Curr Opin Ophthalmol, 2000 Oct, 11(5), 336 - 41 Eye muscle surgery; Murray T; In the past year experimental studies have analyzed the ease with which specific sutures can be adjusted, have investigated ways to prevent adhesions in animal models, and have studied variations of the inferior oblique at the surgical capture site . Our knowledge of rectus extraocular muscle pulleys continues to improve, and the value of botulinum toxin type A in the treatment of several conditions has been further documented . New surgical techniques include slanted recessions of the lateral rectus muscles, combined monocular resection and bilateral anterior transposition of the inferior oblique, and intraoperative use of acetylcholine during inferior oblique myectomy . Favorable results have been reported after clinically important modifications to the superior oblique muscle silicone expander and anterior transposition of the inferior oblique procedures, as well as after bilateral inferior rectus muscle recession in dysthyroid ophthalmopathy . Conjunctival inclusion cysts, anterior segment ischemia despite microvascular dissection, and corneal topographic changes are reported as complications occurring after strabismus surgery . Recent publications discussing these issues are reviewed here. Anal Chem, 2000 Dec 15, 72(24), 6019 - 24 Gangliosides as receptors for biological toxins: development of sensitive fluoroimmunoassays using ganglioside-bearing liposomes; Singh AK et al.; Gangliosides, glycosphingolipids present in the membranes of neuronal and other cells, are natural receptors for a number of bacterial toxins and viruses whose sensitive detection is of interest in clinical medicine as well as in biological warfare or terrorism incidents . Liposomes containing gangliosides mimic cells that are invaded by bacterial toxins and can be used as sensitive probes for detecting these toxins . We discuss detection of three bacterial toxins-tetanus, botulinum, and cholera toxins using ganglioside-bearing liposomes . Tetanus and botulinum toxins selectively bind gangliosides of the G1b series, namely, GT1b, GD1b, and GQ1b; and cholera toxin binds GM1 very specifically . Unilamellar liposomes containing GT1b or GM1 as one of the constituent lipids were prepared by extrusion through polycarbonate membranes . To impart signal generation capability to these liposomes, fluorophore-labeled lipids were incorporated in the bilayer of liposomes . The fluorescent liposomes, containing both a marker (rhodamine) and a receptor (GT1b or GM1) in the bilayer, were used in sandwich fluoroimmunoassays for tetanus, botulinum, and cholera toxins and as low as 1 nM of each toxin could be detected . The apparent dissociation constants of liposome-toxin complexes were in 10(-8) M range, indicating strong binding . This is the first report on detection of tetanus and botulinum toxins based on specific recognition by gangliosides . The fluorescent liposomes are attractive as immunoreagents for another reason as well--they provide enormous signal amplification for each binding event as each liposome contains up to 22,000 rhodamine molecules . The present approach using receptors incorporated in bilayers of liposomes offers a unique solution to employ water-insoluble receptors, such as glycolipids and membrane proteins, for sensitive detection of toxins and other clinically important biomolecules. Nervenarzt, 2000 Dec, 71(12), 1007 - 11 {Optimized therapy of spastic syndrome by combination intrathecal baclofen with botulinum toxin}; Vogt T et al.; Intrathecal administration of baclofen has proved to be an effective treatment of spasticity related to CNS damage . Especially patients with spinal spasticity due to traumatic spinal cord injury or transverse myelitis showed a dramatic reduction of spasticity and improvement of their Ashworth scores . The results are, however, often disappointing in patients with muscular hypertension of the extensor muscles, which is frequently found in patients with multiple sclerosis or cerebral hypoxia . In the latter, using intrathecal baclofen may be restricted by serious side effects . Botulinumtoxin A is widely used in patients with various forms of dystonia . It has also been studied in spastic disorders, where local injections were valuable in relieving focal spasticity in hemiparetic patients and in infantile cerebral palsy . It is used only cautiously in severe paraspasticity . The case reports of 4 patients with incomplete and complete paraparesis due to spinal cord injury, neurodegenerative pyramidal disorder, and cerebral hypoxia demonstrate that a combination of intrathecal baclofen and botulinumtoxin A can improve clinical benefits and reduce side effects. Acta Otorhinolaryngol Ital, 2000 Jun, 20(3), 187 - 91 {Post-parotidectomy Frey's syndrome . Treatment with botulinum toxin type A}; Cavalot AL et al.; The Frey's syndrome, manifest after parotid trauma, is characterized by head and neck hyperemia and abundant sweating of the hyperemic skin in response to gustatory stimuli . The use of the botulin toxin to treat the symptoms in patients with Frey's syndrome has been described in numerous studies . For some time up until now our Center has achieved excellent results using the group A botulin toxin to overcome the hypertonus of the cricopharyngeal muscle in patients who had undergone laryngectomy and were rehabilitated with voice button . We have sought to extend the use of this toxin to Frey's syndrome, a relatively frequent complication of parotidectomy . A total of 86 patients participated in the study: 41 males (47.6%) and 45 females (52.4%) ranging in age from 25 to 77 years (average age 51 years) . Of these patients 7 (8.1%) had undergone post-operative radiotherapy . Of the 86 patients studied, 18 referred significant symptoms in terms of abundance and frequency . The syndrome was considered severe if the symptoms were present at each meal and if the patient indicated a significant worsening of his quality of life . Intermittent episodes were indicated by 22 patients . The remaining 46 (43.5%) did not complain of any symptoms . The exact extension of the cervicofacial gustatory sweating was evaluated using the Minor test and the involved region was divided into 1 square centimeters sections . The amount of skin surface involved ranged from 10 to 80 square centimeters . The type A neurotoxin was frozen and was reconstituted with a sterile saline solution at a final concentration of 2.5 UI/0.1 ml . The intracutaneous infiltration was performed without anesthesia, infiltrating 0.1 ml of solution, containing 2.5 UI of toxin into the center of each 1 square centimeters section . Statistical analysis was performed to evaluate the potential relationship between how long the treatment was effective, incidence of recurrence, seriousness of the crises and the following variables: age, sex, histology, cutaneous surface involved, injected dose of botulin toxin and post-operative radiotherapy . In the group of 18 patients with severe symptoms (20.9%) the benefit was immediate in all cases although the recurrence rate was 50% . The Frey's syndrome symptoms disappeared within 7 days of infiltration . In the group of 22 patients with less severe involvement (25.5%), the treatment gave positive, definitive results in 16 patients (72.7%) . Those patients whose symptoms persisted were treated a second time with an infiltration of 2.5 UI per square centimeters . We feel that the use of the type A botulin toxin is the most appropriate treatment for the Frey's syndrome . In fact, such treatment offers the following advantages: it is effective within 7 days, has limited side effects, can be applied on an outpatient basis, is inexpensive and is positively considered by the patients. Rev Neurol (Paris), 2000 Dec, 156(12), 1087 - 94 {Focal dystonia: clinical, etiologic and therapeutic aspects}; Tranchant C; Blepharospasm, spasmodic torticoli, and writer's cramp are the most frequently observed forms of focal dystonia . Primary dystonia is often a hereditary condition with a dominant autosomal mode of transmission and variable penetrance . Secondary conditions are generally the expression of a lesion to the basal ganglia due to an iatrogenic cause or exceptionally the inaugural sign of a metabolic disease . The basal ganglia play an important role in the pathophysiology of this reciprocal innervation disorder but progress in genetics may help better understand the different molecular mechanisms involved . Treatment relies on botulin toxin associated with physical therapy depending on the localization . Drug therapy is often disappointing due to minimal efficacy and poor tolerance. Eur J Neurol, 2000 Nov, 7(6), 713 - 8 Electromyographic evaluation of cervical dystonia for planning of botulinum toxin therapy; Dressler D; The success of botulinum toxin (BT) injections for treatment of cervical dystonia depends on precise identification of dystonic muscles and on quantification of their dystonic involvement . Conventionally, this is attempted by clinical examination analysing the dystonic head position . In this presentation, a more systematic approach is sought by using an electromyography (EMG)-based evaluation procedure . In 10 consecutive patients with cervical dystonia not previously exposed to BT clinical examination, analysing the dystonic head position was performed to classify patients into four groups with similar dystonic head positions . Additionally, a 2-channel concentric needle EMG was used to measure the amplitudes of dystonic and maximal voluntary activities in sternocleidomastoid (SCM), splenius capitis (SC) and trapezius/semispinalis capitis (T/SS) muscles bilaterally . The ratio between both amplitudes, the dystonia ratio, was used to quantify dystonic muscle involvement . In all patients dystonia ratios could be calculated . In patients with similar head positions, EMG evaluation revealed different qualitative and quantitative dystonic involvement patterns . In six patients, there were discrepancies in identification of dystonic muscles between clinical examination and EMG evaluation . EMG evaluation excluded dystonic involvement in five patients . All excluded muscles were SCM . In one of these patients, additional T/SS involvement was detected by EMG evaluation . In one patient, SC involvement was revealed by EMG evaluation . All dystonic muscle involvement detected by EMG evaluation represented genuine dystonic muscle coactivation rather than compensatory muscle activity . The EMG evaluation presented allows quantitative and qualitative identification of dystonic muscle involvement which cannot be achieved by clinical examination . Both pieces of information may be helpful for optimization of BT therapy. Brain, 2001 Jan, 124(Pt 1), 47 - 59 Abnormal interaction between vestibular and voluntary head control in patients with spasmodic torticollis; Munchau A et al.; The functional status of vestibulo-collic reflexes in the sternocleidomastoid (SCM) muscles was investigated in 24 patients with spasmodic torticollis using small, abrupt 'drops' of the head . None had been treated with botulinum toxin injections during at least 4 months preceding the study . Eight of the patients, four of whom had been studied before surgery, were also studied after selective peripheral denervation of neck muscles . The reflex was of normal latency and duration in the 'passive drop' condition, in which subjects were instructed not to oppose the fall of the head . To study voluntary interaction with the reflex response, subjects were then asked to flex the neck as quickly as possible after onset of the head drop ('active drop') . In this condition, voluntary responses in patients were delayed, smaller and less effective in counteracting the head fall than in normal subjects . The same abnormalities were also found in patients after surgery when the head posture was improved . Somatosensory/auditory voluntary reaction times in SCM were normal, as was the latency of the startle reflex . We conclude that voluntary interaction with the vestibulo-collic reflex is disrupted in patients with spasmodic torticollis, a finding which corroborates the patients' aggravation of their symptoms by head or body perturbations . Lack of effective interaction between two major systems controlling head position may contribute to torticollis. Z Gastroenterol, 2000 Nov, 38(11), 899 - 903 Manometrically-guided endoscopic injection of botulinum toxin for esophageal achalasia: a pilot trial; Wehrmann T et al.; AIMS: Some patients gained only short-term response (< 6 months) after botulinum toxin (BTX) injection for achalasia . This may be due to an incorrect site of injection when targeting the lower esophageal sphincter by using endoscopic landmarks only . PATIENTS AND METHODS: 7 elderly patients (4 females, 67 +/- 20 years) with classical achalasia received manometrically-guided botulinum toxin injection by means of a double-channel endoscope . Thereafter, they were clinically re-evaluated at 6 weeks and later on at bi-monthly intervals . RESULTS: The mean symptom score decreased 6 weeks after the manometrically-guided BTX-treatment from 12 +/- 2 (before BTX) to 6 +/- 2 points (p = 0.02) . However, according to the study criteria one patient did not respond to BTX-injection and underwent subsequent cardiomyotomy . The LES-resting pressure was found not to be altered in this patient (6 weeks after BTX-injection) but manometry revealed a marked decrease of the LES-tone in 3 other patients who benefitted from BTX-injection . 