Gastrointest Endosc, 2001 Dec, 54(6), 754 - 9 Treatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: a prospective study with long-term follow-up; Storr M et al.; BACKGROUND: Diffuse esophageal spasm is a rare esophageal motility disorder for which there are no satisfactory pharmacologic alternatives for treatment . The aim of this study was to investigate whether botulinum toxin (BTX) injection is an effective short- and long-term treatment for patients with symptoms caused by diffuse esophageal spasm . Whether recurrence of clinical symptoms can be successfully retreated by BTX injection was also studied . METHODS: Nine symptomatic patients (6 women, 3 men; 57-86 years) with manometrically proven diffuse esophageal spasm underwent BTX injection . One hundred IU BTX were diluted in l0 mL of saline solution and injected endoscopically at multiple sites along the esophageal wall beginning in the region of the lower esophageal sphincter and moving proximally in 1- to 1.5-cm intervals, and into endoscopically visible contraction rings . Symptom scores based on an analogue scale for dysphagia, regurgitation, and noncardiac chest pain were assessed before and after therapy, 1 day thereafter, and at 1 and 6 months . RESULTS: Symptoms improved immediately in 7 (78%) patients after 1 injection session . After 4 weeks 8 (89%) patients were in remission with a decrease in total symptom score . The total symptom score decreased from a median 8.0 (interquartile range: 6.75; 9.0) before treatment to 2.0 (1.5; 3.75) after 1 day (p < 0.01) and to 2.0 (interquartile range: 0.75; 3.0) after 1 month (p < 0.01) . After 6 months all 8 patients with a response at 1 month still had a symptom score of 3 or less without further treatment . Subsequently 4 patients required reinjection 8, 12, 15, or 24 months after the initial treatment with similarly good results . No serious adverse effects were observed . CONCLUSIONS: BTX injection at several levels of the tubular esophagus is an effective treatment for patients with symptoms caused by diffuse esophageal spasm . Symptom relapse can be effectively treated by repeated BTX injection. Invest Ophthalmol Vis Sci, 2001 Dec, 42(13), 3158 - 64 Long-term changes in myosin heavy chain composition after botulinum toxin a injection into rat medial rectus muscle; Kranjc BS et al.; PURPOSE: To study long-term changes of extraocular muscles after botulinum toxin (Botx) A-induced paralysis, with special emphasis on myosin heavy chain (MyHC) isoform pattern in muscle fibers . METHODS: Botx A (5 IU) was injected into the ocular medial rectus (MR) muscles of adult rats . After 1, 5, and 8 months muscle cross sections were examined immunohistochemically, histochemically, and morphometrically . MyHC content was analyzed by gel electrophoresis . RESULTS: Paralyzed MR muscles displayed mildly atrophic and hypertrophic muscle fibers and decreased oxidative metabolism, due to decreased succinate dehydrogenase activity . However, muscle morphology was not grossly disturbed . MyHC profile was shifted toward slower isoforms . Electrophoretic analysis showed that the share of MyHCI, and especially of MyHCIIa and MyHCIIx/d, increased several fold, whereas the share of MyHCIIb decreased heavily during the first 5 months . Immunohistochemical analysis generally mirrored the results obtained by electrophoresis . Moreover, specific extraocular MyHC isoform MyHCeom disappeared and could not be detected during the whole experimental period . The portion of MyHCIIb relatively increased 8 months after Botx A injection, although the MyHC profile was still far from normal . CONCLUSIONS: These long-lasting changes in Botx A-paralyzed ocular MR muscles most probably reflect their inability to regain their unique functional characteristics after new motor end plate formation and recovery of muscle contraction. Phys Med Rehabil Clin N Am, 2001 Nov, 12(4), 833 - 74, vii-viii Botulinum neurotoxin intramuscular chemodenervation . Role in the management of spastic hypertonia and related motor disorders; Yablon SA; There is a range of interventions available in the management of spastic hypertonia among patients with central nervous system injury . Many of these treatment options can be used concurrently with great effectiveness . Although manifestations of spastic hypertonia vary from patient to patient, they usually are not limited to one site . Nevertheless, problematic spastic muscle overactivity may be localized to one or more specific extremities, and these may be referred to as examples of focal dysfunctional spasticity . Botulinum neurotoxin (BTX) intramuscular chemodenervation procedures are an important therapeutic technique in focal spasticity management . Magnitude and duration of response varies with successful selection and localization of targeted muscles, spasticity severity, BTX dosage, and chosen functional goals . In focal dysfunctional spasticity and related motor disorders, BTX injections have demonstrated efficacy and safety when performed by clinicians familiar with the agent, regional anatomy, the specific condition, and patient being treated. Curr Opin Neurol, 2001 Dec, 14(6), 771 - 6 Botulinum treatment of spasticity: why is it so difficult to show a functional benefit? Sheean GL. Clinical experience seems to indicate that botulinum toxin injections can, in selected patients with upper motor neurone syndrome, reduce spasticity and improve voluntary movement and active function . However, double-blind placebo-controlled trials have had difficulty showing active functional improvement, despite the clear ability of botulinum toxin to reduce spasticity . This prompts a re-analysis of the basic assumption that spasticity impairs voluntary movement and a review of the methodology of the clinical trials . Motor dysfunction is usually caused by weakness and the other "negative" features of upper motor neurone syndrome, rather than muscle overactivity . Recent research has explored the pathophysiological basis of the voluntary movement disorder, in particular the role of the various forms of motor overactivity, which might be amenable to botulinum toxin treatment . The failure of double-blind placebo-controlled clinical trials to show improvement in active function is, to a large extent, a result of their methodology, especially patient selection, injection protocols, and the choice of outcome measures . Clinical trials need to be re-designed and based upon expert experience and a better understanding of the pathophysiology of the motor disorder. Gerontology, 2001 Nov-Dec, 47(6), 295 - 9 Spasticity: a rehabilitation challenge in the elderly; Barnes MP; There is no doubt that spasticity is a significant cause of disability in the elderly . Regrettably, it is a condition that is often poorly treated and can result in a range of unnecessary complications which can cause further problems for the disabled person and their family . There are now a number of effective treatment options . However, before such options are defined the specific goals of rehabilitation need to be clarified and an appropriate outcome measure chosen in order to determine when such goals are being met . The treatment should be multidisciplinary and input from both the physician and a physiotherapist is essential . Involvement of the elderly person with spasticity, and often their family, is also important in the education process . Simple physiotherapy interventions can be remarkably helpful, including attention to positioning and seating . The role of the physician initially focuses on oral medication . Although we still have older drugs including diazepam, baclofen and dantrolene there are now more modern drugs including tizanidine and, more recently, gabapentin . However, most spasticity is focal in origin and thus requires focal treatment . Although phenol nerve blocks are sometimes helpful the use of botulinum toxin is now to be highly recommended . There is now clear evidence of the efficacy of botulinum toxin, which has been a significant advance in our management of spasticity . More advanced and difficult to treat problems can be alleviated by intrathecal baclofen or sometimes intrathecal phenol or, as a last resort, surgical intervention . The advent of lycra garments for the overall management of more diffuse spasticity is now becoming both fashionable and effective . Conclusion: The management of spasticity in the elderly person is a significant challenge to the rehabilitation team and a combined approach can produce significant benefit for the disabled elderly person . Dysphagia, 2001 Fall, 16(4), 244 - 8 Cricopharyngeal muscle hypertrophy associated with florid myositis; Bachmann G et al.; Hypertrophy of the cricopharyngeal muscle is a serious clinical condition that can cause severe dysphagic symptoms, including prolonged deglutition and postdeglutitive aspiration . Although the therapeutical concepts are well established, the pathogenic mechanism of cricopharyngeal hypertrophy remains unclear . We present a patient with a ten-year history of progressive dysphagia . The neurological and MRI findings were normal . However, videocineradiography showed severe hypertrophy of the cricopharyngeal muscle . This condition was first treated by injections of botulinum toxin, which did not alleviate the symptoms . Next, myotomy and muscle biopsy were performed . Histological evaluation disclosed lymphoplasmacellular florid myositis, single-fiber atrophy, and muscle fiber necrosis with phagocytosis . There were no signs of inclusion body myositis or oculopharyngeal muscular dystrophy . Our finding of severe cricopharyngeal muscle hypertrophy associated with myositis has been published previously (n = 34) . The study presented here shows cricopharyngeal dysphagia associated with various systemic diseases, including motor neuron disease, general granulomatous disease, dermatomyositis, or inclusion body myositis . Isolated changes of the cricopharyngeal muscle were described in 65% of the cases. Zhonghua Er Bi Yan Hou Ke Za Zhi, 1998 Oct, 33(5), 291 - 3 {Blepharospasm and hemifacial spasm treated with botulinum A toxin injection}; Wang J et al.; OBJECTIVE: To study the efficacy of botulinum A toxin (BTA) injections for the treatment of blepharospasm and hemifacial spasm (HFS) . METHODS: Twelve patients with blepharospasm and thirty eight patients with HFS were treated with BTA local injections (2.5 U to 5 U for each injection) . RESULTS: Of the fifty patients, ten (86.7%) in blepharospasm and thirty two (84.2%) in HFS were completely relieved, two (13.3%) and five (13.2%) were remarkably relieved respectively, zero and one (2.6%) were partial relieved respectively . All patients experienced relief from spasm . The duration of the effect in blepharospasm were 10 to 24 weeks (mean, 18 weeks) and in HFS 14 to 32 weeks (mean, 22 weeks) . The local side effects were transient and mild, including minor facial paralysis in eight patients, ptosis in four patients and tearing in four patients . No systemic adverse and allergic reactions were noted . CONCLUSION: Botulinum A toxin local injection is a safe, effective and simple means for the treatment of blepharospasm and HFS. Ann Otol Rhinol Laryngol, 2001 Nov, 110(11), 1045 - 50 Botulinum toxin type A induces apoptosis in nasal glands of guinea pigs; Rohrbach S et al.; Nasal hypersecretion is predominantly caused by overaction of nasal glands, which are mainly under cholinergic control . In this work, we investigated the influence of botulinum toxin A (BTA) on the nasal mucosal tissue of the maxillary sinus turbinates of guinea pigs (n = 10) that were painlessly sacrificed 10 days (short-term group) or 3 months (long-term group) after local treatment with 20 units of BTA (Botox) or 0.2 mL of 0.9% sodium chloride (control) . Histologic investigation of the nasal mucosal tissue of the BTA-treated animals (short-term group) showed degeneration of glands and ducts and apoptotic nuclei on TUNEL staining of these structures . The control animals revealed normal glandular tissue and no apoptosis . The animals of the long-term group showed almost normal glandular tissue and only a few apoptotic nuclei . In conclusion, BTA induces temporary apoptosis in the nasal glandular compartment of guinea pigs. ORL J Otorhinolaryngol Relat Spec, 2001 Nov-Dec, 63(6), 382 - 4 Minimally invasive application of botulinum toxin type A in nasal hypersecretion; Rohrbach S et al.; We report on the effect of the local application of botulinum toxin A on nasal hypersecretion in a female patient with intrinsic rhinitis . 20 units of botulinum toxin A (Botox) was inserted into each nostril using a small sponge in close contact with the lower and middle turbinates . The effect was scored by the patient and by rhinomanometry . Nasal hypersecretion diminished clearly 5 days after the treatment . The rhinomanometric flow increased 2 weeks after the application . No side effects occurred . We conclude that this minimal invasive method of local botulinum toxin application might be a very effective and safe option for the treatment of nasal hypersecretion of different etiologies . Arch Facial Plast Surg, 2001 Oct-Dec, 3(4), 268 - 9 Botulinum toxin A for mentalis muscle dysfunction; Papel ID et al.; OBJECTIVE: To describe the use of botulinum toxin A for treatment of mentalis muscle dysfunction secondary to failed augmentation mentoplasty . DESIGN: Clinical observations were made in the treatment of mentalis muscle dysfunction . Patients with the postmentoplasty signs of mental skin dimpling and soft tissue ptosis were injected with 20 U of botulinum toxin A and observed for visual and functional improvement . Photographs were taken for documentation . SETTING: Private facial plastic surgery practice . PATIENTS: Three patients with a history of failed augmentation mentoplasty were identified and signs/symptoms recorded . Each patient was treated with 20 U of botulinum toxin A and observed for clinical improvement . MAIN OUTCOME MEASURES: Pretreatment and posttreatment photographs of active and passive mentalis function together with patient satisfaction surveys . RESULTS: Of the 3 patients treated, all reported alleviation of the mentalis dysfunction and improved appearance . The symptoms began to return as the botulinum toxin A effects subsided . CONCLUSIONS: Botulinum toxin A is a safe and effective treatment of mentalis dysfunction secondary to failed augmentation mentoplasty . The effects are predictable, although temporary. Biochem Soc Trans, 2001 Nov, 29(Pt 6), 742 - 5 Regulation of glycine transporters; Lopez-Corcuera B et al.; The regulation of neurotransmitter transporters is a central aspect of their physiology . Recent studies that focused on syntaxin-1 transporter interactions led to the postulation that syntaxin-1 is somehow implicated in protein trafficking . Because syntaxin-1 is involved in the exocytosis of neurotransmitters and it interacts with glycine transporter 2 (GLYT2), we stimulated exocytosis in synaptosomes and examined its effect on GLYT2 surface-expression and transport activity . We found that GLYT2 is rapidly trafficked first towards the plasma membrane and then internalized under conditions that stimulate vesicular glycine release . However, when syntaxin-1 was inactivated by pre-treatment of synaptosomes with the botulinum neurotoxin C, GLYT2 was unable to reach the plasma membrane but still was able to leave it . These results indicate the existence of a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-mediated regulatory mechanism that controls the surface expression of GLYT2 . Syntaxin-1 is involved in the transport of GLYT2 to, but not its retrieval from, the plasma membrane . Immunogold-labelling on purified vesicular preparations from synaptosomes showed that GLYT2 is present in small synaptic-like vesicles . This may represent neurotransmitter transporter that is being trafficked . The subcellular distribution of the glycine transporters was further examined in PC12 cells that were stably transfected with the fusions of GLYT1 and GLYT2 with green fluorescent protein . There was a clear difference in their intracellular distribution, GLYT1 being present mainly on the plasma membrane and GLYT2 being localized mainly on large, dense-core vesicles . We are trying to find signal sequences responsible for this differential localization. Drugs, 2001, 61(13), 1921 - 43 Cervical dystonia pathophysiology and treatment options; Velickovic M et al.; Dystonia is a syndrome of sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal posturing . Cervical dystonia (CD) is a form of dystonia that involves neck muscles . However, CD is not the only cause of neck rotation . Torticollis may be caused by orthopaedic, musculofibrotic, infectious and other neurological conditions that affect the anatomy of the neck, and structural causes . It is estimated that there are between 60,000 and 90,000 patients with CD in the US . The majority of the patients present with a combination of neck rotation (rotatory torticollis or rotatocollis), flexion (anterocollis), extension (retrocollis), head tilt (laterocollis) or a lateral or sagittal shift . Neck posturing may be either tonic, clonic or tremulous, and may result in permanent and fixed contractures . Sensory tricks ('geste antagonistique') often temporarily ameliorate dystonic movements and postures . Commonly used sensory tricks by patients with CD include touching the chin, back of the head or top of the head . Patients with CD are classified according to aetiology into two groups: primary CD (idiopathic--may be genetic or sporadic) or secondary CD (symptomatic) . Patients with primary CD have no evidence by history, physical examination or laboratory studies (except primary dystonia gene) of any secondary cause for the dystonic symptoms . CD is a part of either generalised or focal dystonic syndrome which may have a genetic basis, with an identifiable genetic association . Secondary or symptomatic CD may be caused by central or peripheral trauma, exposure to dopamine receptor antagonists (tardive), neurodegenerative disease, and other conditions associated with abnormal functioning of the basal ganglia . In the majority of patients with CD, the aetiology is not identifiable and the disorder is often classified as primary . Unless the aetiological investigation reveals a specific therapeutic intervention, therapy for CD is symptomatic . It includes supportive therapy and counselling, physical therapy, pharmacotherapy, chemodenervation {botulinum toxin (BTX), phenol, alcohol}, and central and peripheral surgical therapy . The most widely used and accepted therapy for CD is local intramuscular injections of BTX-type A . Currently, both BTX type A and type B are commercially available, and type F has undergone testing . Pharmacotherapy, including anticholinergics, dopaminergic depleting and blocking agents, and other muscle relaxants can be used alone or in combination with other therapeutic interventions . Surgery is usually reserved for patients with CD in whom other forms of treatment have failed. Biochem Biophys Res Commun, 2001 Nov 16, 288(5), 1231 - 7 Site-directed mutagenesis identifies active-site residues of the light chain of botulinum neurotoxin type A; Rigoni M et al.; Botulinum neurotoxins (BoNTs) are metalloproteases which block neuroexocytosis via specific cleavage and inactivation