Expert Opin Pharmacother, 2004 Jul, 5(7), 1517 - 22 Pharmacotherapy of pompholyx; Wollina U et al.; Pompholyx is an inflammatory vesicobullous disorder of the palms and soles . The condition is difficult to treat because of the peculiarities of the affected skin, namely, the thick horny layer and richness of sweat glands . The cornerstones of topical therapy are corticosteroids, although calcineurin inhibitors seem to be effective as well . Topical photochemotherapy with 8-methoxypsoralen is as effective as systemic photochemotherapy or high-dose ultra violet Type A-1 irradiation . Systemic therapy is often necessary in bullous pompholyx . Corticosteroids are used commonly, although no controlled studies have been published . For recalcitrant cases corticosteroids are combined with immunosuppressants . A new evolving treatment seems to be the intradermal injection of botulinum toxin. Headache, 2004 Jul-Aug, 44(7), 636 - 41 Off-label prescribing of drugs in specialty headache practice; Loder EW et al.; OBJECTIVE: To assess the extent of off-label prescribing in specialty headache practice . METHODS: A prospective record was kept of all prescriptions written during a 30-day period in a tertiary care headache program affiliated with two teaching hospitals . Each drug was categorized as "on-label," defined as approved by the FDA for a headache or general pain indication, and used in accordance with label instructions, or "off-label," defined as any use of a drug not covered in the FDA-approved package insert . RESULTS: A total of 379 prescriptions were written during a 30-day period . One hundred and seventy-eight prescriptions (47%) met the criteria for off-label use . In all, 23 categories of off-label treatment were prescribed during the study, but just 4 accounted for over half of all off-label prescriptions: newer antiepileptic drugs such as topiramate and lamotrigine (each accounted for n = 26, 15% of off-label prescriptions), newer antidepressants, especially venlafaxine (n = 27; 15% of off-label prescriptions), and botulinum toxin type A (n = 13; 7% of off-label prescriptions) . Two hundred and one prescriptions met criteria for on-label use . The largest percentages of prescriptions written for approved, on-label indications were for triptans (n = 74; 37% of on-label prescriptions), and nonsteroidal anti-inflammatory drugs (n = 64; 32% of on-label prescriptions) . CONCLUSIONS: Off-label prescribing is common in the specialty management of headache conditions . We conclude that it is within the current standard of care, and an integral part of practice, to use off-label medications in the treatment of complex headache conditions. Dermatol Clin, 2004 Jul, 22(3), 257 - 62, v Other biologic toxin bioweapons: ricin, staphylococcal enterotoxin B, and trichothecene mycotoxins; Henghold WB 2nd; The ideal biologic warfare agent is lethal, easy, and inexpensive to produce in large quantities, stable in aerosol for/with the ability to be dispersed over wide areas, has no effective treatment or vaccine, and is communicable from person to person . With the exception of the last characteristic, the biologic toxins (ricin, staphylococcal enterotoxin B, T-2 mycotoxin, and botulinum) possess all the properties mentioned . This article will discuss the first three biologic toxins, with an emphasis on particular points of interest to the dermatologist . Botulinum toxin will be covered in another article. Disabil Rehabil, 2004 Jun 17, 26(12), 756 - 60 Does spasticity result from hyperactive stretch reflexes? Preliminary findings from a stretch reflex characterization study; Salazar-Torres Jde J et al.; PURPOSE: To characterize the stretch reflex response of the biceps brachii in stroke patients with elbow spasticity (prior to or within 15 min of treatment with botulinum toxin) and non-impaired volunteers with the aim of quantifying the stretch reflex excitability and observe the differences between the groups . METHODS: A cross-sectional study . Stretch reflexes from the biceps brachii were elicited following a controlled elbow extension . The amplitude, latency, rise time and duration, calculated from surface EMG recordings from the biceps brachii, were used to characterize the stretch reflex response . RESULTS: Seventeen non-impaired and 14 stroke patients participated . The amplitude was significantly lower in stroke patients than in non-impaired volunteers (p<0.05) . The latency was significantly shorter in stroke patients than in non-impaired volunteers (p<0.05) . There were no significant differences in rise time or duration (p>0.10) . DISCUSSION: Reduction in the amplitude in stroke patients was unexpected suggesting the stretch reflex is not necessarily hyper-excitable in people with clinically diagnosed spasticity . Latency differences suggest decreased presynaptic inhibition and/or increased motor neurone excitability can occur following a stroke . However, carry over effects from previous botulinum toxin treatment may have confounded amplitude measurements . Further work evaluating the excitability of the stretch reflex independent of Botulinum toxin and its contribution to resistance to passive stretching is being conducted. Disabil Rehabil, 2004 Mar 18, 26(6), 335 - 45 Non-surgical management of ankle contracture following acquired brain injury; Singer BJ et al.; BACKGROUND AND PURPOSE: The purpose of this study was to document the outcome of non-surgical management of equinovarus ankle contracture in a cohort of patients with acquired brain injury admitted to a specialist Neurosurgical Rehabilitation Unit . METHODS: This prospective descriptive study examined all patients with a new diagnosis of moderate to severe acquired brain injury (Glasgow Coma Scale score </=12) admitted for rehabilitation over a 1 year period . Ankle dorsiflexion range and plantarflexor/invertor muscle activity were evaluated weekly during the period of hospitalization . Contracture was defined as maximal passive range of motion </= 0 degrees dorsiflexion, with the knee extended, on a minimum of two measurement occasions . Patients were retrospectively allocated to one of four treatment outcome categories according to ankle dorsiflexion range, type of intervention required and response to treatment . RESULTS: Ankle contracture was identified in 40 of the 105 patients studied . Contracture resolved with a standard physiotherapy treatment programme, including prolonged weight-bearing stretches and motor re-education, in 23 patients . Contracture persisted or worsened in 17 of 40 cases, all of whom exhibited dystonic muscle overactivity producing sustained equinovarus posturing . Ten of 17 cases required serial plaster casting (+/- injection of botulinum toxin type A) in order to achieve a functional range of ankle motion . Remediation of ankle contracture was not considered a priority in the remaining seven patients due to the severity of their overall disability . CONCLUSION: The incidence of ankle contracture identified in this population was considerably less than previously reported . Reduced dorsiflexion range was remediated with standard physiotherapy treatment in over half of the cases . Additional treatment with serial casting +/- botulinum toxin type-A injection was required to correct persistent or worsening contracture in one quarter of cases . Dystonic extensor muscle overactivity was a major contributor to persistent or progressive ankle contracture. Int J Neurosci, 2004 Jun, 114(6), 633 - 53 Spinal cord injury: reversing the incorrect cortical maps by inductive lability procedure; Krishnan RV; Within the brain-stem and on the cerebral cortex there are locomotor control centers arranged in a ladder-form control system . These centers are somatotopic, self-organizing neural network maps capable of simultaneously learning and task execution . In spinal cord injury (SCI) these self-organized maps get erroneously re-organized and maladaptively stabilized . The extent and quality of sensory-motor recovery, if any appears, is affected by and compromised due to incorrect mapping processes . The treatment method based on inductive lability procedure (Krishnan, 2003a, 2003b, 2003c) uses botulinum toxin for the purpose . It recreates competition among synapses in a locomotor training-based corrective re-self-organization of the maps in various steps of the ladder. Am Fam Physician, 2004 Jun 1, 69(11), 2628 - 34 Sialorrhea: a management challenge; Hockstein NG et al.; Sialorrhea (drooling or excessive salivation) is a common problem in neurologically impaired children (i.e., those with mental retardation or cerebral palsy) and in adults who have Parkinson's disease or have had a stroke . It is most commonly caused by poor oral and facial muscle control . Contributing factors may include hypersecretion of saliva, dental malocclusion, postural problems, and an inability to recognize salivary spill . Sialorrhea causes a range of physical and psychosocial complications, including perioral chapping, dehydration, odor, and social stigmatization, that can be devastating for patients and their families . Treatment of sialorrhea is best managed by a clinical team that includes primary health care providers, speech pathologists, occupational therapists, dentists, orthodontists, neurologists, and otolaryngologists . Treatment options range from conservative (i.e., observation, postural changes, biofeedback) to more aggressive measures such as medication, radiation, and surgical therapy . Anticholinergic medications, such as glycopyrrolate and scopolamine, are effective in reducing drooling, but their use may be limited by side effects . The injection of botulinum toxin type A into the parotid and submandibular glands is safe and effective in controlling drooling, but the effects fade in several months, and repeat injections are necessary . Surgical intervention, including salivary gland excision, salivary duct ligation, and duct rerouting, provides the most effective and permanent treatment of significant sialorrhea and can greatly improve the quality of life of patients and their families or caregivers. Scand J Plast Reconstr Surg Hand Surg, 2004, 38(2), 100 - 5 Advancement of the frontalis muscle for ptosis of the brow associated with essential blepharospasm; Nemoto Y et al.; We evaluated our results of advancement of the frontalis muscle to correct brow ptosis associated with blepharospasm in five patients who had difficulty opening their eyelids as a result of ptosis even after injections of botulinum toxin . The frontalis muscle was retracted inferiorly and connected directly to the skin of the eyebrow . Postoperatively the level of the eyebrow was raised above the superior orbital rim in all cases during the observation period (4 to 15 months) . Although the operation did not improve muscle spasms, it successfully shortened the duration of involuntary closure of the eyelid . The only postoperative complication was lymphoedema of the eyelids . Results of postoperative injection of botulinum toxin were satisfactory . Advancement of the frontalis muscle corrects brow ptosis without major complications, and is complementary to injection of botulinum toxin. J Urol, 2004 Jul, 172(1), 240 - 3 Intravesical resiniferatoxin versus botulinum-A toxin injections for neurogenic detrusor overactivity: a prospective randomized study; Giannantoni A et al.; PURPOSE: We investigated the effectiveness and safety of intravesical resiniferatoxin (Sigma Chemical Co., St . Louis, Missouri) and botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients with neurogenic detrusor overactivity unresponsive to conventional anticholinergic therapy . MATERIALS AND METHODS: A total of 25 patients were randomly assigned to receive intravesically 0.6 microM resiniferatoxin in 50 ml of 0.9% NaCl or injections into the detrusor muscle of 300 units botulinum A-toxin diluted in 30 ml 0.9% NaCl . Clinical evaluation and urodynamics were performed at baseline, and at 6, 12 and 18 months after treatment . RESULTS: In both arms there was a significant decrease in catheterization and incontinent episodes, and a significant increase in first detrusor contraction and maximum bladder capacity at 6, 12 and 18-month followup . There were no local side effects with either treatment . Botulinum-A toxin induced a significant decrease in the frequency of daily incontinence episodes (p <0.05), a significant increase in first uninhibited detrusor contraction (p <0.01) in maximum bladder capacity (p <0.01), and a significant decrease in maximum pressure of uninhibited detrusor contractions (p <0.01) compared to resiniferatoxin at 6, 12 and 18-month followup . CONCLUSIONS: In spinal cord injured patients with refractory neurogenic detrusor overactivity, intravesical resiniferatoxin and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with decreases in detrusor overactivity and restoration of urinary continence in a large proportion of patients . Botulinum-A toxin injections provided superior clinical and urodynamic benefits compared to those of intravesical resiniferatoxin. J Neurol Neurosurg Psychiatry, 2004 Jul, 75(7), 951 - 7 Botulinum toxin in clinical practice; Jankovic J; Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications . This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data . Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction . When injected not more often than every three months, the risk of blocking antibodies is slight . Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications. Rinsho Shinkeigaku, 2004 Jan, 44(1), 20 - 4 {A case report of acute polyradiculoneuritis developing after multiple injections of botulinum toxin for cervical dystonia}; Onoue H et al.; A 68-year-old man receiving four times of injection of botulinum toxin type A for cervical dystonia developed acute polyradiculoneuritis 10 weeks after the final injection . He had been complaining of paresthesia in four limbs after the second injection of the treatment . On neurological examination, bilateral facial palsy, bulbar palsy, difficulty of breath, flaccid paralysis of all limbs, sensory disturbance of all modality and areflexia in all limbs, and positive Laseque sign were noted . Albuminocytological dissociation was present in the CSF and the conduction velocity was significantly impaired in all peripheral nerves examined . After receiving two times of intravenous highdose IgG and two times of pulse therapy, his neurological deficits gradually improved . To our knowledge, this is the third case report of acute polyradiculoneuropathy developing after botulinum toxin therapy, suggesting that botulinum toxin therapy is involved in the pathogenesis in our case. J Neurochem, 2004 Jul, 90(1), 1 - 8 The synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis; Reisinger C et al.; Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles . In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion . Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to synaptophysin or when existing as a homodimer . The synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25 . Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins . The stimulation-induced dissociation of the synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium . However, the synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium . The dissociation of synaptobrevin from synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event . This finding further supports the modulatory role the synaptophysin/synaptobrevin complex may play in mature neurones. Mov Disord, 2004 Jun, 19(6), 663 - 6 A novel movement disorder of the lower lip; Kleopa KA et al.; Four patients, aged 25 to 42 years presented with acute onset of a movement disorder characterized by a tonic, sustained, lateral and outward protrusion of one half of the lower lip . The movement disorder was present at rest, while in some patients, it was also present during speech . In all cases, the abnormal lip posture could be suppressed voluntarily . Neurological examination was otherwise normal . Extensive laboratory investigation failed to reveal any causative factors for secondary focal dystonia . Treatment with oral medications and botulinum toxin was mostly ineffective . Spontaneous remissions were frequent . Zhonghua Er Bi Yan Hou Ke Za Zhi, 2004 Feb, 39(2), 97 - 101 {Experimental studies for botulinum toxin type A on allergic rhinitis in the rat}; Wen WD et al.; OBJECTIVE: To study the effect of botulinum toxin-A on inhibiting rhinorrhea, on expression of VIP at nasal mucosa, on morphometrical change with an immunohistochemical and histological methods in rats allergic rhinitis . METHODS: Ovalbumin sensitized the rat as animal model of allergic rhinitis . Animals were divided into control group (n = 8), allergic group (n = 12), allergic animal treated by BTX-A group (n = 6) . VIP immunoreactivity at nasal mucosa in the rat allergic rhinitis was studied by immunohistochemical . The morphometrical changes at nasal mucosa were observed by histological staining methods . RESULTS: The results showed that the symptoms of allergic rhinitis, nasal rhinorrhea and sneezing, were remarkably relieved after ovalbumin application in the rat . The nasal rhinorrhea symptom diminished after BTX-A treated . The quantity of nasal secretion were significantly reduced(P < 0.05) in allergic one treated by BTX-A group as compared with allergic group . Hematoxylin and eosin staining demonstrated that no edema, small vessels were found in the nasal mucosa and after BTX-A treatment, but edema, vasodilational and inflammational cell infiltration were observed in the allergic group . Immunohistochemical study revealed that VIP immunoreactive fibers in the nasal mucosa showed a marked decrease after BTX-A application, but the density and a large number of VIP fibers were significantly found in the allergic group . CONCLUSION: The results suggested that local BTX-A treatment was a selective and non-traumatic method to reduce a long lasting desensitization of the nasal mucosa, to alleviate nasal congestion, rhinorrhea and sneezing, and to reduce the sensory neuron sensitivity of the mucosa. Otolaryngol Head Neck Surg, 2004 Jun, 130(6), 770 - 9 Practice parameter: laryngeal electromyography (an evidence-based review); Sataloff RT et al.; This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders . The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders . The review yielded 584 articles of which 33 met the predefined inclusion criteria . The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial . A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the 2 techniques and no significant treatment benefit . Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia . There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them . There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications. Minerva Urol Nefrol, 2004 Mar, 56(1), 79 - 87 New therapeutic options for refractory neurogenic detrusor overactivity; Giannantoni A et al.; AIM: Current pharmacologic treatment of detrusor overactivity relies on anticholinergic drugs . However, they often have untolerable side effects so that they are administered in doses insufficient to restore urinary continence . Recently, intravesical instillations and injections into the detrusor muscle of new pharmacological agents have been developed . The present study report our own experience in the treatment of detrusor overactivity with intravesical administrations of vanilloid agents and with botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients . In particular, we compared the clinical and urodynamic effects of the 2 drugs in an attempt to find a new and valid therapeutic option in those cases unresponsive to conventional treatment . METHODS: Seventy-five patients with spinal cord injury and refractory detrusor overactivity were included in the study: 35 patients received repeated intravesical instillations of resiniferatoxin (RTX) dissolved in normal saline; 40 patients received repeated injections of 300 units botulinum A-toxin diluted in 30 ml normal saline . Clinical assessment and urodynamics were performed at baseline and 6, 12 and 24 months after treatment . RESULTS: With both treatments there was a significant reduction in mean catheterization and episodes of incontinence and a significant increase in mean first involuntary detrusor contraction and in mean maximum bladder capacity at 6, 12 and 24 months after therapy . We did not detect any local side effects with either treatment . Botulinum-A toxin significantly reduced also the maximum pressure of uninhibited detrusor contractions more than RTX at all follow-up time points . CONCLUSION: In patients with spinal cord injury and refractory detrusor overactivity intravesical RTX and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with reduction of detrusor overactivity and restoration of urinary continence in most patients . Botulinum-A toxin injection provided better clinical and urodynamic benefits than intravesical RTX. J Voice, 2004 Jun, 18(2), 261 - 74 Practice parameter: laryngeal electromyography (an evidence-based review); Sataloff RT et al.; This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders, including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders . The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders . Thirty-three of the 584 articles met the predefined inclusion criteria . The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial . A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the two techniques and no significant treatment benefit . Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia . There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them . There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications. J Voice, 2004 Jun, 18(2), 254 - 5 Bilateral vocal fold paralysis: an unusual treatment with botulinum toxin; Andrade Filho PA et al.; We presented a patient with bilateral vocal fold paralysis treated with intralaryngeal Botox injection to improve the glottal airway . The use of Botox in this manner has not been previously reported and highlights the value and role of intralaryngeal Botox in changing the configuration of the glottis . The concept and various approaches for using Botox to alter pathologic vocal fold position is reviewed and discussed. Can J Gastroenterol, 2004 Jun, 18(6), 397 - 9 Injection of botulinum toxin A to the upper esophageal sphincter for oropharyngeal dysphagia in two patients with inclusion body myositis; Liu LW et al.; Inclusion body myositis (IBM) is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles . Dysphagia is reported in up to 86% of IBM patients . Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia . This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients. Electrophoresis, 2004 Jun, 25(10-11), 1705 - 13 Microfluidic tectonics platform: A colorimetric, disposable botulinum toxin enzyme-linked immunosorbent assay system; Moorthy J et al.; A fabrication platform for realizing integrated microfluidic devices is discussed . The platform allows for creating specific microsystems for multistep assays in an ad hoc manner as the components that perform the assay steps can be created at any location inside the device via in situ fabrication . The platform was utilized to create a prototype microsystem for detecting botulinum neurotoxin directly from whole blood . Process steps such as sample preparation by filtration, mixing and incubation with reagents was carried out on the device . Various microfluidic components such as channel network, valves and porous filter were fabricated from prepolymer mixture consisting of monomer, cross-linker and a photoinitiator . For detection of the toxoid, biotinylated antibodies were immobilized on streptavidin-functionalized agarose gel beads . The gel beads were introduced into the device and were used as readouts . Enzymatic reaction between alkaline phosphatase (on secondary antibody) and substrate produced an insoluble, colored precipitate that coated the beads thus making the readout visible to the naked eye . Clinically relevant amounts of the toxin can be detected from whole blood using the portable enzyme-linked immunosorbent assay (ELISA) system . Multiple layers can be realized for effective space utilization and creating a three-dimensional (3-D) chaotic mixer . In addition, external materials such as membranes can be incorporated into the device as components . Individual components that were necessary to perform these steps were characterized, and their mutual compatibility is also discussed. Urology, 2004 Jun, 63(6), 1071 - 5 Use of botulinum-A toxin for the treatment of refractory overactive bladder symptoms: an initial experience; Rapp DE et al.; OBJECTIVES: To define the role of botulinum toxin type A (botulinum-A) intradetrusor injections in the treatment of patients with symptoms of bladder overactivity in whom previous anticholinergic therapy has failed . METHODS: Thirty-five patients (29 women and 6 men) with frequency, urgency, and/or urge incontinence received 300 U of botulinum-A toxin injected transurethrally at 30 sites within the bladder . Patients were evaluated at 3 weeks and 6 months after treatment by completion of the short forms of the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory (UDI-6), as well as questions assessing global response to the treatment . RESULTS: After 3 weeks, the mean IIQ-7 score decreased from 19.4 to 13.9 (P = 0.0006) and the mean UDI-6 score decreased from 16.8 to 12.8 (P = 0.0003) . Overall, 21 (60%) of 35 patients reported slight to complete improvement of voiding symptoms after 3 weeks . Among the initial responders followed up for 6 months, the mean IIQ-7 score improved from 20.6 to 15.1 (P = 0.008) and the mean UDI-6 score improved from 16.9 to 13.5 (P = 0.008) . Mild hematuria, pelvic pain, and dysuria were seen in 7 patients, lasting for 3 days or less after the procedure . CONCLUSIONS: Botulinum-A toxin injections may provide improvement in symptoms associated with bladder overactivity in a subset of patients . Improvement may be seen for at least 6 months after treatment . The procedure was well tolerated with minimal side effects . Additional study to define the role of injections in a broad group of patients with irritative voiding symptoms is warranted. Wiad Lek, 2004, 57(1-2), 80 - 4 {Chronic anal fissure--conservative or surgical treatment?}; Sandelewski A et al.; Chronic anal fissure is one of the most common anus diseases . The main ailments reported by the sick are: stubborn pain connected with defecation and bleeding . Etiopathogenesis of this disease has not been exactly explained yet . The most important factors are anodermal blood flow disturbances and excessive cramp of internal anal sphincter (IAS) . Lateral sphincterotomy is the main way of treatment . However, a very dangerous complication as a stool incontinence may occur . As far as a pharmacological treatment is concerned, nitric oxide donors, calcium channel antagonist and botulinum toxin have been used . In some patients threatened with stool incontinence botulinum toxin may be used as an alternative way of treatment right after surgical treatment . Other ways of conservative treatment seem to be less effective due to the side effects and the frequency of repeating doses . The view on the etiopathogenesis of anal fissure, the ways of surgical treatment and the mechanism of activity of drugs used in the conservative treatment are presented in this paper. Am J Gastroenterol, 2004 Jun, 99(6), 1029 - 36 Complexities of managing achalasia at a tertiary referral center: use of pneumatic dilatation, Heller myotomy, and botulinum toxin injection; Vela MF et al.; PURPOSE: The purpose of this study is to describe the results and complexity of treatment for achalasia patients presenting to a single esophagologist at a tertiary referral center and to make treatment recommendations based on this experience . METHODS: Retrospective chart review of achalasia patients treated between 1994 and 2002 . Symptoms, manometric and timed barium esophagram results, and treatments/outcome at CCF determined . RESULTS: 232 patients (51% male, mean age = 53) were evaluated . Untreated patients (n = 184): Pneumatic dilatation (PD) used in 111 patients . Symptoms and barium emptying improved in 86% and 54%, respectively . Nineteen (17%) patients required subsequent Heller myotomy (HM) . Perforation rate: 3/111 (2.7%) patients . 