5 of the 6 patients, who initially benefited from BTX-injection, relapsed 10 months (range, 6-13 months) after their initial BTX-treatment . They all were treated with repeated BTX-injections . At completion of the study (1.5-year follow-up) the mean symptom score of the 6 patients was still significantly lower (6 +/- 2 points) than before study entry (p = 0.03) . CONCLUSION: Manometrically-guided endoscopic BTX-injection is a simple, safe and highly effective (during 1.5-year follow-up) technique for treatment of esophageal achalasia . With the manometrically-guided injection technique one may obtain a longer lasting symptomatic response than with the traditional method of BTX-application. J Neurol, 2000 Oct, 247(10), 787 - 92 A prevalence study of primary dystonia in eight European countries; Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group; There have been few epidemiological studies of dystonia . Most previous studies have provided estimates based on few cases . A European prevalence study was undertaken to provide more precise rates of dystonia by pooling data from eight European countries . Diagnosed cases were ascertained by adult neurologists with specialist movement disorder (and botulinum toxin) clinics . The crude annual period prevalence rate (1996-1997) for primary dystonia was 152 per million (95% confidence interval 142-162), with focal dystonia having the highest rate of 117 per million (108-126) . Prevalence rates for cervical dystonia, blepharospasm and writer's cramp were as follows: 57 (95% confidence interval 51-63), 36 (31-41), and 14 (11-17) . The age-adjusted relative rates were significantly higher in women than in men for segmental and focal dystonias with the exception of writer's cramp . Comparing rates between centres demonstrated significant variations for cervical dystonia, blepharospasm and writer's cramp, probably due to methodological differences . Our results provide the first data on the prevalence of primary dystonia and its subtypes across several European countries . Due to under-ascertainment of cases, our rates should be seen as conservative and an under-estimate of the true prevalence of dystonia. J Nat Toxins, 2000 Nov, 9(4), 381 - 408 Bacterial toxins--an overview; Lahiri SS; Toxins are non-replicating agents of biological origin . They are non-infectious, non-contagious, and non-curable by antibiotics or chemotherapeutic agents . However, individuals can be protected by vaccination . The multifactorial nature of virulence of toxin and toxin producers, produces comparative and cooperative pathogenesis, and this makes studies all the more difficult . Antibody raised against all components helps in this pursuit . The toxins have been classified into seven different classes and over 44 bacterial toxins have been discussed . The botulinum toxin is by far the most toxic substance in the world . All the toxins produced are either secreted out, called exotoxins (proteins), or are entrapped in the cell membrane, called endotoxins (lipopolysaccharides) . These toxins are di-chain molecules, internalized into the cell by receptor mediated endocytosis, and ADP-ribosylation is the most common mode of action . The toxins produced by bacteria are enterotoxins, neurotoxins, cytotoxins, lysins (e.g., hemolysin), gangrene producing toxins . However, a single bacteria often produces more than one toxin . Bacterial toxins, which are primarily harmful, are also being used for the cure of cancer, killing of mosquito larvae, understanding of basic sciences like ADP-ribosylation, etc. Infect Immun, 2001 Jan, 69(1), 570 - 4 High-affinity, protective antibodies to the binding domain of botulinum neurotoxin type A; Pless DD et al.; Monoclonal antibodies (MAbs) were prepared against the putative binding domain of botulinum neurotoxin A (BoNT/A), a nontoxic 50-kDa fragment . Initially, all fusion products were screened against the holotoxin BoNT/A and against the binding fragment, BoNT/A H(C) . Eleven neutralizing hybridomas were cloned, and their specific binding to BoNT/A H(C) was demonstrated by surface plasmon resonance, with dissociation constants ranging from 0.9 to <0.06 nM . Epitope mapping by real-time surface plasmon resonance showed that the antibodies bound to at least two distinct regions of the BoNT/A H(C) fragment . These MAbs will be useful tools for studying BoNT/A interactions with its receptor, and they have potential diagnostic and therapeutic applications. Dig Dis Sci, 2000 Oct, 45(10), 2079 - 83 Achalasia presenting as acute airway obstruction; Arcos E et al.; Achalasia presenting as acute airway obstruction is an uncommon complication . We report the case of an elderly woman with previously undiagnosed achalasia who presented with acute respiratory distress due to megaesophagus . Emergency endotracheal intubation and insertion of a catheter into the esophagus, with continuous aspiration was required . Upon introduction of the esophageal catheter an abruptand audible air decompression occurred, with marked improvement of the clinical picture . Endoscopic injection of botulinum toxin was chosen as the definitive treatment with good clinical result . The pathophysiology of the phenomenon of esophageal blowing in achalasia is unclear, but different hypothetical mechanisms have been suggested . One postulated mechanism is an increase in upper esophageal sphincter (UES) residual pressure or abnormal UES relaxation with swallowing in achalasia patients . We reviewed the UES manometric findings in 50 achalasia patients and compared it with measurement performed in 45 healthy controls . We did not find any abnormalities in UES function in any of our achalasia patients group, or in the case under study . An alternative hypothesis postulates that airway compromise in patients with achalasia results from the loss UES belch reflex (abnormal UES relaxation during esophageal air distension), and in fact, an abnormal UES belch reflex was evidenced in our case. Otolaryngol Head Neck Surg, 2000 Dec, 123(6), 669 - 76 Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study; Binder WJ et al.; OBJECTIVE: The object of this clinical experience was to evaluate the correlation between pericranial botulinum toxin type A (BOTOX, Allergan Corp, Irvine, CA) administration and alleviation of migraine headache symptoms . Study Design and Setting: A nonrandomized, open-label study was performed at 4 different test sites . The subjects consisted of 106 patients, predominantly female, who either (1) initially sought BOTOX treatment for hyperfunctional facial lines or other dystonias with concomitant headache disorders, or (2) were candidates for BOTOX treatment specifically for headaches . Headaches were classified as true migraine, possible migraine, or nonmigraine, based on baseline headache characteristics and International Headache Society criteria . BOTOX was injected into the glabellar, temporal, frontal, and/or suboccipital regions of the head and neck . Main outcome measures were determined by severity and duration of response . The degrees of response were classified as: (1) complete (symptom elimination), (2) partial > or =50% reduction in headache frequency or severity), and (3) no response {neither (1) nor (2)} . Duration of response was measured in months for the prophylactic group . RESULTS: Among 77 true migraine subjects treated prophylactically, 51% (95% confidence interval, 39% to 62%) reported complete response with a mean (SD) response duration of 4.1 (2.6) months; 38% reported partial response with a mean (SD) response duration of 2.7 (1.2) months . Overall improvement was independent of baseline headache characteristics . Seventy percent (95% confidence interval, 35% to 93%) of 10 true migraine patients treated acutely reported complete response with improvement 1 to 2 hours after treatment . No adverse effects were reported . CONCLUSIONS: BOTOX was found to be a safe and effective therapy for both acute and prophylactic treatment of migraine headaches . Further research is needed to explore and develop the complete potential for the neuroinhibitory effects of botulinum toxin. Int J Med Microbiol, 2000 Oct, 290(4-5), 381 - 7 Pseudomonas aeruginosa exoenzyme S, a bifunctional type-III secreted cytotoxin; Barbieri JT; Our recent studies have shown ExoS to be a bifunctional type-III secreted cytotoxin . Intracellular expression of the amino terminus of ExoS (C234) in eukaryotic cells stimulates actin reorganization without cytotoxicity, which involves small-molecular-weight GTPases of the Rho subfamily . Expression of the carboxyl terminus of ExoS comprises an ADP-ribosyltransferase domain, which is cytotoxic when expressed in cultured cells (Pederson and Barbieri, 1998) . Rho and Ras are molecular switches, which control numerous cellular processes . Recent signaling studies suggest that there is crosstalk between Rho and Ras (Keely et al, 1997) . Ras and Rho also contribute to wound healing processes and tissue regeneration . Recent studies have shown that microinjection of endothelial cells with activated Ras stimulated their motility, while microinjection of Ras-blocking antibodies inhibited cellular motility that is a component of the wound healing process (Fox et al., 1994) . In addition, hepatocyte growth factor/scatter factor (HGF/ SF) and epidermal growth factor stimulate cellular motility through the Ras signal transduction pathway (Ridley et al., 1995) . Rac and Rho are also involved in motility and tissue regeneration, since dominant negative Rac inhibits the cellular motility stimulated by HGF/SF (Santos et al., 1997) and inhibition of Rho by either C . difficile ToxA and ToxB or the C . botulinum C3 transferase inhibits wound healing (Santos et al., 1997) . Inhibition of tissue regeneration and wound healing appear to play a role in the pathogenesis of C . difficile, since treatment of gastrointestinal mucosa with C . difficile ToxA and ToxB alone inhibits regeneration of the gastric mucosa . Thus, ExoS may contribute to the establishment of P . aeruginosa infections by inhibiting wound healing and tissue regeneration by two mechanisms . The amino terminus of ExoS could inhibit Rho function and wound healing in a manner similar to C . difficile . Alternatively, ExoS could inhibit the cellular motility and angiogenesis required for wound healing by ADP-ribosylating Ras . Through the inhibition of tissue regeneration and wound healing, ExoS may play a pivotal role in chronic disease by maintaining sites of colonization . Inhibition of Ras or Rho signaling may also interfere with both innate and acquired immunity . Small-molecular-weight GTP-binding proteins of the Ras superfamily are required for cellular processes, such as phagocytosis, as Rho proteins contribute to phagocytosis (Caron and Hall, 1998) . Since Ras functions upstream of Rho in cellular signaling processes (Ridley et al., 1995), ADP-ribosylation of Ras by ExoS or the inhibition of Rho function by C234 may inhibit phagocytosis of P . aeruginosa by macrophages . Other studies indicate that Ras plays a role in T cell activation (Cantrell, 1994) . Thus, ExoS may inhibit acquired immunity by inhibiting T-cell activation. Neurol Neurochir Pol, 1999, 32 Suppl 6, 9 - 13 {Achievements, disappointments and hopes in neurological therapy in the 20th century}; Domzal TM; Only in the second half of the 20th century a breakthrough occurred in the traditional neurological therapeutic methods based up to that time mainly on bromine with valerian extract and vitamins B . Later on in that century several great discoveries were made which improved greatly the effectiveness of the neurological therapy: psychopharmacology which began with the introduction of chlorpromazine and reserpine, the use of corticosteroids for which the Nobel award was given, levodopa introduction for Parkinson's disease, non-steroid antiinflammatory agents and the demonstration of their action mechanism /also Nobel award/, immunotherapy, botulin toxin for the treatment of dystonias and thrombolytic drugs possibly the drugs of the future . The main disappointment is the broad chasm between the progress made in diagnostic methods and the low effectiveness of therapy in strokes, amyotrophic lateral sclerosis, Alzheimer's disease and other degenerative neurological diseases . Many problems arose with the introduction of levodopa changing the course and clinical pattern of Parkinson's disease . The problem of our times are the adverse effects of pharmacotherapy . The low effectiveness of the new drugs used in epilepsy is also disappointing . A hope for the future is the new direction in therapy--the use of genes and also the use of monoclonal antibodies and neurotrophic agents . It is to be expected that in the near future medicine will find effective methods for the treatment of malignant neoplasms. J Gastroenterol Hepatol, 2000 Oct, 15(10), 1100 - 4 Botulinum toxin for achalasia in children; Ip KS et al.; BACKGROUND: Injection of botulinum toxin (BTx) into the lower esophageal sphincter (LES) of adult patients with achalasia results in the effective relief of symptoms . The aim of the present study was to examine the effectiveness of BTx in pediatric patients suffering from achalasia . METHODS: Seven patients suffering from achalasia with or without prior treatment were treated with intrasphincteric injection of BTx . The median duration of follow up was 15 months . RESULTS: All seven patients improved . The median interval before recurrence of symptoms was 4 months (range 1-14 months) . There was an inverse relationship between the pretreatment LES pressure and the duration of response (r=-0.6) . The mean pretreatment LES pressure in the subgroup with a response greater than 6 months was 38+/-10 mmHg compared with 61+/-12 mmHg in the other four patients (P= 0.05) . All seven patients required retreatment . CONCLUSION: Botulinum toxin is effective in relieving symptoms in pediatric patients suffering from achalasia, producing a sustained response beyond 6 months in 43% of patients. Neurol Neurochir Pol, 2000 Jul-Aug, 34(4), 775 - 82 {Rubral tremor of Holmes, rare case of pathological tremor: case report}; Slawek J et al.; The authors present a very rare case of Holmes tremor (previously known as rubral or midbrain tremor) . In all described till now cases the tremor was due to a known and revealed in laboratory or neuroimaging cause . We present an unusual case of a 42-year old woman with unilateral tremor of right extremities (mostly proximal part of upper extremity) which started abruptly 3 years ago . She had no suffer any serious disease before the onset