus surgery with adjustable sutures has a statistically significant better, final result than surgery without adjustable sutures . Patients' satisfaction and percentage change in angle of deviation is also much higher in the adjustable sutures group . As age, sex, number of previous surgeries, previous injections of botulinum toxin, and type and amount of deviation do not influence the final outcome, this type of surgery can be performed in virtually all types of patients.

Ann Readapt Med Phys, 2003 Jul, 46(6), 380 - 5
{EMG support in botulinum toxin treatment}; Monnier G et al.; INTRODUCTION: The aim of this work is to sum up how the use of EMG improves BT therapy . METHOD: A systematic review of the literature in the Pub Med computer database, along with a manual biography, allowed us to choose the most synthetic and the most pertinent publications according to our own practical experience . RESULTS: There is no consensus of opinion, but the great majority of authors emphasize the importance of EMG in the different stages of botulinum toxin treatment: before injections, at the time of the injection, and finally during the follow-up after the first injection or after the repeated injections that transient efficiency make necessary . DISCUSSION: A symptomatic therapeutic means recently recognized in focal dystonias and spasticity, BT is injected locally into the muscles to be treated . EMG can be used: at pre-injection for physiopathological evaluation but above all to establish a diagnosis and precise pre-intervention evaluation; at the moment of injection to provide guidance in precise muscle selection and for maximum efficiency with reduced, therefore less costly, doses . It also limits the risk of product diffusion susceptible of causing iatrogenic side effects and/or auto-immunisation resulting in resistance to the toxin; during follow-up, to understand why treatment failed and to look for changes in the dystonia pattern leading to objective re-evaluations and adapted reinjections.Although neglected by some, electrological logistics seem to us, as to many other practitioners who inject, to be a considerably helpful aid, particularly at the moment of injection when targeting the muscle to be treated.

Ann Readapt Med Phys, 2003 Jul, 46(6), 375 - 9
{Use of botulinum toxin type A in neuro-ORL}; Perie S et al.; Dystonia is the result of abnormal contractions of muscles, which may disturb activities between agonist and antagonist muscles . Since synchronization of laryngeal and masticatory muscles is highly necessary to allow opening and closure of the larynx or the mouth, expression of dystonia is especially exhibited . Focal laryngeal dystonia may disturb phonation, but also breathing or swallowing, which may be difficult to identify . In ORL, the botulinum toxin is used to treat focal dystonias, especially laryngeal (spamodic dysphonia being predominant) and oromandibular dystonias . Beside these indications, intracutaneous injections of botulinum toxin may be helpful in Frey's syndrome in patients with gustatory sweating; injections in the upper esophageal sphincter are also performed in cricopharyngeal dysphagia although this indication is mainly controversial.

Ann Readapt Med Phys, 2003 Jul, 46(6), 361 - 74
{Skin, wrinkles and botulinum toxin}; Nicolau PJ et al.; OBJECTIVE: To present an up-to-date analysis about the use of botulinum toxin for treating facial lines and wrinkles.Method . - A systematic search of the literature was conducted to select the most recent or relevant publications on this topic, through Medline . RESULTS: Out of the 583 articles retrieved, 90 were finally selected for the study . DISCUSSION: Validity of using botulinum toxin for cosmetic use is demonstrated, together with contra-indications and different methods to objectivate the results . The different available types of toxin are presented and compared . Modalities of preparation, conservation, and waste disposal are detailed . Anatomical bases of muscular facial balance are reviewed, with techniques of injection presented for each site, and also with adjunctive procedures . Complications and side effects are described and analysed . Most complications can be prevented through: perfect knowledge of local anatomy;use of small volumes;orientation of the needle bevel towards the muscle body, injection within the muscle body if thick, more superficial if thin;application of ice on the skin pre- and post-injecting . Adding epinephrin or diluting with xylocaine and epinephrin is not commonly used . CONCLUSION: Botulinum toxin has found its way as a major component of the therapeutic armamentarium . Its efficacy for facial rejuvenation has made it extremely popular, but its use does follow strict rules, and should be restricted to soundly trained practitioners.

Ann Readapt Med Phys, 2003 Jul, 46(6), 353 - 60
{Digestive tract and botulinum toxin}; Gaudric M et al.; INTRODUCTION: the aim of this work was to check literature to assess botulinum toxin injection efficacy in gastrointestinal motor disorders with special emphasis on controlled clinical trials . METHODS: literature was carried out with the Medline data bank . RESULTS: seventy three articles in French and in English including a recent general review were retained . Comparative clinical trials only concerned achalasia and anal fissure . The other gastrointestinal motor disorders only gave rise to open non-controlled trials assessed on clinical end points . DISCUSSION: this review of literature helps to determine usefulness and safety of Botulinum toxin injection in the treatment of esophageal achalasia and anal fissure . The main limitation is its brief duration of action . Studies concerning the others spastic motor disorders are based on unknown physiopathology and controlled trials are required to assess its efficacy . CONCLUSION: botulinum toxin is increasingly used for gastrointestinal motor disorders with worthwhile results . Its efficacy has been yet established for only two disorders : it has a valuable palliative role in achalasia and may be curative for anal fissure.

Ann Readapt Med Phys, 2003 Jul, 46(6), 346 - 52
{Botulinum toxin type A in children: evaluation of indications with a review of the literature}; Bertrand H et al.; INTRODUCTION: The aim of this study is to review the literature to indications of botulinum toxin type A in children . METHOD: We review the international literature from 1990 to 2002 by querying the Pubmed database with the keywords "children" and "botulinum toxin" . RESULTS: Two hundred and forty-eight articles are retrieved . We selected the most relevant 64 articles among them . Several questions remain pending: which optimal dose, which periodicity for injections, which optimal age to prolong efficiency? The main criteria to estimate efficiency is functional ability improvement . No significant side effects are noted . The main use of botulinum toxin is the management of the spastic lower limb in cerebral palsy . DISCUSSION: This review of the literature makes it possible to specify the interests and the operational limits of botulinum toxin in the child . Its effectiveness with the upper limb is not proven . The other indications remain to be studied in a more precise way . CONCLUSION: This review shows many studies give the indications of botulinum toxin in children . The main indication is the lower limb spaticity in cerebral palsy . New prospective and double-blind studies should be performed with larger samples.

Ann Readapt Med Phys, 2003 Jul, 46(6), 338 - 45
{Sialorrhea, hyperhidrosis and botulinum toxin}; Monnier G et al.; OBJECTIVE: The first clinical studies indicate that Botox provides effective treatment for hyperhidrosis and sialorrhea . The aim of this work is to sum up current evaluation of this use . METHOD: A systematic literature search was conducted on the Pub Med database, along with on chapters in other publications . The most interesting articles in relation to our own personal experience were chosen . RESULTS: Despite recent use of BT to treat focal hyperhidrosis, there have been numerous publications since 1997 . However, the injected areas have not been listed so frequently . Axillary hyperhidrosis has been studied most; it is also in this case and in the case of gustatory sweating that the best results have been obtained . Publications about palmar and especially plantar hyperhidrosis are much rarer, almost anecdotic . It has been demonstrated to a lesser extent that BT injections are effective in these cases . Literature about sialorrhea is just beginning . However, the reduction of the production of saliva following intra parenchymatic injection of toxin into the parotid and submandibular glands, thus rarifying drooling, has been demonstrated.For each of the pathological indications, both the injection techniques and the optimal doses remain to be determined . DISCUSSION: Because BT blocks all cholinergic transmission, including the autonomous nervous system, it was plausible to expect a reduction in sweating and salivation on local injection of the product . In fact, the first publications indicated such efficiency without serious side effects.For hyperhidrosis, there has developed a consensus for making intracutaneous injections only . Of the injections in axillary areas, the palms of the hands, the plantar regions, the face or other cutaneous areas, palmoplantar hyperhidrosis is the least accessible, in any case causes the most technical problems, because of difficulty in pain management . For sialorrhea and the drooling that accompanies certain chronical neurological diseases, BT seems to have very promising effects . However, it has not been precisely determined whether to inject the parotid gland, the submandibular gland, or both . Necessary and sufficient means of targeting are still imprecise . It also remains to be determined the number of sites per gland and the doses to be injected.

Ann Readapt Med Phys, 2003 Jul, 46(6), 333 - 7
{Bruxism, temporo-mandibular dysfunction and botulinum toxin}; Chikhani L et al.; Tooth grinding and tooth clenching are unvoluntary mainly nocturnal habits that result in an hypertrophy of masseter and temporalis muscles with an unbalance between opening and closing muscles of the jaw and lead to an alteration of mandibular condyles movements and to hyper pressure in the temporo-mandibular joints (TMJ) which can generate severe pain . Intra muscular injections of botulinum toxin permit to restablish the balance between closing and opening muscles, to relieve pain, to treat masseteric hypertrophy with improvement of face outline and to recover a normal cinetic of temporo-mandibular joints . Moreover, botulinum toxin injections permit to quit habits of tooth grinding and clenching and one single session of injections is curative for 2/3 of the patients . There are no side effects apart from slight diffusion to superficial muscles of the face resulting in a "fixed" smile for about 6 to 8 weeks . So injections of botulinum toxin in masseter and temporalis muscles are an efficient treatment of bruxism and TMJ dysfunction, cheap with no lasting side effect.

Ann Readapt Med Phys, 2003 Jul, 46(6), 329 - 32
{Botulinum toxin A and musculoskeletal pain}; de Seze MP et al.; INTRODUCTION: Relaxant muscle properties and pain relieve effectiveness in neurological spasmodic disorders of botulinum toxin A (BTXA) suggested its relevance to relieve musculoskeletal pain . The aim of this article was to collect literature data and to assess the different analgesia indications of BTXA proposed in the treatment of musculoskeletal pains . METHOD: The international literature was carried out with the Medline data bank using keywords toxin and pain . Only clinical trials have been analysed . RESULTS: Three hundred and seventeen articles were collected and 12 clinical trials were retained . They are focused on 4 chronic diseases, neck pain, tennis elbow, Piriformis syndrome and low back pain . Results of the 6 chronic neck pain studies are contradictory and emphasize the difficulty to display a satisfactory analgesia effect of BTXA in this indication . Results of the studies concerning other indications (tennis elbow, Piriformis syndrome and low back pain) seem to be more effective and clinically pertinent . DISCUSSION: Analgesia BTXA effect seems to be conditioned by the presence of an objective muscular spasm or stringy disease inducing musculoskeletal pain . CONCLUSION: The first data concerning use of BTXA to treat musculoskeletal pains are few and are worth specifying by other studies.

Ann Readapt Med Phys, 2003 Jul, 46(6), 326 - 8
{Efficacy of botulinum toxin A for the treatment of detrusor hyperreflexia}; Denys P et al.; OBJECTIVE: To determinate the efficacy of botulinum toxin to treat refractory urinary incontinence due to bladder hyperreflexia . METHOD: The international medical literature was reviewed from the Medline and Pubmed database . DISCUSSION: The usual first line treatment of detrusor hyperreflexia is parasympathicolytic drugs and self cathterization . In case of lack of efficacy or severe side effects, a surgical procedure (enterocystoplasty) can be performed . 300 units of Botox injected into the detrusor permit a significant increase of bladder capacity and a significant decrease of maximal detrusor pressure for at last 6 months . But we did not find any double blind controlled studies in this indication and no fundamental studies focused on the mechanism of action of botulinum toxin on the bladder muscle . It is now impossible to conclude on the long term efficacy and toxicity . CONCLUSION: Botulinum toxin injected into the detrusor muscle seems to be an efficient treatment of bladder hyperreflexia for 6 months in patients resistant to parasympathicolytic drugs . Long term efficacy and mechanism of action is actually not known.

Ann Readapt Med Phys, 2003 Jul, 46(6), 319 - 25
{Detrusor-sphincter dyssynergia and botulinum toxin}; Parratte B et al.; OBJECTIVE: Botulinum toxin (BT) injection into the external urethral sphincter is a promising therapy for neurogenic voiding disorders due to detrusor-sphincter dyssynergia (DSD) . However the optimal treatment protocol remains unclear . METHOD: A PubMed reference search and manual bibliography review were performed, along with a search in the Annales de readaptation et de medecine physique and in the reports of the International French-language Society of Urodynamics and the International Continence Society, which allowed us to select twelve pertinent articles with PubMed, two articles from the Annales and two conference reports . Our analysis gave special emphasis to assessment criteria, application, dosage and BT injection technique . RESULTS: Used for the first time in 1988 in spinal cord injury patients to reduce outflow obstruction due to DSD, BT injections have been shown to be a valuable alternative management of bladder dysfunction with DSD . They have been proposed in neurological patients unable to perform self-catheterisation, after drug failure and before surgery . Parameters for results assessment are mostly clinical (increased free interval between voiding, decreased post-void residual urine volumes), urodynamic (improvement in bladder emptying, increase in functional bladder capacity and decrease in urethral pressure) and electromyographic (denervation of striated urethral sphincter) . The literature data regarding type of BT, dosage and protocol vary widely . Duration of action is from 2 to 12 months . Both transurethral and transperineal injections monitored by EMG are equally effective in improving detrusor-sphincter dyssynergia . CONCLUSION: With few side effects and satisfactory medium-term results, BT should be recommended as a component of DSD therapies . We propose a practical method for BT use.

Ann Readapt Med Phys, 2003 Jul, 46(6), 312 - 8
{Botulinum toxin in headache}; Simon O et al.; Use of botulinum toxin in headache is a recent method . More and more studies are dedicated to this method . However, despite the large number of published studies, results are contradictory . It is actually difficult to conclude that this therapy is effective or not due to the disparity of clinical studies . Nevertheless, some results are encouraging and studies with a large number of patients have to be done . Here, we take stock about pathophysiological data on the effect of botulinum toxin on pain . Then, we'll report a review of clinical studies available on literature.

Ann Readapt Med Phys, 2003 Jul, 46(6), 307 - 11
{Movement disorders and botulinum toxin in neurology}; Sangla S et al.; Botulinum toxin has been a useful treatment in many movement disorders and more recently in other non-neurological motor dysfunctions for more than 15 years . Here, we review the various indications in neurology, mainly in the field of movement disorders . From 1973 to 2002, we searched the Medline database on this topic . We selected the most useful and relevant papers, with a special interest in dystonia . We summarized the results in the main indications (spasmodic torticollis, bleparospasm, hemifacial spasm) and in other manifestations such as writer's cramp, oromandibular dystonia, tremor, tics and myoclonus . We discuss the data of literature and compare them with the experience of the French movement disorders groups.

Ann Readapt Med Phys, 2003 Jul, 46(6), 303 - 6
{Botulinum toxin and traumatic brain injury}; Duprey E et al.; Botulinum toxin is a successful focal spasticity therapy . The aim of this article is to study the data of the literature concerning its utilisation in traumatic brain injured patients, whom motor and tonus disturbances are polymorphic, in their clinical presentation as well as in their evolution . Although there are few studies concerning its utilisation in such patients, none of them being controlled, its use seems interesting in focal spasticity treatment . It can contribute to improve functional abilities and comfort for these patients.

Ann Readapt Med Phys, 2003 Jul, 46(6), 299 - 302
{Multiple sclerosis and botulinum toxin}; Lamotte D et al.; INTRODUCTION: The aim of this work was to collect litterature datas to have an indication of botulinum toxin in multiple sclerosis disease . METHOD: The international literature relating the years 1982-2002 was carried out with the Medline data bank . The article presenting of the controlled studies were mainly retained . RESULTS: Thirty-seven articles were indexed, 6 were retained according to our criteria . The selected articles show mainly a use of botulinum toxin in the spasticity . The principal criteria of evaluation were the muscular tone, the spasms, the pain, the or passive amplitude of joint.Two articles report the effectiveness of toxin injection in acquired nystagmus and the paralysis of a vocal fold . DISCUSSION: This review shows that the principal indication of toxin in multiple sclerosis is spasticity with a good effectiveness of the treatment . However controlled-placebo studies among these patients are still very few . The side effects are rare but sometimes appearance of muscular weakness always making discuss the existence of a push . It is necessary to take account of these effects and their consequences before proposing the treatment . CONCLUSION: Botulinum toxin has an indication in the treatment of spasticity of patients with multiple sclerosis . However more studies are necessary with more sits of injection to fix the good indications.