of SNARE proteins . Such proteolysis accounts for the extreme toxicity of these neurotoxins and of their prolonged effect . The recently determined structures of BoNT/A and/B allows one to design active-site mutants to probe the role of specific residues in the proteolysis of SNARE proteins . Here we present the results of mutations of the second glutamyl residue involved in zinc coordination and of a tyrosine and a phenylalanine residues that occupy critical positions within the active site of BoNT/A . The spectroscopic properties of the purified mutants are closely similar to those of the wild-type molecule indicating the acquisition of a correct tertiary structure . Mutation of the Glu-262* nearly abolishes SNAP-25 hydrolysis as expected for a residue involved in zinc coordination . The Phe-266 and Tyr-366 mutants have reduced proteolytic activity indicating a direct participation in the proteolytic reaction, and their possible role in catalysis is discussed . Dent Clin North Am, 2001 Oct, 45(4), 685 - 700 Headaches and their relationship to sleep; Biondi DM; Despite the complex influences of normal sleep physiology and sleep disorders on the development or presentation of headache, it is important to recognize and understand these relationships . Successful outcomes depend on the provision of treatment interventions specifically directed toward each condition . Nocturnal or early morning headaches that are associated with OSA are often eradicated after the sleep disorder is successfully managed with CPAP, oral appliances, or surgery . Substantial improvement in headache can also result from the successful management of other sleep disorders that may incite headaches such as heavy snoring, PLMS, or the various forms of insomnia . To improve headache patterns associated with bruxism and TMD, it is often necessary to formulate a multidisciplinary treatment approach that combines oral appliance therapy, stress management, biofeedback, oromandibular physical therapy, and, at times, pharmacologic treatment (i.e., tricyclic antidepressant, intramuscular botulinum toxin injections) . There are still many gaps in the understanding of the interrelationships of sleep physiology and headache pathophysiology . More well-designed clinical trials are needed so that enough data can be amassed for the formulation of evidence-based guidelines or consensus statements that can better delineate the identification, diagnostic evaluation, and treatment of sleep-related headache disorders and headaches that develop as a consequence of disordered sleep. HNO, 2001 Oct, 49(10), 807 - 13 {Blocking secretion of exocrine glands in the head-neck area by administration of botulinum toxin A . Therapy of a rare disease picture}; Ellies M et al.; BACKGROUND: Hypersecretion disorders of the exocrine glands of the head and neck area are a therapeutic problem in the field of otorhinolaryngology . In the present study, we demonstrate the effectiveness of local injections of botulinum toxin A to block secretions of exocrine glands of the head and neck area . PATIENTS AND METHODS: Four patients suffering from hypersecretion disorders received local injections of botulinum toxin A . Two patients suffered from disorders of the salivary glands: one presented an idiopathic hypersialorrhea and another a salivary fistula after parotidectomy . A third patient suffered from epiphora and a further patient presented severe hyperhidrosis on the pilose head region . In a retrospective clinical study, the outcome of therapy was evaluated by clinical examination and chemical parameters . RESULTS: Clear blocking of secretion in the treated glands could be demonstrated in all four cases . Possible side effects of the treatment could not be observed . CONCLUSIONS: The present study was able to demonstrate a clear blocking of secretion of the exocrine glands of the head and neck region through botulinum toxin A, offering an improvement in therapy especially for the innovative indication of blocking the salivary glands of the head. Pediatrics, 2001 Nov, 108(5), 1062 - 71 Botulinum toxin type a neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial; Koman LA et al.; BACKGROUND: Focal spasticity of the gastrocnemius-soleus muscles causes equinus gait in children with cerebral palsy (CP) . Botulinum toxin type A (BTX-A), a neuromuscular blocking agent, reduces muscle tone/overactivity in dystonia, stroke, and CP . OBJECTIVE: A prospective, open-label, multicenter clinical trial evaluated the long-term safety and efficacy of repeated intramuscular injections of BTX-A on equinus gait in CP children . METHODS: Nine centers enrolled 207 children . BTX-A injections (4 U/Kg) were given approximately every 3 months (maximum dose 200 U per treatment) . Outcome measures included a Physician Rating Scale of gait, ankle range of motion measurements, and the incidence and profile of adverse events . RESULTS: One hundred fifty-five (75%) of 207 children completed at least 1 year with a total of 302 patient years of BTX-A treatment . The mean duration of BTX-A exposure was 1.46 years per patient . Dynamic gait pattern on the Physician Rating Scale improved in 46% of patients (86/185) at first follow-up . The response was maintained in 41% to 58% of patients for 2 years . Both gait pattern and ankle position improved at every visit . The most common treatment-related adverse events included increased stumbling, leg cramps, leg weakness, and calf atrophy in 1% to 11% of patients . No treatment-related serious adverse events were reported . Only 6% (7/117) of patients with pre- and postantibody samples had both detectable antibodies and a subsequent treatment failure . CONCLUSION: BTX-A proved both safe and effective in the chronic management of focal muscle spasticity in children with equinus gait. Gac Med Mex, 2001 Sep-Oct, 137(5), 403 - 11 {Botulin toxin as treatment for spasticity and dystonia in infantile cerebral paralysis}; Aguilar-Rebolledo F et al.; Treatment of spasticity and dystonia in PCI with Botulinum toxin A . BACKGROUND: Botulinum-A (NxTxBoA) toxin produce neuromuscular blockade, it has been effective with therapeutic purposes in strabismus, focal dystonias and spasticity . OBJECTIVE: Evaluate the therapeutically effects off NxTxBoA in cerebral palsy (CP) spastic and/or dystonic in children . Prospective study . MATERIAL AND METHODS: 12 CP patients (8 spastic and 4 spastic/dystonic) were treated with NxTxBoA in affected muscles at least for 2 doses by up 12 months . The indication was: improve limb function, to avoid surgical correction or improve hygienic or dressing . Ashworth Spasticity Scale (ASS), functional scale for Dystonic Sindou-Millet (SMS) and O'Brien Global Assessment Scale (OGAS) were used to evaluate improvement . STATISTICAL METHODS: No parametric tests, Wilcoxon's rang's test and sign test were used with p < 0.05 . RESULTS: Total doses session was 3-10 U/kg . AAS showed muscle spasticity improvement in two grades in 8 patients, and one grade in the rest (p = 0.004) . SMS showed the muscle dystonic improve up 60% in two patients improve 50% in others (p = 0.006) . OGAS demonstrated a good correlation . Mean treatment effect during 4.8 months (rank 4 to 10 m) . Two patients had side effects, general weakness, instability, and focal haematoma . CONCLUSIONS: Botulinum toxin type A proved a highly useful adjuvant therapy and conservative management in CP. Nervenarzt, 2001 Oct, 72(10), 787 - 90 {Effectiveness of botulinum toxin A in the treatment of gustatory sweating}; Kuttner C et al.; Frey's syndrome is present in almost all patients after parotidectomy . Gustatory sweating reduces quality of life . Injections of botulinum toxin A have recently been described as effective . This study was designed to evaluate the efficacy of this new treatment . Nineteen patients with severe gustatory sweating following superficial parotidectomy were treated . One unit/cm2 botulinum toxin A was injected intracutaneously into the affected area once . Minor's starch iodine test was performed to prove the outcome of therapy 4 weeks later . Eight patients lost their sweating . However, another seven patients had some blue spots on their cheeks . In four patients whose sweating had extended beyond the hairline, remnants of gustatory sweating showed up . Overall, the affected area of gustatory sweating could be reduced by botulinum toxin A from an average of 31 cm2 before treatment to 4 cm2 after treatment . Although there were some remnants of sweating in a few patients, Frey's syndrome was gone in all cases . No side effects could be observed . Intracutaneous injections of botulinum toxin A are highly effective and safe in treatment of gustatory sweating. Cochrane Database Syst Rev . 2001;(4):CD001332. Anti-spasticity agents for multiple sclerosis; Shakespeare DT et al.; BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care . A variety of oral and parenteral medications are available . OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients . SEARCH STRATEGY: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies . SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration . DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised . Missing data were collected by correspondence with principal investigators . A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed . MAIN RESULTS: Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria . Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs . Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive . REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing . The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed. J Eur Acad Dermatol Venereol, 2001 May, 15(3), 207 - 11 Subcutaneous curettage vs . injection of botulinum toxin A for treatment of axillary hyperhidrosis; Rompel R et al.; BACKGROUND: Axillary hyperhidrosis is a functional non-inflammatory abnormality of the eccrine sweat glands . The cause of genuine hyperhidrosis is unknown and, therefore, no specific corrective therapy is available and conservative treatment often fails . Subcutaneous sweat gland curettage of the axillae is one of the proven surgical modalities . Local injection of botulinum toxin A (BT-A) is a promising new conservative approach . OBJECTIVE: The purpose of this study was to compare the efficacy of subcutaneous curettage vs . injection of BT-A in axillary hyperhidrosis . METHODS: A total of 113 patients (36.3% males, 63.7% females) suffering from genuine axillary hyperhidrosis were treated by either subcutaneous curettage (n = 90) or local injection of BT-A (n = 23) . Median follow-up period was 23.5 months . Questionnaires were handed out to patients for a subjective assessment of symptoms before treatment, 6 months after the procedure, and at the time of last follow-up . The patients were asked to rate the amount of axillary sweating based on a score ranging from 1 (no axillary secretion) to 6 (maximum axillary secretion) . The subjective scores of sweating at rest, at high temperatures, under physical stress, under emotional stress and after spicy meals were assessed . RESULTS: The patients' subjective assessments of the overall outcome after subcutaneous curettage were 'very good' in 36.4%, 'good' in 29.9% and 'satisfactory' in 16.9% . The subjective score of axillary sweating at rest was reduced to 40.0% after 6 months, and finally to 45.7% at the end of follow-up (median: 28.2 months) . Patients treated by BT-A injection assessed outcome as 'very good' in 39.1%, 'good' in 21.7% and 'satisfactory' in 8.7% . Sweating at rest was reduced to 48.5% after 6 months, and finally to 68.8% at the end of follow-up (median: 16.1 months) . The mean duration of the antiperspiration effect of BT-A was 7.6 months (median: 7 months), but there were two cases of long durations, i.e . 14 and 18 months . CONCLUSIONS: Subcutaneous curettage and injection of BT-A both present major advantages compared with earlier methods . Subcutaneous curettage offers the same permanent efficacy but far fewer side-effects than sympathectomy, and less scarring than local excisional procedures, respectively . Of the conservative approaches BT-A is by far the most efficacious . Patients should be informed of the advantages and disadvantages of both methods. Int J Clin Pharmacol Ther, 2001 Oct, 39(10), 460 - 3 Botulinophilia: contraindication for therapy with botulinum toxin; Harth W et al.; Botulinum toxin inhibits neuromuscular transmission and is one of the most potent toxins . It has proven to be effective in the treatment of hyperhidrosis and is being more frequently demanded for therapy . Patients with body dysmorphic disorder also seek costly treatment with botulinum toxin . This botulinophilia is a new venenophilia . Body dysmorphic disorder is defined as a preoccupation with an imagined defect in appearance . If a slight physical anomaly is present, the person's concern is markedly exessive . The patient's preoccupation causes clinically significant distress or impairment in socially, occupational, or other important areas of functioning . The sweat test according to Minor is negative . Patients with botulinophilia are among the most difficult patients managed by the dermatologist . They are demanding and time-consuming . In our clinic, 23.1% of a series of patients seeking treatment with botulinum toxin screened positive for body dysmorphic disorder . Botulinophilia is a contraindication for therapy with botulinum toxin but is an indication for psychotherapy. Am J Physiol Heart Circ Physiol, 2001 Nov, 281(5), H2124 - 32 Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons; Morris JL et al.; The role of the soluble NSF attachment protein receptor (SNARE) protein complex in release of multiple cotransmitters from autonomic vasodilator neurons was examined in isolated segments of guinea pig uterine arteries treated with botulinum neurotoxin A (BoNTA; 50 nM) . Western blotting of protein extracts from uterine arteries demonstrated partial cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) to a NH2-terminal fragment of approximately 24 kDa by BoNTA . BoNTA reduced the amplitude (by 70-80%) of isometric contractions of arteries in response to repeated electrical stimulation of sympathetic axons at 1 or 10 Hz . The amplitude of neurogenic relaxations mediated by neuronal nitric oxide (NO) was not affected by BoNTA, whereas the duration of peptide-mediated neurogenic relaxations to stimulation at 10 Hz was reduced (67% reduction in integrated responses) . In contrast, presynaptic cholinergic inhibition of neurogenic relaxations was abolished by BoNTA . These results demonstrate that the SNARE complex has differential involvement in release of cotransmitters from the same autonomic neurons: NO release is not dependent on synaptic vesicle exocytosis, acetylcholine release from small vesicles is highly dependent on the SNARE complex, and neuropeptide release from large vesicles involves SNARE proteins that may interact differently with regulatory factors such as calcium. Pediatr Surg Int, 2001 Sep, 17(7), 521 - 3 The treatment of internal anal sphincter achalasia with botulinum toxin; Messineo A et al.; Internal anal sphincter (IAS) achalasia is a disorder of defecation in which the IAS fails to relax . Botulinum toxin (BT), which has been successfully used to relax the anal and lower esophageal sphincters, was injected twice into the IAS of one adolescent and three infants with manometric, radiologic, and in 2 cases histochemical diagnosis of anal achalasia: in the adolescent a third injection was necessary . Spontaneous defecation was achieved in all patients following the second injection . In one case a diagnosis of short-segment Hirschsprung's disease was obtained after the second injection . Local infiltration of BT into the IAS proved effective in the treatment of IAS achalasia . Double-blind studies and longer follow-up periods are needed to better evaluate these preliminary results and define the limits of this promising therapy. Ann Otol Rhinol Laryngol, 2001 Oct, 110(10), 941 - 5 Adductor spasmodic dysphonia and botulinum toxin treatment: the effect on well-being; Langeveld TP et al.; Adductor spasmodic dysphonia (AdSD) is a controversial and enigmatic voice disorder . It is generally accepted that it has a neurologic, although undetermined, cause, and it is accompanied by much psychological and physical distress . In this prospective study, standardized psychometric tests were used to assess the personality characteristics and psychological and somatic well-being of 46 patients with AdSD . Moreover, the effect of botulinum toxin (Botox) treatment on their well-being was evaluated . No significant differences could be detected between patients and a representative norm group concerning 7 personality characteristics . Nevertheless, before treatment, there were significantly more psychological and somatic complaints . After establishment of a normal to near-normal voice with Botox injections, these complaints were reduced to normal levels--a finding suggesting these phenomena to be secondary to the voice disorder . These findings, and the normal personality characteristics, do not support a psychogenic cause of AdSD. J AAPOS, 2001 Oct, 5(5), 327 - 8 Traumatic rupture of the medial rectus muscle; Ling R et al.; Traumatic rupture of an extraocular muscle, in the absence of significant injury to the globe and adnexa, is uncommon . We report the case of a patient with an isolated mid-belly rupture of the medial rectus muscle following ocular trauma and describe the technique of repairing the ruptured muscle by suturing the distal segment to the Tenon sleeve of the proximal segment . This was combined with postoperative botulinum toxin injection to the ipsilateral lateral rectus muscle . Good primary position alignment was achieved 7 months after surgery . The patient regained a useful horizontal field of binocular single vision totaling 27 degrees. Toxicon, 2001 Dec, 39(12), 1815 - 20 A comparison of the safety margins of botulinum neurotoxin serotypes A, B, and F in mice; Aoki KR; This study compared the respective intramuscular (IM) safety margins of two preparations of botulinum toxin (BTX) serotype A and one preparation each of BTX serotypes B and F in mice . Mice received an IM injection (0-200 U kg(-1) body weight) of BTX-A (BOTOX or DYSPORT), an experimental preparation of BTX-B (WAKO Chemicals, Inc.), or an experimental preparation of BTX-F (WAKO) . An observer who was masked to treatment scored muscle weakness using the Digit Abduction Scoring (DAS) assay . Peak DAS responses were plotted and IM ED(50) values calculated . The safety margin for each BTX preparation was calculated as a ratio of the IM median lethal dose after hind limb injection to the median effective dose in the DAS assay (IM LD(50)/IM ED(50)) . Experiments were repeated 4-6-times for each preparation (10 mice/dose) . Mean safety margin values were highest for BTX-F (WAKO; 16.7+/-3.9) and one of the BTX-A preparations (BOTOX; 13.9+/-1.7) . Mean safety margins values for the other BTX-A preparation (DYSPORT) and BTX-B (WAKO) were significantly lower (7.6+/-0.9 and 4.8+/-1.1, respectively) . Thus, the BTX preparations exhibited different safety margins in mice . These results support the hypothesis that the preparations are unique therapeutics and are not interchangeable based on a simple