of symptoms and her family history was also negative . The tremor was present at rest but accelerated during specific postures and active movements . The laboratory tests including: copper and ceruloplasmin concentrations, blood analysis for acanthocytes, evoked potentials, EEG, CT, MRI, MRA and SPECT did not reveal any significant changes . Treatment attempts with neuroleptics, clonazepam, L-dopa, valproic acid, biperiden were almost completely ineffective except local injections of botulinum toxin (Botox, Allergan, 150 U) into the muscles of right arm girdle which moderately alleviated tremor . We did not find any underlying pathology as a cause of tremor, clinically the same as symptomatic cases described in literature . We suggest the possibility of idiopathic origin of tremor in our case, although a very small size of lesion (f.i . ischaemic) could be undetectable in the described tests. Rev Stomatol Chir Maxillofac, 2000 Oct, 101(4), 189 - 91 {Treatment of recurrent luxation of the temporomandibular joint with botulinum toxin}; Gilles R et al.; We report the case of a 70-year-old man who suffered recurrent dislocations of the temporomandibular joint secondary to severe Parkinson syndrome . The patient was given repeated injections of botulinum toxin . After 3 injections over a 9-month period, no further dislocation occurred . Botulinum toxin may be an alternative to surgery. J Pediatr Surg, 2000 Dec, 35(12), 1733 - 6 A prospective study of botulinum toxin for internal anal sphincter hypertonicity in children with Hirschsprung's disease; Minkes RK et al.; BACKGROUND: Internal anal sphincter hypertonicity with nonrelaxation can cause persistent constipation and obstructive symptoms in children after surgery for Hirschsprung's disease . Intractable symptoms traditionally have been treated with anal myectomy, which may be ineffective or complicated by long-term incontinence . The authors evaluated prospectively the use of intrasphincteric botulinum toxin for these patients . METHODS: Eighteen children were studied (age 1 to 13; median, 4 years) . Botulinum toxin was injected (total dose 15 to 60 U) into 4 quadrants of the sphincter . Resting sphincter pressure was measured in 14 patients before and after injection . Ten have had 1 to 5 additional injections (total dose, 30 to 60 U per injection) . RESULTS: Four patients had no improvement in bowel function, 2 had improvement for less than 1 month, 7 had improvement for 1 to 6 months, and 5 had improvement more than 6 months . Nine of those with symptomatic improvement longer than 1 month had pressures measured, with a documented decrease in 8 . Five with no significant clinical improvement had pressure measurements, with a decrease in 3 . There were no adverse effects associated with botulinum toxin injection . Four children had new encopresis postinjection, which was mild and resolved in each case . CONCLUSIONS: Intrasphincteric botulinum toxin is a safe and less-invasive alternative to myectomy for symptomatic internal sphincter hypertonicity . Persistent symptoms, despite a fall in sphincter pressure, suggest a nonsphincteric etiology . Repeat injections often are necessary for recurrent symptoms. Hepatogastroenterology, 2000 Sep-Oct, 47(35), 1203 - 4 Restoration of propulsive peristalsis of the esophagus in achalasia; Hep A et al.; The set consisting of 3 patients with esophageal achalasia diagnosed by manometry, pseudoachalasia excluded by esophagoscopy and endosonography, was treated with combined conservative procedure . Botulinum toxin 250u (Dysport) was applied to the area of lower esophageal sphincter and after 7 days balloon dilatation was carried out . Treatment efficacy was evaluated by the data obtained about the subjective condition, manometrically and endoscopically . The spine condition was evaluated in all patients before treatment and functional blockades were released by manual medicine and even by acupuncture . We succeeded in restoring propulsive peristalsis of the esophagus in all of them . It is objectively proven in the longest duration of 44 months in the case of a patient treated with a balloon dilatation. J Neurol Sci, 2000 Dec 1, 181(1-2), 89 - 97 Botulinum toxin type-A treatment in spastic paraparesis: a neurophysiological study; Pauri F et al.; OBJECTIVE: The aim of this study was to verify the action of Botulinum toxin type-A (BoNT-A) by means of neurophysiological techniques, in patients presenting lower limb spasticity and requiring BoNT-A injections in the calf muscles, due to the poor response to medical antispastic treatment . SUBJECTS AND METHOD: Patients presenting paraparesis were enrolled . They underwent clinical evaluation for spasticity according to the Ashworth scale and neurophysiological recordings including: motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the leg area; compound motor action potential (cMAP) to tibial nerve stimulation, F-wave, and H-reflex before the treatment and 24 h, 2 weeks and 1 month after the injection of BoNT-A . In all patients, gastrocnemius was treated and in some cases soleus or tibialis posterior muscles were also injected . RESULTS: In all patients, BoNT-A injections induced a clear clinical improvement as showed by the reduced spasticity values of the Ashworth scale . A significant increment of MEP latency and central conduction time (CCT) duration were observed 2 weeks after the treatment only in the injected muscles . CONCLUSIONS: Prolonged MEP latencies and CCT after BoNT-A injections is probably due to a central alteration in responsiveness of spinal motor neurons to descending impulses from the corticospinal tracts . Such changes represent objective parameters heralding clinical efficacy of treatment. Curr Treat Options Neurol, 2000 Sep, 2(5), 393 - 400 Blepharospasm and Hemifacial Spasm; Boghen DR et al.; The main objective in the treatment of blepharospasm is to decrease or cease the unwanted, repeated forced closure of the eyelids . This is best achieved by the use of botulinum toxin . In a minority of patients, botulinum toxin is either ineffective or poorly tolerated . In this group of patients, a trial with oral medication in the following order is warranted: trihexyphenidyl, baclofen, clonazepam, and tetrabenazine . Before going to the next medication, each of these drugs should be administered at the highest tolerated dosage for a period of 1 or 2 months . If, as often happens, all pharmacologic treatment attempts fail, and the patient is too disabled to remain untreated, he or she can be referred to an experienced plastic surgeon for a myectomy of the eyelid protractors . For treatment of apraxia of eyelid opening, botulinum toxin should be administered as the first treatment . If this fails, and vision is significantly impaired, the patient may be referred to a plastic surgeon for a frontalis suspension of the eyelid . Treatments of hemifacial spasm are aimed at decreasing or ending the annoying twitches of one side of the face . In this disorder, interference with vision is not a problem unless the contralateral eye is amblyopic . Despite isolated reports of spasm relief by drugs such as carbamazepine, oral medication is unlikely to be helpful . Botulinum toxin is the preferred treatment in hemifacial spasm patients . In some patients, relief from spasms can only be obtained at the cost of an ipsilateral upper lip droop of varying severity . Patients who are dissatisfied with the results of treatment with botulinum toxin, and are not willing to tolerate their condition, can be referred to an experienced neurosurgeon for microvascular decompression of the facial nerve . Pending success of ongoing attempts to reduce adverse effects, we believe that doxorubicin chemomyectomy, a recent treatment that has been used for both facial spasm and blepharospasm, is best administered in a research setting. Curr Treat Options Neurol, 2000 May, 2(3), 275 - 285 Dystonia; Bressman SB et al.; Therapy for most people with dystonia is symptomatic, directed at lessening the intensity of the dystonic contractions . For a small minority of patients (eg, those with dopa-responsive dystonia, Wilson's disease, or psychogenic dystonia), specific therapy directed at one of the many causes of dystonia is available . Before initiating treatment, clinicians need to decide if a patient has a form of dystonia amenable to such therapy . The most sensitive and least costly method to diagnose DRD is a therapeutic trial of levodopa . It is, therefore, recommended to treat all those with dystonia beginning in childhood or adolescence with low-dose levodopa . For patients with generalized or segmental signs who do not respond to levodopa, other oral medications, including anticholinergics, baclofen, and benzodiazepines, may provide mild to moderate relief; these medications are often given in combinations . For those with focal dystonia, most having adult-onset disease, botulinum toxin A injections often effectively control contractions . The injections produce transient weakness and need to be repeated, generally every 3 to 5 months . There is growing renewed interest in surgical treatment . Peripheral denervating procedures may be helpful for patients with torticollis who do not obtain adequate benefit with botulinum toxin A . The central procedures of pallidotomy and pallidal stimulation are under study; their place in the treatment of the many dystonia subtypes (eg, limb vs axial, generalized vs focal, primary vs secondary) still needs to be established . There are very few studies evaluating physical and psychological therapies or the impact of diet or lifestyle in dystonia . Most clinicians consider physical therapy, including massage, a potential adjunct to medical therapy, and psychological support and stress reduction may help individuals cope with this chronic and frequently disabling condition. Curr Treat Options Neurol, 2000 May, 2(3), 205 - 214 Tardive Dyskinesia; Tarsy D; Although there are many published studies on the treatment of tardive dyskinesia (TD), relatively few treatments have proven to be consistently useful in clinical practice . Reviewed critically, most treatments have produced only slight to moderate benefit in less than half the patients treated . Emphasis instead is on prevention, prompt detection, and management of early and potentially reversible cases . If a patient develops dyskinesia while taking an antipsychotic drug (APD), ideal management is immediate discontinuation of the APD, if this is psychiatrically feasible . The manifestations of TD should be documented and the patient examined to exclude other possible causes of dyskinesia . APDs should then be withheld in the hope that the dyskinesia will disappear . Although the dyskinesia may fade within several weeks, it has the potential to recur if APD treatment is reintroduced . Psychiatric reevaluation to consider alternative psychiatric diagnoses or treatments is strongly advised . If there is no alternative to reintroducing an APD for psychiatric treatment, then an atypical neuroleptic should be considered . Because dyskinesia is very often not disturbing enough to require treatment, the need for treatment of TD should be carefully assessed . For mild dyskinesia, low doses of a benzodiazepine (eg, clonazepam) may reduce the amount of both dyskinesia and associated anxiety . Anticholinergic drugs are unhelpful and may aggravate TD but, similar to their effect in idiopathic dystonia, may be effective in tardive dystonia . Botulinum toxin injections are of considerable value in managing localized forms of tardive dystonia, such as retrocollis or blepharospasm . Tetrabenazine and reserpine are presynaptic dopamine depletors that may have considerable efficacy in TD, especially tardive dystonia; however, their use is often limited by side effects . Based on the rationale that TD may be due to formation of free radicals, vitamin E has been used for treatment of TD, with mixed results . In some patients with persistent and disabling TD that fails to remit even after the patient is no longer taking an APD, it may be necessary to resume treatment eventually with a typical APD . This approach should be considered only as a last resort to suppress TD, however, because it carries the risk of preventing remission and possibly aggravating TD . In this case, further attempts to taper and discontinue the APD are recommended . At present, there is no evidence that established TD continues to progress in severity with continued APD exposure . This nonprogressive character of TD may provide to be a consolation to the patient and family and is also of potential medical-legal importance. Curr Treat Options Neurol, 1999 Mar, 1(1), 68 - 73 Acquired Nystagmus; Averbuch-Heller L; Patients with acquired forms of nystagmus may suffer from oscillopsia and blurred vision; abolishing or reducing nystagmus ameliorates these symptoms . Ideally, treatment of nystagmus should be directed against the pathophysiologic mechanism responsible . Identification of nystagmus pattern is important in directing therapy and occasionally requires electronic eye movement recording for precise characterization . Patients with acquired pendular nystagmus, particularly those with multiple sclerosis, often benefit from gabapentin, a drug with few side effects . Scopolamine, clonazepam, and valproate are also useful in some patients . A new drug, memantine, was effective in treating pendular nystagmus in one study, but it has not yet been approved for use in the United States . Periodic alternating nystagmus usually responds to baclofen . Central vestibular nystagmus, including downbeating and upbeating forms, can be treated with baclofen or clonazepam . In some patients, treatment of an underlying condition, such as periodic ataxia, Whipple's disease, and Chiari malformation, abolishes nystagmus and improves vision . If pharmacologic therapy fails, optical devices can be considered in selected patients . Injections of botulinum toxin and surgery to weaken extraocular muscles are prone to induce diplopia and may precipitate plastic-adaptive