Ann Readapt Med Phys, 2003 Jul, 46(6), 296 - 8
{Botulinum toxin and spinal cord injury}; Ben Smail D et al.; OBJECTIVE: To realize a clarification about the interest of the use of botulinum toxin in spinal cord injured patients . METHOD: Interrogation of Medline database (crossing of botulinum toxin and spinal cord injury) . We have also analyzed data from R . Poincare Hospital in 2001 . RESULTS: Three articles of the twenty-five selected, treated effectively of botulinum toxin effect in the limbs muscles of spinal cord injured patients . DISCUSSION: There are some indications of botulinum toxin in spinal cord injured patients ASIA C and D when spasticity induce focal functional discomfort . Indications are exceptional for ASIA A and B patients . No study showed improvement of functional abilities after botulinum toxin injection in spinal cord injured patients . Published studies only covered small number of patients.

Ann Readapt Med Phys, 2003 Jul, 46(6), 286 - 95
{Post stroke hemiplegia: interest of botulinum toxin injection at the upper limb}; Rousseaux M et al.; OBJECTIVES: To present data about the effect of botulinum toxin injection on the upper limb of stroke patients . METHODS: We used the Medline data bank . Analysis took into account the international classification of functioning and disability . Important technical or pragmatic points were analysed separately . RESULTS: Botulinum toxin reduces spasticity of the injected muscles, with a mean gain of about 1 point on the Ashworth scale in the 4 to 6 weeks post injection, but with a large variability . This is associated to an increase in the passive range of motion, especially at wrist, and at times to a facilitation of active movements, when they are still possible . Improvement in functional tests is observed when fair proximal and distal motricity persists . Reduction in the dependence in daily living activities has not been shown by group studies . Several patients have an improvement in using the hand for blocking and transporting objects, mainly in a facilitating position (pronation, partial wrist flexion) . Comfort of patients and caregivers is more regularly improved . Results are partially predictable; improvement in function is observed in patients with fair distal motricity (extension) and low spasticity, and improvement in comfort in those with severe spasticity and low motricity . CONCLUSION: Further studies are required, on one hand for better assessment of distal functional improvement, on the other hand at earlier phases of the disease.

Ann Readapt Med Phys, 2003 Jul, 46(6), 281 - 5
{Post stroke hemiplegia: lower limb benefit from botulinum toxin (review)}; Yelnik AP et al.; OBJECTIVE: To clarify the conditions governing the use of botulinum toxin (BTX) for post-stroke lower limb spastic disorders: indications, choice of muscles, doses, and duration of efficacy . METHOD: Review of the international literature using the Medline and the Reedoc data banks . RESULTS: Seven controlled studies were reviewed, including in particular 2 studies vs placebo and one vs phenol, 7 open studies or case series closely related to this topic and 4 open studies partly dedicated to it . The usefulness of BTX for the treatment of equinovarus has been demonstrated . The main muscles to be treated are the soleus, gastrocnemius and tibialis posterior . The treatment proposed for toe clawing is BTX injection into the flexor digitorum longus and flexor hallucis longus, and for great toe permanent extension, injection of the extensor hallucis longus . The quadriceps femoris, the tibialis anterior or the hamstrings have only be treated in isolated cases . When the treatment is effective, its benefit may last for more than 6 months . DISCUSSION: A few controlled trials have demonstrated the efficacy of BTX for post stroke lower limb spasticity . The results of all the controlled and open trials argue in favor of its efficacy, but this still requires more thorough analysis . CONCLUSION: Botulinum toxin has a place together with other local treatments for post-stroke spasticity, but a precise guide to its use, especially its dosage, and it's effectiveness compared to that of other treatments, need further study.

ORL J Otorhinolaryngol Relat Spec, 2003 May-Jun, 65(3), 140 - 3
Immunohistochemical evidence of nNOS and changes after intraglandular application of botulinum toxin A in cephalic salivary glands of adult rats; Ellies M et al.; The purpose of our study was to investigate the possible influence of local injections of botulinum toxin A on the activity of neuronal nitric oxide synthase (nNOS) in cephalic salivary glands of adult rats . The role of nitric oxide (NO) as a possible neuromodulator of vascular regulation and in particular regulation of secretion in the upper respiratory and aerodigestive tract is discussed . We present immunohistochemical evidence of nNOS in the salivary glands of female adult Wistar rats, both in native (untreated) glands and after intraglandular injection of botulinum toxin A under general anesthesia . Other than in the untreated glands, there was a significant decrease in nNOS in the treated organs which became stronger with extended toxin exposure time . After our laboratory had already shown a decrease in acetylcholinesterase immunoreactivity after injection of botulinum toxin A into the cephalic salivary glands of the rat, the present study discusses a possible participation of NO in the regulation of secretion from these organs . As a conclusion, it might be assumed that the influence of botulinum toxin A on nNOS in the cephalic salivary glands of the rat is able to explain the sometimes longer duration of the toxin effect at the neuroglandular junction than at the motor endplate .

J Otolaryngol, 2003 Jun, 32(3), 185 - 9
Selective denervation: reinnervation for the control of adductor spasmodic dysphonia; Allegretto M et al.; OBJECTIVES: The objective of this study was to evaluate the efficacy of a new surgical procedure for adductor spasmodic dysphonia (AddSD) . This surgery involves the bilateral selective division of the adductor branches of the recurrent laryngeal nerves with immediate reinnervation of the distal nerve trunks with branches of the ansa cervicalis (selective denervation-reinnervation) . METHODS: Our first six patients to undergo this procedure were enrolled in the study . All patients suffered from AddSD and had previously received botulinum toxin A (Botox, Allergen, Markham, ON) therapy . Patients were recorded preoperatively and all underwent the same surgical procedure performed by the same lead surgeon . All patients were surveyed postoperatively and then re-recorded . Expert and untrained judges undertook perceptual evaluation of voice quality . Voice samples were also objectively evaluated for aphonic voice breaks . RESULTS: No major surgical complications were noted . Patient satisfaction was excellent, and five of the six patients no longer require botulinum toxin therapy . In five of the six patients, the majority of untrained and expert listeners perceived the postoperative voice to be superior . Objectively, the rate of aphonic voice breaks was also reduced in five of the six patients.

Ophthal Plast Reconstr Surg, 2003 May, 19(3), 177 - 81
Benign essential blepharospasm among residents of Olmsted County, Minnesota, 1976 to 1995: an epidemiologic study; Bradley EA et al.; PURPOSE: To describe the incidence, patient demographics, and response to treatment of benign essential blepharospasm (BEB) in a population-based cohort . METHODS: In this epidemiologic study, we searched the Rochester Epidemiology Project database for patients diagnosed with blepharospasm or related disorders between 1976 and 1995 . The incident rate denominator was based on a linear interpolation of decennial census data from Olmsted County . The 95% confidence interval for the incidence rate was based on the Poisson distribution . RESULTS: Olmsted County residents (n = 295) were diagnosed with blepharospasm or related disorders between 1976 and 1995 . Of these, 8 patients met the criteria for BEB . The calculated incidence rate of BEB is 1.2 persons per 100,000 population per year (95% CI, 0.37 to 2.02) . At the time of BEB diagnosis, the median patient age was 61.5 years, and symptoms had been present for a median of 24 months . Four patients were men and 4 were women . Four of the 8 patients had Meige syndrome . Three of 4 patients treated with oral medications reported symptomatic improvement . Botulinum toxin injection was offered to all patients, but only 4 elected treatment . All who were treated with botulinum toxin had temporary symptomatic improvement . No patient underwent surgical treatment for BEB . Two patients had resolution of symptoms within the follow-up period . CONCLUSIONS: BEB is a rare disorder . In this small, population-based sample, women and men were affected with equal frequency, and half of patients had lower facial dystonia (Meige syndrome) . Only half of patients with BEB elected botulinum toxin injections, and none required surgery . Disease remission occurred in 2 of 8 patients.

IDrugs, 2003 Aug, 6(8), 773 - 80
Bioterrorism: a new frontier for drug discovery and development; Shailubhai K; Only a few years ago bioterrorism was considered a remote concern but today it has reached the forefront of the public imagination following recent terrorist attacks around the world . The disaster of September 11 2001, followed by anthrax letters sent via the US postal system, and now the renewed tension in the Middle East, have all brought the possibility of bioterrorism a little closer to reality . A number of biological agents could be used in a terrorist attack, including anthrax, botulinum, plague, smallpox, staphylococcal and streptococcal toxins, and the list of emerging pathogens is evolving rapidly . The serious diseases that these agents produce could cause considerable morbidity and mortality if used in a terrorist attack . This evolving threat presents the medical, public health and scientific communities with pressing challenges . The present research efforts in academia are primarily focused on the basic research on the pathogens that are considered to be bioweapons for terrorist attack . Thus, collaborative efforts between academic institutes, pharmaceutical industries and governmental agencies are warranted to translate basic research into drugs, vaccines and diagnostic tests . This review provides a brief overview of the threat from biological weapons and the current biodefense strategy to prevent and control outbreaks of diseases caused by intentional release of these bioweapons of mass destruction.

Skin Therapy Lett, 2003 Jun, 8(5), 4 - 7
Treatment of hand eczema; Veien NK et al.; Hand eczema is a common skin disease that tends to become chronic and may interfere with many types of work . Emollients have been shown to be useful in reducing eczema activity and in the primary prevention of hand eczema . Protection of the hands is very important for the prevention of hand eczema and is a fundamental aspect of the treatment of hand eczema . Although topical corticosteroids are the mainstay of treatment, few studies of their rational use, efficacy and side-effects have been conducted . A combination of tacrolimus and topical corticosteroids may reduce the risk of steroid-associated side-effects . Systemic treatment with immunosuppressants such as cyclosporine and methotrexate show promising results, and acitretin may suppress keratotic hand eczema . Botulinum toxin has been used with success in the treatment of dyshidrotic hand eczema . PUVA is effective as a systemic treatment . Bath-PUVA treatment, UVB and Grenz rays can also suppress hand eczema.

Dis Colon Rectum, 2003 Aug, 46(8), 1097 - 102
Botulinum toxin (botox) reduces pain after hemorrhoidectomy: results of a double-blind, randomized study; Davies J et al.; PURPOSE: Pain after hemorrhoidectomy appears to be multifactorial and dependent on individual pain tolerance, mode of anesthesia, postoperative analgesia, and surgical technique . Spasm of the internal sphincter is believed to play an important role . The aim of this study was to assess the role of botulinum toxin in reducing pain after Milligan-Morgan hemorrhoidectomy . METHODS: This was a double-blind study of 50 consecutive patients undergoing Milligan-Morgan hemorrhoidectomy and assigned to an internal sphincter injection of 0.4 ml of solution containing either botulinum toxin (20 U; Botox) or normal saline . Patients were managed according to standardized perioperative analgesic and laxative regimens . Pain was assessed by use of daily visual analog scores and analgesia requirements for the first seven postoperative days . RESULTS: Patients randomized to receive botulinum toxin had lower daily average and maximal visual analog scores throughout the study period . The difference reached significance on both Day 6 (P < 0.05) and Day 7 (P < 0.05) . There was no significant difference (P = 0.12) in morphine requirements in the first 24 hours (botulinum group, 16 (range, 6-27) mg; placebo arm, 22 (range, 13-41) mg) . Patients who received Botox used 19 (range, 8-36) coproxamol tablets in the first seven days after surgery compared with 23 (range, 10-40) in the placebo arm (P = 0.63) . CONCLUSIONS: Those patients who had botulinum toxin had significantly less pain toward the end of the first week after surgery . Reduction in spasm within the internal sphincter is the presumed mechanism of action . This is the first reported randomized, controlled trial using botulinum toxin in hemorrhoidectomy.

Hong Kong Med J, 2003 Aug, 9(4), 293 - 4
Use of botulinum toxin type A in a case of persistent parotid sialocele; Chow TL et al.; Sialocele is an uncommon complication of parotidectomy . Most cases resolve after conservative therapy consisting of repeated aspiration and pressure dressing . The condition is, however, occasionally resistant to such therapy . We report on a 52-year-old Chinese man who had a 10-year history of right parotid swelling . Following fine-needle aspiration cytology, Warthin's tumour was diagnosed, but after elective parotidectomy, a swelling developed and parotid sialocele was diagnosed . Botulinum toxin type A was given after the sialocele had persisted for almost 3 weeks after surgery, and after conservative management had been tried; the sialocele disappeared after two doses of treatment . Botulinum toxin therapy was thus an effective method of treating persistent sialocele.

J Laryngol Otol, 2003 Jul, 117(7), 544 - 8
Botulinum toxin injection for failed tracheo-oesophageal voice in laryngectomees: the Sunderland experience; Ramachandran K et al.; Spasm of the pharyngo-oesophageal segment is one of the important causes of tracheo-oesophageal voice failure . Traditionally it has been managed by either prolonged speech therapy, surgical pharyngeal myotomy or pharyngeal plexus neurectomy with varying degrees of success . Botulinum neurotoxin has been found to be effective in relieving pharyngo-oesophageal segment spasm . Since 1995, we have used botulinum toxin injection on 10 laryngectomees with either aphonia or hypertonicity due to pharyngo-oesophageal segment spasm . Early results were analysed by the Sunderland Surgical Voice Restoration Rating scale . Seven of the 10 patients, who were previously completely aphonic, developed voice following this therapy and are using their valve choice as their only method of communication . Out of the three patients who were treated for hypertonic voice, two did derive some benefit from the procedure . One patient developed a hypotonic voice, which lasted for a few months.

Plast Reconstr Surg, 2003 Aug, 112(2), 628 - 33; discussion 634-5
Endoscopic brow lift: a retrospective review of 628 consecutive cases over 5 years; Chiu ES et al.; Since its introduction in 1992, endoscopic brow lift has gained tremendous recognition because it has been promoted as a novel technique to correct brow ptosis as well as glabella rhytids in a minimally invasive manner with fewer complications than the classic coronal brow lift method . In this retrospective study, 628 endoscopic brow lift procedures performed over a 5-year period (1997-2001) at Manhattan Eye Ear and Throat Hospital were reviewed . The number of endoscopic brow lift procedures performed at this institution has declined 70 percent . The purpose of this study was to elucidate the causes of this striking trend by soliciting the opinions of 21 New York plastic surgeons on their current brow ptosis management . The response rate was 84 percent (21 of 25 surgeons contacted) . Currently, 25 percent of the interviewed plastic surgeons perform endoscopic brow lift regularly, 50 percent of the plastic surgeons perform endoscopic brow lift occasionally, and 25 percent of the participants no longer perform endoscopic brow lift . While most patients (70 percent) were satisfied with their results, only 50 percent of the plastic surgeons were pleased with the long-term results (after more than 2 years of follow-up) . Observed postsurgical complications of endoscopic brow lift included alopecia, hairline changes, infected hardware, brow asymmetry requiring surgical revision, prolonged forehead/brow paresthesia, frontal branch nerve paralysis, and scalp dysesthesia . These complications were similar to those resulting from open brow lifts . Seventy-one percent of the surveyed New York plastic surgeons routinely administered botulinum toxin type A (Botox) within 6 months of the endoscopic brow lift procedure . Possible explanations for the decline in the overall number of endoscopic brow lift procedures include the following: (1) the selection criteria for the ideal endoscopic brow lift patients are currently more limited; (2) other techniques equal or surpass endoscopic brow lift in effectiveness and predictability; and (3) endoscopic brow lift is ineffective in the majority of patients . There is no single superior surgical procedure for brow ptosis management available at this time.

Arq Neuropsiquiatr, 2003 Jun, 61(2B), 473 - 7 Epub 2003 Jul 28.
Holmes tremor in association with bilateral hypertrophic olivary degeneration and palatal tremor: chronological considerations . Case report; Rieder CR et al.; Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubro-olivary pathway and presents clinically as palatal tremor . We present a 48 year old male patient who developed Holmes' tremor and bilateral HOD five months after brainstem hemorrhage . The severe rest tremor was refractory to pharmacotherapy and botulinum toxin injections, but was markedly reduced after thalamotomy . Magnetic resonance imaging permitted visualization of HOD, which appeared as a characteristic high signal intensity in the inferior olivary nuclei on T2- and proton-density-weighted images . Enlargement of the inferior olivary nuclei was also noted . Palatal tremor was absent in that moment and appears about two months later . The delayed-onset between insult and tremor following structural lesions of the brain suggest that compensatory or secondary changes in nervous system function must contribute to tremor genesis . The literature and imaging findings of this uncommon condition are reviewed.