dose ratio. Spine, 2001 Oct 15, 26(20), 2283 - 8 Spinal lordosis with marked opisthotonus secondary to dystonia musculorum deformans: case report with surgical management; Fricka KB et al.; STUDY DESIGN: A case report of severe spinal lordosis with marked opisthotonus and retrocollis secondary to dystonia musculorum deformans is presented . OBJECTIVE: To describe a case of dystonia musculorum deformans with progressive spinal lordosis and its surgical treatment . SUMMARY OF BACKGROUND DATA: Four patients with correction of coronal spinal deformity associated with dystonia musculorum deformans have been reported in the literature . No reports of sagittal spinal deformity treated with surgical instrumentation and fusion were found . METHODS: A retrospective chart and radiographic review of a single case was conducted . RESULTS: Orthotic management and pharmacologic therapy with botulinum toxin injections were unsuccessful in controlling the deformity . Severe spinal lordosis (170 degrees ) from occiput to sacrum was corrected surgically, allowing an upright posture . CONCLUSION: Dystonia musculorum deformans is a rare condition resulting in coronal or sagittal plane deformities . When other treatment methods are unsuccessful, surgical instrumentation and arthrodesis may correct the deformity and improve function. Neurophysiol Clin, 2001 Aug, 31(4), 239 - 46 Interventional neurophysiology of the sacral nervous system; Vodusek DB; Clinical neurophysiological tests have been introduced for the sacral neuromuscular system to aid with diagnosis of neurogenic conditions involving the lower urinary tract, anorectal and sexual dysfunction . The tests have, however, the potential to be of value in different interventions outside of the neurophysiological laboratory . EMG monitoring can be used for exact application of botulinum toxin by the relatively non-invasive transcutaneous approach in treatment of male detrusor sphincter dyssynergia . Checking for compound muscle action potentials of the external anal sphincter is proposed as the best method for exact placement of wire electrodes close to the 3rd sacral roots in treating lower urinary tract dysfunction by 'neuromodulation' . Presently the most established use of clinical neurophysiological techniques--outside the laboratory--as related to the sacral neuromuscular system is in the operating theatre . These tests have been introduced to identify relevant structures, for instance pudendal afferents within dorsal sacral roots, which should be spared during rhizotomy procedures for treatment of spasticity . Modified techniques are used intraoperatively to monitor the integrity of the lower sacral reflex arc (the bulbocavernosus reflex) or the lower sacral afferents throughout the spinal cord (pudendal SEP) . Clinical neurophysiological tests are expected to become established in several interventions involving the sacral neuromuscular system. Neurophysiol Clin, 2001 Aug, 31(4), 220 - 9 Botulinum toxin in motor disorders: practical considerations with emphasis on interventional neurophysiology; Traba Lopez A et al.; After a brief review of the pharmacological properties of the botulinum toxin (BT), its mechanism of action on the nerve endings of the neuromuscular junctions, and the general therapeutic principles and adverse side effects, we discuss the advantages of interventional neurophysiology for the treatment of focal motor disorders by means of botulinum toxin A (BTA) muscle infiltration . Electromyography (EMG) provides a valuable objective information in the diagnosis of many motor disturbances and enables the precise identification of the muscles that contribute to the abnormal movement or posture . The use of EMG guidance for BTA injection seems advisable in every muscle but it become indispensable in those difficult to access, deeply located or partially atrophied by previous toxin infiltrations . The EMG study also serves to localise the areas with the highest abnormal activity and the motor point of the muscle, where the injection of toxin exerts its maximal effect . Consequently, lower doses of BTA can be employed without decreasing the efficacy of treatment but reducing the potential risk of side effects, antibody production and the cost of treatment . Electrophysiological diagnosis and BTA treatment may be performed during the same exploration . Considerations on the particular aspects and lines of action are given referring to the main focal muscular hyperactivity motor disorders such as cervical, oromandibular and laryngeal dystonias, blepharospasm, writer's cramp, hemifacial and hemimasticatory spasms, infantile and adult forms of spasticity and some other focal disturbances such as strabismus, detrusor-sphincter dyssynergia and anismus. J Biol Chem, 2001 Dec 7, 276(49), 45979 - 87 Epub 2001 Oct 04. Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus involve G alpha(13) and RhoA; Shepard LW et al.; The Kaposi's sarcoma herpesvirus (KSHV) open reading frame 74 encodes a G protein-coupled receptor (GPCR) for chemokines . Exogenous expression of this constitutively active GPCR leads to cell transformation and vascular overgrowth characteristic of Kaposi's sarcoma . We show here that expression of KSHV-GPCR in transfected cells results in constitutive transactivation of nuclear factor kappa B (NF-kappa B) and secretion of interleukin-8, and this response involves activation of G alpha(13) and RhoA . The induced expression of a NF-kappa B luciferase reporter was partially reduced by pertussis toxin and the G beta gamma scavenger transducin, and enhanced by co-expression of G alpha(13) and to a lesser extent, G alpha(q) . These results indicate coupling of KSHV-GPCR to multiple G proteins for NF-kappa B activation . Expression of KSHV-GPCR led to stress fiber formation in NIH 3T3 cells . To examine the involvement of the G alpha(13)-RhoA pathway in KSHV-GPCR-mediated NF-kappa B activation, HeLa cells were transfected with KSHV-GPCR alone and in combination with the regulator of G protein signaling (RGS) from p115RhoGEF or a dominant negative RhoA(T19N) . Both constructs, as well as the C3 exoenzyme from Clostritium botulinum, partially reduced NF-kappa B activation by KSHV-GPCR, and by a constitutively active G alpha(13)(Q226L) . KSHV-GPCR-induced NF-kappa B activation is accompanied by increased secretion of IL-8, a function mimicked by the activated G alpha(13) but not by an activated G alpha(q)(Q209L) . These results suggest coupling of KSHV-GPCR to the G alpha(13)-RhoA pathway in addition to other G proteins. J Neurosci, 2001 Oct 15, 21(20), 8270 - 7 Coincident spiking activity induces long-term changes in inhibition of neocortical pyramidal cells; Holmgren CD et al.; In pyramidal cells, induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission by coincidence of presynaptic and postsynaptic activity is considered relevant to learning processes in vivo . Here we show that temporally correlated spiking activity of a pyramidal cell and an inhibiting interneuron may cause LTD or LTP of unitary IPSPs . Polarity of change in synaptic efficacy depends on timing between Ca(2+) influx induced by a backpropagating train of action potentials (APs) in pyramidal cell dendrites (10 APs, 50 Hz) and subsequent activation of inhibitory synapses . LTD of IPSPs was induced by synaptic activation in the vicinity of the AP train (<300 msec relative to the beginning of the train), whereas LTP of IPSPs was initiated with more remote synaptic activation (>400 msec relative to the beginning of the AP train) . Solely AP trains induced neither LTP nor LTD . Both LTP and LTD were prevented by 5 mm BAPTA loaded into pyramidal cells . LTD was prevented by 5 mm EGTA, whereas EGTA failed to affect LTP . Synaptic plasticity was not dependent on activation of GABA(B) receptors . It was also not affected by the antagonists of vesicular exocytosis, botulinum toxin D, and GDP-beta-S. Br J Pharmacol, 2001 Oct, 134(3), 507 - 20 Determination of effects of antiepileptic drugs on SNAREs-mediated hippocampal monoamine release using in vivo microdialysis; Murakami T et al.; 1 . To elucidate possible mechanisms underlying the effects of carbamazepine (CBZ), valproate (VPA) and zonisamide (ZNS) on neurotransmitter exocytosis, the interaction between these three antiepileptic drugs (AEDs) and botulinum toxins (BoNTs) on basal, Ca(2+)- and K(+)-evoked release of dopamine (DA) and serotonin (5-HT) were determined by microdialysis in the hippocampus of freely moving rats . 2 . Basal release of monoamine was decreased by pre-microinjection of the syntaxin inhibitor, BoNT/C, but only weakly affected by the synaptobrevin inhibitor, BoNT/B . Ca(2+)-evoked release was inhibited by BoNT/C selectively . K(+)-evoked release was reduced by BoNT/B predominantly and BoNT/C weakly . 3 . Perfusion with low and high concentrations of CBZ and ZNS increased and decreased basal monoamine release, respectively . Perfusion with VPA increased basal 5-HT release concentration-dependently, whereas basal DA release was affected by VPA biphasic concentration-dependently, similar to CBZ and ZNS . This stimulatory action of AEDs on basal release was inhibited by BoNT/C predominantly . 4 . Ca(2+)-evoked monoamine release was increased by low concentrations of CBZ, ZNS and VPA, but decreased by high concentrations . These effects of the AEDs on Ca(2+)-evoked release were inhibited by BoNT/C, but not by BoNT/B . 5 . K(+)-evoked monoamine release was reduced by AEDs concentration-dependently . The inhibitory effect of these three AEDs on K(+)-evoked release was inhibited by BoNT/B, but not by BoNT/C . 