ocular motor changes that eventually negate the beneficial effect. Curr Treat Options Neurol, 1999 Mar, 1(1), 33 - 43 Cervical Dystonia (Torticollis); Brin MF et al.; During the initial consultation, the patient is introduced to the five basic treatment options, acknowledging that in most cases, the choice is in the patient's control . The options are 1) supportive/social treatment, 2) physical therapies, 3) oral and intrathecal pharmacotherapy, 4) injection (botulinum toxin type A ) therapy, and 5) surgical therapy . Although a patient may be an obvious candidate for a specific intervention, the patient needs to be aware of the options, including those that he or she chooses not to use . Combination therapies are often appropriate . The option of supportive therapy is applicable in nearly all situations . All patients are encouraged to join a dystonia advocacy association . To accomplish this, literature is made available to them, and the telephone number of the local dystonia chapter is provided . For most patients with focal dystonia or symptoms limited to one region, such as those with cervical dystonia, local injections of botulinum toxin type A are core treatment . For those who cannot be treated effectively with BTX-A, or for those in whom BTX-A has failed, pharmacotherapy is instituted . Pharmacotherapy can often "take the edge off" symptoms that remain after BTX-A therapy . Physical therapies are recommended as complementary treatment for most patients receiving BTX-A in an attempt to extend the benefit from BTX-A . BTX-A may substantially change motor patterns, requiring physical therapies to help the patient relearn normal postures and functional control . In refractory cases when all other measures have failed, peripheral or brain surgery is considered . With our advancing understanding of the genetics of dystonia, it is hoped that specific therapy to either halt the progression of or bring additional relief to dystonic spasms will be available shortly. Curr Treat Options Neurol, 1999 Mar, 1(1), 6 - 13 Essential Tremor; Lambert D et al.; Multiple pharmacologic treatments have been studied, but propranolol and primidone have proven to be the most effective medications . It is unlikely that a patient will respond miraculously to another medication if his or her response to propranolol and primidone is minimal . Some subsets of essential tremor, however, such as the kinetic predominant type, may respond better to other medications . Mildly affected patients may not need treatment at all, and the potential benefits must always be weighed against the possible side effects . The main benefit of botulinum toxin injection is for head tremor, whereas its efficacy in hand tremor is variable . If a patient does not respond to adequate doses of propranolol or primidone, deep brain stimulation should be considered because it carries the lowest risk of the available surgical procedures; usually, it should be given preference over thalamotomy . It is important for the physician to realize the multitude of symptomatic treatments available . Beyond the conventional and often effective oral medications, use of newer treatments such as botulinum toxin, thalamotomy, and deep brain stimulation can often reduce tremor and lead to a greater quality of life for patients with ET. Br Med Bull, 2000, 56(2), 476 - 85 Management of spasticity in stroke; Bhakta BB; Spasticity treatment must be considered in relation to other impairments with functional goals defined prior to intervention . The effects of muscle co-contraction and involuntary limb movement associated with exaggerated cutaneous reflexes or effort as well as stretch reflex hyperexcitability need to be considered . Exacerbating factors such as pain must be identified . Physical therapy and conventional orthoses are the mainstays of spasticity management during acute rehabilitation . Botulinum toxin shows promise but needs further evaluation in the context of acute rehabilitation . Phenol chemodenervation can produce good results in spasticity refractory to standard treatments . Muscle strengthening exercises may be appropriate in chronic hemiparesis without adversely affecting tone . Electrical stimulation may be a useful adjunct to other spasticity treatments . Difficulty demonstrating functional benefit from antispasticity treatment may imply that interventions directed at single motor impairments whether weakness or spasticity are not likely to result in functional benefit, but it is their combination that is important. Orthopade, 2000 Sep, 29(9), 808 - 13 {Torsion deformities in the lower extremities in patients with infantile cerebral palsy: pathogenesis and therapy}; Brunner R et al.; Patients with spastic cerebral palsy often develop torsional deformities at the level of hip, shank or foot . The abnormal muscle activity such as spasticity or the increase of tone are considered as the major cause . The present study shows that the gait pattern is another cause which may lead to deformities . The study is based on gait analysis of 13 patients and 8 normal controls . The major and significant differences in gait kinematics were toe walking, toeing-in and internal rotation at the hip in the patients whereas the unaffected control group had a physiological heel-toe gait . The difference in torsional moments at the hip, knee and ankle were statistically significant . At the knee and the ankle a decrease in the internal rotation moment was found, whereas at the hip a paradoxical curve pattern with a more externally directed rotation moment was seen . These differences in torsional moments can explain the external rotation at the foot and/or shank as well as the increase in femoral anteversion, although they might be primarily caused by the deformity itself . Because a constantly acting force, however, changes the bony form and/or shape, the abnormal moments can be considered as a factor leading to deformities . A heel-toe gait seems to be mandatory for an efficient prophylaxis . Torsional deformities at the shank require a corrective osteotomy which is performed at the supramalleolar site and fixed by an unilateral, external fixator . Malrotations at the hip usually show two components: the functional part can be corrected by lengthening and weakening the tensor fasciae latae and the ventral parts of the glutei, using stretching exercises, botulinum toxin A or operative lengthening and releases . The increased femoral anteversion needs to be corrected by a femoral derotation osteotomy . Patients with cerebral palsy show a reduced control of their legs; therefore, balance internal torsion should not be corrected to neutral and overcorrection must be avoided . A remaining slight internal rotation after correction will help to spontaneously stabilize the leg if it gives way at initial contact, by "falling underneath the centre of gravity" . If the leg is in neutral or external rotation, the patient needs to realign the centre of gravity over the dynamically unstable leg, showing a trunk-lean over the leg, the Duchenne limp. Arch Dis Child, 2000 Dec, 83(6), 481 - 7 Randomised double blind placebo controlled trial of the effect of botulinum toxin on walking in cerebral palsy; Ubhi T et al.; BACKGROUND: Cerebral palsy is the commonest cause of severe physical disability in childhood . For many years treatment has centred on the use of physiotherapy and orthotics to overcome the problems of leg spasticity, which interferes with walking and can lead to limb deformity . Intramuscular botulinum toxin (BT-A) offers a targeted form of therapy to reduce spasticity in specific muscle groups . AIMS: To determine whether intramuscular BT-A can improve walking in children with cerebral palsy . DESIGN: Randomised, double blind, placebo controlled trial . METHODS: Forty patients with spastic diplegia or hemiplegia were enrolled . Twenty two received botulinum toxin and 18 received placebo . The primary outcome measure was video gait analysis and secondary outcome measures were gross motor function measure (GMFM), physiological cost index (PCI), and passive ankle dorsiflexion . RESULTS: Video gait analysis showed clinically and statistically significant improvement in initial foot contact following BT-A at six weeks and 12 weeks compared to placebo . Forty eight per cent of BT-A treated children showed clinical improvement in VGA compared to 17% of placebo treated children . The GMFM (walking dimension) showed a statistically significant improvement in favour of the botulinum toxin treated group . Changes in PCI and passive ankle dorsiflexion were not statistically significant . CONCLUSION: The study gives further support to the use of intramuscular botulinum toxin type A as an adjunct to conventional physiotherapy and orthoses to reduce spasticity and improve functional mobility in children with spastic diplegic or hemiplegic cerebral palsy. Biochimie, 2000 Sep-Oct, 82(9-10), 943 - 53 Identification of the characteristics that underlie botulinum toxin potency: implications for designing novel drugs; Simpson LL; Botulinum toxin is a uniquely potent substance whose natural site of action is the peripheral cholinergic nerve ending . A substantial amount of information on the cellular, subcellular and molecular aspects of toxin action has been accumulated, and as a result a sound understanding of the basis for toxin potency has been developed . The principal characteristics of the toxin molecule that account for its potency are its ability: a) to be absorbed from the gut with minimal degradation; b) to bind to receptors that maximize the prospects of a pathophysiologic outcome; c) to act by a multiplicative (viz., enzymatic) mechanism; and d) to modify a substrate that is essential for neuronal function . Interestingly, the same properties that account for potency can also be exploited to utilize the toxin as a research tool and as a therapeutic agent . Several specific examples of ways to use the toxin advantageously are presented, including: a) development of oral medications and vaccines; b) analysis of subcellular mechanisms that govern transcytosis; c) identification of cell surface markers characteristic of cholinergic nerve endings; and d) analysis of specific aspects of exocytosis, such as spontaneous quantal release and synchronous quantal release . In all likelihood, further studies on the mechanism of botulinum toxin action will reveal yet further opportunities for utilizing it as a research tool or therapeutic agent. Exp Neurol, 2000 Dec, 166(2), 205 - 12 Ciliary neurotrophic factor is required for motoneuron sprouting; Siegel SG et al.; We used mutant mice that lack the gene for ciliary neurotrophic factor (CNTF) to test the hypothesis that it is an endogenous sprouting factor . Fibers in the lateral gastrocnemius muscle were either partially denervated by transection of one of the branches of its nerve or paralyzed by intramuscular injection of botulinum toxin . This results in a significant sprouting response at the terminals of intact motoneurons in normal animals . We did not detect sprouting produced by either stimulus in mice lacking CNTF . When exogenous CNTF was administered to CNTF knockout mice following partial muscle denervation, they mounted a typical sprouting response . Thus CNTF is a critical factor in the process of sprout formation after both partial denervation injury and neuromuscular paralysis . It may function as part of a cellular compensatory mechanism after neuronal injury . Schweiz Rundsch Med Prax, 2000 Oct 12, 89(41), 1657 - 63 {Diagnosis and therapy of anorectal diseases (excluding constipation and venereal diseases)}; Muller A et al.; In the last couple of years, the anorectum has been of great interest to gastroenterologists . With new diagnostic tools and a refinement of technique, together with new therapeutic modalities, interesting research results have been obtained . These results may be beneficial to patients therapy . The patients history, inspection and palpation of the anorectum remain the basic, essential features of diagnosis . Based on the symptoms and possible differential diagnosis, further investigation is necessary: Anorectal physiology and anal endosonography are also regarded as essential investigative techniques in a colorectal laboratory . Great progress has been made in the medical treatment in proctology in two areas: Biofeedback techniques and botulinum toxin injection . In the following article, definitions, symptoms, diagnosis and therapeutic modalities of common anorectal disorders are described. Pol Merkuriusz Lek, 2000 Aug, 9(50), 572 - 4 {Poisoning with botulinum neurotoxin--diagnostic difficulties}; Grygorczuk S et al.; Intoxication with botulinum neurotoxin, which occurs frequently in Poland, may cause serious diagnostic difficulties . As no assays for laboratory detection of botulinum toxin are available and the biological test on mice requires time before results are obtained, diagnosis must be based on clinical findings and patient's epidemiological history . Quick diagnosis and early administration of therapy with equine antitoxin is essential for patient's recovery . The effectiveness of antitoxin therapy is considered to be significantly reduced if the treatment is not started shortly after the onset of the disease . We describe a case of a patient in whom, because of diagnostic difficulties, antitoxin therapy was introduced with much delay . However, it proved highly efficient and lead to gradual recovery. J Oral Maxillofac Surg, 2000 Nov, 58(11), 1251 - 6 The effect of local injection of botulinum toxin A on the parotid gland of the rat: an immunohistochemical and morphometric study; Ellies M et al.; PURPOSE: In this investigation, the effect of a local injection of botulinum toxin A on the concentration of acetylcholinesterase in the parotid gland of the rat was examined . MATERIALS AND METHODS: After local injection into the parotid glands of female Wistar rats, the treated glands were excised, and immunohistochemical staining for acetylcholinesterase was performed . To discover possible