J Am Acad Dermatol, 2003 Aug, 49(2), 213 - 6
Pharmacologic denervation of frown muscles enhances baseline expression of happiness and decreases baseline expression of anger, sadness, and fear; Heckmann M et al.; BACKGROUND: Individuals with intense frowning are commonly perceived as expressing negative emotions . Anger, fear, and sadness are associated with corrugator ("frown") muscle activity . OBJECTIVE: We sought to study how faces were perceived by others after denervation of frown muscles with localized botulinum toxin injections for treatment of facial frown lines . METHODS: Facial photographs were taken from volunteers before and after botulinum toxin injection . These photographs were shown to viewers who were naive to the procedure and asked to rate the expressed intensity of anger, sadness, fear, and happiness . As reference for this task we used a standard set of pictures of facial affect displaying different intensity levels for each emotion tested . RESULTS: Of 40 viewers, 39 were able to discriminate different intensity levels (0%, 25%, 50%, 75%, and 100%) of emotional affect in the control task . According to their ratings faces with denervated frown muscle activity expressed relatively less anger (-40%), fear (-49%), sadness (-10%), and more happiness (+71%) . CONCLUSION: Frown muscle activity is essential for both negative and positive emotional expressions . Temporary denervation using botulinum toxin enhances the facial expression of positive emotion resulting in a shift rather than a loss of facial affect.

Am J Med, 2003 Aug 1, 115(2), 134 - 42
Essential tremor: differential diagnosis and current therapy; Pahwa R et al.; Essential tremor is a common movement disorder that affects between 5 and 10 million persons in the United States . It is characterized primarily by an action and postural tremor most often affecting the arms, but it can also affect other body parts . Essential tremor is a progressive neurologic disorder and can cause substantial disability in some patients . Although there is no cure for essential tremor, pharmacologic and surgical treatments can provide some benefit . Primidone and propranolol are first-line treatments . Other medications with potential efficacy include benzodiazepines, gabapentin, topiramate, and botulinum toxin . Patients with medication-resistant tremor may benefit from thalamotomy or deep brain stimulation of the thalamus . The use of medical and surgical therapies can provide benefit in up to 80% of patients with essential tremor.

Urology, 2003 Aug, 62(2), 259 - 64; discussion 264-5
Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study; Maria G et al.; OBJECTIVES: To evaluate the therapeutic role of botulinum toxin injection in men with benign prostatic hyperplasia . METHODS: Men with benign prostatic hyperplasia were enrolled in a randomized, placebo-controlled study . After a baseline evaluation, each participant received 4 mL of solution injected into the prostate gland . Patients in the control group received saline solution and patients in the treated group received 200 U of botulinum toxin A . The outcome of each group was evaluated by comparing the symptom scores, serum prostate-specific antigen concentration, prostate volume, postvoid residual urine volume, and peak urinary flow rates . RESULTS: Thirty consecutive patients were enrolled . No local complications or systemic side effects were observed in any patient . After 2 months, 13 patients in the treated group and 3 in the control group had subjective symptomatic relief (P = 0.0007) . In patients who received botulinum toxin, the symptom score was reduced by 65% compared with baseline values and the serum prostate-specific antigen concentration by 51% from baseline . In patients who received saline, the symptom score and serum prostate-specific antigen concentration were not significantly changed compared with the baseline values and 1-month values . Follow-up averaged 19.6 +/- 3.8 months . CONCLUSIONS: Botulinum toxin injected into the prostate seems to be a promising approach for the treatment of benign prostatic hyperplasia . It is safe, effective, and well-tolerated . Furthermore, it is not related to the patient's willingness to complete treatment.

Ned Tijdschr Geneeskd . 2003 Jul 12;147(28):1356.
{Diagnostic image (147) A man with gustatory sweating . Frey's syndrome}; van den Hoogen FJ et al.; A 73-year-old man suffered from gustatory sweating after submandibular gland removal . Frey's syndrome was diagnosed and successfully treated with intracutaneous injections with botulinum A toxin.

Headache, 2003 Jul-Aug, 43 Suppl 1, S25 - 33
Botulinum neurotoxin for the treatment of migraine and other primary headache disorders: from bench to bedside; Dodick DW; Botulinum toxin type A, a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction including cervical dystonia, blepharospasm, and hemifacial spasm . It inhibits neuromuscular signaling by blocking the release of acetylcholine at the neuromuscular junction . The biological effects of the toxin are transient, with normal neuronal signaling returning within approximately 3 to 6 months postinjection . Recent clinical findings suggest that botulinum toxin type A may inhibit pain associated with migraine and other types of headache . However, the mechanism by which this toxin inhibits pain is not fully understood and is under investigation . Research findings suggest that botulinum toxin type A inhibits the release of neurotransmitters from nociceptive nerve terminals and, in this way, may possess an analgesic effect . A number of retrospective open-label chart reviews and 3 double-blind, placebo-controlled trials have demonstrated that localized injections of botulinum toxin type A significantly reduce the frequency, severity, and disability associated with migraine headaches . Although the majority of patients in these studies experienced no botulinum toxin type A-mediated side effects, a small percentage of patients did report transient minor side effects including blepharoptosis, diplopia, and injection-site weakness . Currently, 4 randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A as a novel treatment for migraine and other types of headache . These studies may provide further evidence that botulinum toxin type A is an effective option for the preventive treatment of migraine.

Headache, 2003 Jul-Aug, 43 Suppl 1, S16 - 24
Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins; Dolly O; Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation . At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors . Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis . Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin . Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine . There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds . The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation . This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.

Headache, 2003 Jul-Aug, 43 Suppl 1, S9 - 15
Evidence for antinociceptive activity of botulinum toxin type A in pain management; Aoki KR; The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types . The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions . In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity . Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized . Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity . The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release . The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems . The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A . In these studies, botulinum toxin type A was found to block the release of glutamate . Furthermore, Fos, a product of the immediate early gene, c-fos, expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin . These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization . The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways . Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine.

J Drugs Dermatol, 2003 Aug, 2(4), 435 - 41
Systemic and topical drugs for aging skin; Kockaert M et al.; The rejuvenation of aging skin is a common desire for our patients, and several options are available . Although there are some systemic methods, the most commonly used treatments for rejuvenation of the skin are applied topically . The most frequently used topical drugs include retinoids, alpha hydroxy acids (AHAs), vitamin C, beta hydroxy acids, anti-oxidants, and tocopherol . Combination therapy is frequently used; particularly common is the combination of retinoids and AHAs . Systemic therapies available include oral retinoids and vitamin C . Other available therapies such as chemical peels, face-lifts, collagen, and botulinum toxin injections are not discussed in this article.

Head Neck, 2003 Aug, 25(8), 624 - 8
Treatment of gustatory sweating (Frey's syndrome) with botulinum toxin A; Eckardt A et al.; BACKGROUND: Gustatory sweating is a common complication of parotid surgery . Injection of botulinum toxin A has been reported as a safe and effective treatment option for patients with Frey's syndrome . PATIENTS AND METHODS: A total of 69 patients who had undergone superficial parotidectomy because of adenoma were evaluated with respect to the incidence of Frey's syndrome and treatment interest . Minor's iodine starch test was used to detect the affected skin area . Affected skin areas were documented using a digital camera; skin areas were evaluated morphometrically . A single injection of Botox per 1 cm(2) skin field was administered to those patients interested in treatment . RESULTS: Of 43 patients (62%) with gustatory sweating, 33 patients requested treatment . The affected skin area varied from 16 cm(2) to 81 cm(2) . The individual Botox dosage ranged from 16 to 80 IU . All relevant clinical symptoms of sweating disappeared within 1 week after a single injection . Treatment was well tolerated with no side effects . CONCLUSION: Botox A injection is a safe and effective treatment with long-lasting effects for patients with extensive gustatory sweating .

Arch Phys Med Rehabil, 2003 Jul, 84(7), 1085 - 6
Use of botulinum toxin type A on orthopedics: a case report; Saenz A et al.; Botulinum toxin type A is effective in treating neurologic entities with increased muscle tone . Few reports show the benefits of this treatment for orthopedic conditions . We present the case of a 54-year-old man who manifested bilateral pectoralis major stiffness and bilateral shoulder pain; he had a score of 6 on a visual analog scale (VAS) . Complex regional pain syndrome (type I) after cardiac surgery, which had already been resolved, was significant in the patient's clinical background . On examination, neither increases in muscle tone nor signs of tendinous or joint pathology was found . However, the patient experienced significant pain when both pectorals were stretched . The patient's Constant score, a validated scale of shoulder function, was 45/100 on the right shoulder and 41/100 on the left . The patient's shoulder stiffness and pain neither responded to rehabilitation (stretching exercises, passive mobilization, electrostimulation) nor to oral medication (alprazolam, gabapentin) . Despite the lack of increased muscle tone, we decided to administer botulinum toxin type A to control pain . Subsequently, pain intensity was reduced to 4 on a VAS on both sides, and functionality improved (Constant scale score, 62 on the right side; 60 on the left) . This improvement enabled the patient to resume his job as a building supervisor, which required active involvement in physical construction work.

Semin Cutan Med Surg, 2003 Jun, 22(2), 131 - 5
Botulinum neurotoxin type B--a rapid wrinkle reducer; Jacob CI; Botulinum toxin has been used for temporary muscle paralysis for over 13 years . The off label use of neurotoxins include treatment of dynamic lines on the face and treatment of hyperhidrosis . Several forms of botulinum toxin exist, but only 2 serotypes are available commercially . Botulinum toxin B (BoTX B) is a recently US Food and Drug Administration (FDA) approved neurotoxin used for the treatment of cervical dystonia . Investigations into the use of BoTX B for skin rejuvenation have shown rapid paralysis and reduction of wrinkles . This overview highlights the current reports on the efficacy, duration, and safety of BoTX B when used for cosmetic procedures.

Eur Urol, 2003 Aug, 44(2), 165 - 74
Botulinum toxin as a new therapy option for voiding disorders: current state of the art; Leippold T et al.; Botulinum toxin is a presynaptic neuromuscular blocking agent inducing selective and reversible muscle weakness up to several months when injected intramuscularly in minute quantities . Different medical disciplines have discovered the toxin to treat mainly muscular hypercontraction . In urology, indications for botulinum-A toxin have been neurogenic detrusor overactivity, detrusor-sphincter dyssynergia, motor and sensory urge and, more recently, chronic prostatic pain . The available literature was reviewed using Medline Services . The keywords "botulinum-A toxin", "detrusor-sphincter dyssynergia", "neurogenic bladder", "spinal cord injury", "denervation", "chronic prostatic pain", "chronic urinary retention" were used to obtain references . A toxin injection is effective to treat detrusor-sphincter dyssynergia when injected either transurethrally or transperineally . After treatment, external urethral sphincter pressure, voiding pressure and post-void residual volume decreased . The effect lasts between 2 to 9 months depending on the number of injections . Best indications seem to be multiple sclerosis and incomplete spinal cord injury patients suffering from neurogenic detrusor overactivity and detrusor-sphincter dyssynergia . According to the previous results, the use of botulinum-A toxin injections into the external urethral sphincter has been extended to a variety of bladder obstructions and to decrease outlet resistance in patients with acontractile detrusor . In cases of successful treatment, spontaneous voiding re-occurs and catheterization can be resumed . Injections of the toxin into the external urethral sphincter also seem to have a beneficial effect on chronic prostatic pain, presumably by reducing hypertonicity and hyperactivity of the external urethral sphincter . Injections of botulinum-A toxin into the detrusor muscle has first been tested to treat neurogenic detrusor activity in spinal cord injured patients and in myelomeningocele children . Long lasting (mean 9 months) detrusor relaxation occurs after injection of usually 300 units of Botox) . Continence is restored in about 95% of the patients and anticholinergic drugs can be markedly reduced or even stopped . Excellent results of botulinum-A toxin injections into the detrusor in neurogenic detrusor overactivity have lead to an expansion of this treatment to incontinence due to idiopathic detrusor overactivity . Although preliminary results are promising, adequate dosage of the toxin required for this indication is not yet known . In conclusion, it appears that botulinum toxin injection into either the external urethral sphincter or the detrusor offers new promising treatment options for many different urological dysfunctions . However, large controlled trials are absolutely required to establish the role of botulinum-A toxin injections in the fields of urology and neurourology on evidence based medicine.

Circulation, 2003 Aug 19, 108(7), 876 - 81 Epub 2003 Jul 21.
RhoA influences the nuclear localization of extracellular signal-regulated kinases to modulate p21Waf/Cip1 expression; Zuckerbraun BS et al.; BACKGROUND: The 42/44-kD mitogen-activated protein kinases (extracellular signal-regulated kinases, ERKs) regulate smooth muscle cell (SMC) cell-cycle progression and can either promote or inhibit proliferation depending on the activation status of the small GTPase RhoA . RhoA is involved in the regulation of the actin cytoskeleton and converges on multiple signaling pathways . However, the mechanism by which RhoA modulates ERK signaling is not well defined . The purpose of this investigation was to examine whether RhoA regulates ERK downstream signaling and cellular proliferation through its effects on the cytoskeleton and the nuclear localization of ERK . METHODS AND RESULTS: Treatment of SMCs with Clostridia botulinum C3 exoenzyme, which inhibits RhoA activation, decreased SMC proliferation to 24+/-7% of that of controls and increased p21Waf1/Cip1 transcription and protein levels . These effects of RhoA were reversed by inhibition of ERK phosphorylation . However, inactivation of RhoA did not alter levels of ERK phosphorylation but did increase nuclear localization of phosphorylated ERK . In addition, immunostaining demonstrated that phosphorylated ERK associated with the actin cytoskeleton, which was disrupted by C3 exoenzyme . Leptomycin B, an inhibitor of Crm1 that results in ERK nuclear accumulation, similarly increased p21Waf1/Cip1 . CONCLUSIONS: RhoA inhibition increased levels of phosphorylated ERK in the cell nucleus . Inhibition of RhoA or pharmacological inhibition of nuclear export resulted in increased p21Waf1/Cip1 expression and decreased SMC proliferation, effects that were partially dependent on ERK . RhoA regulation of the actin cytoskeleton may determine ERK subcellular localization and its subsequent effects on SMC proliferation.

Pain Med, 2003 Jun, 4(2), 206 - 10
Botulinum toxin a improved burning pain and allodynia in two patients with spinal cord pathology; Jabbari B et al.; OBJECTIVE: To report the effect of botulinum toxin A in two patients with burning pain and allodynia of spinal cord origin . DESIGN, SETTING, PATIENTS: Two patients with spinal cord lesions at the cervical level (tumor and stroke) experienced exquisite skin sensitivity and spontaneous burning pain in dermatomes corresponding to the cord lesions . Botulinum toxin A (Botox) was injected subcutaneously at multiple points (16 to 20 sites, 5 units/site) in the area of burning pain and allodynia . RESULTS: Both patients reported significant improvement in spontaneous burning pain and allodynia in visual analogue scale and clinical measures . The analgesic effect of botulinum toxin A lasted at least 3 months and was sustained over follow-up periods of 2 and 3 years with repeated administration at 4-month intervals . CONCLUSION: Subcutaneous application of botulinum toxin A relieved central burning pain and allodynia in two patients with spinal cord pathology.

Eur J Ophthalmol, 2003 May, 13(4), 331 - 6
Treatment of blepharospasm with botulinum neurotoxin type A: long-term results; Calace P et al.; PURPOSE: To describe the long-term efficacy and side effects of treatment of blepharospasm with botulinum neurotoxin type A (Botox) . METHODS: A total of 178 patients with blepharospasm were treated by injections of botulinum toxin in the Eye Clinic of the University of Naples from 1980 to 2001 . The severity of spasm for each patient was graded on a four-point scale . Duration of improvement was assessed and reported in months . RESULTS: Of 178 cases, 10 were lost to follow-up; of the remaining patients, 93% reported improvement after treatments . The mean duration of improvement was 3.6 months . Twelve patients (76%) who underwent more than 14 treatments maintained stable relief . Three patients (1.7%) had a total remission of spasms . Side-effects were local; none of the 168 patients experienced any systemic or toxic reaction . CONCLUSIONS: Botulinum toxin therapy for blepharospasm can provide long-lasting relief and reduction of spasms in the majority of patients . This therapy has the advantages of being safe, simple, and repeatable.