16% required proton-pump inhibitor (PPI) for GERD . HM was used in 72 patients (81% laparoscopic) . Symptoms and barium emptying improved in 89% and 44%, respectively . PPI required in 53% . Botulinum toxin (Botox) was used in 39 older patients (mean age = 71); symptom improvement lasted for a mean 6.2 months, with frequent need for repeated injection (mean: 1.7, range: 1-7) . About 43% required additional treatment with a different modality . Esophagectomy was done in three patients . Patients with prior surgery (n = 48): PD (n = 10) achieved symptom and barium emptying improvement in 67% and 11%, comparable to redo HM (n = 21) with 57% symptom improvement and 38% improved emptying . Esophagectomy required in eight patients . CONCLUSIONS: Successful management of achalasia can be complex and may require more than one treatment modality . PD and HM are presently the best treatments for untreated achalasia with similar efficacy but greater PPI use after surgery . Both are less successful after prior HM. Arch Phys Med Rehabil, 2004 Jun, 85(6), 902 - 9 The effect of combined use of botulinum toxin type A and functional electric stimulation in the treatment of spastic drop foot after stroke: a preliminary investigation; Johnson CA et al.; OBJECTIVE: To investigate the effect of combined botulinum toxin type A (BTX) and functional electric stimulation (FES) treatment on spastic drop foot in stroke . DESIGN: Nonblinded randomized controlled trial . SETTING: Hospitals . PARTICIPANTS: Consecutive sample of 21 ambulant adults within 1 year after stroke with a spastic drop foot, of whom 18 completed the study . INTERVENTIONS: The treatment group received BTX injections (Dysport) on 1 occasion into the medial and lateral heads of the gastrocnemius (200U each) and tibialis posterior (400U each) muscles and FES, used on a daily basis for 16 weeks to assist walking . Both groups continued with physiotherapy at the same rate . MAIN OUTCOME MEASURES: Walking speed, Physiological Cost Index, Modified Ashworth Scale, Rivermead Motor Assessment, and Medical Outcomes Study 36-Item Short-Form Health Survey . RESULTS: Walking speed increased over 12 weeks in both control (P=.020) and treatment groups (nonstimulated, P=.004; stimulated, P=.042) . The baseline corrected (analysis of covariance) increase in mean walking speed at 12 weeks, relative to controls, was.04m/s (95% confidence interval {CI},.003-.090) without stimulation, and.09m/s (95% CI,.031-.150) with stimulation . CONCLUSIONS: Combined treatment effectively improved walking and function . A larger study is needed to quantify the treatment effect and to investigate its impact on quality of life. Eur Surg Res, 2004 May-Jun, 36(3), 165 - 71 Does botulinum type-A toxin affect motor activity after proctocolectomy and ileal pouch-anal anastomosis? An experimental study in dogs; Willis S et al.; AIM OF THE STUDY: The use of anticholinergic drugs has provided a useful therapeutic approach to reduce stool frequency in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) . Botulinum type-A (BTA) toxin has been shown to specifically block acetylcholine release in the intestinal wall . Therefore this study investigated the effect of BTA on small intestinal and J-pouch motility after IPAA . MATERIAL AND METHODS: Proctocolectomy and IPAA were performed in 4 dogs . The motility of the small intestine and the ileal pouch was recorded by serosal electrodes and strain gauge transducers . The intestinal transit time was determined radiologically and pouch compliance was determined manometrically . Multiple measurements were performed before and after endoscopic injection of BTA into the pouch wall . RESULTS: This treatment did not significantly influence stool frequency, intestinal transit time or pouch compliance . Intrinsic pouch motility was characterized by irregular contractions, the amplitudes and frequencies of which remained unchanged after BTA administration . With the exception of lower contraction amplitudes directly proximal to the pouch, there were no significant differences in the characteristics of the migrating myoelectric complex or in the fed pattern of the small intestine and ileal pouch . CONCLUSIONS: BTA does not significantly affect ileal pouch motility . The beneficial effects of anticholinergic drugs therefore seem to be due to their multifactorial mode of action and not to the inhibition of cholinergic neurons in the pouch . Ophthalmology, 2004 Jun, 111(6), 1255 - 62 Strabismus surgery for adults: a report by the American Academy of Ophthalmology; Mills MD et al.; OBJECTIVE: To describe the effectiveness and safety of surgical treatment of adult patients with strabismus, and to review the reported functional benefits and complications of strabismus surgery for adults . METHODS: A literature search was conducted in September 2001 . It was repeated and updated in April 2003, with retrieval of relevant citations . Panel members reviewed the articles and rated them according to their relevance to the topic and methodology . RESULTS: The literature search identified 49 reports that describe the surgical treatment of strabismus in adult patients and meet predetermined review criteria . Of these reports, 2 were of randomized controlled trials, and 1 addressed the primary objective of this review . In this randomized study of adults with strabismus, direct comparison of surgical correction with botulinum toxin A chemodenervation indicated that surgical treatment was superior to botulinum toxin A in realigning the eyes (76.9% vs . 29.4%, P = 0.027) . Several large case series of adults with strabismus (level III evidence) with successful surgical realignment rates of 68% to 85% have been reported . Functional benefits of surgical treatment are reported in many patients . These include elimination of diplopia, development of binocular fusion, expansion of binocular visual fields, and improvement of head position . Surgical complications, including new, postoperative diplopia (1%-14%) or scleral perforation (0.8%-1.8%), occur in a minority of patients . Unplanned reoperations (subsequent strabismus procedures that were not anticipated as part of a staged treatment) were needed in up to 21% of patients in large case series of comitant strabismus, and in up to 50% of patients with thyroid ophthalmopathy . CONCLUSIONS: Despite the paucity of level I evidence from randomized controlled trials, the existing literature suggests that surgical treatment of adults with strabismus is safe and effective in improving ocular alignment . In many cases it improves visual function, based largely on level III evidence . Risks include unplanned reoperation, postoperative diplopia, and scleral perforation . Additional level I studies of surgical treatment of adult patients would help to document the effectiveness and substantiate the safety of this treatment. Nervenarzt, 2004 Apr, 75(4), 336 - 40 {Long-term treatment of phantom- and stump pain with Botulinum toxin type A over 12 months . A first clinical observation}; Kern U et al.; Recently we were able to describe the successful treatment of phantom pain and stump pain with botulinum toxin A in a first pilot study.This case report over a 1-year period now demonstrates that long-term treatment for this indication is possible . We injected 4 x 25 IU of botulinum toxin A (Botox) into trigger points of the stump muscles of a lower limb amputee who suffered from severe phantom and stump pain . With four injections performed every 3 months, the patient became almost completely pain-free, and his intrathecal morphine therapy could be reduced to 40% of the initial dose . Intrathecal clonidine was eliminated completely, as were the oral analgesics . A surgical treatment suggested for the stump pain was no longer necessary, and we suppose that botulinum toxin can also improve the tolerance of artificial limbs in cases of stump pain. Rev Neurol, 2004 May 16-31, 38(10), 971 - 8 {Guidelines for the treatment of spasticity in adults using Botulinum toxin}; Aguilar-Barbera M et al.; AIMS: The introduction of Botulinum toxin type A (BTA) in the treatment of spasticity in adults was a large step forward in neurology and it is currently seen as the first choice treatment in focal spasticity . In an attempt to achieve the optimisation of this therapeutic resource, different clinical guidelines have been drawn up which include reviews of the evidence available about the indications and use of BTA . Spasticity is characterised by the presence of involuntary muscular hyperactivity that is often associated to pain, deformity and functional disability . From the clinical point of view, the advantages of BTA are obvious (ease of use and dosage determination, long lasting effects, reversibility should the response be inappropriate, etc.) and far outweigh its drawbacks . It can only be used after a proper selection of patients, of the therapeutic aims and of the muscular areas to be treated, and a tailor-made programme of rehabilitation must also be drawn up . Increasing experience in its use suggests that its early administration is effective in preventing or reducing the complications arising from spasticity . CONCLUSIONS: BTA is effective in the treatment of spasticity and plays a significant role if the clinical objectives involve functional aspects . At present a large amount of well-documented experience concerning its indications, effects and safety in clinical practice is already available. Ann Acad Med Singapore, 2004 May, 33(3), 324 - 8 Hemifacial spasm in Singapore: clinical characteristics and patients ' perceptions; Au WL et al.; INTRODUCTION: The aim of this study was to determine the clinical characteristics and patients ' perception of hemifacial spasm (HFS) in Singapore . MATERIALS AND METHODS: A clinical survey of 137 consecutive patients with HFS seen in our Botulinum Toxin Clinic over a 15-month period was undertaken . RESULTS: Forty-six men and 91 women were interviewed . Their mean age at onset of HFS was 48 years . The median disease duration was 60 months (range, 2 to 360 months) . Left-sided spasm was common in 51.8 % of patients, and the orbicularis oculi was the first muscle to be affected in 86.1 % of them . The majority (65 %) had the spasm aggravated by stress and anxiety . In fact, 32 patients perceived stress and anxiety as a possible aetiology of HFS . Stroke was a main concern in 17 patients and 7 patients thought the spasm was a sign of demonic possession or a bad omen . The spasm embarrassed 75.2 % of the patients, rendered 65 % of them depressed, affected the vision in 60.6 % of them and compromised their work performance in 35.8 % . Overall, treatment was delayed by a median interval of 6 months from onset of symptoms (range, 0 to 132) . More than half (53.3 %) tried traditional therapies (acupuncture or herbal medicine), while only 48.2 % had botulinum toxin as the initial treatment . All patients eventually received botulinum toxin injections and more than 90 % showed improvement at 1 month posttreatment . CONCLUSIONS: The clinical characteristics and patients ' perception of HFS in Singapore were presented . HFS affects patients both psychosocially and functionally . Effective treatment with botulinum toxin exists and should be provided early to the patients. Ann Otol Rhinol Laryngol, 2004 May, 113(5), 349 - 55 Tremor laryngeal dystonia: treatment of the lateral cricoarytenoid muscle; Maronian NC et al.; Tremor laryngeal dystonia is a clinical entity distinct from adductor laryngeal dystonia, according to perceptual, stroboscopic, and fine-wire electromyographic findings . Treatment with botulinum toxin has proven more difficult for tremor laryngeal dystonia than for adductor laryngeal dystonia, yet no treatment variations have been considered that might produce improved clinical results . We present 81 patients with a clinical presentation of tremor laryngeal dystonia who were treated with a variety of approaches with botulinum toxin . On the basis of both fine-wire electromyographic findings and clinical response, currently 44 of those patients are being followed up after at least 3 injections . Twenty-one patients (48%) are maintained on lateral cricoarytenoid injections, and 23 (52%) are maintained on thyroarytenoid muscle injections . The electromyographic findings of this group are presented along with their clinical outcome . According to our findings, the majority of patients with tremor laryngeal dystonia can be successfully treated with botulinum toxin if the practitioner includes injections to the lateral cricoarytenoid muscle as a treatment option. Ann Otol Rhinol Laryngol, 2004 May, 113(5), 341 - 8 Treatment of the interarytenoid muscle with botulinum toxin for