changes in cell morphology after local application of botulinum toxin A, morphometric measurements also were performed on the excised parotid glands . RESULTS: In contrast to the untreated, physiologic saline-injected, glands, there was a decrease in the concentration of acetylcholinesterase in the glands treated with botulinum toxin . No persistent changes in the number of acinar cells could be observed . Conclusions: Because the cholinergic pathway of the autonomic nervous system has great importance in the secretion of fluid from the salivary glands, blocking this pathway and local application of botulinum toxin offers a possible therapeutic option for the treatment of hypersalivation in various otolaryngologic and neurologic diseases. Pharmacopsychiatry, 2000 Sep, 33 Suppl 1, 14 - 33 Tardive drug-induced extrapyramidal syndromes; Marsalek M; The clinical features, outcomes, differential diagnoses, epidemiology, risk factors, and treatment approaches to tardive drug-induced extrapyramidal syndromes (EPS) are reviewed . Tardive forms of dyskinesia (TD), dystonia (TDt), akathisia (TA), Gilles de la Tourette syndrome (TGTS), myoclonus (TM), and parkinsonism (TP) are described . Moreover, pharmacological and topographical subtypes of TD are discussed . While TD, TDt, and TA are clearly delineated syndromes, there are limited data on TGTS, TM, and the questionable TP . TDt is distinguished from TD by clinical and treatment-related variables . Epidemiological studies provide evidence of better prognosis for TD compared with both TDt and TA . Two distinct groups of variables were found to be associated with a higher risk for TD: an exogenous factor (neuroleptic treatment variables and alcohol or drug abuse) and a factor of predisposition (elderly, female, affective disorder diagnosis, presence of EPS, diabetes mellitus type II, and signs of central vulnerability) . In contrast, being younger and male was associated with TDt . A significant relationship between the hyperkinetic forms of tardive EPS was confirmed . Therapeutic strategy differs for the mild, moderate, and severe forms of tardive EPS . Using low doses of antipsychotics is a good preventive approach . Reducing the dose or switching to an atypical antipsychotic is the usual, but not yet fully explored, first therapeutic step . Clozapine, an antipsychotic with antidyskinetic and antidystonic effectiveness, is the second treatment step . Various suppressors of tardive movements were tested in controlled trials, mainly in TD . GABAergic benzodiazepines (clonazepam), adrenergic antagonists (propranolol, clonidine), antioxidants (alpha-tocopherol), and calcium channel blockers (nifedipine) are useful in the third step of treatment of more severe tardive EPS . Unlike TD, TDt and (partially) TA improve on higher doses of anticholinergic medication . Local injection of botulinum A toxin markedly ameliorates focal tardive dystonia over several months . Less verified therapeutic interventions are discussed. Toxicon, 2001 May, 39(5), 651 - 7 Anomalous enhancement of botulinum toxin type A neurotoxicity in the presence of antitoxin; Sheridan RE et al.; The neutralization of botulinum toxin serotype A with polyclonal equine antitoxin was studied in isolated mouse hemidiaphragms and compared to the same action in live mice . The biological activity of the toxin in the isolated muscle could be markedly reduced with excess antitoxin, estimated as 3:1 molar ratios of IgG Ab:toxin or better . Toxin neutralization in vivo required higher ratios of Ab:toxin, ranging from 30:1 at high toxin doses and increasing to 100:1 at 10xLD50 toxin . At equimolar Ab to toxin ratios in the isolated muscle, the biological activity of the toxin underwent a statistically significant increase . This paradoxical effect of the polyclonal antisera was serotype selective and independent of the presence or absence of hemagglutinin in the toxin . The enhancement of toxin activity was subsequently localized to occupancy of one of four epitopes on the toxin using monoclonal antibodies to mimic the effect of the antitoxin . The enhancement of toxin activity suggests that botulinum toxin may undergo a conformational change upon binding antibodies to certain domains . This phenomenon could contribute to the observed concentration dependent changes in neutralization efficacy with antitoxin in vivo. Pol Merkuriusz Lek, 2000 Jul, 8(49), 474 - 5 {Electromyography monitoring in the treatment of torticollis with botulinum toxin}; Domzal TM et al.; The new method of treatment chronic torticollis is injection into affected muscles botulinum's toxin . Some physicians in diagnostic procedure, treatment and monitoring use needle electromyography (nEMG) . The aim of our study was the estimation of the value of nEMG in chronic torticollis treatment . We examined 34 patients with chronic torticollis 4 weeks after botulinum's toxin injection into affected muscles . We have been looking for denervations signs in affected muscles . We found denervations signs in 26 patients . In both muscles sterno-cleido-mastoideus and trapezius we found denervations signs in 13 patients, only in sterno-cleido-mastoideus muscles in 9 patients and in 4 patients only in trapezius muscles . 17 patients from this group improved . The overall rate of improvement in this group was 65% . In 8 patient we didn't find any denervation signs but the rate of improvement in this group was extremely high--87% . CONCLUSION: EMG examination doesn't play deciding role in the monitoring of torticollis treatment with botulinum toxin. Br J Dermatol, 2000 Oct, 143(4), 824 - 7 Effective treatment of frontal hyperhidrosis with botulinum toxin A; Kinkelin I et al.; BACKGROUND: Focal hyperhidrosis is a common condition mostly confined to the axillae, palms and soles . In some individuals, predominantly men, increased sweating of the forehead may be the major complaint and may interfere with the person's quality of life . Botulinum toxin A has been shown to be a very effective treatment for focal hyperhidrosis of the axillae and palms . OBJECTIVES: To assess the response in 10 men suffering from frontal hyperhidrosis treated with botulinum toxin A . METHODS: Botulinum toxin A Botox was injected at multiple sites evenly distributed over the forehead (mean dose 86 mouse units) . RESULTS: The mean +/- SEM amount of sweat was significantly reduced, 4 weeks after treatment, from 173.8 +/- 38.6 mg min(-1) to 53.7 +/- 17.6 mg min(-1) . The effect lasted at least 5 months in nine of the 10 patients . All patients subjectively judged the treatment as very effective . Minor side-effects included painful injections and a transient weakness of forehead muscles without ptosis . CONCLUSIONS: In this study, we provide evidence that botulinum toxin A is an effective and safe treatment for frontal hyperhidrosis. Aliment Pharmacol Ther, 2000 Nov, 14(11), 1469 - 77 Endoscopic injection of botulinum toxin in patients with recurrent acute pancreatitis due to pancreatic sphincter of Oddi dysfunction; Wehrmann T et al.; AIM: To evaluate the technical feasibility, safety, and short-term efficacy of botulinum toxin injection for pancreatic sphincter of Oddi dysfunction and to analyse whether the symptomatic response to botulinum toxin might be a predictor of outcome for endoscopic sphincterotomy . METHODS: Fifteen consecutive patients (nine female, aged 38 +/- 12 years) with frequent attacks (median four) of acute pancreatitis within 6 months, and manometrically proven pancreatic sphincter of Oddi dysfunction underwent endoscopic injection of 100 units of botulinum toxin into the major papilla . All patients underwent prospective follow-up thereafter and in cases of recurrent pancreatitis manometry this was repeated and pancreatic sphincterotomy was performed . RESULTS: No side-effects occurred after botulinum toxin injection in any patient . Within 3 months after botulinum toxin treatment, 12 out of 15 patients remained asymptomatic (80% primary response) . Only one out of three patients without symptomatic benefit showed continued elevated pancreatic sphincter pressure at manometry and only this patient benefited from pancreatic sphincterotomy later on . Eleven of the 12 patients initially responding to botulinum toxin injection developed a symptomatic relapse 6 +/- 2 months after botulinum toxin treatment . These patients then achieved long-term clinical remission from pancreatic or combined (biliary and pancreatic, n=5) sphincterotomy (median follow-up, 15 months) . CONCLUSION: Endoscopic botulinum toxin injection into the papilla of Vater is a safe procedure for treatment of pancreatic sphincter of Oddi dysfunction that may provide short-term relief in about 80% of the patients . Those patients who respond to botulinum toxin may subsequently gain definitive cure from sphincterotomy. FEBS Lett, 2000 Nov 3, 484(2), 129 - 32 A tetanus toxin sensitive protein other than VAMP 2 is required for exocytosis in the pancreatic acinar cell; Padfield PJ; The neurotoxin sensitivity of regulated exocytosis in the pancreatic acinar cell was investigated using streptolysin-O permeabilized pancreatic acini . Treatment of permeabilized acini with botulinum toxin B (BoNT/B) or botulinum toxin D (BoNT/D) had no detectable effect on Ca(2+)-dependent amylase secretion but did result in the complete cleavage of VAMP 2 . In comparison, tetanus toxin (TeTx) treatment both significantly inhibited Ca(2+)-dependent amylase secretion and cleaved VAMP 2 . These results indicate that regulated exocytosis in the pancreatic acinar cell requires a tetanus toxin sensitive protein(s) other than VAMP 2. Singapore Med J, 2000 May, 41(5), 209 - 13 Botulinum toxin A in the treatment of hemiplegic spastic foot drop--clinical and functional outcomes; Chua KS et al.; PURPOSE OF STUDY: This study investigated the effects of intramuscular Botulinum toxin A (BTX-A) in 7 ambulatory chronic hemiplegic subjects (5 male, 2 female) who had spastic hemiplegic foot drop . BASIC PROCEDURES: An open label study involving intramuscular injections of Botulinum toxin A (dilution 10 U/0.1 ml) was performed in ambulatory chronic hemiplegics . Tone as measured by the Modified Ashworth Scale (MAS), passive ankle joint range of motion (PROM), briskness of ankle reflexes, gait velocity, motor functional status and effects on the use of walking aids were measured at baseline, 3 and 12 weeks post-injection . MAIN FINDINGS: All subjects except I showed a significant decrease in MAS from 3.43 +/- 0.54 at baseline to 2.0 +/- 1.15 at 3 weeks post-injection, which was maintained during the 3 month study duration . The median change in PROM was 17.0 degrees (SD 12.1 degrees) at 3 weeks and 5.0 degrees (SD 7.1 degrees) at 12 weeks (p = 0.25) Gait velocity and Modified Barthel Index mobility scores which measured motor functional status were not significantly altered post-injection.The injections were generally well-tolerated and there were no serious adverse side effects . PRINCIPAL CONCLUSIONS: Although significant decreases in muscle tone were observed and maintained after intramuscular Botulinum toxin A during the 3 month study period, this regional intervention did not significantly influence functional status, gait velocity and the use of ambulatory aids. Funct Neurol, 2000 Jul-Sep, 15(3), 147 - 55 Functional and clinical changes in upper limb spastic patients treated with botulinum toxin (BTX); Panizza M et al.; Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks . In order to study the usefulness of botulinum toxin type A (BTX) as a therapy for spasticity, we studied 15 patients affected by spasticity secondary to stroke . Tests included: clinical evaluation of tone (Ashworth scale); active angles of extension and flexion at elbow and wrist; Hmax/Mmax ratio from flexor carpi radialis (FCR); Hreflex presynaptic inhibition from FCR during vibration; Task score; and video recording . Patients were injected with BTX into one or more muscles with total doses not exceeding 200 International Units (IU) . The tests were performed immediately prior to injection and repeated 2 weeks afterwards . Furthermore, in eight patients, testing was also performed one month after BTX injection . Between two weeks and one month after BTX there were no statistically significant differences . A statistically significant difference in the Task and Ashworth scores before and after treatment emerged (p < 0.0014), but only 6 patients showed a clear improvement in motor performance . Overall, we observed an improvement in the angle of active extension and flexion at the wrist and elbow . There were no significant changes in the Hmax/Mmax ratio and the Hreflex presynaptic inhibition during vibration . All the patients reported a subjective improvement . The results suggest that subjective benefits can be gained from the use of BTX in patients affected by spasticity, and that the degree of motor improvement seems to depend on the motor recovery obtained before treatment. J Physiol, 2000 Nov 1, 528(Pt 3), 489 - 96 Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex; Zilberter Y; Dual whole-cell recordings were made in layer 2/3 of the rat neocortex in synaptically connected pyramidal cells and fast-spiking non-accommodating (FSN) interneurons . In 75% of cell pairs (n = 80), the cells formed reciprocal synaptic connections . Trains of backpropagating action potentials in pyramidal cells induced Ca2+ transients in dendrites followed by inhibition of unitary IPSPs . IPSP depression was prevented by loading pyramidal cells with 5 mM BAPTA or EGTA . IPSP depression was mimicked by the metabotropic glutamate receptor (mGluR) agonist ACPD and was prevented by a mixture of the mGluR antagonists CPCCOEt and EGLU.IPSP depression was prevented by loading pyramidal cells with the antagonists of vesicular exocytosis botulinum toxin D (light chain) and GDP-beta-S . It is concluded that Ca2+-dependent release of a retrograde messenger, most probably glutamate, from pyramidal cell dendrites suppresses the inhibition of pyramidal neurons via activation of mGluRs