Curr Opin Neurol, 2003 Aug, 16(4), 515 - 21
Myoclonus; Agarwal P et al.; PURPOSE OF REVIEW: Myoclonus, one of the most common involuntary movement disorders, poses particular challenges for the treating physician . The evaluation of a patient with myoclonus depends completely on the clinical history and examination, supported when necessary by electrophysiology, neuroimaging and selected genetic and laboratory testing . The sudden, shock-like jerks which define myoclonus may be highly disabling, and when they persist, often require treatment . RECENT FINDINGS: In a paper published in this journal, we reviewed the published trials of antimyoclonic agents, and formulated a treatment algorithm based on the available evidence . In the current paper, we present our approach for evaluating patients with myoclonus, and suggest practical guidelines for treating patients based on the pre-2000 literature and on studies published in the last 2 years . The newer medications which are being used in management of myoclonus are levetiracetam and gamma-hydroxybutyric acid . Levetiracetam is especially useful for posthypoxic myoclonus and gamma-hydroxybutyric acid for alcohol-sensitive myoclonus . A combination of medications is often needed to obtain adequate control of symptoms . Botulinum toxin is also being introduced for focal myoclonus with encouraging results . SUMMARY: There are no approved medications for myoclonus, and most therapies are borrowed from the antiepileptic and psychiatric armamentarium . Nonetheless, there is a logic to the choice and dosing of antimyoclonic drugs, and we hope that by applying a few simple principles, neurologists will approach the care of these patients with confidence.

Orbit, 2003 Sep, 22(3), 193 - 8
The use of botulinum toxin A in the treatment of functional epiphora; Whittaker KW et al.; AIM: The purpose of this study was to investigate the hitherto undescribed effects of botulinum toxin A injected into the lacrimal gland in patients with functional epiphora . METHODS: A prospective non-comparative interventional case series study was designed to include patients with functional epiphora who presented to the Oculoplastic unit at the Wolverhampton and Midland Counties Eye Infirmary . Botulinum toxin A (2.5-5 units) was injected into the palpebral lobe of the lacrimal gland on the worst affected side via a transconjunctival approach under topical anaesthesia . Patients underwent a Schirmer test and provided a subjective evaluation of their epiphora symptoms, indoors and outdoors, at baseline and at 1, 4 and 13 weeks after injection . The mean score for symptoms indoors and outdoors was calculated . RESULTS: Fourteen patients agreed to take part in the study . Subjective epiphora scores improved in 8 out of the 11 patients (72.7%) who completed 13 weeks of follow-up . Schirmer test results showed objective reduction in tearing from baseline but did not strongly correlate with the subjective epiphora scores . Transient mild ptosis and diplopia were experienced by two patients . CONCLUSION: The results from this small pilot study are encouraging, although larger, controlled trials are needed to assess the optimal dose of BTX-A, its long-term efficacy and safety, and the role of multiple injections.

Rev Neurol, 2003 Jul 1-15, 37(1), 80 - 2
{Use of botulinum toxin in the preventive and palliative treatment of the hips in children with infantile cerebral palsy}; Pascual-Pascual SI; INTRODUCTION: The bilateral spastic cerebral palsy (CP) usually produces hip abnormalities, already presents in many cases before 2 years of age, whose diagnostic requires X ray because clinical exam do not detect some of them . The prognosis of CP hip disorders with conventional treatment is bad, progressive, and limits the possibility of independent gait . Botulin toxin type A infiltrated in adductors, medial ischiotibials and iliopsoas, in addition to physiotherapy and orthosis, gives better results . PATIENTS, METHODS AND RESULTS: In our cases (98 cases, 193 hips) the natural evolution before (BT A) treatment had been of progressive lateral migration of femoral head (86% got worse, and 11,4% became luxated), and after the onset of it the progression stopped in 74% of hips and reverted in other 14% . CONCLUSIONS: It is very important to start early the BT A treatment and infiltrate systematically every 3 4 months in order to obtain good results . Stopping the treatment increase the chances of subluxation or luxation . BT A is also a good treatment for hip pain in spastic CP.

Rev Neurol, 2003 Jul 1-15, 37(1), 74 - 80
{Botulinum toxin Type A . Indications and results}; Poo P et al.; INTRODUCTION: Since introduction for clinical in the 80s, the botulinum toxin type A is being used with effectiveness in the treatment of different disorders that goes with exaggerated muscular activity . Numerous studies have been demonstrated useful for focal treatment of spasticity . PATIENTS AND METHODS: Some indications of the botulinum toxin type A for the treatment of the cerebral palsy are reviewed, emphasizing that it use must be in a global planning . The positive results and adverse events are reviewed, of a series of 278 patients with spastic cerebral palsy . RESULTS: 19% of these patients have had a slightly positive answer, with modification of the tone but without functional repercussion, 49% have had a moderate answer, 17.5% have a good improvement and a 5% have presented good improvement for a long time . Of 224 patients with more than a year of evolution, the 9.5% have presented adverse reactions, but they have always been slight and transient . CONCLUSION: The botulinum toxin type A can be considered effective and safe for the treatment of spasticity, whenever the indication is correct and it is accompanied by a treatment of physiotherapy well oriented.

Curr Opin Neurol, 2003 Jun, 16(3), 341 - 5
The evolving management of migraine; Ashkenazi A et al.; PURPOSE OF REVIEW: To review recent advances in acute and preventive migraine treatment . RECENT FINDINGS: The number of migraine drugs continues to expand, allowing for more flexible and tolerable treatment plans . Two new triptans, frovatriptan and eletriptan, and a nasal formulation of zolmitriptan have been recently developed . Eletriptan is effective for acute migraine treatment and may have some pharmacologic and clinical advantages . Frovatriptan has a longer half-life and lower headache recurrence rates compared with other triptans . It may be useful for patients who have prolonged attacks and high headache recurrence rate . Zolmitriptan nasal spray has a rapid onset of action and high efficacy . It should be considered when patients have rapid-onset attacks, especially when associated with severe nausea or vomiting . The butyrophenone neuroleptic droperidol is very effective in aborting acute migraine attacks . Central nervous system side effects are common, however, and the ECG should be monitored . Botulinum toxin type A shows promise as a safe, tolerable and effective drug for migraine prevention, with the unique advantages of almost no systemic adverse events and a long interval between treatments . The anticonvulsant topiramate is effective for migraine prevention . Cognitive side effects are of less concern with the lower doses needed for migraine . The angiotensin converting enzyme receptor blocker candesartan appears to be effective and highly tolerable in the prevention of migraine, but needs to be further evaluated . SUMMARY: New drugs expand the spectrum of migraine treatment both for the acute attack and for prevention.

JSLS, 2003 Apr-Jun, 7(2), 165 - 9
Laparoscopic Heller myotomy with epiphrenic diverticulectomy; Pitchford TJ et al.; BACKGROUND AND OBJECTIVES: To describe the technique and results of laparoscopic Heller myotomy and Toupet fundoplication combined with epiphrenic diverticulectomy . CASE REPORT: A 75-year-old man presented to our institution complaining of dysphagia to solid foods and liquids . The preoperative preparation included a barium swallow, esophagoscopy, and esophageal manometry . Three months earlier, the patient had a botulinum toxin injection, which provided temporary relief . Ten months later, the patient underwent a laparoscopic Heller myotomy and Toupet fundoplication combined with an epiphrenic diverticulectomy . RESULTS: No complications occurred . The patient tolerated clear liquids on postoperative day 1; on postoperative day 2, he was discharged tolerating full liquids . He returned to full activity in 1 week . CONCLUSIONS: Epiphrenic diverticulectomy combined with treatment for the underlying motor disorder and gastroesophageal reflux prevention is an accepted practice . We demonstrate that this rare problem can be approached with the laparoscopic technique . Given this favorable result, we plan to continue this technique and establish a longer follow-up and wider series.

J Oral Maxillofac Surg, 2003 Jul, 61(7), 774 - 8
Type A botulinum toxin in the treatment of chronic facial pain associated with masticatory hyperactivity; von Lindern JJ et al.; PURPOSE: Chronic hyperactivity of the masticatory muscles is a common functional disorder associated with chronic facial pain and headache . The positive therapeutic effect of botulinum toxin type A on functional disorders and pain symptoms has been known in connection with the treatment of cervical dystonia . The purpose of this report is to assess whether the targeted reduction of masticatory muscular hyperactivity by local injection treatment with botulinum toxin type A can improve facial pain headache symptoms in the event that other treatment methods prove ineffective . Materials and Methods: In an randomized blinded placebo-controlled study, 90 patients (60 verum and 30 placebo) with chronic facial pain were treated with botulinum toxin type A (Botox; Allergan, Ettlingen, Germany) injections into masticatory muscles . RESULTS: Ninety-one percent of patients who received botulinum toxin improved by a significant mean reduction of approximately 3.2 on a visual analog pain scale . By comparison with t test and chi(2) test, there was a significant difference compared with the placebo group (P <.01) . CONCLUSIONS: The local injection of botulinum toxin type A constitutes an innovative and adequately efficient treatment method for chronic facial pain associated with hyperactivity of the masticatory muscles . An improvement in the painful symptoms can be expected in up to 90% of patients who do not respond to conservative treatment methods.

Eye, 2003 Jul, 17(5), 610 - 2
A new grading system for assessing orbicularis muscle function; Rahman R et al.; PURPOSE: To establish an objective parameter (orbicularis function) to measure the efficacy of botulinum toxin treatment in weakening the orbicularis of blepharospasm and hemifacial spasm sufferers . METHODS: The following scale has been used by one of the authors (VTT) in his botulinum clinic for several years: Grade 0: Incomplete eyelid closure.Grade 1: Lids just closing, minimal resistance to overcome.Grade 2: Closing well, some resistance, easily overcome.Grade 3: Strong closure, can be overcome with difficulty.Grade 4: Very strong closure, cannot be overcome or overcome with extreme difficulty.In order to establish the interobserver agreement, one consultant ophthalmologist, three ophthalmologists in training, and one nurse practitioner evaluated the same 65 patients, undergoing treatment with botulinum toxin for essential blepharospasm and hemifacial spasm . Observers assessed orbicularis function by asking each patient to close both eyes forcefully, while the observer tried to open them manually . The measure of agreement across the observers was estimated by kappa statistics . RESULTS: Overall interobserver agreement (kappa=0.54) was satisfactory . We used Kruskal-Wallis nonparametric test to determine agreement between the observers . The P-values for both right and left eyes were well above 0.05, indicating good consistency between the observers when using this grading system . CONCLUSIONS: A simple, new, five-point, clinical grading system for orbicularis muscle function is presented . Medical staff with different levels of experience can use it reliably.

Parkinsonism Relat Disord, 2003 Aug, 9(6), 355 - 9
Idiopathic foot dystonia treated with intramuscular phenol injection; Kim JS et al.; We describe a patient who developed involuntary, painless, dystonic contraction of the left foot on walking . The patient had been treated with botulinum toxin A without benefit . Examination showed that walking brought on a spasmodic twisting of the left foot, with extension and eversion of the ankle . The patient underwent an intramuscular phenol injection, which abolished the foot dystonia . This case suggests that intramuscular phenol treatment may be an alternative for patients where botulinum toxin was unable to relieve the dystonias.

J Clin Neurosci, 2003 Jul, 10(4), 434 - 8
Spasmodic dysphonia: clinical features and effects of botulinum toxin therapy in 169 patients-an Australian experience; Tisch SH et al.; Adductor spasmodic dysphonia (SD) is a focal laryngeal dystonia, characterised by strangled, effortful speech with breaks in pitch and phonation . Injection of laryngeal muscles with BTX is widely used in the treatment of SD . A consecutive series of 169 patients with SD, of whom 144 were treated with BTX injections, seen at St . Vincent's Hospital between 1983 and 1999 were studied prospectively . Patients underwent neurological, quantitative voice and otolaryngological assessment . Females (62.1%) outnumbered males (37.9%) and the mean age at diagnosis was 56 years (range 19-88) . Adductor SD (89.4%) was more frequent than abductor SD (1.8%) or mixed SD (4.7%) . Stridor was present in 14 patients (8.3%) and in 7 was the sole manifestation of the laryngeal dystonia . The median treatment outcome score was excellent in 63.2%, very good in 18.5%, satisfactory in 14.7% and unsatisfactory in 3.5% . Poorer treatment outcome was associated with abductor SD (OR = 4.69, CI {1.23, 17.92} p=0.024} and age >65 (OR = 2.83, CI {0.95, 8.42} p=0.049) . Mild post-injection paralytic dysphonia was associated with longer lasting treatment (4.42 vs . 3.62 months p<0.001) and superior treatment outcome rating (1.37 vs . 1.81 p<0.001) . We conclude that BTX injections are highly effective and severe adverse events are rare . Older age and abductor SD may confer a relatively poorer treatment outcome . Mild post-injection paralytic dysphonia may be a marker for more effective and lasting treatment in adductor SD.

Methods Find Exp Clin Pharmacol, 2003 Jun, 25(5), 387 - 408
Gateways to clinical trials; Bayes M et al.; Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses . The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity(R), the drug discovery and development portal, This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101 . (c) 2003 Prous Science . All rights reserved.

Aliment Pharmacol Ther, 2003 Jul 1, 18(1), 1 - 16
Review article: botulinum toxin in the therapy of gastrointestinal motility disorders; Gui D et al.; Since 1980, botulinum toxin has been employed for the treatment of various voluntary muscle spastic disorders in the fields of neurology and ophthalmology . More recently, botulinum toxin has been proved to be effective in the therapy of dyskinetic smooth muscle disorders of the gastrointestinal tract . Achalasia and anal fissure are the gastrointestinal disorders in which botulinum toxin therapy has been most extensively investigated . Botulinum toxin is the best treatment option for achalasia in patients whose condition makes them unfit for pneumatic dilation or surgery . In anal fissure, botulinum toxin is highly effective and may become the treatment of choice . In the future, botulinum toxin application in the gastrointestinal tract will be extended to many other gastrointestinal disorders, such as non-achalasic motor disorders of the oesophagus, dysfunction of Oddi's sphincter, achalasia of the internal anal sphincter and others . This article describes the mechanism of action, rationale of employment, indications and side-effects of botulinum toxin application in smooth muscle disorders of the gastrointestinal tract, and compares the results of different techniques of botulinum toxin therapeutic application.

J Drugs Dermatol, 2002 Jul, 1(1), 17 - 22
Botulinum toxin B: the new option in cosmetic injection; Spencer JM; Botulinum toxin, one of nature's most toxic substances, is the unlikely source of one of cosmetic dermatology's most popular new injectable treatment options . This article describes the physiological and biological workings of the several structurally similar but antigenically distinct serotypes of botulinum toxin, and provides clinical studies comparing and contrasting the key ingredients in Botox, Dysport, and Myobloc (Neurobloc).

J Drugs Dermatol, 2002 Sep, 1(2), 147 - 51
Type A botulinum toxin: a new treatment for axillary and palmar hyperhidrosis; Rusciani L et al.; Hyperhidrosis is an invalidating condition, and one that is difficult to treat . It is characterized by an excessive and uncontrolled production of sweat by the sweat glands, often causing psychological, social, and occupational problems for the patient . Hyperhidrosis can be distinguished in two forms: idiopathic (of unknown etiology), or secondary, due to an alteration of the endocrine system (ex: hyperthyroidism, neuropathy, neoplasia etc.) It is found in about 0.3-0.5% of the population and can be localized (axillary, palmar, plantar, facial) or diffused . The subcutaneous injection of type A botulinum toxin, until now used only for the treatment of blepharospasm or hemifacial spasm, has shown to be a useful treatment for localized hyperhidrosis . The objective of the authors is to evaluate the therapeutic efficacy, safety, and management of botulinum toxin treatment in patients affected with axillary or palmar hyperhidrosis resistant to conventional therapies.

J Cell Biol, 2003 Jul 7, 162(1), 125 - 37
Hrs regulates early endosome fusion by inhibiting formation of an endosomal SNARE complex; Sun W et al.; Movement through the endocytic pathway occurs principally via a series of membrane fusion and fission reactions that allow sorting of molecules to be recycled from those to be degraded . Endosome fusion is dependent on SNARE proteins, although the nature of the proteins involved and their regulation has not been fully elucidated . We found that the endosome-associated hepatocyte responsive serum phosphoprotein (Hrs) inhibited the homotypic fusion of early endosomes . A region of Hrs predicted to form a coiled coil required for binding the Q-SNARE, SNAP-25, mimicked the inhibition of endosome fusion produced by full-length Hrs, and was sufficient for endosome binding . SNAP-25, syntaxin 13, and VAMP2 were bound from rat brain membranes to the Hrs coiled-coil domain . Syntaxin 13 inhibited early endosomal fusion and botulinum toxin/E inhibition of early endosomal fusion was reversed by addition of SNAP-25(150-206), confirming a role for syntaxin 13, and establishing a role for SNAP-25 in endosomal fusion . Hrs inhibited formation of the syntaxin 13-SNAP-25-VAMP2 complex by displacing VAMP2 from the complex . These data suggest that SNAP-25 is a receptor for Hrs on early endosomal membranes and that the binding of Hrs to SNAP-25 on endosomal membranes inhibits formation of a SNARE complex required for homotypic endosome fusion.