6 . These findings suggest that the therapeutic-relevant concentration of CBZ, VPA and ZNS affects exocytosis of DA and 5-HT, the enhancement of syntaxin-mediated monoamine release during resting stage, and the inhibition of synaptobrevin-mediated release during depolarizing stage. Eye, 2000 Dec, 14(Pt 6), 873 - 8 Efficacy and complications of dose increments of botulinum toxin-A in the treatment of horizontal comitant strabismus; Sener EC et al.; PURPOSE: To investigate the efficacy and complications associated with dose increments of botulinum toxin-A (BTA) for comitant horizontal strabismus patients . METHODS: Twenty-five esotropic (ET) and 45 exotropic (XT) patients received 2.5-20 U of BTA injection . Parameters for achieving less than 10 prism dioptres (pd) of horizontal deviation and percentage correction of the pretreatment deviation were assessed for injections of less than 10 U and more than 10 U of BTA . Induced ptosis and vertical deviation were examined within and after 6 months of follow-up . RESULTS: The mean pretreatment deviations were 38.6 +/- 2.5 pd and 37.6 +/- 1.9 pd for the ET and XT groups, respectively . After receiving 1.6 and 1.5 injections on average, improvement to less than 10 pd at the primary position occurred in 32% of ET and 22% of XT patients; the difference was not statistically significant . The percentage corrections of the ET patients were 41.4 +/- 9.3% and 36.9 +/- 5.6% in those treated with less than 10 U and more than 10 U of BTA respectively; the difference between the two groups was insignificant . For the XT patients the values were 42.1 +/- 7.4% and 28.9 +/- 3.5% respectively, which also were not statistically significantly different . Frequency of induced ptosis was more common in ET than XT patients (p = 0.01) and this difference was more pronounced with increased doses of BTA (7.7% in ET and 5.3% in XT patients with less than 10 U of BTA, and 24.0% in ET and 4.3% in XT patients with more than 10 U of BTA) . Ptosis resolved completely within 6 weeks in all cases . Induced vertical deviation with less than 10 U of BTA was encountered in one case of ET (11.1%, 9 pd) and in another case of XT (8.3%, 4 pd), increasing to 60.0% (2-20 pd) and 38.8% (4-16 pd) respectively with more than 10 U of BTA injection . In about a year, induced vertical deviation resolved in approximately 40%, and decreased in 30% of the cases . CONCLUSION: Increasing the dose of BTA is clinically effective in larger deviations, although statistically indifferent, especially in ET compared with XT . However, an increased dose is accompanied by increased incidence of induced ptosis and vertical deviation . Ptosis is temporary, but vertical deviation may persist for a long time and may present a cosmetic problem for some patients when more than 10 U of BTA is used. Invest Ophthalmol Vis Sci, 2001 Oct, 42(11), 2542 - 6 Long-term outcome and predictor variables in the treatment of acquired esotropia with botulinum toxin; Tejedor J et al.; PURPOSE: To determine the long-term results of botulinum therapy in acquired esotropia and to identify predictors of a satisfactory outcome . METHODS: Sixty-eight children (age range, 8-64 months) with acquired esotropia were enrolled in a prospective study . Botulinum toxin A was injected in the two medial recti . Motor and sensory statuses were evaluated at 1 and 2 weeks; 3, 6, and 12 months; and every year after the last injection . Univariate and multivariate logistic regression analyses were performed to relate motor and sensory outcome to variables recorded as potential predictors . RESULTS: After an average follow-up of 4.8 years since the last injection, motor success was obtained in 36 children with one injection (52.9%), increasing to 48 (70.6%) and 60 (88.2%) children after two and three injections, respectively . Forty-eight (70.6%) patients had at least peripheral fusion (category 1 binocularity) and 32 (47.1%) had stereoacuity of at least 400 seconds of arc (category 2 binocularity) . Higher hypermetropia, less severe amblyopia, and a smaller angle of esotropia were the best predictors of motor success . Minimal amblyopia and favorable motor alignment were associated with better binocularity outcome . CONCLUSIONS: Botulinum is an effective long-term treatment of acquired esotropia . It is especially useful in children with high hypermetropia, minimal amblyopia, and small esotropic deviation. Clin Lab Med, 2001 Sep, 21(3), 593 - 605 Toxins as weapons of mass destruction . A comparison and contrast with biological-warfare and chemical-warfare agents; Madsen JM; Toxins are toxic chemical compounds synthesized in nature by living organisms . Classifiable by molecular weight, source, preferred targets in the body, and mechanism of action, they include the most potent poisons on the planet, although considerations of production, weaponization, delivery, environmental stability, and host factors place practical limits on their use as WMD . The two most important toxin threats on the battlefield or in bioterrorism are probably botulinum toxin (a series of seven serotypes, of which botulinum toxin A is the most toxic for humans) and SEB, an incapacitating toxin . Ricin and the trichothecene mycotoxins, including T-2 mycotoxin, are of lesser concern but are still potential threats . Botulinum toxin is a neurotoxin, ricin and trichothecene mycotoxins are membrane-damaging proteins, and SEB is a superantigen capable of massive nonspecific activation of the immune system . The clinical intoxications resulting from exposure to and absorption (usually by inhalation) of these agents reflect their underlying pathophysiology . Because of the hybrid nature of toxins, they have sometimes been considered CW agents and sometimes BW agents . The current trend seems to be to emphasize their similarities to living organisms and their differences from CW agents, but examination of all three groups relative to a number of factors reveals both similarities and differences between toxins and each of the other two categories of non-nuclear unconventional WMD . The perspective that groups toxins with BW agents is logical and very useful for research and development and for administrative and treaty applications, but for medical education and casualty assessment, there are real advantages in clinician use of assessment techniques that emphasize the physicochemical behavior of these nonliving, nonreplicating, intransmissible chemical poisons. Traffic, 2001 Oct, 2(10), 717 - 26 Actin microfilaments facilitate the retrograde transport from the Golgi complex to the endoplasmic reticulum in mammalian cells; Valderrama F et al.; The morphology and subcellular positioning of the Golgi complex depend on both microtubule and actin cytoskeletons . In contrast to microtubules, the role of actin cytoskeleton in the secretory pathway in mammalian cells has not been clearly established . Using cytochalasin D, we have previously shown that microfilaments are not involved in the endoplasmic reticulum-Golgi membrane dynamics . However, it has been reported that, unlike botulinum C2 toxin and latrunculins, cytochalasin D does not produce net depolymerization of actin filaments . Therefore, we have reassessed the functional role of actin microfilaments in the early steps of the biosynthetic pathway using C2 toxin and latrunculin B . The anterograde endoplasmic reticulum-to-Golgi transport monitored with the vesicular stomatitis virus-G protein remained unaltered in cells treated with cytochalasin D, latrunculin B or C2 toxin . Conversely, the brefeldin A-induced Golgi membrane fusion into the endoplasmic reticulum, the Golgi-to-endoplasmic reticulum transport of a Shiga toxin mutant form, and the subcellular distribution of the KDEL receptor were all impaired when actin microfilaments were depolymerized by latrunculin B or C2 toxin . These findings, together with the fact that COPI-coated and uncoated vesicles contain beta/gamma-actin isoforms, indicate that actin microfilaments are involved in the endoplasmic reticulum/Golgi interface, facilitating the retrograde Golgi-to-endoplasmic reticulum membrane transport, which could be mediated by the orchestrated movement of transport intermediates along microtubule and microfilament tracks. J Neurol Sci, 2001 Sep 15, 190(1-2), 95 - 7 Recurrent jaw dislocation after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis; Tan EK et al.; Botulinum toxin (BTX) has been used successfully to treat various movement disorders, and is increasingly used for many other medical conditions . Sialorrhoea is a disabling symptom in many neurological patients including those with Parkinson's disease, stroke and amyotrophic lateral sclerosis (ALS) . BTX has recently been shown to be effective for treating sialorrhoea.We report an ALS patient who developed recurrent jaw dislocation following BTX treatment for sialorrhoea to highlight the observation that intraparotid BTX may be complicated by jaw dislocations in some at-risk ALS patients . Clinicians using BTX to treat sialorrhoea in ALS need to be aware of this potentially serious complication. J Am Acad Dermatol, 2001 Oct, 45(4), 508 - 14 Quantification of the efficacy of botulinum toxin type A by digital image analysis; Heckmann M et al.; BACKGROUND: Botulinum toxin type A (BT-A) is increasingly being used by dermatologists for correction of frown lines . Because objective measurements of clinical results appear to be difficult, several different treatment protocols have been issued purely empirically or on the basis of subjective ratings . OBJECTIVE: Our purpose was to establish objective parameters to measure the efficacy of BT-A for correction of hyperkinetic facial lines . METHODS: Thirty consecutive patients received BT-A injections for correction of