located in FSN interneuron nerve terminals. Ear Nose Throat J, 2000 Oct, 79(10), 788 - 9, 792, 794 passim Botulinum toxin in otolaryngology: a review of its actions and opportunities for use; Neuenschwander MC et al.; Botulinum toxin has several important properties that make it an ideal chemical denervator . These include its high degree of specificity for the neuromuscular junction, its ability to induce temporary and reversible denervation, and its limited degree of side effects and complications . Botulinum toxin is being used safely in a wide variety of clinical settings by many different specialists . In otolaryngologic practice, it is being administered for the treatment of at least a dozen conditions, including various dysphonias, dystonias, and spasms as well as torticollis, facial nerve paralysis, and hyperkinetic facial lines . Studies have shown that botulinum toxin injections have a high rate of success in temporarily relieving symptoms. Muscle Nerve, 2000 Nov, 23(11), 1752 - 6 Utility of an EMG mapping study in treating cervical dystonia; Van Gerpen JA et al.; Intramuscular injections of botulinum toxin are the cornerstone of treatment for cervical dystonia . Controversy exists regarding the necessity for EMG-guided injections . We compared the clinical examination of four movement disorder specialists to an electromyographic (EMG) mapping study . Clinical predictions of individual muscle involvement were only 59% sensitive and 75% specific . Muscle hypertrophy, shoulder elevation, and dominant head vector did not bolster clinical accuracy . An EMG mapping study facilitates identification of dystonic muscles in cervical dystonia, which may enhance botulinum toxin therapy . Eur Neurol, 2000, 44(3), 153 - 5 Posttraumatic focal dystonia of the shoulder; Hollinger P et al.; Posttraumatic movement disorders remain a controversial issue with focal dystonia being a prominent representative . Focal dystonia of the shoulder without concomittant cervical dystonia is a rare event . We describe 2 patients who, after minor trauma, developed focal dystonia of the shoulder with severe chronic pain . Response to local botulinum toxin A was favorable in 1 patient . Eur Neurol, 2000, 44(3), 144 - 6 Long-term remission of idiopathic cervical dystonia after treatment with botulinum toxin; Giladi N et al.; Botulinum toxin type A (BTX-A) treatment for cervical dystonia is traditionally considered a purely symptomatic treatment . BTX-A blocks acetyl choline exocytosis for 3-6 months and most patients require reinjection after this period . We report on 6 patients (mean age 41.6 years, range 18-69) with idiopathic cervical dystonia who were treated with BTX-A injections and became asymptomatic for 2-4 years . Four patients showed remission after the first BTX-A treatment, 1 patient after the second set of injections and 1 after the third session . Amelioration of neck dystonia was observed within 1-4 weeks after the last BTX-A treatment and all 6 patients are symptom-free, off antidystonic medications for over 2 years . The possibility that BTX-A treatment may increase the chances of development of clinical remission in patients with idiopathic cervical dystonia is discussed . Eur Neurol, 2000, 44(3), 139 - 43 Remote effects of chronic botulinum toxin treatment: electrophysiologic results Do not indicate subclinical remodelling of noninjected muscles; Fertl E et al.; This study investigates the remote effects of botulinum toxin injections by examining the motor unit architecture of noninjected distant muscles . In 21 dystonia patients treated with botulinum toxin (n = 11, mean cumulative dose = 815 mU; n = 10, mean cumulative dose = 7,207 mU) and 10 control individuals, a blinded single-fiber electromyography of the vastus lateralis muscle was performed . The main outcome measure was fiber density (FD), thus measuring the effect of different cumulative doses on remote reinnervation . FD was normal in all patients treated with botulinum toxin . FD did not differ between the three groups studied . No relationship was found between FD and cumulative dose . Therefore, in this specific patient population, muscles remote to the site of injection showed no FD change months after the injection . We conclude that there was no evidence of remote reinnervation and remodelling of motor units with cumulative chemodenervation . Semin Thorac Cardiovasc Surg, 2000 Jul, 12(3), 201 - 5 Laparoscopy or thoracoscopy for achalasia; Nguyen NT et al.; Achalasia is an esophageal motor disorder of unknown etiology . Typical manometric findings include aperistalsis of the esophageal body coupled with elevated pressure and incomplete relaxation of the lower esophageal sphincter during swallowing . Medical treatments consist of pneumatic dilatation or injections of botulinum toxin . Surgical treatment consists of Heller's myotomy with or without an antireflux procedure . Relief of dysphagia symptoms can be achieved in 85% to 94% of patients undergoing surgical treatment . In the past decade, the minimally invasive approach for the treatment of achalasia has been proven feasible, safe, and effective . We review the role of thoracoscopy and laparoscopy and address controversies in the management of patients with achalasia. Am J Gastroenterol, 2000 Oct, 95(10), 2737 - 45 A cost-minimization analysis of alternative treatment strategies for achalasia; Imperiale TF et al.; OBJECTIVE: The aim of this study is to compare the costs per cure of alternative strategies for the treatment of achalasia . METHODS: A cost-minimization model compared three strategies for otherwise healthy adults of any age with achalasia: 1) laparoscopic Heller myotomy with fundoplication (LHM); 2) pneumatic dilation (PD), with LHM reserved for treatment failures; 3) botulinum toxin (Botox) injection of the lower esophageal sphincter, with PD reserved for treatment failures . Probabilities of short- and long-term efficacy, treatment failure, symptomatic recurrence rates, and complications were derived from the published literature . Only direct costs were considered during the 5-yr time horizon . RESULTS: Respective reference case costs per cure of PD, Botox, and LHM strategies were $3,111, $3,723, and $10,792 . Despite short- and long-term efficacy of 96% and 94%, respectively, the LHM strategy was most costly . Initial PD remained less costly than initial Botox, provided that rates of PD efficacy and perforation were > or = 70% and < 9.5%, respectively, and cost of a Botox session was > or = $450 . The results were not sensitive to the probabilities of short- and long-term response to Botox, recurrence after PD, LHM efficacy, and post-LHM gastroesophageal reflux disease, nor to the costs of LHM and PD . CONCLUSIONS: For otherwise healthy patients with achalasia, initial PD is the least costly strategy provided that the PD perforation rate remains < 10% . Initial Botox is less costly only when nonendoscopic-related costs decrease by 25% . Initial LHM is the most costly strategy under all clinically plausible scenarios . Subsequent analyses should include a longer time horizon and an assessment of patient ference for each strategy. Postgrad Med, 2000 Oct, 108(5), 151 - 2, 155-6, 159-60 Strategies for controlling dystonia . Overview of therapies that may alleviate symptoms; Adler CH; Dystonia is an involuntary movement disorder characterized by twisting, turning, and posturing . This disorder may affect a single body part or may be more generalized, but the pathophysiology remains unclear . The treatment of choice for most of the focal dystonias is botulinum toxin injections, although oral medications occasionally may be beneficial . Surgical treatment of dystonia may be performed peripherally or centrally but is usually reserved for patients in whom other forms of therapy fail. Cancer, 2000 Oct 15, 89(8), 1659 - 63 Frey syndrome: treatment with type A botulinum toxin; von Lindern JJ et al.; BACKGROUND: Frey syndrome was first described by Baillarger in 1853 . Frey provided a detailed analysis and description as "auriculotemporal syndrome" in 1923 . According to the literature, even the most recent therapeutic measures described for the treatment of patients with Frey syndrome have little chance of success and a high incidence of side effects . Thus, a type of treatment is desirable that can suppress the symptoms of Frey syndrome and can offer a good success rate, minimum invasiveness, and few side effects . METHODS: The experience of the authors and data from the literature confirmed the efficacy of type A botulinum toxin treatment for patients with Frey syndrome up to a maximum observation period of 3 years . RESULTS: In the current study, seven patients with severe, symptomatic Frey syndrome after parotidectomy were treated successfully with type A botulinum toxin . CONCLUSIONS: The method of local, intracutaneous treatment with type A botulinum toxin for patients with Frey syndrome is effective, virtually side-effect free, and minimally invasive . J Neurol, 2000 Aug, 247(8), 630 - 2 The sternocleidomastoid test: an in vivo assay to investigate botulinum toxin antibody formation in humans; Dressler D et al.; In a small number of patients treated with botulinum toxin (BT) antibody (Ab) formation occurs . BT Ab can be detected by the mouse protection assay (MPA) or by the mouse diaphragm assay (MDA) . Both methods, however, have major drawbacks . We tested a method for detecting BT Ab which measures the BT-induced reduction in the electromyographic amplitude of the mean maximal voluntary activation (M-EMG) of the sternocleidomastoid muscle . The M-EMG reduction was compared in 17 patients with cervical dystonia and secondary BT therapy failure to the M-EMG reduction previously measured in controls . Values more than 2 SD below the mean of controls were considered abnormal . Six patients showed BT Ab on the MPA and MDA; all of these had abnormal M-EMG reductions . Eleven patients showed no BT Ab on MPA and MDA testing; in ten of these the M-EMG reduction was normal, and in one it was pathological, but MDA testing later changed to positive under continued BT therapy . The sternocleidomastoid test is easy to perform and produces quantitative results . Since its sensitivity and specificity are at least as good as those of the MDA and the MPA, it can replace them. Cochrane Database Syst Rev . 2000;(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: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, 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-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria . Only thirteen of these studies used the Ashworth scale, of which only three of the six 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. Baillieres Best Pract Res Clin Gastroenterol, 1999 Apr, 13(1), 131 - 43 Botulinum toxin for spastic gastrointestinal disorders; Hoogerwerf WA et al.; Botulinum toxin (BTX) is one of the most potent inhibitors of acetylcholine from nerve endings, and this accounts for its toxic properties as well as its therapeutic application in a variety of neuromuscular syndromes . This review focuses on the growing use of BTX in the so-called 'spastic' disorders of the gastrointestinal tract . These include achalasia, for which the short-term efficacy of the intrasphincteric injection of BTX has been well established . However, because of the chronicity of this condition, repeated injections of the toxin may be required at regular intervals . In contrast, the relatively short duration of action may be an advantage in disorders such as chronic anal fissure, where the benefit of this therapy has now been demonstrated in hundreds of patients . There are many other sphincteric and non-sphincteric syndromes in the gut for which the efficacy of this agent is being actively tested . These include non-cardiac chest pain, post-operative pylorospasm and sphincter of Oddi dysfunction . Skeletal muscle sphincters, such as the upper oesophageal sphincter or the external anal sphincter/puborectalis muscle, may also be targeted, with good effect . In some of these conditions, the local injection of BTX may serve as a useful therapeutic trial, facilitating the decision to institute more invasive forms of therapy . The cumulative short-term experience with BTX in the gut to date suggests that it is a relatively simple and safe therapy . The use of BTX represents a novel approach for gastrointestinal motility disorders, and the rapidly expanding list of successful applications holds promise for a more widespread use of similar agents in the future . Additional studies on long-term outcome are eagerly awaited. Arch Phys Med Rehabil, 2000 Oct, 81(10), 1408 - 15 Motor control testing of upper limb function after botulinum toxin injection: a case study; Hurvitz EA et al.; OBJECTIVE: To evaluate changes in upper extremity function in a hemiparetic patient after treatment with botulinum toxin (BTX) using motor-control testing (MCT) techniques . DESIGN: Interventional with longitudinal study, open label . SETTING: A children's hospital and a motor-control laboratory at a major academic center . PARTICIPANTS: A 16-year-old male with right hemiparetic cerebral palsy and a healthy 12-year-old control subject . INTERVENTIONS: BTX injections to the elbow and wrist flexors . MAIN OUTCOME MEASURES: MCT was used to examine 4 upper extremity movements: forward reach, bilateral rhythmic movements (both muscle homologous and direction homologous), isometric pinch, and hand tapping . The patient was tested before treatment and at 2, 4, 6, 12, 18, and 24 weeks after treatment . In addition, range of motion (ROM), the Ashworth scale of spasticity, Functional Independence Measure, and the mobility and activities of daily living (ADL) sections of the Pediatric Evaluation of the Disability Inventory were performed . RESULTS: Forward reach demonstrated little change initially despite patient reports of "feeling looser." Improvement was noted after 18 weeks, but returned to baseline level at 24 weeks . Bilateral rhythmic movements also showed slight improvement at 18 weeks . Pinch