Ann Dermatol Venereol, 2003 May, 130(5), 511 - 3
{Efficacy of botulinum toxin A in the treatment of axillary and palmar hyperhidrosis: 10 cases}; Maillard H et al.; Axilliary and palmar hyperhidrosis can become a considerable social and psychological handicap . Local treatments are not always effective and endoscopic thoracic sympathectomy is not without side effects . The efficacy of botulinum toxin has recently been demonstrated in axillary and palmar hyperhidrosis . Between June 2001 and June 2002, we treated all the patients presenting with axillary and palmar hyperhidrosis, resistant to classical treatments, with intradermal injections of botulinum toxin A (Dysport) . The aim was to assess the interest of this technique at moderate doses, in a prospective, open, controlled study . PATIENTS AND METHODS: The hyperhidrotic areas, revealed by Minor's test, were treated with intradermal injections of 100 U of Dysport in the axilliary form and 250 U in the palmar form . Patients were seen after 1 month and 6 months and underwent a Minor's test, photographic control and they filled-in a questionnaire to measure their satisfaction . RESULTS: Ten patients: 9 women and 1 man aged 19 to 63, were included . Three of them consulted for palmar hyperhidrosis and 7 for auxiliary hyperhidrosis . Within 2 to 7 days, treatment was successful in all patients . The follow-up was of 3 to 12 months . The satisfaction index was comprised between 7/10 and 9/10 . The relapse-free interval was of 2 to 9 months . Three patients were given a second injection, which doubled the relapse-free period . Side effects included pain with the palmar injections and moderate headaches.DISCUSSION: This French study confirms the efficacy of botulinum toxin A in the treatment of axillary and palmar hyperhidrosis with relatively low doses (100 U of Dysport per armpit and 250 U per palm) . This is an easily reproducible, well tolerated, method without major side effects.

Eur J Ophthalmol, 2003 Jun, 13(5), 415 - 23
Visual performance after congenital nystagmus surgery using extended hang back recession of the four horizontal rectus muscles; Alio JL et al.; PURPOSE: To evaluate the results of surgical correction of congenital nystagmus based on the use of extensive recessions of the four horizontal rectus muscles . The outcome of this procedure in terms of visual performance of the patients has been analyzed in follow-ups of at least 1 year . METHODS: Surgery was performed on 42 patients . An extended retroequatorial recession of the four horizontal rectus muscles was performed between 13 and 15 mm from the muscle insertion with hang back sutures in every case . Preoperatively, all cases showed either a horizontal pendular (4 cases) or jerk nystagmus (38 cases) . RESULTS: After surgery, all cases showed full preservation of ductions in all gaze positions . Torticollis decreased in all cases . Binocular best-corrected vision improved in 19 (45.2%) patients and in the remaining 23 (54.8%) it remained unchanged . Consecutive exotropia was observed postoperatively in 7 patients . A second surgical procedure was performed in 9 cases (21.4%) and a botulinum injection in 3 cases (7%) . All cases of diplopia resolved . Patient satisfaction was high in 38 cases (96%) . CONCLUSIONS: Extended recession of horizontal rectus muscles using hang back sutures offers a good option for the surgical correction of sensorial and neuromuscular nystagmus, providing improvement in binocular best-corrected vision in 45% of the patients (21.4% more than 0.2 logMar units), a high satisfaction rate, and few associated complications . In patients with low vision this can be considered a success that may improve quality of life.

Clin J Pain, 2003 Jul-Aug, 19(4), 269 - 75
Use of botulinum toxin in the treatment of chronic myofascial pain; De Andres J et al.; BACKGROUND: Myofascial pain syndrome (MPS) is defined as acute or chronic pain with sensory or motor autonomic symptoms, referred from active myofascial triggering points with associated dysfunction . Previous studies have suggested the usefulness of botulinum toxin A (BTX-A) in the treatment of MPS since it is capable of controlling muscular spasms, as well as other alternative mechanisms of action . OBJECTIVES: To analyze the efficacy of BTX-A treatment and its effect on daily life activities assessing pain reduction using a visual analogue scale (VAS); degree of improvement in physical impairment and disability scoring in the Oswestry low back pain questionnaire; and psychologic status using the Hospital Anxiety and Depression Scale (HAD), in patients suffering from MPS . METHOD: An open-label interventional prospective trial was conducted in 77 patients diagnosed of refractory MPS (defined as the presence of muscle spasm with pain on mobilization or stretching, plus the existence of trigger points with associated referred pain), resistant to both conservative management and to physical therapy . The BTX-A dosages for the different muscles were chosen according to a standardized protocol . Electromyographic guidance was used to localize the motor end plate prior to injection in superficial muscles; while fluoroscopic guidance was employed to evidence intramyofascial spread of the contrast solution within deep muscles . The assessment of treatment efficacy was based on a pain VAS applied before enrollment, at 15, 30, and 90 days and upon completion of the study; the Lattinen test to establish a relationship between pain intensity and its corresponding impact on daily living; and the HAD scale to assess psychologic stress, performed both before treatment and at the end of the study; and the Oswestry Questionnaire was used to evaluate patients' ability to carry out daily life activities according to their degree of physical impairment and disability scores . RESULTS: The global analysis revealed a positive correlation between the VAS score prior to treatment and the scoring at 15, 30, and 90 days . This correlation was maintained when analyzing independently for superficial or deep muscles . The correlation coefficients for HAD scores and the Lattinen test values showed a significant association between pre- and post-treatment findings . No adverse events were recorded for 83.1% of the cases . CONCLUSIONS: The results of this study are consistent with other studies showing the efficacy of BTX-A for treating pain in MPS . The evaluation of the psychologic dimension of this disorder and its associated disability can provide valuable information for the adequate management of these patients and for assessing treatment outcome.

J Assoc Physicians India, 2003 Mar, 51, 276 - 9
Clinical features, assessment and treatment of essential tremor; Panicker JN et al.; Essential tremor is the most common of the movement disorders, being 20 times more common than Parkinson's Disease . It is characterised by postural and kinetic tremor which maximally affects the hands . It can be assessed by physiological techniques, subjective clinical methods, objective clinical methods and handicap/disability scales . Accelerometry, spirography and handwriting assessment, volumetry and handicap/disability questionnaires are commonly used methods . Primidone and propranolol are the first-line drugs . Several second-line drugs have been identified . Surgical techniques include lesioning or stimulation of the ventral lateral thalamus . Alcohol and botulinum toxin A are found to reduce tremor amplitude as well.

Ann Chir Plast Esthet, 2003 Jun, 48(3), 143 - 51
{Optimal forehead rejuvenation . Combining endoscopy-peel-botulinum toxin}; Mole B; The combining of a traditional resurfacing technique (trichloracetic or phenol peel) with 2 recent technological advances (endoscopic forehead plasty, botulinum toxin) may enhance the forehead rejuvenation in a more natural way . The disappointing results of some of our earlier results on a serie of 70 consecutive foreheadplasties can probably be attributed to the weakness of the suspension through percutaneous sutures . This has been remedied since 1998 by the systematic use of transosseous suspensions . The growing success of botulinum toxin explains the noticeable decrease of endoscopic surgery . This type of procedure is now used to correct significant frontal ptosis requiring an uplifting of no more than 1,5 cm, thereby avoiding the unnatural results encountered in many publications . Some benefits can be obtained by the way of a transpalpebral approach without using the endoscope; nowadays, upper blepharoplasties are almost systematically done in the majority of our cases in order to obtain the most natural result . Light peels and botulinum toxin injections can maintain this result relatively easily.

Am J Ophthalmol, 2003 Jul, 136(1), 99 - 105
Quantitative changes in botulinum toxin a treatment over time in patients with essential blepharospasm and idiopathic hemifacial spasm; Snir M et al.; PURPOSE: To evaluate the quantitative changes in botulinum toxin A (BTA) treatment required over time to achieve relief for 3 to 4 months in patients with essential blepharospasm (EBS) and idiopathic hemifacial spasm (IHFS) . DESIGN: Interventional case series . METHODS: In this retrospective longitudinal study in an institutional ophthalmologic outpatient clinic, data were retrieved from patient files and a comparison between patients with EBS and IHFS was performed . The patient population consisted of 27 patients, 17 with EBS and 10 with IHFS, who were treated for the first time with BTA injections and were followed up for 4 to 6 consecutive years . All patients initially received 12 or more courses of treatment with a lower dose (<or=20 U) and were then switched to a higher dose (>20 U) . The main outcome measures were the shift in the dose-response relationship between the lower and higher doses and were analyzed with respect to four variables: average number of treatments, dosage, duration of therapy, and interval of symptomatic relief . RESULTS: In the EBS group the mean dose for each patient changed from 16.0 +/- 1.4 U (lower dose) to 24.2 +/- 1.4 U (higher dose) . The shift occurred after a mean of 8.8 +/- 2.9 treatments per patient given for a mean of 33.5 +/- 13.3 months . The mean interval of relief was longer with the lower dose than with the higher dose (4.0 +/- 1.4 months vs 3.2 +/- 1.0 months, respectively) . In the IHFS group, the mean dose / patient changed from 16.8 +/- 1.2 U to 25.0 +/- 1.8 U, and the switch occurred after a mean of 6.5 +/- 2.3 treatments given over a mean period of 23.8 +/- 6.6 months . The mean duration of treatment with the lower dose was shorter than with the higher dose . The interval of relief was similar for both dose ranges (3.8 +/- 10 months and 4.1 +/- 1.3 months, respectively) . The IHFS group switched to the higher dose earlier, by both number and duration of treatments, than the EBS group . Only minor and transient side effects of treatment were observed in both groups . CONCLUSIONS: Botulinum toxin A is an effective and safe treatment for EBS and IHFS . The dose in our study was increased over time by 50% to achieve 3 to 4 months of symptomatic relief with minimal complications.

Ann Otol Rhinol Laryngol, 2003 Jun, 112(6), 499 - 505
Botulinum toxin management of adductor spasmodic dysphonia after failed recurrent laryngeal nerve section; Sulica L et al.; This study examined botulinum toxin type A (BTX-A) treatment of adductor spasmodic dysphonia patients who had previously undergone recurrent laryngeal nerve section that failed to control symptoms . Information was retrieved from records of patients treated by our group between 1984 and 1999 . Complete records with standardized outcome measurements were available for 181 BTX-A injection sessions in 16 patients who had had nerve section . These were compared to previously published information regarding 4,621 sessions in 639 adductor spasmodic dysphonia patients also treated by our group . Treatment with BTX-A resulted in significant improvement in voice function in the studied patients (change, 38.2% +/- 24.5%; p < .0001) . The onset of effect took place approximately 2.3 days after treatment, and the peak effect about 10.0 days after treatment . The therapeutic effect lasted 14.1 weeks on the average . These features were not significantly different from those observed in adductor spasmodic dysphonia patients as a whole . The incidence of complications was also comparable . However, lower baseline and peak posttreatment perceptions of voice function in the nerve section group were statistically significant (baseline, 45.6% +/- 23.0% versus 52.4% +/- 22.0%; peak, 83.8% +/- 16.4% versus 89.7% +/- 13.0%; both p < .001) . We conclude that BTX-A is effective in the treatment of adductor spasmodic dysphonia in patients who have had recurrent nerve section . However, nerve section may adversely affect perceived voice function and may make botulinum toxin therapy less satisfactory . Because of this finding, and because of the unusual pathological features of the focal dystonias, irreversible means of treating adductor spasmodic dysphonia should be approached with caution.

Brain Res Bull, 2003 Jul 15, 61(2), 165 - 71
Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions; Smith CP et al.; The present experiments compared the inhibitory effects of botulinum toxin A (BoNT-A) and botulinum toxin D (BoNT-D) on neurally evoked contractions of rat bladder strips . We examined the effect of fatigue (trains of 100 shocks at 20Hz every 20s for 10min) followed by non-fatigue stimulation (trains of 100 shocks at 20Hz every 100s for 20min) on the onset of effect and potency of the two toxins . For non-fatigue experiments, strips were untreated (n=4); or incubated with 1.36nM BoNT-A (n=4) . During fatigue experiments, strips were untreated (n=5); or treated with either 1.36nM BoNT-A (n=6) or 0.8nM BoNT-D (n=6) . In non-fatigue experiments, BoNT-A produced significant decreases in contractile area after 1h of stimulation compared to untreated strips (P<0.05) . After three series of fatigue stimulation, differences in recovery amplitude and area between untreated versus BoNT-A, and untreated versus BoNT-D bladder strips, were statistically significant (P<0.05) . The onset of inhibitory effect was quicker in BoNT-D-treated strips, as a significant reduction (P<0.05) in recovery of contractile area was observed after 1h of stimulation compared to both untreated and BoNT-A-treated preparations . In addition, treated (BoNT-A and BoNT-D) and untreated bladder strips responded similarly to atropine, suggesting that the effects of BoNT result from inhibition of both acetylcholine and ATP release . Our results demonstrate that BoNT-D may be a more effective agent to inhibit transmitter release from autonomic nerves of the rat lower urinary tract . Moreover, in our hands, non-fatigue stimulation is as effective as fatigue stimulation in inhibiting bladder strip contractions.

J Neural Transm Suppl, 2003, (64), 35 - 63
Pharmacological approaches to migraine; Diener HCh; Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise . This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis . Analgesics like aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) are effective in treating migraine attacks . Few controlled trials were performed for the use of ergotamine or dihydroergotamine . These trials indicate inferior efficacy compared to serotonin (5-HT)1B/D-agonists (further on called "triptans") . The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan) are highly effective . They improve headache as well as nausea, photo- and phonophobia . The different triptans have minor differences in efficacy, headache recurrence and adverse effects . The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics . Migraine prophylaxis is recommended, when more than 3 attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe . Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline . Recently antiepileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine . The use of botulinum-toxin is under investigation.

Dermatol Surg, 2003 Jul, 29(7), 749 - 54
Botulinum toxin: application into acupuncture points for migraine; Tamura BM et al.; BACKGROUND . : Botulinum toxin has been employed in orthopedics, physiatrics, gastroenterology, gynecology, neurology, pediatrics, general surgery, plastic surgery, and several other specialties . We have applied this drug to treat hyperhidrosis and wrinkles in dermatology; it offers also a secondary benefit: relief for headaches . OBJECTIVE . : We have performed studies based on acupuncture principles in order to develop new botulinum toxin application sites for the treatment of migraine . These additional sites are helpful when patients expect results for both their illness and their wrinkles; whereas some patients will show improvement with the classic treatment for wrinkles, additional sites may be required . METHODS . : Ten patients suffering from migraine, as diagnosed through the criteria proposed by the Headache Classification Committee of the International Headache Society, were selected . We used easily recognizable acupuncture sites for the injection of botulinum toxin . RESULTS . : There was significant improvement in patients with acupuncture site-guided botulinum toxin injection . It showed to be a safe and effective therapy for migraine . CONCLUSION . : There are alternative sites besides those used for the treatment of expression lines, which bring forth an improvement of migraine.

Pharmacol Toxicol, 2003 Jul, 93(1), 1 - 13
The enteric nervous system III: a target for pharmacological treatment; Hansen MB; The past decade has seen major advances in the pharmacological understanding of the nervous system of the gastrointestinal tract, the enteric nervous system, and its importance for gut functions in several states of disease . Indeed, the enteric nervous system has become a promising target in the treatment of many gastrointestinal symptoms and disorders . Some of these new therapeutic concepts, such as botulinum toxin for achalasia and serotonergic drugs for functional bowel diseases, are already in clinical use . This paper is part 3 of three Minireviews in Pharmacology & Toxicology, and presents the neurogastrointestinal pharmacological therapeutic options in gastrointestinal pain, functional gastrointestinal disorders, inflammatory bowel diseases, cancer and related conditions with focus on future drug targets . The diagnosis of gastrointestinal neuropathy, the role of serotonin and related neuroendocrine transmitters, serotonergic drugs, and neurotrophic factors in neurogastrointestinal pharmacology will be addressed in this context.