laryngeal dystonia; Hillel AD et al.; The treatment of laryngeal dystonia with botulinum toxin has provided various degrees of relief to the majority of patients with adductor dysphonia; however, a significant number of patients have limited or no improvement with this type of therapy . It remains unclear why some patients respond to the routine administration of toxin to the thyroarytenoid muscles whereas others do not . Injections into the lateral cricoarytenoid muscles have provided an improved voice in some patients who were unresponsive to injections into the thyroarytenoid muscles . Fine-wire electromyography can demonstrate the particular dystonic activity of these muscles to help determine which muscle is predominantly involved . It can also demonstrate dramatic dystonic activity in the interarytenoid (IA) muscle in many patients . We present the results of 23 patients treated with injections to the IA muscle after demonstration of dystonic IA activity . Ten have benefited from IA therapy . Five of these 10 patients did not have a good result from botulinum toxin until IA injections were added to the treatment plan . In 8 patients, IA therapy provided no improvement, and 5 patients were lost to adequate follow-up . According to fine-wire electromyography and clinical response, the IA muscle is an active dystonic muscle in some patients with laryngeal dystonia and should be treated with botulinum toxin in selected patients. Neurol Neurochir Pol, 2003 Sep-Oct, 37(5), 1135 - 42; discussion 1143 {Intrathecal baclofen in severe spasticity due to multiple sclerosis}; Slawek J et al.; Intrathecal administration of baclofen via programmable pump is a highly effective treatment method in severe spasticity resistant to oral medications . The authors describe a case of severe spasticity with tetraplegia and painful (> 10 a day) muscle spasms in the upper and lower limbs and paraspinal muscles, in a patient with clinically definite diagnosis of multiple sclerosis (MS) . The 34-year-old female patient with a 15-year history of MS, suffering from lower limb spasticity with pes equinovarus since 1995, was treated with very good results with botulinum toxin injections of calf muscles (14 sessions of Dysport 1500iu till 2002) . In the early 2002 she developed tetraplegia with severe, generalized and intractable spasticity . After 4 months of ineffective polytherapy (with high doses of oral baclofen, tizanidine, gabapentine, clonidine, diazepam) and the patient's enormous sufferings (she could neither sit up nor voluntarily change her position in bed), a programmable baclofen pump (Medtronic) was implanted . As soon as a few days after the surgery she could stand, sit and move voluntarily, her painful spasms disappeared, and her bladder catheter was removed . At a 6-month follow-up the effect was stable--she was able to walk a long distance outdoors with the aid of a crutch . The daily dose of the drug is 500 micrograms . No side effects of complications were noted. J Fr Ophtalmol, 2004 Apr, 27(4), 358 - 65 {Botulinum toxin in infantile estropia: long-term results}; Spielmann AC; PURPOSE: To evaluate long term results of botulinum toxin in infantile esotropia . METHODS: Nineteen infants between 6 and 13 Months of age were treated with botulinum toxin injected into the medial recti . The amount of deviation, the different symptoms of infantile esotropia, and the need for surgery were studied . RESULTS: Esotropia reappears frequently with time . Dissociated vertical deviation and manifest/latent nystagmus are only partially improved . Surgery is usually mandatory over the long term . CONCLUSION: Despite some good results, a single botulinum toxin injection is less effective than incisional surgery in treating the different symptoms of infantile esotropia. Dermatol Surg, 2004 Jun, 30(6), 867 - 71; discussion 871 Botulinum toxin a for aesthetic contouring of enlarged medial gastrocnemius muscle; Lee HJ et al.; BACKGROUND: Oversized, muscular calves can cause psychological stress in women . Botulinum toxin A has been used in the treatment of benign masseteric hypertrophy with correction of the squared facial appearance . It is believed that botulinum toxin might also be effective in reducing enlarged calf muscles . OBJECTIVE: This study was performed to investigate the effect of botulinum toxin A in reducing enlarged medial gastrocnemius muscles in volunteers with muscular legs . METHODS: Botulinum toxin A of 32, 48, or 72 U was injected in each medial head of the gastrocnemius muscle in six women . Clinical photography was taken and the leg circumferences were measured . The functional evaluations were performed by examining range of joint motion and motor and sensory examination . RESULTS: All of the enrolled subjects showed a reduction in the medial gastrocnemius muscle after the botulinum toxin injection . The reduction in medial calf was noticed even after 1 week and the effect of was well maintained for 6 months . Leg contouring was obtained by the botulinum toxin treatment . The middle leg circumference showed a slight decrease in five subjects . No functional disabilities were observed . CONCLUSION: Botulinum toxin A can be used to contour the aesthetic enlargement of the medial gastrocnemius muscle with slight reduction in volume . Botulinum toxin-induced atrophy of the muscle caused no functional disabilities and the clinical improvement was well maintained for 6 months after the botulinum toxin A injection. Eur J Neurol, 2004 Jun, 11(6), 361 - 70 Efficacy of pharmacological treatment of dystonia: evidence-based review including meta-analysis of the effect of botulinum toxin and other cure options; Balash Y et al.; The treatment of both generalized and focal dystonia is symptomatic . There is no evidence-based information about the efficacy of the different methods of the pharmacological therapeutic options currently being applied in dystonia . The specific questions addressed by this study were which treatments for dystonia have proven efficacy and which of them have unproven results . Following evidence-based principles, a literature review based on MEDLINE and the Cochrane Library, augmented by manual search of the most important journals was performed to identify the relevant publications issued between 1973 and 2003 . All articles appearing in the professional English literature, including case reports, were considered . In the presence of comparable studies the meta-analysis was performed to obtain pooled information and make a reasonable inference . Based on this review, we conclude: (i) botulinum toxin has obvious benefit (level A, class I-II evidence) for the treatment of cervical dystonia and blepharospasm; (ii) trihexyphenidyl in high dosages is effective for the treatment of segmental and generalized dystonia in young patients (level A, class I-II evidence); (iii) all other methods of pharmacological intervention for generalized or focal dystonia, including botulinum toxin injections, have not been confirmed as being effective according to accepted evidence-based criteria (level U, class IV studies). Aesthetic Plast Surg, 2004 Mar-Apr, 28(2), 114 - 5 Epub 2004 Jun 01. Two-plane injection of botulinum exotoxin A in glabellar frown lines; Ozsoy Z et al.; Botulinum exotoxin A has been used for the treatment of glabellar frown lines . Despite this fact, the effect of the toxin is sometimes either partial or lost in a short time . The muscles responsible for frowning, the corrugator supercilii and depressor supercilii muscles, are attached to the periosteum in the glabellar region under the frontalis muscle deep in the medial aspect . The muscles then course laterally and superficially to insert in the skin superior to the eyebrows . Thus, to get a long-lasting and full effect, the exotoxin has been applied deeply in the medial aspect and superficially in the lateral aspect of the glabellar region . It is concluded that botulinum exotoxin is more effective when it is applied in two planes superficially and deep so that the anatomic course of the corrugator supercilii and the depressor supercilii muscles are followed. Ophthal Plast Reconstr Surg, 2004 May, 20(3), 186 - 9 Increased patient comfort utilizing botulinum toxin type a reconstituted with preserved versus nonpreserved saline; Kwiat DM et al.; PURPOSE: To demonstrate that injection of botulinum toxin type A is less painful when mixed with preserved saline compared with the suggested preservative-free saline reconstitution . METHODS: Two different injections were compared on 20 patients who had prior botulinum toxin type A treatments . Each side was injected with toxin reconstituted with either preserved or nonpreserved (0.9%) saline . The investigators and patients were blinded, and outcome was assessed with a verbal scale . Clinical outcome was subjectively and informally assessed by patient questioning and physician observation . RESULTS: Injection of botulinum toxin type A was noted to be less painful with the use of the preserved compared with the nonpreserved preparation (P<0.0001) . The preserved reconstitution appeared to have no effect on clinical outcome . CONCLUSIONS: Injection of botulinum toxin reconstituted with preserved saline is less painful than nonpreserved saline preparations. Ophthal Plast Reconstr Surg, 2004 May, 20(3), 181 - 5 Botulinum toxin type a for dysthyroid upper eyelid retraction; Morgenstern KE et al.; PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A for treatment of eyelid retraction resulting from thyroid eye disease (TED) during the inflammatory phase of the condition . METHODS: In this prospective, nonrandomized case series, 18 patients with inflammatory eyelid retraction caused by active TED received botulinum toxin type A injection (10, 5, or 2.5 U) for treatment of upper eyelid retraction . Botulinum toxin type A (Allergan, Irvine, CA, U.S.A.) was injected transconjunctivally just above the superior tarsal border in the elevator complex of the upper eyelid . RESULTS: Seventeen of 18 patients (94%) demonstrated a reduced marginal reflex distance (MRD1) after botulinum toxin injection . The average change in MRD1 of the treated eyelid after injection was -2.35 mm (range, 0 to -8.0 mm) . Of the 27 eyelids injected, 33% had a 0- to 1-mm drop in eyelid height, 30% had a 1.5- to 2-mm decrease, 22% had a 2.5- to 3-mm decrease, and 15% had a greater than 3-mm decrease in eyelid height . None of the treated eyelids were noted to increase in height . One patient showed no alteration inafter treatment . One patient had clinically MRD1 significant ptosis and one patient reported worsening of preexisting diplopia after injection . Three patients undergoing unilateral injection had relative contralateral eyelid elevation . All untoward effects resolved spontaneously without sequelae . CONCLUSIONS:: Botulinum toxin type A may be used in the inflammatory stage of thyroid eye disease to improve upper eyelid retraction . Individual response to treatment is variable, but this modality should be considered as a temporizing measure until stability for surgery is reached. Curr Opin Otolaryngol Head Neck Surg, 2004 Apr, 12(2), 133 - 41 The facial nerve in the presence of a head and neck neoplasm: assessment and outcome after surgical management; Guntinas-Lichius O; PURPOSE OF REVIEW: The face is the mirror of personality . Facial expression is the most important part of verbal and nonverbal communication . Patients with head and neck neoplasm and facial palsy are more stigmatized by the latter than by the tumor itself . Facial nerve reconstruction in such a patient is a great challenge . This review gives an overview of the assessment of facial palsy, surgical reconstruction, and postoperative treatment . RECENT FINDINGS: MRI, CT, and electromyography are indispensable tools in the assessment of preoperative facial palsy in patients with head and neck neoplasm . When part of the facial nerve has to be sacrificed during surgery, the best functional results are achieved with direct facial nerve suture, interposition graft, or by a hypoglossal-facial nerve interposition jump anastomosis . The latter is the best choice when the reanimation is planned between 6 months and 2 years after tumor surgery . In any case, the eye is best rehabilitated with upper lid loading . Temporalis muscle transposition gives fast and good results for the restoration of the corner of the mouth after radical surgery . Reanimation by free muscle transfer for head and neck cancer patients is rarely indicated . Botulinum toxin treatment is an excellent postoperative aid for refining the result; the optimal modality of postoperative physiotherapy is still unclear . SUMMARY: Surgical reanimation of the face in head and neck patients has reached a high standard . Strategies to decrease misdirected reinnervation after nerve suture have to be established in clinical practice for further improvement of facial rehabilitation. Curr Opin Otolaryngol Head Neck Surg, 2004 Jun, 12(3), 197 - 203 Botulinum toxin and the management of chronic headaches; Evers S; PURPOSE OF REVIEW: There is an increasing number of reports on botulinum toxin in pain therapy, in particular in headache treatment . Therefore, the studies available from reference systems and published congress contributions on the prophylactic treatment of idiopathic and cervicogenic headache with botulinum toxin were analyzed with respect to study design, headache diagnosis, and the significance of results . RECENT FINDINGS: For the prophylactic treatment of tension-type headache, migraine, and cervicogenic headache, no sufficient positive evidence for treatment with botulinum toxin is obtained from randomized, double-blind, placebo-controlled trials to date . For the treatment of miscellaneous headache, there is some but no consistent positive evidence . SUMMARY: Most open studies and case reports suggest an efficacy of botulinum toxin in headache prophylaxis but double-blind, placebo-controlled studies do not confirm this assumption . Larger controlled studies are needed for a definite evaluation of subgroups that might possibly benefit from such a treatment . Migraine, tension-type headache, and cervicogenic headache cannot be regarded as a general indication for a treatment with botulinum toxin. Brain Dev, 2004 Aug, 26(5), 335 - 8 Laryngeal dystonia in a case of severe motor and intellectual disabilities due to Japanese encephalitis sequelae; Hamano K et al.; Laryngeal dystonia is characterized by stridor due to vocal cord dystonia and is observed in extrapyramidal disorders . Recently, botulinum toxin injection has been used as a primary therapy . Generally, severe motor and intellectual disabilities (SMID) are frequently complicated by various types of respiratory disorders . We report a SMID case with Japanese encephalitis sequelae showing repeated vocal cord abductor disturbance due to laryngeal dystonia, in addition to generalized dystonia, in whom MRI revealed basal ganglia lesions . Tracheostomy was effective for the case, and we believe that botulinum toxin injection may be inappropriate in SMID, both ethically and technically . Also, laryngeal dystonia should be considered as a cause of respiratory disorders in SMID. Foot Ankle Clin, 2004 Jun, 9(2), 339 - 48 Clinical usefulness of botulinum toxin in the lower extremity; Jacks LK et al.; As the literature that pertains to botulinum toxin expands, the scope of treatment options broadens . Although initial uses of botulinum toxin focused around the head and neck, there are many uses for the toxin in the area of the foot and ankle; more possibilities are under investigation every day . We review the uses and techniques for botulinum toxin in the foot and ankle and present results of botulinum toxin treatment in 10 idiopathic toe walkers. J Pain, 2004 May, 5(4), 238 - 40 Botulinum toxin a for vulvodynia: a case report; Gunter J et al.; Vulvodynia is a poorly understood chronic pain condition, and patients who are refractory to standard therapies often pose a therapeutic dilemma . Current treatment modalities include antidepressants, anticonvulsants, biofeedback, pelvic floor physical therapy, and surgery; however, the options are limited for patients who fail to respond to these treatments . We present a case of refractory vulvodynia with severe dyspareunia successfully managed with a novel therapeutic approach combining botulinum toxin A and surgery . PERSPECTIVE: The authors present a case of refractory vulvodynia that was successfully managed with a novel approach that combined botulinum toxin A and surgery . Neuro Endocrinol Lett, 2004 Feb-Apr, 25(1-2), 45 - 8 Cannabinoid agonists in the treatment of blepharospasm--a case report study; Gauter B et al.; The benign essential blepharospasm is a subliminal form of primary torsion dystonia with still uncertain aetiology . It is characterized by involuntary convulsive muscle contractions of the M . orbicularis occuli, accompanied by unbearable pain of the cornea, eye bulb and the muscle itself . It has been suggested that blepharospasm is neurobiologically based on a dysfunction of the basal ganglia and an impairment of the dopamine neurotransmitter system . Therefore, therapy of blepharospasm contains administration of anticholinergic- and tranquillizing drugs as well as botulinum toxin as neuromuscular blocking agent . However serious side effects can be observed as well as failure of therapy . In the brain a dense co-localisation of cannabinoid (CB1) and dopamine (D2)-receptor was identified which had been associated with the influence of cannabinoids on the dopaminergic reward system . Additionally, it has been demonstrated that cannabinoids may have an impact on the central GABAergic and glutaminergic transmitter system and thus might be involved in the influence of movement control . In the present case we administered the cannabinoid receptor agonist Dronabinol (Delta-9-Tetrahydrocannabinol) to a woman suffering from severe blepharospasm . Multiple treatments with botulinum toxin did not reveal a long-lasting beneficial effect . By contrast, treatment with 25 mg Dronabinol for several weeks improved the patients' social life and attenuated pain perception remarkably . This case study demonstrates that the therapy with a cannabinoid agonist may provide a novel tool in the treatment of blepharospasm and maybe of other multifactorial related movement disorders. Neurology, 2004 May 25, 62(10), 1749 - 52 Trigeminal afferent input alters the excitability of facial motoneurons in hemifacial spasm; Ogawara K et al.; OBJECTIVE: To investigate whether skin or muscle afferent input via the trigeminal nerve alters the excitability of facial motoneurons in hemifacial spasm (HFS) . METHODS: Botulinum toxin type A (BTX) was injected only to the orbicularis oculi (O . oculi) muscle of 21 patients with idiopathic HFS, and the excitability of the orbicularis oris (O . oris) motoneurons was monitored . The synkinetic response (SR) of the blink reflex and abnormal muscle response (AMR) were recorded from the O . oris before and after treatment . RESULTS: BTX injections produced marked to moderate improvement in the O . oculi of all 21 patients and in the O . oris of 17 (81%) . The rectified areas of SR1 and SR2 were smaller after treatment . In particular, the AMR area showed a reduction (p = 0.02) . CONCLUSIONS: The significant lessening of spasms in the O . oris after BTX injection to the O . oculi and the concomitant reduction in excitability of O . oris neurons are consistent with the hypothesis that in HFS, skin or muscle afferent volleys via the trigeminal nerve enhance the excitability of facial nerve motoneurons. Clin Dermatol, 2004 Jan-Feb, 22(1), 89 - 93 Botox: beyond wrinkles; Carruthers J et al.; First used and approved over a decade ago for the treatment of strabismus (or misaligned eyes), botulinum toxin (BTX) has demonstrated efficacy in blepharospasm, hemifacial spasm, spastic lower eyelid entropion, and a number of other disorders seen in the traditional medical environment that are characterized by abnormal muscle contraction . Moreover, other conditions-notably some pain and gastrointestinal disorders-have responded to BTX injections. Clin Dermatol, 2004 Jan-Feb, 22(1), 82 - 8 Noncosmetic uses of botulinum toxin; Bentsianov B et al.; Since the introduction of botulinum toxin (BTX) as a therapeutic tool in the 1970s, the number of uses for this substance has increased exponentially . BTX's mechanism of action involves degrading the SNARE proteins blockading the release of acetylcholine into the neuromuscular junction . In many body systems, decrease of contractility, strength, and tension of certain muscle groups result in improved clinical outcomes . Applications now include cosmetic, gastroenterologic, otolaryngologic, genitourinary, neurologic, and dermatologic uses . In fact, BTX can be considered as a potential treatment in any situation involving inappropriate or exaggerated muscle contraction . Currently, the FDA has approved BTX-A (Botox) for treating glabellar lines, blepharospasm, strabismus, hemifacial spasm, cervical dystonia, and spasticity . With the addition of cosmetic applications to the FDA's approval list, the use of BTX has increased dramatically. Clin Dermatol, 2004 Jan-Feb, 22(1), 76 - 81 Botulinum neurotoxin for the treatment of migraine and other primary headache disorders; Dodick D et al.; Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction, including cervical dystonia, blepharospasm and hemifacial spasm . It inhibits neurouscular signaling by blocking the release of acetylcholine at the neuromuscular junction . The biological effects of the toxin are transient with normal neuronal signaling returning within approximately 3-6 months post injection . Recently, clinical findings suggest that BoNT/A may inhibit pain associated with migraine and other headache types . The mechanism by which this toxin inhibits pain is under investigation, recent findings suggest that it inhibits the release of neurotransmitters from nociceptive nerve terminals and in this way may exert an analgesic effect . A number of retrospective open-label chart reviews and three placebo-controlled double-blind trials have demonstrated that localized injections of BTX-A significantly reduce migraine frequency, severity, and migraine-associated disability . The majority of patients in these studies experienced no BoNT/A mediated side effects; however, a small percentage of patients did report transient minor side effects including blepharoptosis, dipolpia, and injection-site weakness . Currently there are several large-scale randomized, placebo-controlled clinical trials in progress evaluating the efficacy, optimal dosing and side effect profile of this toxin as a novel treatment for migraine and other headache types . These studies may provide further evidence that BoNT/A is an effective option for the preventive treatment of migraine. Clin Dermatol, 2004 Jan-Feb, 22(1), 66 - 75 Contraindications and complications with the use of botulinum toxin; Klein AW; Cosmetic use of BTX has skyrocketed in recent years, especially since the approval of BTX-A for treatment of glabellar lines . Complications and adverse reactions can easily arise, particularly for the novice injector . This paper provides insights from an experienced physician on how to avoid these complications, and how to treat them when and if they occur . The main cosmetic uses for BTX are analyzed for possible complications and adverse events . Injection techniques are discussed . Comparisons between BTX-A and BTX-B are given to point out the need for different injection techniques based on the product being used . Treatment recommendations for the Glabella, Brow, Crow's Feet, Upper Lip Wrinkling/Lines, Depressor Anguli Oris, Nasolabial Folds, Mentalis, Neck and Hyperhidrosis are discussed, as well as systemic complications . It is important for the injecting physician to be familiar with these potential complications, even though the use of BTX has been safe and generally well tolerated, because it will lead to even greater success with the use of BTX. Clin Dermatol, 2004 Jan-Feb, 22(1), 60 - 5 Botulinum toxin-B and the management of hyperhidrosis; Baumann LS et al.; A new serotype of botulinum toxin has recently arrived in the US . Botulinum toxin type B (BTX-B), known as Myobloc in the United States and as Neurobloc in Europe, is one of seven different antigenic members of the botulinum toxin family, five of which the human nervous system is susceptible to . Like botulinum toxin type A (BTX-A), BTX-B has been used for a myriad of both dermatologic and nondermatologic problems since its recent approval by the FDA for the treatment of cervical dystonia in December 2000 . It is currently not approved however, for a cosmetic use but has been used for this purpose in an "off-label" fashion . It has followed in the therapeutic footsteps of BTX-A in the prevention and treatment of facial wrinkles such as crow's feet and glabellar frown lines . In addition, one of its current and popular uses is in the management of hyperhidrosis, a disease in search of a long needed treatment . This past year researchers have been investigating the efficacy as well as defining the dosing and application regiments of BTX-B in the treatment of hyperhidrosis . In addition, recent studies have been examining its side effect profile, which may be very different than that seen with BTX-A . There are only a handful of studies in the literature examining the cosmetic applications of BTX-B . This chapter will review what is currently known about BTX-B and its current use in regards to the treatment of hyperhidrosis. Clin Dermatol, 2004 Jan-Feb, 22(1), 53 - 9 Inguinal, or Hexsel's hyperhidrosis; Hexsel DM et al.; Inguinal Hyperhidrosis (IH) is a focal and primary form of hyperhidrosis in which the individual has intense sweating in the inguinal region . It usually appears in adolescence, not later than the age of 25, in the most cases, and continues into adulthood . With a sample of 26 patients we described Inguinal Hyperhidrosis (IH) . Fifty percent of the patients have a positive family history of this condition or other forms of focal or generalized hyperhidrosis, which suggests a familial pattern . Biopsies performed on the inguinal area in a patient with IH and control patient showed normal histology . Excessive perspiration in the inguinal area significantly affects the quality of life of the patients . It is an embarrassing condition that produces large wet stains on the clothes, therefore making daily activities difficult and compromising the emotional, professional and social life of the affected patients . The therapies commonly used for other forms of focal hyperhidrosis are not yet referred in the literature specifically for IH . Intradermal injections from botulinum toxin provide positive results for the patients and controls the sweating for 6 months or more . It is a simple, safe and effective treatment for this condition and the results significantly improve the quality of life of the affected individuals. Clin Dermatol, 2004 Jan-Feb, 22(1), 45 - 52 Hyperhidrosis and botulinum toxin A: patient selection and techniques; Glogau RG; Focal idiopathic excessive eccrine sweating presents most commonly as an affliction of three anatomically distinct area: the axillae, the palms and soles, and the upper face . The true incidence is not known, but about half of the