force increased significantly after 2 weeks, but declined again at 6 weeks . Improvements occurred in ROM and the Ashworth rating of spasticity, but were not temporally associated with each other or with MCT results . Functional assessment data did not change during the study period . CONCLUSIONS: Improvements in more complex motor tasks were noted after significant delay from the time of treatment, while simpler tasks demonstrated a more rapid improvement, followed by a rapid return to baseline levels . This case suggests that MCT techniques can provide quantitative and qualitative data, which can add new information about upper extremity motor disability and the outcome of treatment. Schweiz Med Wochenschr, 2000 Sep 9, 130(36), 1272 - 8 {Aging skin: physiological bases, preventive measures and therapeutic modalities}; Boni R et al.; The average lifespan has increased considerably in our society . Since the skin represents the most visible organ of ageing, there is increasing interest in the physiology and treatment of wrinkles, elastosis and senile xerosis . Cutaneous ageing is a complex phenomenon consisting of genetically determined intrinsic ageing and extrinsic ageing, the latter due to sun exposure, cigarette smoking and exposure to irritants . A number of biological changes can be found during the cutaneous ageing process, including decrease of epidermal, dermal and subcutaneous cellular components and changes in the immune system . Treatment modalities include the use of emollients in the treatment of senile xerosis, and topical retinoic and glycolic acid preparations, chemical peels, botulinum, collagen and hyaluronic acid injections, dermabrasion, CO2, and Nd:Yag laser resurfacing in the treatment of wrinkles. Eye, 2000 Jun, 14 ( Pt 3A), 347 - 52 Riolan's muscle: action and indications for botulinum toxin injection; Mackie IA; PURPOSE: To study the effect of injecting botulinum toxin into the region of Riolan's muscle in three conditions, namely the typical form of essential blepharospasm, the palpebral form of essential blepharospasm and hemifacial spasm . METHOD: Six patients with the typical form of essential blepharospasm and 4 patients with the palpebral form of essential blepharospasm, all of whom had previously been treated with conventional bilateral periorbital injections, were treated with injections of the toxin into the region of Riolan's muscle at the medial and lateral extremities of the upper lids . Thirty patients with hemifacial spasm, all of whom had previously been treated with conventional periorbital injections, were treated with injections of the toxin into the region of Riolan's muscle at the medial and lateral extremities of the upper lid on the affected side . RESULTS: Five of 6 patients with typical essential blepharospasm preferred the Riolan's injections and one had no preference . All of the four patients with the palpebral form of essential blepharospasm preferred the Riolan's injections . They, previously, had hardly been able to open their eyes . Twenty-six of the patients with hemifacial spasm preferred the Riolan's injections; the other 4 decided to continue with periorbital injections . The amount of toxin used in this new method of treatment is considerably less than that used in conventional methods for these diseases . CONCLUSION: Riolan's injections of botulinum toxin are the preferred modality of treatment for all types of blepharospasm and cost considerably less. Eur Urol, 2000 Oct, 38(4), 393 - 9 Perisphincteric injection of botulinum toxin type A . A treatment option for patients with chronic prostatic pain? Zermann D, Ishigooka M, Schubert J, Schmidt RA. BACKGROUND: Chronic prostatic pain is still a diagnostic and therapeutic problem . The clinical observation that prostatic and pelvic pain is accompanied by motoric and sensoric disorders of the pelvic floor muscles led to the hypothesis that prostatic pain roots in a changed processing of afferent and efferent information with the central nervous system (CNS) . METHODS: Neuro-urological work-up of 11 male patients with chronic prostatic pain was completed . This included a clinical evaluation of pelvic floor function, urodynamic investigation of bladder and urethra function and a cystoscopy to exclude morphological aberrations . A transurethral perisphincteric injection of 200 units botulinum toxin type A (BTX) was followed by a 2- to 4-week visit to evaluate their influence on the neuro-urological symptomatology . RESULTS: All chronic prostatic pain patients suffered from a pathological pelvic floor tenderness, an inability of sufficient conscious pelvic floor control, a urethral hypersensitivity/hyperalgesia and a urethral muscle hyperactivity . Basic parameters of bladder function (capacity, sensitivity, compliance) were normal . The BTX injection was followed by a pelvic floor muscle weakening and a relief of prostatic pain and urethral hypersensitivity/hyperalgesia . A botulinum-related decrease of the functional urethral length, the urethral sphincter closure pressure, the postvoid residual volume and an increase of the peak and average uroflow were objectivated . CONCLUSION: A weakening of the urethral sphincter muscle via blocking acetylcholine release by BTX injection is followed by pain relief and symptom improvement . It can therefore be concluded that a barrage of nociceptive information from the dysfunctional pelvic floor overflood the CNS and induce a changed CNS processing . Interrupting the efferent branch of the disturbed central circle is one opportunity to treat chronic prostatic pain. Stroke, 2000 Oct, 31(10), 2402 - 6 A randomized, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo in upper limb spasticity after stroke; Bakheit AM et al.; BACKGROUND AND PURPOSE: We sought to define an effective and safe dose of botulinum toxin type A (Dysport) for the treatment of upper limb muscle spasticity due to stroke . METHODS: This was a prospective, randomized, double-blind, placebo-controlled, dose-ranging study . Patients received either a placebo or 1 of 3 doses of Dysport (500, 1000, 1500 U) into 5 muscles of the affected arm . Efficacy was assessed periodically by the Modified Ashworth Scale and a battery of functional outcome measures . RESULTS: Eighty-three patients were recruited, and 82 completed the study . The 4 study groups were comparable at baseline with respect to their demographic characteristics and severity of spasticity . All doses of Dysport studied showed a significant reduction from baseline of muscle tone compared with placebo . However, the effect on functional disability was not statistically significant and was best at a dose of 1000 U . There were no statistically significant differences between the groups in the incidence of adverse events . CONCLUSIONS: The present study suggests that treatment with Dysport reduces muscle tone in patients with poststroke upper limb spasticity . Treatment was effective at doses of Dysport of 500, 1000, and 1500 U . The optimal dose for treatment of patients with residual voluntary movements in the upper limb appears to be 1000 U . Dysport is safe in the doses used in this study. J Voice, 2000 Sep, 14(3), 410 - 21 The treatment of essential voice tremor with botulinum toxin A: a longitudinal case report; Warrick P et al.; The purpose of this study was to evaluate the effects of bilateral botulinum toxin injection into the thyroarytenoid (TA) muscles of a patient with essential voice tremor . Acoustic and aerodynamic data were collected weekly over a 16-week period . Flexible nasolaryngoscopy was performed prior to injection and 2, 6, 10, and 16 weeks postinjection . Perceptual analyses of the acoustic and nasolaryngoscopic data were performed . A reduction in frequency tremor and, to a lesser extent, amplitude tremor was observed during the 1-10 week period . Estimated laryngeal resistance decreased after injection and was accompanied in perceptual measures by a reduction in vocal effort, laryngeal tremor, and supraglottic hyperfunction . Essential voice tremor can be successfully attenuated with bilateral percutaneous injection of botulinum toxin A into the vocalis muscle. Cell Calcium, 2000 Sep, 28(3), 161 - 9 Evidence for a vesicle-mediated maintenance of store-operated calcium channels in a human embryonic kidney cell line; Alderton JM et al.; Direct microinjection of the clostridial neurotoxins botulinum neurotoxin A light chain or tetanus neurotoxin into cells of a human embryonic kidney cell line significantly reduced calcium entry after depletion of internal calcium stores by cyclopiazonic acid, a reversible inhibitor of the sarcoplasmic-endoplasmic reticular calcium-ATPases . Botulinum neurotoxin A light chain specifically hydrolyzes a synaptosomal-associated protein of 25 kilodaltons (SNAP-25), and tetanus neurotoxin specifically hydrolyzes synaptobrevin-2 (vesicle-associated membrane protein 2, VAMP-2) and cellubrevin (vesicle-associated membrane protein 3, VAMP-3) . Since these substrate proteins are required for vesicle docking and fusion, inhibition of store-operated calcium entry by botulinum neurotoxin A light chain and tetanus neurotoxin supports a model in which vesicle fusion is a prerequisite for activation of store-operated calcium entry . Brefeldin A, a fungal metabolite that interferes with vesicle traffic, partially reduced calcium entry following store depletion . The size of the reserve pool of vesicles or parallel vesicle recycling pathways employing brefeldin A-sensitive and brefeldin A-insensitive ADP-ribosylation factors may explain the failure of brefeldin A to completely inhibit store-operated calcium entry. Clin Neuropharmacol, 2000 Jul-Aug, 23(4), 226 - 8 Polyradiculoneuritis after botulinum toxin therapy for cervical dystonia; Burguera JA et al.; A 40-year-old man with cervical dystonia developed an acute inflammatory demyelinating polyradiculoneuritis after botulinum toxin type A treatment . Some cases of idiopathic brachial plexopathy and polyradiculoneuritis have been reported to date . Although a causal relationship is not firmly established, the clinical temporal profile suggests a pathogenic relationship . In patients with cervical dystonia, further use of type A botulinum toxin should be considered contraindicated, and the use of another type of botulinum toxin should be taken into consideration. Clin Neuropharmacol, 2000 Jul-Aug, 23(4), 203 - 7 A pharmacoeconomic evaluation of botulinum toxin in the treatment of spasmodic torticollis; Brefel-Courbon C et al.; We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life . Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA . All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient) . We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile {NHP}), and adverse reactions . Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo) . During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo) . Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment . Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis. FEBS Lett, 2000 Sep 29, 482(1-2), 119 - 24 Structure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site; Ginalski K et al.; Clostridial neurotoxins embrace a family of extremely potent toxins comprised of tetanus toxin (TeNT) and seven different serotypes of botulinum toxin (BoNT/A-G) . The beta-trefoil subdomain of the C-terminal part of the heavy chain (H(C)), responsible for ganglioside binding, is the most divergent region in clostridial neurotoxins with sequence identity as low as 15% . We re-examined the alignment between family sequences within this subdomain, since in this region all alignments published to date show obvious inconsistencies with the beta-trefoil fold . The final alignment was obtained by considering the general constraints imposed by this fold, and homology modeling studies based on the TeNT structure . Recently solved structures of BoNT/A confirm the validity of this structure-based approach . Taking into account biochemical data and crystal structures of TeNT and BoNT/A, we also re-examined the location of the putative ganglioside binding site and, using the new alignment, characterized this site in other BoNT serotypes. Int J Food Microbiol, 2000 Sep 25, 60(2-3), 117 - 35 Research on factors allowing a risk assessment of spore-forming pathogenic bacteria in cooked chilled foods containing vegetables: a FAIR collaborative project; Carlin F et al.; Vegetables are frequent ingredients of cooked chilled foods and are frequently contaminated with spore-forming bacteria (SFB) . Therefore, risk assessment studies have been carried out, including the following: hazard identification and characterisation--from an extensive literature review and expertise of the participants, B . cereus and C . botulinum were identified as the main hazards; exposure assessment--consisting of determination of the prevalence of hazardous SFB in cooked chilled foods containing vegetables and in unprocessed vegetables, and identification of SFB representative of the bacterial community in cooked chilled foods containing vegetables, determination of heat-resistance parameters and factors affecting heat resistance of SFB, determination of the growth kinetics of SFB in vegetable substrate and of the influence of controlling factors, validation of previous work in complex food systems and by challenge testing and information about process and storage conditions of cooked chilled foods containing vegetables . The paper illustrates some original results obtained in the course of the project . The results and information collected from scientific literature or from the expertise of the participants are integrated into the microbial risk assessment, using both a Bayesian belief network approach and a process risk model approach, previously applied to other foodborne hazards. Br J Oral Maxillofac Surg, 2000 Oct, 38(5), 466 - 71 Botulinum toxin: new treatment for temporomandibular disorders; Freund B et al.; BACKGROUND: Temporomandibular disorders (TMDs) affect the face and jaws, and cause chronic pain and dysfunction in