J Voice, 2003 Jun, 17(2), 255 - 64
Immunologic characterization of spasmodic dysphonia patients who develop resistance to botulinum toxin; Park JB et al.; The immune status of six spasmodic dysphonia patients who became resistant to botulinum toxin was compared to that of a series of patients who remained responsive . The two groups were similar in terms of age, sex, and cumulative dose of toxin . Five of the resistant patients had a significant titer of anti-botulinum toxin IgG antibodies, as determined by enzyme-linked immunosorbent assay (ELISA) . These same five resistant patients had a circulating titer of anti-heavy chain antibodies, but only three of these patients had a circulating titer of anti-light chain antibodies, as determined by Western blotting . By contrast, none of the responsive patients had antibodies against the holotoxin or its two chains . Interestingly, two of the resistant patients also had a low circulating titer of anti-botulinum toxin IgA antibodies . None of the responsive patients was IgA-positive . The cumulative dose of botulinum toxin administered to resistant patients was lower than that customarily associated with emergence of immunity in dystonia patients.

Eur J Neurol, 2003 Jul, 10(4), 415 - 9
Botulinum toxin in the management of childhood muscle spasticity: comparison of clinical practice of 17 treatment centres; Bakheit AM; At least two randomized controlled trials (RCTs) have shown botulinum toxin type A (BtxA) to be efficacious and safe when used in the management of muscle spasticity in children . However, the need to use standard treatment protocols in these studies obscures some aspects of routine clinical practice that may have important effect on clinical outcomes . The purpose of this study was to seek additional information on the use of BtxA that is not usually captured by RCTs . This was performed by reviewing the clinical practice of practitioners in 17 treatment centres in Europe . The details of treatment with BtxA, including the dose, site and frequency of injections and the use of anaesthesia or sedation, were abstracted from the patient's records . Information was also obtained on the response to treatment and the occurrence and severity of adverse events . The data on 758 children who received a total of 1,594 treatments in 17 different clinics in Europe were analysed . Ninety-four per cent of patients had cerebral palsy . There was a general agreement on the indications for treatment but the average dose of BtxA used varied between centres . One treatment centre used general anaesthesia (GA) prior to injections in most patients . The reported efficacy and adverse events profile was similar for all centres . The evidence from routine clinical practice for the efficacy and safety of BtxA in the management of muscle spasticity in children, as described in this study, is in agreement with that of most of the open-label and RCTs published to date . The present study also demonstrates the disagreement between clinicians on the optimal dose of BtxA for individual muscles and confirms that the injections can be carried out without GA in almost all cases.

J Child Neurol, 2003 May, 18(5), 325 - 30
Natural history of Oppenheim's dystonia (DYT1) in Israel; Anca MH et al.; The question of whether a fetus carrying the GAG deletion on the DYT1 gene responsible for Oppenheim's dystonia should be aborted is frequently raised . The objective of this study was to characterize the clinical spectrum and natural course of Oppenheim's dystonia in Israel . Thirty-three patients (19 male) with genetically confirmed Oppenheim's dystonia were evaluated . The Dystonia Rating Scale (maximum score 120) and the Disability Scale (maximum score 30) were used to score severity at the last visit . After a mean of 15.5 +/- 13.8 years of symptoms, the mean Dystonia Rating Scale and Disability Scale scores were 22.7 +/- 14.7 and 7.7 +/- 4.3, respectively . Twenty-one patients (63.6%) have progressed into generalized dystonia . Five patients (15%) are wheelchair bound and three (9%) are using walking aids . All patients have normal cognitive function . Baclofen, trihexyphenidyl, and botulinum toxin were the drugs used . Nine patients (one patient had both) underwent neurosurgical intervention: thalamotomy for six (two bilateral) and pallidotomy for four (three bilateral) . The bilateral pallidotomy provided only short-term benefit . The modern treatments combining drugs, botulinum toxin, and functional neurosurgery allow most patients with Oppenheim's dystonia to have independence and a relatively good quality of life.

Am J Phys Med Rehabil, 2003 Jun, 82(6), 485 - 8
Stroke-induced trismus in a pediatric patient: long-term resolution with botulinum toxin A; Spillane KS et al.; We present a case of prolonged resolution of stroke-induced trismus after botulinum toxin A treatment in a 9 1/2-yr-old boy . The patient had an idiopathic right posterior fossa hemorrhage with resultant spastic quadriparesis, ataxia, dysarthria, and dysphagia . He developed right-sided trismus with only fair response to stretch . Several months after discharge, the patient had worsening trismus with an interincisal distance of only 0.4-0.7 cm and difficulty with oral hygiene and eating . The patient was treated with botulinum toxin A to the masseter muscles with minimal response . Four months later, he received botulinum toxin A to the bilateral masseter and temporalis muscles and to the right medial and lateral pterygoid muscles, with more improvement . His third and last botulinum toxin A treatment was to the bilateral masseter, temporalis, lateral, and medial pterygoid muscles in larger doses . He had an excellent response, maintaining an interincisal distance of 2.5 cm 1 yr later, with significant improvement in speaking and chewing.

J Rehabil Med, 2003 May, (41 Suppl), 60 - 5
Long-term modification of spasticity; Ward AB; This review of the long-term management of spasticity addresses some of the clinical dilemmas in the management of patients with chronic disability . As it is important for clinicians to have clear objectives in patient treatment, the available treatment strategies are set out . Why is it important to treat spastic patients and what treatment does one use? When should one consider a change in the strategy and why is it necessary to have a clear discharge policy from the service to avoid serious logistic problems? The review reiterates the role of physical treatment in the management and thereafter the maintenance of patients with spasticity . There are now a number of good papers on the use of botulinum toxin in spasticity, but this review sets out their context in clinical management and briefly mentions the use of phenol nerve blockade and intrathecal baclofen in clinical practice . Finally, how does one justify the use of an agent regarded as expensive? It is important to use outcome measures that are valid and sensitive to change, and an example is given of ways of demonstrating benefit.

J Neurosurg, 2003 Jun, 98(6), 1247 - 54
Selective peripheral denervation for the treatment of intractable spasmodic torticollis: experience with 168 patients at the Mayo Clinic; Cohen-Gadol AA et al.; OBJECT: Selective peripheral denervation is currently the primary surgical treatment for intractable cervical dystonia . The authors assessed preoperative factors to determine which, if any, correlated with outcomes in patients with torticollis who had undergone this procedure . METHODS: The records of 168 consecutive patients who had undergone selective peripheral denervation for cervical dystonia between 1988 and 1996 at the Mayo Clinic were reviewed . There were 89 women (53%) and 79 men (47%) with a mean age of 53.4 years . Selection of muscles for denervation was based on the patient's clinical presentation and electromyography mapping results . The most common torticollis vectors were rotational in 141 patients (84%) and laterocollis in 59 (35%) . Seventy patients (42%) presented with combined vectors . The technique used to remedy both conditions involved denervation of the ipsilateral posterior cervical paraspinal and splenius capitis muscles . Denervation of the sternocleidomastoid muscle was performed on the contralateral side for rotational torticollis and on the ipsilateral side for laterocollis . A rigorous physical therapy program followed surgery . At the 3-month postoperative evaluation, 125 patients (77%) of the 162 who were available for follow up had moderate to excellent improvement in their head position, and pain was moderately to markedly improved in 131 patients (81%) . The long-term follow up lasted a mean of 3.4 years and was undertaken in 130 patients . The original level of moderate to excellent improvement in head position and pain was retained in at least 71 patients (70%) . Outcome was not predicted by preoperative head position, severity of abnormal posture of head, symptom duration, presence of tremor or phasic dystonic movements, or failure to respond to botulinum toxin treatment . Five patients recovered from postoperative complications including one myocardial infarction, one pulmonary embolism, and three respiratory failures . Three patients suffered from persistent C-2 distribution dysesthesias and three from slight shoulder weakness; one had a wound infection, and one died of respiratory arrest . CONCLUSIONS: Selective peripheral denervation is an effective method of achieving lasting improvement of dystonia in most patients with intractable torticollis.

Eur Urol, 2003 Jul, 44(1), 139 - 43
Botulinum-a toxin detrusor injection as a novel approach in the treatment of bladder spasticity in children with neurogenic bladder; Schulte-Baukloh H et al.; OBJECTIVES: Children with neurogenic hyper-reflexive bladder in whom classical therapy with anticholinergic drugs and intermittent catheterization fails are threatened by high intravesical pressure, vesicoureteral reflux, and impairment of kidney function . Surgery, such as bladder augmentation, is often necessary in such cases . To obviate surgery in these high-risk children, we investigated the use of detrusor injection of botulinum-A toxin (Botox) . METHODS: Our subjects were 20 children with hyper-reflexive detrusor muscle and high bladder pressure, over 40 cmH(2)O despite anticholinergic therapy . After baseline urodynamic measurements, we injected botulinum-A toxin into the detrusor muscle at 30-50 sites at 12 U/kg of body weight up to a maximum of 300 U . Follow-up cystometric measurements were taken two to four weeks and three and six months after injection . RESULTS: From basic measurements to follow-up cystometry, mean reflex volume changed from 97.1 ml before injection to 178.6 ml after four weeks (p<0.01) and to 162.8 ml after three months (p<0.01) . After six months mean reflex volume returned to 119.3 ml (n.s.) . Maximal bladder capacity changed from 163.1 ml to 219.9 ml (p<0.01), to 200.6 ml (p<0.01) and to 222.4 ml (p<0.01), respectively, and maximal detrusor pressure changed from 59.6 cmH(2)O to 34.9 cmH(2)O (p<0.01), to 46.7 cmH(2)O (n.s.) and to 61.8 cmH(2)O (n.s.), respectively . CONCLUSION: Botulinum-A toxin (Botox) is effective when injected into the hyper-reflexive detrusor muscle . It is a valuable treatment option in the management of neurogenic bladder . The effect lasts about six months, and then reinjection is necessary.

Anal Bioanal Chem, 2003 Oct, 377(3), 469 - 77 Epub 2003 Jun 13.
Array biosensor for detection of toxins; Ligler FS et al.; The array biosensor is capable of detecting multiple targets rapidly and simultaneously on the surface of a single waveguide . Sandwich and competitive fluoroimmunoassays have been developed to detect high and low molecular weight toxins, respectively, in complex samples . Recognition molecules (usually antibodies) were first immobilized in specific locations on the waveguide and the resultant patterned array was used to interrogate up to 12 different samples for the presence of multiple different analytes . Upon binding of a fluorescent analyte or fluorescent immunocomplex, the pattern of fluorescent spots was detected using a CCD camera . Automated image analysis was used to determine a mean fluorescence value for each assay spot and to subtract the local background signal . The location of the spot and its mean fluorescence value were used to determine the toxin identity and concentration . Toxins were measured in clinical fluids, environmental samples and foods, with minimal sample preparation . Results are shown for rapid analyses of staphylococcal enterotoxin B, ricin, cholera toxin, botulinum toxoids, trinitrotoluene, and the mycotoxin fumonisin . Toxins were detected at levels as low as 0.5 ng mL(-1).

Arch Dermatol, 2003 Jun, 139(6), 731 - 6
Botulinum toxin type a is a safe and effective treatment for axillary hyperhidrosis over 16 months: a prospective study; Naumann M et al.; OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A (BTX-A) (BOTOX) over 16 months in the treatment of bilateral primary axillary hyperhidrosis . DESIGN: A 16-month study with initial double-blind randomization to 50 U of BTX-A or placebo per axilla . After 4 months, participants could receive up to 3 further treatments with open-label BTX-A over 12 months . SETTING: Fourteen dermatology or neurology clinics in Germany, Belgium, and the United Kingdom . PARTICIPANTS: Of 207 individuals aged between 17 and 74 years who had persistent bilateral primary axillary hyperhidrosis that interfered with daily activities, 174 (84%) completed the study . The baseline gravimetric assessment was a spontaneous sweat production of 50 mg or greater in each axilla prior to initial treatment . MAIN OUTCOME MEASURES: At week 4 after each treatment, the response rate of subjects who had at least a 50% reduction from baseline in axillary sweating, as measured by gravimetric assessment, was evaluated . Adverse events were spontaneously reported throughout the study, together with quality-of-life parameters and assessment of neutralizing antibodies to BTX-A . RESULTS: Over the 16-month period, 356 BTX-A treatments were given to 207 subjects . After placebo treatment, the response rate at week 4 was 34.7% . After the first, second, and third treatment with BTX-A, response rates at week 4 were 96.1%, 91.1%, and 83.3%, respectively . For subjects receiving more than 1 treatment, the mean duration between BTX-A treatments was approximately 7 months; however, 28% of subjects completed the study after only 1 BTX-A treatment . Subjects' satisfaction after treatments was consistently high, their quality of life improved, and there was a reduction in the impact of the disease on their lives . The safety profile of BTX-A after repeated treatments was excellent and no confirmed positive results for neutralizing antibodies to BTX-A occurred . CONCLUSION: Repeated intradermal injections of BTX-A over 16 months for treatment of primary axillary hyperhidrosis is safe and efficacious.

Ther Umsch, 2003 May, 60(5), 275 - 81
{Conservative and surgical therapy of urinary incontinence and bladder complaints in the man}; Danuser H et al.; Treatment of incontinence and bladder complaints in the male should be directed to the cause whenever possible . Frequently, however, only symptomatic therapy is possible . Urge incontinence or overactive bladder due to obstruction should primarily be treated by eliminating the obstruction . Medical and surgical treatment methods are available for benign prostatic hyperplasia, bladder neck hypertrophy and prostatic cancer . In contrast, bladder neck sclerosis and uretheral strictures can only be treated surgically . Anticholinergics are primarily indicated if urge symptoms/incontinence persist after obstruction has been relieved or if urge incontinence occurs without obstruction . Seldom, in special cases injection of Botulinustoxin A or augmentation of the bladder may be indicated . Another possible cause of urge symptoms is urinary tract infection . This should be adequately treated according to resistance studies and the cause of the infection determined . In cases of overflow incontinence the infravesicle obstruction must be sought and treated . If limited detrusor contractability is the cause of overflow incontinence and the bladder cannot be emptied through pressmicturition, parasympathicometics may be of help . By insufficient effect, the procedure of intermittent self-catheterization must be taught . If this is not possible, the last resort is placement of a transuretheral or percutaneous catheter for continuous drainage . Stress incontinence is a rare complication in men, usually following prostatic surgery . It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis . Supravesicular urinary diversion is occasionally necessary after conservative and less invasive surgical measures have been exhausted and symptomatic suffering persists . Neurogenic disturbances in bladder capacity and/or emptying can be treated conservatively, medically, surgically or a combination of these depending upon the site of the lesion and the resulting urodynamic patterns.

Arq Neuropsiquiatr, 2003 Jun, 61(2A), 256 - 8 Epub 2003 Jun 09.
Botulinum toxin for treatment of Frey's syndrome: report of two cases; Teive HA et al.; Frey's syndrome is a phenomenon of hemifacial flushing and sweating after gustatory stimulus, usually secondary to surgical trauma over the parotid gland, although other injury mechanisms may be seen . It is accepted as a result of aberrant regeneration of facial autonomic nerve fibers . Treatment evolved from ineffective medical and surgical approaches to botulinum toxin . We evaluate the effectiveness and safety of botulinum toxin in the treatment of this complication in two patients.