patients referred to us with this condition have at least one first-degree relative similarly affected . Only a fraction of patients afflicted are thought to seek medical care because of the social stigma, lack of understanding on the part of medical providers as to the cause and nature of the problem, and, until now, lack of effective nonsurgical therapy . A large social sample is required to accurately measure both the incidence and the exact nature of the genetic influence. Clin Dermatol, 2004 Jan-Feb, 22(1), 40 - 4 Anatomy of the sweat glands, pharmacology of botulinum toxin, and distinctive syndromes associated with hyperhidrosis; Kreyden OP et al.; For a long period the therapeutic modalities to treat focal hyperhidrosis (HH) were very limited . Due to this the problem of focal HH was delt with stepmotherly . Nowadays we can consider BTX as the therapy of choice for axillary HH after topical treatment with aluminium salts have failed . The amount of successful reports on botulinum toxin (BTX) in the treatment of focal HH brought a change and the interest for this specific disorder grew . This article gives details on anatomy and physiology of sweating and mechanism of BTX . Further distinctive syndromes associated with HH, which all can be treated with BTX like localized unilateral hyperhidrosis (LUH), Ross' Syndrome and Frey' Syndrome are presented . A diagnosis of primary HH is usually based on the patients's history, typical younger age and visible signs of excessive sweating . Before treatment it is important to objectify focal HH with performing sweat tests such like Minor starch test and/or gravimetry . The total number of sweat glands is somewhere between 2 and 4 million and only about 5% are active at the same time, indicating the enormous potential for sweat production . The eccrine sweat gland is a long-branched tubular structure with highly coiled secretory portion and a straight ductular portion . Sweat is produced by clear and dark cells and is a clear hypotonic, odorless fluid . In response to nerve impulses, Acetylcholine (ACh) is released from the presynaptic nerve endings and then binds to postsynaptic cholinergic receptors presumably present in the basolateral membrane of the clear cells . This activates a complex in- and efflux of electrolytes creating the hypotonic sweat . Injection of BTX leads to temporary chemodenervation with the loss or reduction of activity of the target organ . BTX is consisted of a heavy and a light chain . The structural architecture of BTX comprises three domains-L, H(N) and H(C)-each with a specific function in the mechanism of cell intoxication . The heavy chain is responsible for binding to the nerve cell, whereas the light chain catalyzes the proteolysis of one of the three SNARE proteins (Snap-25, Vamp or Syntaxin) depending to the serotype of BTX (7 serotypes A-G) . Once cleaved by BTX, the SNARE proteins cannot become part of the complex capable of mediating the vesicle membrane fusion and therefore prevents the release of ACh and hence transmission of the nerve impulse. Clin Dermatol, 2004 Jan-Feb, 22(1), 34 - 9 Botulinum toxin types A and B: comparison of efficacy, duration, and dose-ranging studies for the treatment of facial rhytides and hyperhidrosis; Yamauchi PS et al.; One of the most common etiologic forces for the persistence of facial rhytides is the repetitive contraction of the intrinsic muscles that are necessary for facial expression . These include the forehead lines, crow's feet, glabellar rhytides, and wrinkles in the lower face . Although filling agents such as collagen and laser procedures can help reduce the appearance of these lines, they do not address the underlying forces that cause these wrinkles to persist . Botulinum toxin type-A and type-B are neurotoxins that address these issues and result in the relaxation of the intrinsic facial muscles and subsequent resolution of these dynamic facial rhytides . This article will compare the efficacy, duration, dose ranging studies, and safety in the treatment of facial rhytides with both types of toxins . In addition, the treatment of hyperhidrosis with type-A and type-B botulinum toxin will also be discussed. Clin Dermatol, 2004 Jan-Feb, 22(1), 29 - 33 The cosmetic use of botulinum toxin type B in the upper face; Sadick NS; Facial wrinkles involving the forehead, glabellar, and/or periorbital regions are a common esthetic problem and are directly related to overactivity of the underlying facial musculature . For instance, the development of glabellar wrinkles is related, at least in part, to the dynamics of the underlying procerus, corrugator supercilii, and orbicularis oculi muscles . Facial lines are considered problematic because they produce the appearance of aging . In some cases, they can also be misinterpreted as manifestations of negative emotions (eg, anger, anxiety, sadness), fatigue, or stress . In recent years, botulinum toxin injections have become one of the most popular therapies for the treatment of hyperfunctional facial lines . After injection, the toxin acts to paralyze or weaken facial mimetic muscles . This reduces or eliminates the appearance of wrinkles and is extremely safe. Clin Dermatol, 2004 Jan-Feb, 22(1), 23 - 8 Botulinum toxin type B (Myobloc): pharmacology and biochemistry; Callaway JE; Purified toxin complexes have found a niche in the treatment of clinical disorders involving muscle hyperactivity . This report describes the fundamental biochemical properties of the commercially available form of Botulinum Toxin Type B and compares these attributes to the Type A form of the Toxin . Both neurotoxins act to inhibit the release of acetylcholine at the neuromuscular junction, causing muscle paralysis . The different serotypes are structurally and functionally similar; however, specific differences in neuronal acceptor binding sites, intracellular enzymatic sites, and species sensitivities suggest that each serotype is its own unique pharmacologic entity . Data are provided on the biochemical properties and long-term stability of the Type B product, which is uniquely formulated as a liquid product. Clin Dermatol, 2004 Jan-Feb, 22(1), 18 - 22 Cosmetic uses of botulinum toxins for lower aspects of the face and neck; Lowe NJ et al.; The ability of botulinum toxin A (BTX-A) to improve the appearance of facial lines was first reported among patients who had been receiving injections for facial dystonias or surgical procedures . Since that time, there has been very extensive use of this treatment for relaxation of a wide variety of facial muscles and also for platysmal lines of the neck . Considerable experience over the last decade or longer confirms the safety and efficacy of BTX-A in the treatment of upper facial lines . BTX-A has been used also lower facial indications, but published papers are mainly uncontrolled observations on patients . Unlike the placebo-controlled studies on the upper face, there is a lack of controlled studies for lower face and neck BTX-A treatment . This article will summarize the use of BTX-A for the lower face and its role as combination treatment . Examples of combinations that may be used with BTX-A resurfacing, nonablative skin rejuvenation and skin fillers . Although little used at present, Botulinum Toxin B will be briefly discussed. Clin Dermatol, 2004 Jan-Feb, 22(1), 14 - 7 Facial esthetics and patient selection; Habbema L; Preventing patient dissatisfaction is a primary goal when performing botulinum toxin-A injections . By taking the correct approach with careful patient selection, ensuring safety and minimizing the risk of complications and side effects, the practitioner can largely eliminate patient dissatisfaction with this therapy . Basic understanding of facial esthetics and concepts of beauty are helpful to optimize patient satisfaction. Clin Dermatol, 2004 Jan-Feb, 22(1), 3 - 13 Facial anatomy; Bentsianov B et al.; Botulinum toxin acts at the neuromuscular endplate, which requires precise delivery of the drug to achieve a desired clinical result . A thorough understanding of the complex anatomic structures of the face and their effect on facial form and function, coupled with an appreciation of facial esthetics and the balanced muscle actions that produce resting and active facial form, will result in accurate and reproducible clinical effects . Utilizing some general anatomic principles in combination with specific individual facial features and variations will enable the physician to consistently find the optimum injection sites and combination of other therapies for desired outcomes. Biochem Biophys Res Commun, 2004 Jun 18, 319(1), 66 - 71 Comparison of the pH-induced conformational change of different clostridial neurotoxins; Puhar A et al.; Clostridial neurotoxins are internalized inside acidic compartments, wherefrom the catalytic chain translocates across the membrane into the cytosol in a low pH-driven process, reaching its proteolytic substrates . The pH range in which the structural rearrangement of clostridial neurotoxins takes place was determined by 8-anilinonaphthalene-1-sulfonate and tryptophan fluorescence measurements . Half conformational change was attained at pH 4.55, 4.50, 4.40, 4.60, 4.40, and 4.40 for tetanus neurotoxin and botulinum neurotoxin serotypes /A, /B, /C, /E, and /F, respectively . This similarity indicates the key residues for the conformation transition are strongly conserved . Acidic liposomes support the conformational rearrangement shifting the effect versus higher pH values, whereas zwitterionic liposomes do not . The disulfide bridge linking the light and the heavy chains together needs to be oxidized to allow toxin membrane insertion, indicating that in vivo its reduction follows exposure to the cytosol after penetration of the endosomal membrane. HNO, 2004 Jul, 52(7), 635 - 41 {Botulinum toxin in otorhinolaryngology}; Rohrbach S et al.; BACKGROUND AND OBJECTIVES: Through its anticholinergic effect, botulinum toxin is a suitable therapeutic option for dysfunctions of the muscular and the autonomic nervous system . PATIENTS/METHODS: Beside the classical indications like facial hyperkinesis (i.e . blepharospasm, hemifacial spasm), the treatment of complex dystonias (oromandibular dystonia, spasmodic dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful . Botulinum toxin is an alternative treatment of tension type headache and migraine . A new indication of botulinum toxin application may involve the treatment of nasal hypersecretion through the effect on the nasal glands . RESULTS: The positive therapeutic effect starts a few days after treatment and lasts longer in disorders of the autonomic nervous system . Because of its temporally limited therapeutic effect, the patients need further treatment . Side-effects are rare . CONCLUSIONS: Botulinum toxin is an effective treatment for a variety disorders with different etiologies and has very few side effects. Expert Opin Pharmacother, 2004 May, 5(5), 1015 - 21 Alternative use of botulinum toxin in urology; Maan Z et al.; Botulinum toxin A is used in the treatment of lower urinary tract symptoms due to detrusor sphincter dysynergia and detrusor hyper-reflexia (neurogenic detrusor deficiency) . The toxin acts by producing paralysis of muscle tissue and has been shown to be safe and effective in the treatment of conditions caused by increased muscle tonicity and spasticity . Here the literature is reviewed chronologically, the established and emerging indications for the urological use of botulinum toxin evaluated and future applications are also considered. Rinsho Shinkeigaku, 2003 Nov, 43(11), 880 - 2 {Neurological effects of chemical and biological weapons}; Inoue N; Neurological manifestations of chemical and biological weapons are reviewed . Nerve agents in current use, storage, or production include tabun, sarin, soman and VX . The initial effects of exposure to a nerve agent depend on the dose and on the route of exposure . Sarin, the agent studied most thoroughly in man in Matumoto and Tokyo attacked by Aum shinrikyo will cause miosis, rhinorrehea and shortness of breath are initial complaints immediately after inhalation exposure of the vapor . The severe cases showed loss of consciousness and convulsions . Respiratory arrest may occur . The most toxic of the nerve agents is VX . It is thought to be 100 times as toxic as sarin for humans by the percutaneous rout . The similar findings to sarin exposure are also observed in cases exposured to VX . Atropin and PAM will be effective in the early stage . BZ (benzilate) is a delayed onset incapacitation agent . It causes severe hallucination . The cyanide compounds are among the most rapidly acting of war gases, resulting in death . Anthrax has been the most attractive biological weapon for a long time . Anthrax is an acute bacterial infection of the skin and lungs in man and animals . Meningoencephalitis has been reported in the terminal stage in anthrax infection . In autopsy, it is really confirmed in the characteristic findings of the meningeal abnormality . The potential weaponization of variola virus continues to pose a military threat because the aerosol infectivity of the virus and the development of susceptible populations . A high rate of lethality, a staunch resistance to treatments and a rapid onset of severe generalised muscle weakness make botulinum toxin a suitable agent for biological warfare particularly by oral administration. Neurologia, 2004 Jun, 19(5), 260 - 3 {Influence of botulinum toxin treatment on previous primary headaches in patients with cranio-cervical dystonia}; Pascual J; INTRODUCTION: Preliminary data suggest some beneficial effects of botulinum toxin type A (BT-A) on primary headaches . OBJECTIVE: To analyze the subjective influence of BT-A on previous primary headaches of those patients receiving this treatment due to a variety of cranio-cervical dystonia (CD) . PATIENTS AND METHODS: All patients receiving BT-A due to CD were interviewed with an ad hoc questionnaire on the presence or not of headaches prior to BT treatment . Diagnosis and subjective effects of BT-A on these previous headaches were recorded . RESULTS: Thirty-eight patients (28 women) were interviewed; 21 (19 women) reported a history of previous primary headache (12 migraine, 10 tension-type headache) . Nine (41 %) reported sustained response ( > 50 % reduction in headache frequency) since the beginning of BT-A treatment . Patients with cervical dystonia or those receiving high doses ( > 50 U) showed the best responses . Age, gender, pain location, duration of BT-A treatment and headache diagnosis did not seem to correlate with response . CONCLUSIONS: BT-A seems to have sustained beneficial effect on primary headaches of some patients with CD, especially at doses higher than 50 U and in patients with the diagnosis of spasmodic torticollis. Drugs Today (Barc), 2004 Mar, 40(3), 205 - 12 The role of botulinum toxin in neurourology; Schurch B; Botulinum toxin is a presynaptic neuromuscular blocking agent that induces a selective and reversible muscle weakness of up to several months when injected intramuscularly in minute quantities . Different medical disciplines have applied the toxin to treat mainly muscular hypercontraction . For neurourologically impaired patients, the reported successful treatment of neurogenic detrusor overactivity and detrusor sphincter dyssynergia with botulinum-A toxin is a promising alternative option to conservative medication or surgery . This review of the literature presents current indications, techniques for and results of the use of botulinum toxin in neurourologically impaired patients and aims to give an insight into this new therapeutic option . c) 2004 Prous Science . All rights reserved Methods Find Exp Clin Pharmacol, 2004 Apr, 26(3), 211 - 44 Gateways to clinical trials; Bayes M et al.; Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses . The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin; Tadalafil, tesmilifene hydrochloride, theratope, tipifarnib, tirapazamine, topixantrone hydrochloride, trabectedin, traxoprodil, Tri-Luma; Valdecoxib, valganciclovir hydrochloride, vinflunine; Ximelagatran; Ziconotide. Arch Facial Plast Surg, 2004 May-Jun, 6(3), 188 - 91 Botulinum toxin for masseter reduction in Asian patients; Ahn J et al.; Asian patients frequently seek aesthetic alteration of hypertrophic masseter muscles to reduce a prominent mandibular angle . Surgical reduction is common in Asia, but botulinum toxin offers a less invasive approach . This pilot study evaluated results of aesthetic lower face narrowing in 20 Asian patients . Initially, 25 U of botulinum toxin (5 U/0.1 mL) was injected at each inferior masseter border; an additional 25 U was injected per side as needed at 1-week intervals . Seven patients (35%) required only 1 injection; 10 (50%) required 2; and 3 (15%) required 3 injections . Maximum reduction was seen at 1 to 2 months; more prominent hypertrophy yielded the most impressive results . Maintenance reinjection took place at 6 to 8 months . Up to 12 months of follow-up is reviewed herein . Two patients (10%) complained of mild fatigue after vigorous chewing and 1 developed mild transient buccal weakness . Nineteen of 20 patients were satisfied. Acta Neurol Scand, 2004 Jun, 109(6), 369 - 73 Orthopedic and neurological complications of cervical dystonia--review of the literature; Konrad C et al.; Cervical dystonia is the most frequent form of focal dystonia . Further, cervical dystonia can occur as a feature of segmental or generalized dystonias and cerebral palsy . Treatment with botulinum toxin to relieve pain and improve functional and psychological outcome is effective, but expensive . However, pharmacoeconomic studies evaluating treatment and disease costs have not taken into consideration the long-term complications of cervical dystonia . Here we present a review of the medical literature on orthopedic and neurological complications arising from cervical dystonia, including cervical spine degeneration, spondylosis, disk herniation, vertebral subluxations and fractures, radiculopathies and myelopathies . In summary, complications are more often reported in generalized dystonia and cerebral palsy than in focal dystonia . The prevalence is not well established, published estimations go from 18 to 41% in selected populations . Awareness of the frequent occurrence of complications and screening for symptoms of radiculomyelopathy in patients with dystonia is essential to avoid irreversible spinal cord damage . Complications of cervical dystonia need to be taken into consideration when weighting risks and calculating costs of the disease and its treatment . Copyright Blackwell Munksgaard 2004 Lancet, 2004 May 15, 363(9421), 1619 - 31 Cerebral palsy; Koman LA et al.; Cerebral palsy, a range of non-progressive syndromes of posture and motor impairment, is a common cause of disability in childhood . The disorder results from various insults to different areas within the developing nervous system, which partly explains the variability of clinical findings . Management options include physiotherapy, occupational and speech therapy, orthotics, device-assisted modalities, pharmacological intervention, and orthopaedic and neurosurgical procedures . Since 1980, modification of spasticity by means of orally administered drugs, intramuscular chemodenervation agents (alcohol, phenol, botulinum toxin A), intrathecally administered drugs (baclofen), and surgery (neurectomy, rhizotomy) has become more frequent . Family-directed use of holistic approaches for their children with cerebral palsy includes the widespread adoption of complementary and alternative therapies; however, the prevalence of their use and the cost of these options are unknown . Traditional medical techniques (physiotherapy, bracing, and orthopaedic musculoskeletal surgery) remain the mainstay of treatment strategies at this time . This seminar addresses only the musculoskeletal issues associated with cerebral palsy and only indirectly discusses the cognitive, medical, and social issues associated with this diagnosis. Rev Laryngol Otol Rhinol (Bord), 2003, 124(5), 315 - 20 {A retrospective study of 91 injections of botulinus toxin into the upper sphincter of the oesophagus}; Verhulst J et al.; OBJECTIVE: To evaluate the results of botulinus toxin in dysphagia arising in the upper sphincter of the oesophagus . MATERIALS AND METHODS: Since June 1995, 64 patients have had botulinus toxin injected into the upper sphincter of the oesophagus for major swallowing disorders . All cases were treated in the dysphagia service, and underwent clinical assessment, video-swallow screening, and swallowing therapy . The patient cohort included various pathological groups--neurological (vascular accident, head injury, cranial nerve disorders, degenerative diseases), postoperative (surgery for carcinoma of the laryngo-pharynx), and functional, whether purely idiopathic or attributable . RESULTS AND CONCLUSIONS: Global analysis of the results shows that botulinus toxin has good efficacy in relaxing the upper sphincter of the oesophagus; this does not always lead to recovery of normal swallowing, but can bring about improvement by assisting in the therapeutic management of the swallowing problem, and in improving the dietary intake. J Pharmacol Exp Ther, 2004 Aug, 310(2), 633 - 41 Epub 2004 May 12. Structural features of the botulinum neurotoxin molecule that govern binding and transcytosis across polarized human intestinal epithelial cells; Maksymowych AB et al.; Experiments were done to help localize the minimum essential domain within the botulinum toxin molecule that is necessary for binding and transport across human gut epithelial cells . The data demonstrated that the neurotoxin alone, in the absence of auxiliary proteins, undergoes transcytosis . The neurotoxin by itself was examined in the single chain (unnicked serotype B) and dichain (nicked serotype B, nicked serotype A) forms, and all displayed the ability to bind and penetrate epithelial barriers . In addition, the single chain and dichain molecules were examined in the oxidized and reduced states, and again all forms were transported . To further define the minimum essential domain, experiments were done with two toxin fragments: 1) the heavy chain, which was derived from native toxin, and 2) the carboxy-terminal portion of the heavy chain, which was generated by recombinant techniques . Interestingly, both fragments were fully competent in crossing epithelial barriers . These data suggest that a polypeptide derived from the toxin could be used as a carrier domain to transport other molecules across epithelial cells . In related experiments, physiological (i.e., potassium depletion) and pharmacological (i.e., chlorpromazine) manipulations were used to implicate clathrin-coated pits/vesicles as the structures responsible for endocytosis of toxin. Urology, 2004 May, 63(5), 868 - 72 Urodynamic evidence of effectiveness of botulinum A toxin injection in treatment of detrusor overactivity refractory to anticholinergic agents; Kuo HC; OBJECTIVES: To investigate the urodynamic changes after detrusor injection of botulinum A toxin in patients with detrusor overactivity refractory to treatment with anticholinergic agents . METHODS: Thirty patients with detrusor overactivity refractory to anticholinergic agents were treated with detrusor injection of botulinum A toxin (Botox) 200 U at 40 sites . Urodynamic parameters and symptom scores were assessed at baseline and 2 weeks and 3 months after the injections . Patients' responses were classified as excellent, improved, or failed . RESULTS: The 12 female and 18 male patients were aged 7 to 83 years (mean 67 +/- 17) . Of the 30 patients, 12 had neurogenic detrusor overactivity, 8 had idiopathic detrusor overactivity, and 10 had previous bladder outlet obstruction or had undergone previous transurethral prostatectomy . After detrusor botulinum A toxin injection, 8 patients regained urinary continence (26.7%), 14 patients had improvement in frequency, urgency, and incontinence (46.7%), and treatment failed 8 patients (26.7%) . The total success rate was 73.3% . Four patients experienced transient urinary retention and six had difficulty urinating after treatment . The urodynamic results showed increased cystometric capacity, decreased voiding pressure, increased postvoid residual urinary volume, decreased voiding efficiency, and increased bladder neck opening time at 2 weeks . The voiding pressure remained low and bladder neck opening time remained increased at 3 months, although the postvoid residual volume and voiding efficiency had returned to baseline levels . The therapeutic effects lasted for 3 to 9 months (mean 5.3) . CONCLUSIONS: Detrusor injection of 200 U of botulinum A toxin is effective in the treatment of detrusor overactivity that is refractory to anticholinergic agents . Patients with detrusor overactivity and inadequate contractility should be carefully selected for this procedure because the postvoid residual urine volume may increase after treatment. Mov Disord, 2004 May, 19(5), 588 - 90 Computed tomographically-controlled injection of botulinum toxin into the longus colli muscle in severe anterocollis; Herting B et al.; We report on a 44-year-old man who suffered from severe anterocollis . Repeated computed tomographically controlled injections of botulinum toxin into the right longus colli muscle allowed a precise location of the needle and injection of the toxin, leading to clear improvement of symptoms . Semin Pediatr Neurol, 2004 Mar, 11(1), 58 - 65 Management of spasticity in children with cerebral palsy; Tilton AH; As one component of the upper motor neuron syndrome, spasticity can have a significant functional impact on the child with cerebral palsy . Treatment planning requires the determination that excess tone interferes with some aspect of function, comfort, or care, and takes into consideration carefully devised goals that meet the needs of the patient and the caregiver . Treatment options include physical therapy, oral medications, chemodenervation with botulinum toxin or phenol, rhizotomy, intrathecal baclofen, and orthopedic surgery . The uses and limitations of each is discussed, and evidence for efficacy in cerebral palsy is reviewed. Eye, 2004 May, 18(5), 466 - 9 A single transcutaneous injection with Botox for dysthyroid lid retraction; Shih MJ et al.; PURPOSE: To evaluate the safety and efficacy of injections with botulinum toxin type A (BTTA,Botox), given transcutaneously, in the treatment of upper lid retraction associated with thyroid eye disease (TED) . METHODS: A total of 15 patients (21 eyes) with a stable (TED) condition, and a euthyroid state, were enrolled into the study . There were 12 females and three males from ages 23 to 52 years . A single injection, at the centrally superior tarsal border transcutaneously, aiming at the levator aponeurosis and Muller muscle, was administered into each eyelid with 5-6 U of Botox . All patients were followed regularly for 4-6 months . Any complications, such as ptosis, diplopia, pain,or lid ecchymosis were recorded . RESULTS: All patients, except one, experienced much reduction of palpebral fissure . The mean difference of MRD1 between pre- and postinjections of Botox at the first week was -3.1 mm, and the effect remained, at least, for 2 months . There were temporary complications of ptosis