many people . As in other conditions involving the musculoskeletal system, controlling the myogenous component is an integral part of treatment . In this study, we evaluated subjective and objective responses to treatment with botulinum toxin A (BTX-A) in a group of 46 patients with TMDs . METHODS: 46 subjects with TMD were enrolled in this uncontrolled study and treated with BTX-A 150U . Both masseter muscles were injected with 50 U each and both temporalis muscles with 25 U each under electromyographic guidance . Subjects were assessed at two-week intervals for eight weeks . Outcome measures included subjective assessment of pain by visual analogue scale (VAS), measurement of mean maximum voluntary contraction (MVC), interincisal oral opening, tenderness to palpation, and a functional index based on multiple VAS . Medians of the data were taken for each outcome measure at each time point and subjected to Duncan's multiple range test . RESULTS: There were significant (P<0.05) differences in all median outcome measures between the pre-treatment assessment and the four follow-up assessments except for MVC . Although MVC was significantly reduced midway through the study, it had returned to pretreatment values by the final two assessments . All other outcome measures remained significantly different from the pretreatment findings . Paired correlation of variables including age, sex, diagnosis, depression index, and time of onset showed no significant differences . CONCLUSIONS: BTX-A injections produced significant improvements in pain, function, mouth opening, and tenderness to palpation . MVC initially diminished then returned to the initial values . Although the study was uncontrolled, the results strongly suggest that BTX-A reduces severity of symptoms and improves functional abilities for patients with TMD and that these extend beyond its muscle-relaxing effects . Mov Disord, 2000 Sep, 15(5), 973 - 6 Botulinum toxin antibody testing: comparison between the mouse protection assay and the mouse lethality assay; Dressler D et al.; Conventionally, the standard test for detection of antibodies against botulinum toxin (BT-A) has been the mouse lethality assay (MLA) . Because this test has a number of disadvantages, a novel mouse protection assay (MPA) was recently introduced . We sought to compare the results of both tests . Forty-three samples from 38 patients with cervical dystonia and complete or partial subjective BT-A therapy failure underwent simultaneous MPA and MLA testing . Twenty-seven samples showed concordant results in both tests . Eleven of them were MPA- and MLA-positive and 16 MPA- and MLA-negative, resulting in a significant association of the dichotomous test results (Fisher exact test, p <0.01) . Sixteen samples showed discordant results . All of those were MPA-positive and MLA-negative . This excess of MPA-positive results was also significant (Wilcoxon signed-rank test, p <0.001) . Of the patients with MPA-positive samples, 62% had complete and 38% had partial therapy failure . Of the patients with MLA-positive samples, 90% had complete and 10% had partial therapy failure . MPA and MLA results show significant association . Statistical analysis and predominance of partial therapy failure in MPA-positive patients demonstrate higher sensitivity of MPA . With its methodologic advantages, its test parameter being more relevant to BT-A therapy, and its higher sensitivity, the MPA appears to be superior to the MLA. Am J Gastroenterol, 2000 Sep, 95(9), 2185 - 8 Expandable metal stents in achalasia--is there a role? Mukherjee S, Kaplan DS, Parasher G, Sipple MS. OBJECTIVE: Achalasia is treated with pneumatic dilation or myotomy, and botulinum toxin injections are occasionally used . We review our community's experience with expandable metal stents in six patients who failed medical treatment or were poor surgical candidates . METHODS: Eight stents were placed in six patients between July 1995 and November 1997 . Four patients had achalasia and two pseudoachalasia . Four patients underwent successive botulinum toxin injections . One patient only agreed to periodic Maloney dilatations or a stent . Pneumatic dilation was performed in one patient and considered high risk in the rest . All were poor surgical candidates . Three different stents were used: Gianturco Rosch Z stent, Wallstent I, and Wallstent II . RESULTS: One-month mortality and morbidity were 33% and 50%, respectively . Two patients were asymptomatic on a liquid diet for > or =6 months but required repeat endoscopy for recurrent dysphagia because of food bolus impaction and proximal stent migration in each . CONCLUSIONS: Expandable metal stents in achalasia or pseudoachalasia do not provide sustained symptom relief, and their use is associated with unacceptably high morbidity and mortality . We do not recommend the use of these devices in patients who have failed medical therapy or who are poor surgical candidates. Ann Otol Rhinol Laryngol, 2000 Sep, 109(9), 819 - 22 Outcomes assessment following treatment of spasmodic dysphonia with botulinum toxin; Courey MS et al.; Spasmodic dysphonia (SD), a disabling focal dystonia involving the laryngeal musculature, is most commonly treated by the intramuscular injection of botulinum toxin (BTX) . Although the treatment is well tolerated and generally produces clinical voice improvement, it has never been statistically shown to alter the patient's perception of voice quality or general health . Declining resources for medical care mandate that treatment outcomes be documented . A prospective analysis of the effects of BTX on the patient's perception of voice and general health was undertaken . The Voice Handicap Index (VHI) and Short Form 36 (SF-36) surveys were administered to patients before treatment and 1 month after . Pretreatment and posttreatment scores were analyzed with a Student's t-test . On the VHI, improvements in the patients' perception of their functional, physical, and emotional voice handicap reached statistical significance (p < or = .0005) . On the SF-36, patients had statistically significant improvements in mental health (p < or = .03) and social functioning (p < or = .04) . Treatment of SD with BTX significantly lessened the patients' perception of dysphonia . In addition, it improved their social functioning and their perception of their mental health . These outcome measures justify the continued treatment of SD with BTX. Pharmacotherapy, 2000 Sep, 20(9), 1079 - 91 Pharmacotherapy with botulinum toxin: harnessing nature's most potent neurotoxin; Bell MS et al.; Botulinum toxin (BTX), a potent biologic neurotoxin, commonly is associated with lethal outbreaks of food poisoning; however, it also plays a role as a therapeutic agent . Since the 1970s physicians have investigated BTX therapy in patients with neurologic disorders . The number of applications greatly expanded over the years to include certain focal dystonias (blepharospasm, torticollis, laryngeal dystonias, writer's cramp), strabismus, and a wide variety of other indications (gastrointestinal disorders, cosmetic wrinkle correction, spasticity, hyperhidrosis) . BTX's safety and efficacy are reviewed. J Assoc Physicians India, 1999 Mar, 47(3), 267 - 70 Botulinum toxin A--injection for cervical dystonia; Bhaumik S et al.; Spasmodic torticollis or cervical dystonia is the commonest focal dystonia . Botulinum toxin-A (BTX-A) was first used in its treatment in 1985 . We are reporting our experience of treating 17 patients of cervical dystonia with 29 treatment sessions of BTX-A . The patients consisted of 13 men and four women with a mean age of 44.17 +/- 16.25 years who had tried medical therapy earlier . All patients had a combination of two or more abnormal postures of neck . Both Botox and Dysport were used as per availability . The mean dose of BTX-A in splenius capitus was 283.3 +/- 59.86 U of Dysport and 61.3 +/- 5.16 U of Botox and in sternocleidomastoid it was 210 +/- 53.47 U of Dysport and 46 +/- 18.97 U for Botox . After BTX-A injection, the response was observed after a mean of 9.7 +/- 5.7 days and the mean duration of effect was 15.56 +/- 7.13 weeks . Significant improvement of dystonia (global rating > or = 2) was seen after 25 of 29 treatment sessions (86%) and of pain was seen after four of five patients . Only three treatment sessions were followed by complications (10.4%) of these two had mild dysphagia and one had mild "flu-like" syndrome . We conclude BTX-A is safe and effective treatment of cervical dystonia. Curr Rev Pain, 2000, 4(1), 31 - 5 A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of tension-type headache; Porta M; Tension-type headache (TH) is a common condition, the pathophysiology of which remains undetermined . Evidence implicates sustained contraction of pericranial muscles to be a major cause . A recent preliminary study demonstrated the effectiveness of botulinum toxin type A (BTX-A) in patients suffering from chronic TH . To further investigate this, we performed a study to compare the efficacy of BTX-A with the steroid methylprednisolone (both administered with the local anesthetic lidocaine), when administered by injection into the tender points of cranial muscles in patients with TH . A significant decrease in the median pain score (assessed using a standard visual analogue scale ) was observed at 60 days post injection of BTX-A compared with the pain score achieved following steroid therapy . All patients treated with BTX-A experienced a gradual decrease in median pain severity scores at 30 days and 60 days post treatment . The beneficial effects of BTX-A therapy continued to improve 60 days following injection, whereas the effects of steroid therapy at this time point began to decline . This study clearly demonstrates the effectiveness of BTX-A for the treatment of TH. Curr Rev Pain, 1999, 3(6), 427 - 431 Mechanism of Botulinum Toxin in the Relief of Chronic Pain; Guyer BM; For many years, the use of botulinum toxin in the management of dystonia and associated conditions, has been recognized as not only having a beneficial effect on muscle tone and activity, but also to be associated with significant and prolonged pain relief . It is difficult to understand how this effect could be mediated solely on the basis of the toxin's well-known property of chemodenervation of motor end plates . A second mode of action is demonstrated, in which effects on the muscle spindle play a prominent role, and which may enhance analgesia . A hypothesis is presented that a toxin degradation product may provide pain relief by mechanisms yet to be elucidated. J Neurol Neurosurg Psychiatry, 2000 Oct, 69(4), 499 - 506 Evaluating the role of botulinum toxin in the management of focal hypertonia in adults; Richardson D et al.; OBJECTIVES: To investigate the effects of EMG guided botulinum toxin (BTX-A) on impairment and focal disability in adults presenting with focal hypertonia . METHODS: A prospective, randomised, double blind, placebo controlled, parallel group trial was carried out with standardised assessment before and at 3 week intervals until 12 weeks after injection, in patients with focal hypertonia affecting upper or lower limbs . Botulinum toxin or placebo was injected with EMG guidance after multidisciplinary assessment . The modified Ashworth scale of spasticity, percentage passive range of joint motion, subjective rating of problem severity, the Rivermead motor assessment scale, a timed 10 metre walk (lower limb patients), nine hole peg test (upper limb patients), and a modified goal attainment scale were used as outcome measures . The patients were 52 adults; 34 male, 18 female; mean age 40.31, range 16-79 years; mean duration of symptoms 35 months (range 3 months to 22 years) . Diagnoses included cerebrovascular accidents (23), head injury (12), incomplete spinal cord injury (six), tumour (five), cerebral palsy (three), and anoxic episodes (three) . RESULTS: For each variable an overall score for the treatment period was computed by summing the scores from the 3, 6, 9, and 12 week assessments . These overall scores were significantly better in the treated group for the Ashworth scale, percentage passive range of movement, Rivermead lower limb, and subjective rating of problem severity . The significant treatment effect on the Ashworth scale was seen on analysis of variance (ANOVA) at 3 weeks and the subjective rating of problem severity at 3 and 6 weeks . The goal attainment scale score in both groups was similar at 12 weeks . CONCLUSION: Selective use of botulinum toxin to weaken muscles can lead to a reduction in resistance to passive movement about a distal limb joint . This allows for improvements in passive range of movement and focal disability, particularly in patients presenting with focal spasticity of the lower limb. Chest, 2000 Sep, 118(3), 874 - 7 Use of botulinum toxin type A to avoid tracheal intubation or tracheostomy in severe paradoxical vocal cord movement; Maillard I et al.; Paradoxical vocal cord movement (PVCM) is characterized by paradoxical adduction of the vocal cords during inspiration and/or expiration . Patients with severe forms of PVCM can present with acute dyspnea . In this article, we describe a patient with severe PVCM who had required tracheal intubation or tracheostomy at multiple occasions and who presented with acute hypercapnic respiratory failure . Using sedation and intralaryngeal injection of botulinum toxin type A, we could avoid more invasive intervention . Our observation shows that botulinum toxin type A should be considered in the acute care setting for severe PVCM. Curr Gastroenterol Rep, 1999 Jun, 1(3), 198 - 202 Pathophysiology of achalasia; Hirano I; Achalasia is a rare but important condition affecting the myenteric neurons of the esophagus . A number of studies have provided evidence for the preservation of cholinergic innervation to the esophagus in achalasia . This forms the rationale for the treatment of achalasia with botulinum toxin . Identification of nitric oxide as the primary inhibitory neurotransmitter of the g