Cochrane Database Syst Rev . 2003;(2):CD000208.
Miscellaneous treatments for neuroleptic-induced tardive dyskinesia; Soares-Weiser KV et al.; BACKGROUND: Tardive dyskinesia is a disabling movement disorder associated with the prolonged use of neuroleptic medication . This review, one in a series examining the treatment of tardive dyskinesia, will cover miscellaneous treatments not covered elsewhere . OBJECTIVES: To determine whether the following interventions were associated with a reduction of neuroleptic induced tardive dyskinesia: botulin toxin, endorphin, essential fatty acid, EX11582A, ganglioside, insulin, lithium, naloxone, oestrogen, periactin, phenylalanine, piracetam, stepholidine, tryptophan, neurosurgery, or ECT . SEARCH STRATEGY: The initial search of Biological Abstracts (1982-1995), The Cochrane Schizophrenia Group's Register (January 1996), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995) and PsycLIT (1974-1995) was updated by searching Cochrane Schizophrenia Group's Register in July 2002 . References of all relevant studies were searched for further trial citations . Principal authors of trials were contacted . SELECTION CRITERIA: Studies were selected if they focused on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced tardive dyskinesia and compared the use of the interventions listed above versus placebo or no intervention . DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality assessed and data extracted . Data were excluded where more than 50% of participants in any group were lost to follow up . For binary outcomes a random effects risk ratio (RR) and its 95% confidence interval (CI) was calculated . Where possible, the weighted number needed to treat/harm statistic (NNT/H), and its 95% confidence interval (CI), was also calculated . For continuous outcomes, endpoint data were preferred to change data . Non-skewed data from valid scales were to have been synthesised using a weighted mean difference (WMD) . MAIN RESULTS: Fifty-seven references describing 37 different trials were identified by the search strategy . Seven of these were included, 27 excluded, and three await assessment . Ceruletide was not clearly more effective than placebo (n=132, 2 RCTs, RR not any improvement in tardive dyskinesia 0.82 CI 0.6 to 1.1) . This also applied to gamma-linolenic acid, although data were sparse (n=16, 1 RCT, RR no clinical improvement 1.00 CI 0.7 to 1.5), oestrogen (n=12, 1 RCT, RR no clinically important improvement 1.2 CI 0.8 to 1.7), and lithium (n=11, 1 RCT, RR no clinically important improvement 1.39 CI 0.6 to 3.1) . Phenylalanine may even be detrimental (n=18, 1 RCT, MD AIMS score 4.40 CI 1.16 to 7.64) . One small study (n=20) found that insulin was more likely to produce a clinical improvement in tardive dyskinesia than placebo (RR no clinical improvement 0.5 CI 0.3 to 0.9, NNT 2 CI 1 to 5) . REVIEWER'S CONCLUSIONS: There is no strong evidence to support the everyday use of any of the agents included in this review . All results must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study.

Gut, 2003 Jul, 52(7), 966 - 70
Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management; Zarate N et al.; Delayed gastric emptying can be due to muscular, neural, or humoral abnormalities . In the absence of an identified cause, gastroparesis is labelled as idiopathic . We present the case of a patient with severe idiopathic gastroparesis . Pharmacological approaches failed, as well as reduction in gastric emptying resistance with pyloric injection of botulinum toxin and pyloroplasty . Therefore, subtotal gastrectomy was performed . Histological and immunohistochemical study of the resected specimen showed hypoganglionosis, neuronal dysplasia, and a marked reduction in both myenteric and intramuscular interstitial cells of Cajal . To our knowledge, this is the first time these rare histological findings have been described in a patient with idiopathic gastroparesis.

Gastrointest Endosc Clin N Am, 2003 Jan, 13(1), 135 - 45
The Stretta procedure: device, technique, and pre-clinical study data; Utley DS; The initial concept of delivering RF energy to the gastroesophageal junction for the treatment of GERD was based on the well-established safety profile and scientific clinical evidence supporting the effectiveness of this technology in other disease states . As described in this article, the Stretta procedure is an endoluminal procedure inducing collagen tissue contraction, remodeling, and modulation of the triggering threshold for transient LES relaxations . The preclinical experience with this device included feasibility studies to determine optimal treatment parameters and device design . This was followed by longitudinal animal studies to elucidate the mechanism of safety and effect of this intervention as it relates to LES physiology and histopathology . In these studies, RF elevated the LES pressure and gastric yield pressure in a porcine model of botulinum toxin induced LES hypotension . The elevation in GYP more than 6 months was confirmed in a subsequent evaluation . Thickening of the LES after RF delivery has been demonstrated using histopathological evaluation and EUS . Additionally, using a canine model of triggered transient LES relaxations (tLESR), RF significantly reduced the frequency of tLESRs and reflux events . Additional evaluation was performed in human subjects undergoing esophagectomy, confirming feasibility and Histopathologic results of the treatment . Subsequent clinical trials confirm the safety and mechanism of action data of these pre-clinical studies and are presented in this publication.

Fortschr Neurol Psychiatr, 2003 Jun, 71(6), 296 - 305
{Botulinum toxin in tension-type headache}; Jost WH; Botulinum toxin has meanwhile been approved for a number of indications . It is also gaining acceptance in other indications with a major focus on pain . The most common type of headache is tension-type headache (TTH) the pathogenesis of which has not yet been unfolded . As it looks there are vascular, myofascial and supraspinal factors intertwined . It is felt that headache is triggered by myofascial stimuli . The application of botulinum toxin is an intelligent alternative since the favorable effect of pharmacologic and other therapies is limited . Application of BTX should be considered when the pericranial muscles are involved . One of the effects produced lies in the reduction of muscular stress, muscular ischemia and muscle tone . We still don't know whether additional mechanisms such as retrograde uptake and direct antiinflammatory potential are involved . Current data permit the conclusion that headaches are decreased in their frequency and distinctiveness . Significant untoward effects are not to be expected . Neither the ideal dose nor the optimum selection of injection sites have been established as yet, an individual injection scheme is apparently most promising . Injection of the trigger points seems to make sense.

Plast Reconstr Surg, 2003 Jun, 111(7), 2419 - 26; discussion 2427-31
Efficacy of reconstituted and stored botulinum toxin type A: an electrophysiologic and visual study in the auricular muscle of the rabbit; Jabor MA et al.; Once botulinum toxin type A is reconstituted, the manufacturer recommends that it be used in approximately 4 hours . As a result, a significant amount of this costly drug is often discarded because it is not completely used in the recommended period . The purpose of the present study was to compare fresh versus stored reconstituted botulinum toxin type A for (1) initial potency, (2) duration of action, and (3) bacterial colonization.Using a rabbit model, 20 New Zealand White rabbits were divided into four groups (I to IV) . All rabbits had an injection of 2.5 U of reconstituted botulinum toxin into the right anterior auricular muscle . The first group was injected with botulinum toxin type A that was freshly reconstituted and served as the control . The second, third, and fourth groups were injected with botulinum toxin type A that had been reconstituted and stored for 2, 6, and 12 weeks, respectively, in a conventional freezer . Each rabbit had daily visual evaluation of the ear, with the position of auricle being graded from I to III . In addition, each rabbit had a nerve conduction study performed on the right anterior auricular muscle before injection and every 2 weeks after injection . Amplitude was chosen as the principal variable in the data analysis because it is the best predictor of physiologic changes at the muscle motor unit level . The endpoint of the study was defined as the time at which the nerve conduction studies and the visual inspections returned to baseline, preinjection levels . Botulinum toxin type A was also cultured before injection into each group.Overall, the nerve conduction data revealed a trend with a faster recovery (return to baseline) with the stored botulinum toxin . Groups IV and III returned to baseline first, followed by groups II and I . However, there was no significant difference among the groups at 2 and 4 weeks after injection, indicating that initial potency was unchanged . The differences between the groups became significant (p < 0.05) at 6 weeks and onward, suggesting that the duration was affected . Group I (fresh botulinum toxin) and group II (toxin stored for 2 weeks) had comparable outcomes and were not significantly different at any time period . Under visual inspection, the mean recovery time for each group was as follows: group IV, 5.4 weeks; group III, 7.0 weeks; group II, 6.75 weeks; and group I, 7.80 weeks . The results showed significance (p < 0.05) beginning after 3 weeks among some groups . Again, there was an overall quicker trend to return to baseline with the longer storage of the botulinum toxin (groups III and IV) . These results support the authors' conduction study data, which suggest that the initial potency is not affected but the duration of action is . Again, groups I and II had comparable results . Microbiology cultures showed no growth of either aerobic or anaerobic bacteria at 7 days.In conclusion, using the rabbit model, it seems that reconstituted and stored botulinum toxin type A has the same initial potency but the duration of action is affected sometime after 2 weeks of storage . No bacterial contamination was associated with storing unpreserved reconstituted botulinum toxin type A for up to 12 weeks.

Laryngoscope, 2003 May, 113(5), 859 - 66
Ventricular dysphonia: clinical aspects and therapeutic options; Maryn Y et al.; OBJECTIVE/HYPOTHESIS: Ventricular dysphonia, also known as dysphonia plica ventricularis, refers to the pathological interference of the false vocal folds during phonation . Despite its low incidence and prevalence, Vd is a well-known phenomenon in voice clinics . The present report reviews symptoms, etiology, diagnosis, and therapeutic options regarding this voice disorder . STUDY DESIGN: Literature review and case studies . METHODS: The literature pertaining to all clinical aspects of V(D) was reviewed to define diagnostic and therapeutic clinical decision making . RESULTS: Ventricular dysphonia is characterized by a typical rough, low-pitched voice quality resulting from false vocal fold vibration . Ventricular dysphonia may be compensatory when true vocal folds are affected (resection, paralysis) . Noncompensatory types may be of habitual, psychoemotional, or idiopathic origin . Because perceptual symptoms may vary considerably, diagnosis should rely on a meticulous voice assessment, including laryngeal videostroboscopic, perceptual, aerodynamic, and acoustic evaluation . Various therapeutic approaches for the noncompensatory type of ventricular dysphonia may be considered: voice therapy, psychotherapy, anesthetic or botulinum toxin injections, or surgery . CONCLUSION: The study presents the state of the art with respect to ventricular dysphonia and may be helpful in diagnosis and therapeutic decision-making.

Curr Treat Options Neurol, 2003 Jul, 5(4), 291 - 297
Torsion Dystonia in Children; Hinson VK et al.; Medical treatment of childhood-onset dystonia can lead to substantial improvement of the condition, often with much more pronounced benefit than in adults . The authors give every patient a trial of levodopa to assess the possible diagnosis of dopa-responsive dystonia, followed-up with centrally acting anticholinergics such as trihexiphenydil . If needed, baclofen or clonazepam is added or substituted . In focal dystonia or segmental and generalized dystonia with prominent involvement of specific muscle groups, botulinum toxin injections are often used . Pallidal deep brain stimulation is offered to selected patients with medically refractory dystonia . Treatment of secondary dystonias, caused by such conditions as Wilson's disease, requires therapy for the underlying disorder . Physical therapy, splints, and occupational therapy can be useful in some patients . The authors do not use intrathecal baclofen unless there is evidence of accompanying spasticity.

Colorectal Dis, 2002 Nov, 4(6), 430 - 5
The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy; Griffin N et al.; OBJECTIVE: The treatment of anal fissures has evolved over the last 5 years with the development of topical treatments aimed at reducing sphincter hypertonia . This is thought to improve anal mucosal blood flow and promote healing of the fissure . This study reports the use of topical diltiazem in patients with chronic anal fissures that have failed previous treatment with topical 0.2% glyceryl trinitrate (GTN) . PATIENTS AND METHODS: Forty-seven patients with chronic anal fissure who had previously failed at least one course of topical GTN were recruited prospectively from a single centre . Patients were instructed to apply 2 cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for eight weeks . Symptoms of pain, bleeding and itching were recorded on a linear analogue score prior to starting the cream and then repeated at 2 weekly intervals . Patients were asked to report side-effects throughout the study period . Healing of the fissure was assessed after 8 weeks of treatment . RESULTS: Forty-six patients completed treatment; of these, 22 had healed fissures (48%) . Ten of the 24 patients with persistent fissures were symptomatically improved and wished no further treatment . Of the 14 patients who remained symptomatic, one was given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the fissure, 10 were recruited into an ongoing study involving injections of botulinum toxin into the internal anal sphincter and three were referred for surgery . CONCLUSION: This study shows that topical 2% diltiazem is an effective and safe treatment for chronic anal fissure in patients who have failed topical 0.2% GTN . The need for sphincterotomy can be avoided in up to 70% of cases.

J Am Acad Dermatol, 2003 Jun, 48(6), 875 - 7
Reduction in injection pain with botulinum toxin type B further diluted using saline with preservative: a double-blind, randomized controlled trial; van Laborde S et al.; BACKGROUND: Injection with botulinum A exotoxin reconstituted with preserved saline has been shown to be less uncomfortable than injection with the same toxin reconstituted with preservative-free saline . OBJECTIVE: We sought to determine whether injection with botulinum toxin type B is similarly less painful when preservative-containing saline is used to further dilute the product . METHODS: We conducted a double-blind, randomized controlled trial . A total of 15 consecutive adult patients presenting for treatment of upper face dynamic lines received treatment to one side (left or right) of the face with toxin type B further diluted with preservative-containing saline, and to the other side with toxin type B further diluted with preservative-free saline . RESULTS: Of 15 patients, 13 (87%) reported less pain in the halves of their faces treated with the preservative-containing saline (P =.0006) . Pain on the preservative-containing side was on average 32% less among patients as a whole, and 39% less among patients noting some reduction . The 95% confidence interval for pain reduction associated with preservative-containing injection was -46.9% to -16.1% . Neither investigators nor patients observed any difference in clinical efficacy between the 2 treatment sides . CONCLUSIONS: Use of preservative-containing saline to further dilute botulinum toxin type B can significantly decrease patient discomfort on injection.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Jun, 95(6), 642 - 8
Management of the aging forehead: a review; Connor MS et al.; Aging in the upper third of the face manifests as rhytids and ptosis of the frontal, glabellar, and brow regions . Frown lines may occur even in younger individuals as a result of habitual or dynamic forehead muscular hyperactivity . Multiple treatment options have been advocated to address forehead rhytids and brow ptosis . This article reviews 3 of the more commonly used treatment options: collagen, botulinum toxin, and surgical forehead lifting . Additionally, an algorithm is proposed as a guideline for selecting the most appropriate option for a given condition.

Orv Hetil, 2003 May 4, 144(18), 837 - 42
{Applications of the botulinum A toxin}; Zajacz M; The botulinum A toxin inhibits the release of acethylcoline from the vesicles of presynaptic neuronal end plates . Its effect is a transient pharmacological neurectomy . The toxin is used more and more widespreadingly . It selectively inhibits certain muscles or groups of muscles . Its use is of outstanding importance in the treatment of blepharospasm, a disease possibly causing transient functional blindness . This blindness develops randomly, with undetermined duration, therefore it may even threaten the life of the patient . There is no alternative treatment . In ophthalmology, the toxin is used in the therapy of strabismus and nystagmus, as well as replacing entropion operations . Most often its use is suggested in the treatment of focal dystonies, dysphonia, tremor palatinus, dysphagia, spasm of the oesophagus sphincter muscle, nasal hypersecretion, hemifacial spasm, headaches, focal hyperhydrosis, proctalgia fugax, diabetic gastroparesis and difficulties in urination . In the past few years, the toxin has been used for esthetic reasons as well . By relaxing the muscles causing wrinkles, non-permanent result may be reached with its use . The botulinum A toxin does not have general side effects . As local side effects, haematomas and unwanted, transient paresis of the neighboring muscles can be mentioned.

Mov Disord, 2003 Jun, 18(6), 716 - 8
Spasmodic dysphonia in a patient with the A to G transition at nucleotide 8344 in mitochondrial DNA; Peng Y et al.; Dystonia has been described in various diseases affecting mitochondrial function but spasmodic dysphonia, a form of focal dystonia, has not . We present a patient with action myoclonus affecting the hands and arms who carried the most common mutation in mitochondrial DNA causing the myoclonic epilepsy and ragged red fibers (MERRF) syndrome (the A-->G substitution at nucleotide 8344 in the tRNA(Lys) gene) . This patient also had spasmodic dysphonia that was responsive to treatment with intralaryngeal botulinum toxin .

Mov Disord, 2003 Jun, 18(6), 685 - 8
Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism; Mancini F et al.; Drooling is a frequent symptom in Parkinson's disease (PD), occurring in almost 75% of all patients . Although it is now well known that drooling in PD is the result of swallowing difficulties rather than excessive saliva production, few treatments have been developed to reduce it . Clinical studies suggest that botulinum toxin A (BTX) injections into salivary glands are effective in decreasing drooling in PD patients . In this double-blind, placebo-controlled study, 20 patients with parkinsonism (idiopathic PD or multiple system atrophy), were randomly assigned to receive 450 U of BTX (Dysport; Ipsen, Berkshire, UK) or 2 ml of placebo, injected into the parotids and submandibular glands under ultrasonographic guidance . Treatment efficacy and safety were assessed at baseline, 1 week and 3 months after BTX injections using clinical scales (Drooling Severity and Drooling Frequency scales) and side effects surveillance . After treatment, the average secretion of saliva in the BTX group was significantly lower than in the placebo group, as appraised by clinical measurements . No side effects were observed in either group . BTX injection into parotids and submandibular glands, under ultrasonographic guidance, is an effective and safe treatment for drooling in parkinsonism .

