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.<