in three patients and vertical diplopia in two patients, lasting 3-4 weeks . CONCLUSIONS: A single transcutaneous injection with Botox for the treatment of thyroid lid retraction is safe and effective . Some minor complications may occur, such as ptosis and diplopia; however, it may offer an alternative and temporary method for patients with dysthyroid lid retraction, who are waiting for a staged operation of either an orbital decompression or a strabismus surgery or both. Arch Phys Med Rehabil, 2004 May, 85(5), 705 - 9 Botulinum toxin type B in upper-limb poststroke spasticity: a double-blind, placebo-controlled trial; Brashear A et al.; OBJECTIVE: To determine whether botulinum toxin type B (BTX-B) is effective in controlling upper-limb spasticity . DESIGN: A single-site, double-blind, placebo-controlled, randomized trial and open-label study . SETTING: Outpatient . PARTICIPANTS: Subjects with an Ashworth Scale score of 2 or more at the elbow, wrist, and fingers . INTERVENTIONS: Subjects were injected with 10000 U of BTX-B or placebo at the elbow, wrist, and finger flexors.Main outcome measures Measures recorded at weeks 0, 2, 4, 8, 12, and 16, with a 12-week open-label study . Ashworth Scale score, a global assessment of change (GAC), adverse events and mouse neutralization antibody testing . RESULTS: BTX-B did not decrease muscle tone in the elbow, wrist, or finger flexors at 10000 U over the 16-week period . A decrease in Ashworth Scale score for the BTX-B patient group was present at the wrist at week 2 of the double-blind study (P=.003) but was not statistically significant at other visits . In the open-label study, improvement was noted at week 4 for the elbow (P=.039), wrist (P=.002), finger (P=.001), and thumb flexors (P=.002) . In the double-blind study, the Physician GAC did not reach significance . Dry mouth was reported by 8 of 9 BTX-B subjects in the double-blind study . Mouse neutralization antibodies were negative . CONCLUSIONS: Our study does not show a significant decrease in tone from 10000 U of BTX-B . Dry mouth was common. J Urol, 2004 Jun, 171(6 Pt 1), 2128 - 37 Emerging role of botulinum toxin in the management of voiding dysfunction; Smith CP et al.; PURPOSE: In recent years there has been tremendous excitement over the use of botulinum neurotoxin (BTX) to treat various urethral and bladder dysfunctions . BTX is the most potent, naturally occurring toxin known to mankind . Why, then, would a urologist want to use this agent to poison the bladder or urethral sphincter? MATERIALS AND METHODS: We reviewed the recent literature on the mechanisms underlying the effects of BTX treatment and discuss current use of this agent within the urological community, as well as provide perspective on future targets of BTX . The information was gathered from MEDLINE, abstracts from recent urological meetings and personal experience . RESULTS: Injection of BTX appears to have a positive therapeutic effect in multiple urological conditions, including detrusor hyperreflexia and detrusor external sphincter dyssynergia, and nonneurogenic conditions such as pelvic floor spasticity, refractory overactive bladder and, possibly, benign prostatic hyperplasia . Interstitial cystitis may even be potentially helped with bladder BTX injection . CONCLUSIONS: Botulinum toxin is a novel and promising treatment for a variety of lower urinary tract dysfunctions . The basic science behind its mechanism of action and physiology, and published clinical results are impressive . However, since application of BTX in the lower urinary tract has not been approved by the Food and Drug Administration, caution should be used until future properly designed, multicenter randomized studies are completed to assess the safety and efficacy of BTX in urological diseases. J Biol Chem, 2004 Jul 16, 279(29), 30865 - 70 Epub 2004 Apr 30. Synaptotagmins I and II act as nerve cell receptors for botulinum neurotoxin G; Rummel A et al.; Botulinum neurotoxins (BoNTs) induce muscle paralysis by selectively entering cholinergic motoneurons and subsequent specific cleavage of core components of the vesicular fusion machinery . Complex gangliosides are requisite for efficient binding to neuronal cells, but protein receptors are critical for internalization . Recent work evidenced that synaptotagmins I and II can function as protein receptors for BoNT/B (Dong, M., Richards, D . A., Goodnough, M . C., Tepp, W . H., Johnson, E . A., and Chapman, E . R . (2003) J . Cell Biol . 162, 1293-1303) . Here, we report the protein receptor for a second BoNT serotype . Like BoNT/B, BoNT/G employs synaptotagmins I and II to enter phrenic nerve cells . Using pull-down assays we show that only BoNT/G, but neither the five remaining BoNTs nor tetanus neurotoxin, interacts with synaptotagmins I and II . In contrast to BoNT/B, interactions with both isoforms are independent of the presence of gangliosides . Peptides derived from the luminal domain of synaptotagmin I and II are capable of blocking the neurotoxicity of BoNT/G in phrenic nerve preparations . Pull-down and neutralization assays further established the membrane-juxtaposed 10 luminal amino acids of synaptotagmins I and II as the critical segment for neurotoxin binding . In addition, we show that the carboxyl-terminal domain of the cell binding fragment of BoNT/B and BoNT/G mediates the interaction with their protein receptor. Ann Neurol, 2004 May, 55(5), 732 - 5 Clinical impact of antibody formation to botulinum toxin A in children; Herrmann J et al.; We studied the clinical impact of neutralizing antibodies to botulinum toxin A that occurred during long-term treatment of children between 1993 and 2001 . Antibodies were found in high titers in 35 of 110 (31.8%) samples from individual patients . Antibody formation correlated with secondary nonresponse (p < 0.001) . The most significant risk factors for antibody formation were the frequency of treatments (p = 0.0001) and the injection of a higher weight-adapted maximum dose per treatment (p = 0.001). J Physiol, 2004 Jul 1, 558(Pt 1), 99 - 109 Epub 2004 Apr 30. A role for SNAP-25 but not VAMPs in store-mediated Ca2+ entry in human platelets; Redondo PC et al.; Store-mediated Ca2+ entry (SMCE) is a major mechanism for Ca2+ influx in non-excitable cells . Recently, a conformational coupling mechanism allowing coupling between transient receptor potential channels (TRPCs) and IP3 receptors has been proposed to activate SMCE . Here we have investigated the role of two soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs), which are involved in membrane trafficking and docking, in SMCE in human platelets . We found that the synaptosome-associated protein (SNAP-25) and the vesicle-associated membrane proteins (VAMP) coimmunoprecipitate with hTRPC1 in platelets . Treatment with botulinum toxin (BoNT) E or with tetanus toxin (TeTx), induced cleavage and inactivation of SNAP-25 and VAMPs, respectively . BoNTs significantly reduced thapsigargin- (TG) and agonist-evoked SMCE . Treatment with BoNTs once SMCE had been activated decreased Ca2+ entry, indicating that SNAP-25 is required for the activation and maintenance of SMCE . In contrast, treatment with TeTx had no effect on either the activation or the maintenance of SMCE in platelets . Finally, treatment with BoNT E impaired the coupling between naturally expressed hTRPC1 and IP3 receptor type II in platelets . From these findings we suggest SNAP-25 has a role in SMCE in human platelets. Br J Oral Maxillofac Surg, 2004 Jun, 42(3), 272 - 3 Reduction of a chronic bilateral temporomandibular joint dislocation with intermaxillary fixation and botulinum toxin A; Aquilina P et al.; A 71-year-old man was referred to the Department of Oral and Maxillofacial Surgery at Westmead Hospital for investigation of limited jaw movement and facial pain after a cerebrovascular event eight weeks previously . He was found to have bilateral dislocations of the temporomandibular joints (TMJ) and was successfully treated with a combination of intermaxillary fixation (IMF) screws and botulinum toxin A. Eur J Vasc Endovasc Surg, 2004 Jun, 27(6), 571 - 6 Current therapeutic options for treating primary hyperhidrosis; Nyamekye IK; Severe hyperhidrosis can cause extreme embarrassment that may lead to social and professional isolation . Therapeutic strategies to hyperhidrosis should employ the least invasive treatment that provides effective symptom control . The treatment options available for control of hyperhidrosis, non-surgical or surgical, differ in their invasiveness and efficacy . Mechanisms of action of antiperspirants, iontophoresis, cholinergic inhibitor drugs, botulinum toxin, and surgical sympathectomy are reviewed . There is little published evidence in the form of comparative randomised trials to support the use of one treatment over another . However, authors have tended to recommend those therapies that are available to their speciality . Specific therapies should be tailored to the patient's symptoms to gain maximum symptomatic improvement with minimum invasiveness and side-effects . To achieve this, the full range of treatment options should be available to, or accessible by the consulting doctor in order for the patient to have a meaningful choice. Muscle Nerve, 2004 May, 29(5), 628 - 44 Botulinum toxins in neurological disease; Comella CL et al.; Botulinum toxins are among the most potent neurotoxins known to humans . In the past 25 years, botulinum toxin has emerged as both a potential weapon of bioterrorism and as a powerful therapeutic agent, with growing applications in neurological and non-neurological disease . Botulinum toxin is unique in its ability to target peripheral cholinergic neurons, preventing the release of acetylcholine through the enzymatic cleavage of proteins involved in membrane fusion, without prominent central nervous system effects . There are seven serotypes of the toxin, each with a specific activity at the molecular level . Currently, serotypes A (in two preparations) and B are available for clinical use, and have been shown to be safe and effective for the treatment of dystonia, spasticity, and other disorders in which muscle overactivity gives rise to symptoms . This review focuses on the pharmacology, electrophysiology, immunology, and application of botulinum toxin in selected neurological disorders. Curr Pain Headache Rep, 2004 Jun, 8(3), 178 - 84 Prophylactic migraine therapy: emerging treatment options; Bigal ME et al.; In this paper, new treatment options for migraine prevention are reviewed . An overview about migraine pathophysiology is provided and current indications for migraine prevention and new and upcoming preventive medications are discussed briefly . Data are presented on topiramate, levetiracetam, zonisamide, botulinim toxin, tizanidine, nefazodone, lisinopril, candesartan, carabersat, petasites, and coenzyme Q. Protein J, 2004 Jan, 23(1), 39 - 52 Mapping of the antibody-binding regions on the HN-domain (residues 449-859) of botulinum neurotoxin A with antitoxin antibodies from four host species . Full profile of the continuous antigenic regions of the H-chain of botulinum neurotoxin A; Atassi MZ et al.; Previously, we mapped the antibody (Ab) and T-cell recognition regions on the HC domain (residues 855-1296) of the 848-residue heavy (H) chain of botulinum neurotoxin A (BoNT/A) . We have mapped here the HN-domain (residues 449-859) regions that bind protective anti-BoNT/A Abs raised in four different species . We synthesized, purified, and characterized 29 19-residue peptides that spanned the entire HN and overlapped consecutively by 5 residues, and also region L218-231 around the L-chain's substrate-binding site . Human, horse, mouse, and chicken anti-BoNT/A Abs did not bind to the L-peptide but recognized similar HN regions within peptides 519-537/533-551/547-565/561-579 (with slight left- or right-shifts), 743-761, 785-803, and 813-831/827-845 overlap . Recognition of other peptides that bound lower Ab levels showed similarities and also some differences . Peptide 463-481, strongly immunodominant with horse antisera, did not bind human, mouse, and chicken Abs . However, peptide 449-467 bound Abs in these three antisera, and the region may have shifted to the right (peptide 463-481) with horse Abs . The overlap 659-677/673-691 reacted strongly with human Abs whereas with mouse and chicken antisera, only peptide 673-691 showed low reactivity . Horse antisera had no detectable Ab binding to region(s) 659-691 . The Ab-recognition regions on the H chain occupy surface locations in BoNT/A three-dimensional structure, but the great part of the surface is not immunogenic . Regions recognized by the protective antisera of the four different species are prime candidates for inclusion in synthetic vaccine designs. Dig Dis Sci, 2004 Feb, 49(2), 165 - 75 The use of botulinum toxin for the treatment of gastrointestinal motility disorders; Friedenberg F et al.; Botulinum toxin type A is used extensively for the management of gastrointestinal smooth muscle disorders . This review is a comprehensive summary of the current status of this therapy . It includes English-language research from 1966 to 2003 and relevant abstracts from subspecialty meetings from the past 3 years . Botulinum toxin appears to be beneficial for achalasia, gastroparesis, sphincter of Oddi dysfunction, anal fissure and anismus . Very few placebo-controlled trials have been performed despite widespread use of toxin for the past 10 years . Botulinum toxin appears to be safe and side effects are uncommon . Despite uncontrolled data, botulinum toxin is now used for a variety of spastic disorders of GI smooth muscle . In some instances this therapy may preclude the nee