Int J Food Microbiol, 2003 Jul 15, 84(1), 71 - 7
Molecular differentiation of clostridia associated with "blown pack" spoilage of vacuum-packed meats using internal transcribed spacer polymorphism analysis; Broda DM et al.; The 16S-23S rDNA internal transcribed spacer (ITS) polymorphism analysis was assessed for its suitability in rapid discrimination between species of psychrophilic and psychrotolerant clostridia associated with "blown pack" spoilage of vacuum-packed meats . DNA isolated from 10 reference and 20 meat strains of psychrophilic and psychrotolerant clostridia were used as templates in PCR amplification with primers complementary to conserved regions of the 3' end of the 16S rRNA and 5' end of the 23S rRNA genes directly flanking the spacer . The majority of strains showed multi-band ITS patterns when products of spacer amplification were visualised on an agarose gel . With the majority of meat strains, PCR amplification generated single banding pattern for a single clostridial species . However, meat strains of Cl . algidicarnis produced four different ITS banding patterns . With reference strains of psychrophilic and psychrotolerant clostridia, variation in spacer length was also observed between nonproteolytic Cl . botulinum type B (17B), E (Beluga) and F (202F) . On the other hand, the number and size of the ITS amplification products could not be used for a differentiation of Cl . laramiense ATCC 51254(T) from Cl . estertheticum DSM 8809(T), Cl . putrefaciens DSM 1291(T) from Cl . algidicarnis NCFB 2931(T), or Cl . frigidicarnis strains from nonproteolytic Cl . botulinum type B (17B) . The presence of interstrain, and lack of interspecies, ITS polymorphism observed in the present study with some clostridial species may preclude the use of 16S-23S rDNA spacer amplification for species-level discrimination and identification, respectively, of psychrophilic and psychrotolerant clostridia associated with meat spoilage . However, where interstrain, intraspecies heterogeneity of ITS amplification products exists, ITS analysis could be useful for tracing back psychrophilic and psychrotolerant clostridia responsible for meat spoilage to their meat plant sources.

Zhonghua Er Bi Yan Hou Ke Za Zhi, 2002 Jun, 37(3), 180 - 3
{Effects of botulinum toxin-A on facial motoneurons}; Wang J et al.; OBJECTIVE: To examine effects of botulinum toxin-A(BTX-A) intramuscular injection at rat whisker pad on facial motoneurons . METHODS: A total of 54 male Sprague-Dawley rats were used in the present study . A single intramuscular injection of the BTX-A at rat whisker pad as model was employed, using retrograde labeling and immunohistochemical staining methods, to observe the effects of BTX-A on the facial motoneurons survival and the expression of choline acetyltransferase (ChAT) and vescular acetylcholine transporter (VAChT) . Rats received intramuscular injection of 0.9% NaCl served as control . RESULTS: The fluorescence labeled facial motoneurons were all in the lateral subnucleus of facial nucleus after BTX-A injection at rat whisker pad . There was no significant difference of labeled motoneuron number in BTX-A injection group vs control at observed time points (t = 0.022 . P > 0.05) . At 7 d after BTX-A injection, optical density of ChAT and VAChT immunostaining began to increase in facial motoneurons of the lateral subnucleus ipsilateral to the injection side . A maximal increase of this data was observed 14 d after injection; thereafter it declined gradually to normal level . The patterns of changes in optical density of ChAT and VAChT immunostaining in facial motoneurons of the lateral subnucleus contralateral to the injection side were similar to that of ipsilateral . There were significant difference of optical density of ChAT and VAChT immunostaining in facial motoneurons of the lateral subnucleus in BTX-A injection group vs control(t = 3.054, P < 0.05; t = 3.366, P < 0.05) . CONCLUSION: After BTX-A injection at rat one side whisker pad, the number of facial motoneurons innervating muscles of whisker pad in the lateral subnucleus has no change . However, the expression of ChAT and VAChT increase in the facial motoneurons of the lateral subnucleus . These data indicate that BTX-A intramuscular injection at facial nerve target organ doesn't induce the loss of facial motoneurons, and only results in the expression of protein related to acetylcholine changing.

J Exp Biol, 2003 Jul, 206(Pt 13), 2191 - 200
Neurotrophin 4/5 is required for the normal development of the slow muscle fiber phenotype in the rat soleus; Carrasco DI et al.; During normal postnatal development, rat soleus (SOL) muscle fibers undergo a dramatic fast-to-slow myosin heavy chain (MyHC) isoform transformation . We exploited this phenomenon to evaluate the role of neurotrophin 4/5 (NT-4/5) in the regulation of muscle fiber phenotype . Intramuscular injections of recombinant NT-4/5 into the SOL muscle of rat neonates significantly accelerated the normal fast-to-slow MyHC isoform transformation . Sequestration of endogenous NT-4/5 with TrkB-IgG prevented this transformation from occurring . Administration of the other TrkB ligand, brain-derived neurotrophic factor (BDNF), did not affect the normal course of the MyHC isoform transformation in this muscle, indicating that the observed effect is NT-4/5 specific . Botulinum toxin blockade of synaptic transmission significantly disrupted the normal fast-to-slow MyHC isoform switch . Because administration of NT-4/5 to paralyzed muscles failed to restore the normal course of this MyHC transformation, we believe that the effect of NT-4/5 is not directly on the muscle fibers but that it probably activates or forms a type of retrograde signal to motoneurons . The developmental upregulation of NT-4/5 mRNA in rat SOL muscle fibers occurred earlier than the upregulation of MyHC I/b mRNA associated with muscle fiber transformation . This timing is consistent with the idea that NT-4/5 is involved in early events that lead to the upregulation of the slow MyHC isoform in this muscle.

Neurologia, 2003 Jun, 18(5), 280 - 4
{Treatment of sialorrhoea in neurological diseases with trans-dermic injections of botulinum toxin type A in the parotid glands}; Carod Artal FJ; INTRODUCTION: Sialorrhoea is a disabling problem in many patients affected by neurological disorders . Anticholinergic drugs often produce side effects in these patients . Botulinum toxin A (TBA) blocks liberation of acetil-choline in motor and autonomic nerve terminals . METHODS: We report preliminary data about three patients, affected by motor neuron disease, Parkinson's disease and pons infarction respectively . All of them underwent treatment with TBA in both parotid glands to treat sialorrhoea, and were prospectively evaluated . Severity and Frequency Sialorrhoea Scale was used pre-treatment and at 6 weeks . TBA was administered in two points in each gland; a new injection was done at 2 weeks, with a dose ranging between 10 and 20 units in each point . RESULTS: Three males, with a men age of 63.6 years are reported . Sialorrhoea pre-treatment severity score was 5 while pre-treatment frequency score was 4 (continuous sialorrhoea all the days) . Six weeks after TBA injection, two patients scored 2 in severity and frequency (mild sialorrhoea) and third patient had a score of 3 (moderate sialorrhoea) . Side effects were observed neither after TBA injections nor at 6 week follow-up . CONCLUSIONS: Trans-dermic injection of TBA is safe and effective technique to treat sialorrhoea in neurological diseases when used by neurologists with experience, with few side effects.

J Biol Chem, 2003 Aug 15, 278(33), 30534 - 9 Epub 2003 May 21.
Activation of store-operated calcium channels: assessment of the role of snare-mediated vesicular transport; Scott CC et al.; Store-operated calcium channels (SOC) play a central role in cellular calcium homeostasis . Although it is well established that SOC are activated by depletion of the endoplasmic reticulum calcium stores, the molecular mechanism underlying this effect remains ill defined . It has been suggested that SOC activation requires fusion of endomembrane vesicles with the plasmalemma . In this model, SNARE-dependent exocytosis is proposed to deliver channels or their activators to the surface membrane to initiate calcium influx . To test this hypothesis, we studied the requirement for membrane fusion events in SOC activation, using a variety of dominant-negative constructs and toxins that interfere with SNARE function . Botulinum neurotoxin A (BotA), which cleaves SNAP-25, did not prevent SOC activation . Moreover, SNAP-25 was not detectable in the cells where BotA was reported earlier to inhibit SOC . Instead, the BotA-insensitive SNAP-23 was present . Impairment of VAMP function was similarly without effect on SOC opening . We also tested the role of N-ethylmaleimide-sensitive factor, a global regulator of SNARE-mediated membrane fusion . Expression of a mutated N-ethylmaleimide-sensitive factor construct inhibited all aspects of membrane traffic tested, including recycling of transferrin receptors to the plasma membrane, fusion of endosomes with lysosomes, and retrograde traffic to the Golgi complex . Despite this global inhibition of vesicular fusion, which was accompanied by gross alterations in cell morphology, SOC activation persisted . These observations cannot be easily reconciled with the vesicle-mediated coupling hypothesis of SOC activation . Our findings imply that the SOC and the machinery necessary to activate them exist in the plasma membrane or are associated with it prior to activation.

Ann Readapt Med Phys, 2003 Apr, 46(3), 132 - 7
{3D preliminary analysis gait in stroke patients: knee flexion in compensatory strategies}; Laborde A et al.; OBJECTIVE: The aim of this preliminary study was to assess strategies of walking a stride in stroke patients with spastic right hemiplegia . MATERIAL AND METHODS: Gait was recorded in 3D in seven patients without other locomotion disorders . Kinematics data were studied only on the sagittal plane . The position and trajectory markers on the right side were studied during the swing phase in comparison with static standing position . Results were confronted with angular data . RESULTS: Three walking models were defined: 1) near normal gait with normal mobility in the knee; 2) gait with hicking while the flexion of the knee was reduced; 3) gait with a "talus" foot without motor recovery necessitating a pendular movement . DISCUSSION: The second pathological group was characterized with insufficient flexion in the knee in lifting the foot from the floor . In this group, patients adopted a compensation strategy with hicking in making the stride without touching the floor . We raised the question of limiting this adaptive strategy in order to enhance their remaining mobility . CONCLUSION: A 3D strategy gait analysis, before therapeutic choices, seems to confirm the value of analysing kinematic data in stroke patients with hemiplegia . The amplitude of knee mobility and hip compensation strategy can be specifically studied to improve the effectiveness of therapeutic strategies (orthesis, selective tibial neurotomy, botulinum toxin).

Rev Esp Enferm Dig, 2003 Jan, 95(1), 13 - 21, 22-9
Short- and medium-term clinical efficacy of three endoscopic therapies for achalasia: a single-blinded prospective study; Caunedo A et al.; OBJECTIVE: to compare the efficacy of three endoscopic therapies for achalasia and to identify predictors of response . DESIGN: prospective, single-blinded study at short and medium term . MATERIAL AND METHODS: 22 patients (9M/13 F; mean age: 47.45 +/- 21.01 years) with confirmed clinical and manometric achalasia were randomised in three groups: intrasphincteric injections of botulinum toxin (group 1: 10 patients ), injections of 1% polidocanol (group 2:6 patients), and a combined therapy with both of them (group 3: 6 patients) . Clinical response was evaluated by a score (0-5) of tested symptoms (dysphagia, regurgitation and chest pain) at 1 and 24 weeks post-treatment . RESULTS: at 24 weeks post-treatment group 2 had the best complete response (CR) rate (33.33%), whereas CR in both the botulinum toxin and combined therapy groups was 10 and 0%, respectively . Groups 1 and 2 got an overall improvement in clinical score at 1 (p= 0.02) and 24 weeks (p= 0.04) . Five patients (50%) in group 1, two patients (33.33%) in group 2, and three patients (50%) in group 3 needed other therapies (dilation or surgery) because of treatment failure . Separately, neither age nor sex, time from diagnosis or type of therapy could distinguish responders from non-responders in these three groups . However, absence of response within the first week, and an initial clinical score above 7 were predictive factors of poor response at six months . CONCLUSIONS: short- and medium-term clinical response to these endoscopic therapies was limited . The absence of response at seven days and a severe initial clinical score were predictive factors of poor medium-term response.

J Protein Chem, 2003 Feb, 22(2), 147 - 53
Inhibition of neurotransmitter release by peptides that mimic the N-terminal domain of SNAP-25; Apland JP et al.; Botulinum neurotoxin serotypes A and E (BoNT/A and BoNT/E) block neurotransmitter release by cleaving the 206-amino-acid SNARE protein, SNAP-25 . For each BoNT serotype, cleavage of SNAP-25 results in the loss of intact protein, the production of an N-terminal truncated protein, and the generation of a small C-terminal peptide . Peptides that mimic the C-terminal fragments of SNAP-25 following BoNT/A or BoNT/E cleavage were shown to depress transmitter release in bovine chromaffin cells and in Aplysia buccal ganglion cells . Similarly, the N-terminal-truncated SNAP-25 resulting from BoNT/A or BoNT/E cleavage has been found to inhibit transmitter exocytosis in various systems . With one exception, however, the inhibitory action of truncated SNAP-25 has not been demonstrated at a well-defined cholinergic synapse . The goal of the current study was to determine the level of inhibition of neurotransmitter release by N-terminal BoNT/A- or BoNT/E-truncated SNAP-25 in two different neuronal systems: cholinergically coupled Aplysia neurons and rat hippocampal cell cultures . Both truncated SNAP-25 products inhibited depolarization-dependent glutamate release from hippocampal cultures and depressed synaptic transmission in Aplysia buccal ganglion cells . These results suggest that truncated SNAP-25 can compete with endogenous SNAP-25 for binding with other SNARE proteins involved in transmitter release, thus inhibiting neurotransmitter exocytosis.

Dermatol Clin, 2003 Apr, 21(2), 321 - 35
Unusual infectious complications of dermatologic procedures; Garman ME et al.; Because dermatologic procedures disrupt skin integrity, they alter the body's protective barrier and predispose individuals to cutaneous infection . Postoperative wound infections--even with common pathogens such as S . aureus--seldom complicate dermatologic procedures; however, unusual infections have been reported to complicate excisions, biopsies, skin grafts, chemical peels, dermabrasion, laser resurfacing, liposuction, blepharoplasty, and injections (eg, with anesthetic solutions or botulinum toxin) . Numerous environmental and patient risk factors increase the rate of postoperative wound infections, but otherwise healthy individuals undergoing relatively simple procedures are sometimes affected . Obtaining a thorough patient, history (including history of prior HSV infection or any immunocompromising factors) is crucial . Patients should be warned of potential complications, particularly when they are undergoing cosmetic procedures . It is important to maintain a high index of suspicion for possible wound infection in all patients that extends several months postoperatively . Manifestations of unusual postoperative infections are highly variable, and they might be secondary to bacterial, fungal, viral, or parasitic pathogens . Bacterial lesions are often polymicrobial, and bacterial superinfection can exacerbate other wound complications such as HSV reactivation . Most wound infections remain localized, but occasionally systemic disease occurs . For example, cutaneous diphtheria or rapidly growing mycobacteria rarely disseminate, whereas TSS results in systemic disease caused by toxin release . Some unusual postsurgical infections are self-limited, but they can still be potentially life threatening or disfiguring . Antimicrobial prophylaxis might reduce the risk of wound infection in some cases . Clinicians can better care for patients by becoming familiar with the causes and clinical manifestations of unusual dermatologic postoperative wound infections (Table 1) . Following the recognition of an infectious process, appropriate diagnostic procedures allow for pathogen identification and the prompt institution of indicated therapy.

Dermatol Surg, 2003 May, 29(5), 562 - 3
Metallic taste: an unusual reaction to botulinum toxin A; Murray C et al.; BACKGROUND: Botulinum neurotoxin formulations are safe and effective agents for the treatment of facial rhytides . OBJECTIVES: A patient is described who complained of metallic taste after each treatment with botulinum toxin A (BTX-A) . RESULTS: The sensation of metallic taste diminished after successive treatments with BTX-A, despite adequate dosing for cosmetic purposes . CONCLUSION: Metallic taste is associated with the use of numerous medications; however, the pathogenesis remains unclear . Alteration in zinc metabolism, which may occur with BTX-A administration, has been suggested as a possible mechanism . Although this is the first known report of dysgeusia after BTX-A, physicians and patients may be reassured that the taste alteration was self-limited and was not significantly problematic for the patient in our case.

Dermatol Surg, 2003 May, 29(5), 560 - 1; discussion 561
Festoon formation after infraorbital botulinum A toxin: a case report; Goldman MP; BACKGROUND: An injection of the lateral canthus and infraorbital fold is commonly used to soften wrinkles and widen the eye . OBJECTIVE: To illustrate a case report of festooning and to hypothesize as to its cause . METHODS: A 56-year-old man developed festooning of the infraocular area after injection of botulinum toxin A . RESULTS: Prior lower lid blepharoplasty with separation of the infraorbital orbicularis oculi muscle may have weakened the muscle enough to cause festooning with further weakening of the muscle through botulinum toxin A injection . CONCLUSION: Caution must be exercised when performing infraocular injection of botulinum toxin A in patients with prior transtarsal lower lid blepharoplasty.

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