facial expression lines . For each patient a full range of facial expressions was recorded by means of a digital imaging system that allowed identical positioning and illumination before and after treatment . Computer-assisted measurements of brow mobility were used to measure muscular paralysis . RESULTS: Reproducibility of serial photographs by means of a digital overlay technique was confirmed by 4 independent observers . Upward mobility of brows was decreased to 35% at 2 weeks and 71% at 12 weeks after treatment . In contrast, inward mobility (frowning) was decreased to 7% at 2 weeks and 57% at 12 weeks . Brow-to-brow distance in repose increased with treatment by 13% and displayed a negative correlation with age . CONCLUSION: The effects of BT-A on upper face muscular activity can reproducibly be measured by digital image analysis; this is a valuable tool for clinical documentation and evaluation of treatment efficacy . Onset and offset of the effects of BT-A display a longer time course than previously assumed . Tissue qualities such as elasticity contribute measurably to smoothing facial expression lines after BT-A treatment and correlate inversely with age. J Protein Chem, 2001 Apr, 20(3), 221 - 31 Enzymatic autocatalysis of botulinum A neurotoxin light chain; Ahmed SA et al.; Highly purified recombinant zinc-endopeptidase light chain of the botulinum neurotoxin serotype A underwent autocatalytic proteolytic processing and fragmentation . In the absence of added zinc, initially 10-28 residues were cleaved from the C-terminal end of the 448-residue protein followed by the appearance of an SDS-stable dimer and finally fragmentation near the middle of the molecule . In the presence of added zinc, the rate of fragmentation was accelerated but the specificity of the cleavable bond changed, suggesting a structural role for zinc in the light chain . The C-terminal proteolytic processing was reduced, and fragmentation near the middle of the molecule was prevented by adding the metal chelator TPEN to the light chain . Similarly, adding a competitive peptide inhibitor (CRATKML) of the light-chain catalytic activity also greatly reduced the proteolysis . With these results, for the first time, we provide clear evidence that the loss of C-terminal peptides and fragmentation of the light chain are enzymatic and autocatalytic . By isolating both the large and small peptides, we sequenced them by Edman degradation and ESIMS-MS, and mapped the sites of proteolysis . We also found that proteolysis occurred at F266-G267, F419-T420, F423-E424, R432-G433, and C430-V431 bonds in addition to the previously reported Y250-Y251 and K438-T439 bonds. Neurosurgery, 2001 Oct, 49(4), 847 - 54; discussion 854-6 Delayed resolution of residual hemifacial spasm after microvascular decompression operations; Ishikawa M et al.; OBJECTIVE: After microvascular decompression to treat hemifacial spasm (HFS), resolution of the HFS is often gradual . We carefully investigated the course of the gradual resolution of HFS and examined the differences between patients with and without postoperative HFS . METHODS: One hundred seventy-five patients with HFS were monitored, for observation of 1) whether postoperative HFS occurred, 2) when it occurred, and 3) when it disappeared after microvascular decompression . For two groups of patients, with (Group I) and without (Group II) postoperative HFS, we investigated age, sex, spasm side, preoperative facial nerve block (botulinum toxin treatment), decompression material, preoperative HFS period, offender (compressing vessel), temporary and permanent postoperative complications, and electromyographic findings . RESULTS: In Group I (88 patients), postoperative HFS began within 4 days after surgery, a period that we have termed the silent period of postoperative HFS; the median value for the time to resolution was 28 days . The other 87 patients exhibited no postoperative HFS (Group II) . There was a significantly higher incidence of postoperative facial weakness in Group II (Group II, 41.3%; Group I, 25.5%; P = 0.02 by logistic regression analysis) . In Group I, there was no statistically significant relationship between the investigated parameters and the silent period or the postoperative HFS period, as determined by Cox proportional-hazards regression analysis, except for the number of preoperative facial nerve blocks . Electromyographic investigation of F waves revealed facial paresis during the silent period in a patient . CONCLUSION: Approximately 50% of patients with HFS exhibited residual spasm postoperatively . An immediate postoperative silent period of 4 days without spasm was characteristic . One-quarter, one-half, and 90% of the residual spasm resolved by 1 week, 1 month, and 8 months after surgery, respectively. J Neurol Neurosurg Psychiatry, 2001 Oct, 71(4), 499 - 504 Social phobia in spasmodic torticollis; Gundel H et al.; OBJECTIVES: To study the prevalence of psychiatric comorbidity assessed by the use of a structured clinical interview in a large, representative sample of patients with spasmodic torticollis (ST) and to test the hypothesis that social phobia would be highly prevalent . METHODS: In a consecutive cohort of 116 patients with ST treated with botulinum toxin overall psychiatric comorbidity was studied prospectively with the structured clinical interview (SCID) for DSM-IV axis I disorders . Physical disability and psychosocial variables were also assessed with standardised self rating questionnaires . RESULTS: 41.3% of the subjects met DSM-IV clinical criteria A-G for current social phobia as the primary psychiatric diagnosis . This figure rose to 56% including secondary and tertiary psychiatric diagnosis . There was no correlation between severity of disease (Tsui score, severity of pain, body image dissatisfaction score) and psychiatric comorbidity . The only significant predictor of psychiatric comorbidity was depressive coping behaviour (logistic regression analysis, p < 0.01; OR=10.8) . Compared with a representative sample of the general adult population, in the patients with ST the prevalence of clinically relevant social phobia is 10-fold, of mood disorders 2.4-fold, and of lifetime psychiatric comorbidity 2.6-fold increased . CONCLUSIONS: A particularly high prevalence of social phobia was found in the cohort of patients with ST . The finding of a high prevalence of social phobia and depressive coping behaviour as the main predictor of psychiatric comorbidity may make a subgroup of patients with ST particularly amenable to specific psychotherapeutic interventions. Curr Pain Headache Rep, 2001 Oct, 5(5), 407 - 11 Interventional approaches to the management of myofascial pain syndrome; Criscuolo CM; Interventional therapies are a valuable addition to our armamentarium when treating myofascial pain syndromes . When combined with other therapies, interventional techniques can be an effective adjunct in the multidisciplinary management of pain . This article describes current interventional therapies that are employed in treating myofascial pain syndromes . The mainstay of injection therapies, the myofascial trigger point injection, is emphasized . More recent advances, such as the use of botulinum toxin, are also discussed . In addition, other techniques such as acupuncture and the use of laser therapy are mentioned. BMJ, 2001 Sep 15, 323(7313), 596 - 9 Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial; Naumann M et al.; OBJECTIVES: To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis . DESIGN: Multicentre, randomised, parallel group, placebo controlled trial . SETTING: 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom . PARTICIPANTS: Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living . 465 were screened, 320 randomised, and 307 completed the study . INTERVENTIONS: Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhydrotic area of each axilla, defined by Minor's iodine starch test . MAIN OUTCOME MEASURES: Percentage of responders (patients with >/=50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events . RESULTS: At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group . By week 16, response rates were 82% (198) and 21% (16), respectively . The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group . Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks) . Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05) . CONCLUSION: Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. Arch Otolaryngol Head Neck Surg, 2001 Sep, 127(9), 1083 - 5 Outcomes of botulinum toxin treatment for patients with spasmodic dysphonia; Benninger MS et al.; BACKGROUND: Spasmodic dysphonia (SD) is a focal dystonia of the larynx . Although individuals with SD have variable degrees of difficulty in everyday communication and speaking, many report significant impairments . The impact of SD on the quality of life of people with the disorder has not been well measured . OBJECTIVES: To assess the impact of SD using a voice-specific, validated outcomes instrument, the Voice Handicap Index (VHI), and to evaluate the effect of botulinum toxin treatment on quality of life . METHODS: The VHI measures 3 subscales (physical, functional, and emotional) of impact of a voice disorder as well as a total impact score . The VHI was completed by 30 consecutive patients with SD before receiving botulinum toxin injection and 2 to 4 weeks after injection . Pretreatment scores on the VHI were compared with posttreatment scores . RESULTS: Pretreatment scores on the VHI showed significant impairment in all 3 subscales (physical, 25.5; functional, 21.4; and emotional, 20.4) and the total score (67.6) . Statistically significant improvements occurred in all 3 subscale scores and the total score (P =.001) for the 22 patients who completed the posttreatment survey . CONCLUSIONS: Spasmodic dysphonia has a significant impact on patients' perception of quality of life as measured by the VHI . Significant improvements in all 3 subscale scores and the total score on the VHI occur after treatment with botulinum toxin. Headache, 2001 Jul-Aug, 41(7), 658 - 64 Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial; Schmitt WJ et al.; In addition to vascular and supraspinal influences, contraction of craniofacial muscles or central sensitization processes following continuous nociceptive input of craniofacial muscles may play an important role in the pathogenesis of tension-type headache . Chemodenervation induced by botulinum toxin injection is successfully used to decrease muscle tension . If muscle tension is important in this type of headache, then botulinum toxin could be helpful in its treatment . We conducted a randomized, placebo-controlled study to examine the effect of 20 U botulinum toxin injected into frontal and temporal muscles in patients with chronic tension-type headache . During a baseline of 4 weeks and a posttreatment period of 8 weeks, the effect was evaluated with daily records and the West Haven-Yale Multidimensional Pain Inventory . Some improvement in affective variables were demonstrated in the botulinum group, but important outcome variables, such as pain intensity, the number of pain-free days, and consumption of analgesics, were not statistically different between the groups . Reasons for these moderate effects may include the injection sites, dose of botulinum toxin, and duration of treatment. Eur J Neurol, 2001 Sep, 8(5), 451 - 6 Side-effects of intradermal injections of botulinum A toxin in the treatment of palmar hyperhidrosis: a neurophysiological study; Swartling C et al.; Focal palmar hyperhidrosis can be effectively abolished by intradermal injections with botulinum toxin . Muscle weakness of finger grip has been reported as a reversible side-effect of this new treatment . The objective of this work was to measure muscular side-effects after treatment of palmar hyperhidrosis with botulinum toxin . As botulinum toxin has been used in the treatment of pain, we studied whether the toxin might influence afferent thin-fibre function by measuring temperature perception thresholds . Thirty-seven patients treated with botulinum toxin (Botox, Allergan Pharmaceuticals, Irvine, CA, USA) showed a decrease in compound muscle action potential (CMAP) for both abductor pollicis brevis (APB) and abductor digiti minimi (ADM) compared with pre-injection values on average by 64 and 36%, respectively, at 3 weeks which returned nearly to normal at 37 weeks . Muscle power for both finger abduction and finger opposition decreased to a lesser extent . Repetitive nerve stimulation and single fibre electromyography (EMG) showed a disturbed neuromuscular transmission . Thus, despite careful technique with small doses of botulinum toxin injected intradermally, the toxin diffuses to underlying muscles . With regard to the present results, one should be careful in using higher doses of Botox than 0.8 mU/cm(2) in the palmar skin above intrinsic muscles . No influence on thin-fibre function was seen. Infect Immun, 2001 Oct, 69(10), 6511 - 4 Epitope mapping of neutralizing botulinum neurotoxin A antibodies by phage display; Mullaney BP et al.; Single-chain antibodies neutralize activity and bind nonoverlapping epitopes of botulinum A neurotoxin . Two phage display epitope libraries were constructed from the 1.3 kb of binding domain cDNA . The minimal epitopes selected against the single-chain Fv-Fc antibodies correspond to conformational epitopes with amino acid residues 1115 to 1223 (S25), 1131 to 1264 (3D12), and 889 to 1294 (C25). Aliment Pharmacol Ther, 2001 Sep, 15(9), 1389 - 96 Randomized controlled trial comparing botulinum toxin injection to pneumatic dilatation for the treatment of achalasia; Mikaeli J et al.; BACKGROUND: Therapeutic options for achalasia include pharmacological therapy, surgical myotomy, pneumatic dilatation and intrasphincteric botulinum toxin injection . AIM: To compare botulinum toxin injection with pneumatic dilatation in a randomized trial . PATIENTS/METHODS: Forty adults with newly diagnosed achalasia were randomized to receive botulinum toxin (n=20) or pneumatic dilatation (n=20) . Symptom scores were evaluated at 1, 6 and 12 months . Clinical relapse was defined as a symptom score greater than 50% of baseline . Relapsers received a second botulinum toxin injection or pneumatic dilatation . RESULTS: The cumulative 12-month remission rate was significantly higher after a single pneumatic dilatation (53%) compared to a single botulinum toxin injection (15%)(P < 0.01) . The 12-month estimated adjusted hazard for relapse and need for retreatment for the botulinum toxin group was 2.69 times that of the pneumatic dilatation group (95% confidence interval; 1.18-6.14) . When a second treatment was administered to the relapsers in each group, the cumulative remission rate 1 year after initial treatment was significantly higher in the pneumatic dilatation group (100%) compared to the botulinum toxin group (60%) (P < 0.01) . There were no major complications in either group . CONCLUSIONS: Pneumatic dilatation is more efficacious than botulinum toxin in providing sustained symptomatic relief in patients with achalasia . The efficacy of a single pneumatic dilatation is similar to that of two botulinum toxin injections. Allergy Asthma Proc, 2001 Jul-Aug, 22(4), 199 - 202 Treatment update: nonallergic rhinitis; Lieberman P; Chronic nonallergic rhinitis is a diagnosis of exclusion . The pathophysiology underlying this disorder is unknown . There probably are several mechanisms involved and several different variations of this condition . Therapies which have been approved for use in the treatment of chronic nonallergic rhinitis include topical corticosteroids and azelastine . Topical corticosteroid preparations that have received approval are fluticasone, budesonide, and beclomethasone . Topical nasal saline also has been established as a beneficial adjunct to therapy in some instances . Other therapies have included capsaicin, silver nitrate, botulin toxin, and various surgical procedures . These procedures include turbinate reduction, which has been performed by a number of techniques including submucosal diathermy, cryosurgery, laser cautery, and classic resection . Ethmoidal and vidian neurectomies have been performed by excision, diathermy, and cryotherapy . These procedures have met with varying degrees of success. Schweiz Rundsch Med Prax, 2001 Aug 23, 90(34), 1408 - 12 {Treatment of hyperfunctional facial lines with botulinum toxin}; Boni R et al.; Lines and wrinkles in the face are not only due to intrinsic and photoaging, but are also caused by lines of facial expression due to muscular action . Botulinum toxin A, which blocks the cholinergic transmission resulting in flaccid paralysis, is a powerful therapeutic tool in the treatment of frown lines, glabellar lines, crow-feet and platysma-bands . It has to be kept in mind, however, that the benefits of this treatment are transient and repeated injections are necessary . A treatment guide with injection sides and concentration of the toxin is presented in the context of the current literature. Pediatr Neurosurg, 2001 Aug, 35(2), 57 - 65 Selective posterior rhizotomy and intrathecal baclofen for the treatment of spasticity; von Koch CS et al.; Spasticity occurs in children and adults due to a wide range of conditions, including cerebral palsy, head and spinal cord trauma, cerebrovascular accidents and multiple sclerosis . Multiple treatment options have been described, including medical and surgical treatments . Medical treatments include intramuscular botulinum A toxin, oral baclofen and supportive bracing . Surgical approaches include selective posterior rhizotomy, intrathecal baclofen and orthopedic procedures to address deformities . Many reports have been published on these different treatment options, but rarely has a comparison been made between them . Therefore, this review is aimed at comparing selective posterior rhizotomy and intrathecal baclofen injection for spasticity due to cerebral palsy, especially in children . Eur J Pediatr, 2001 Aug, 160(8), 509 - 12 Botulinum toxin A: a new option for treatment of drooling in children with cerebral palsy . Presentation of a case series; Jongerius PH et al.; Drooling beyond the age of 4 years is pathological, particularly if it occurs in children with neurological and developmental impairment and disability . Considering the therapeutic spectrum of botulinum toxin A and in view of the innervation of the salivary glands, we postulated that intraglandular injections into the submandibular glands with botulinum toxin A could reduce the secretion of saliva and consequently decrease drooling . Three patients with cerebral palsy and severe drooling were selected and evaluated over a 4-month period . Under ultrasound guidance, one dose of botulinum toxin A was injected bilaterally into the submandibular glands . Saliva secretion was measured at baseline and repeated four times during the following 4 months . In the three patients, maximal salivary flow rate of the sublingual and submandibular glands was reduced by 51% to 63% . The time of the maximal effect differed among the three children . The parents reported a satisfactory reduction of drooling throughout the whole study period . No objectionable disturbances of oral functions were observed . There was mild transient thickening of saliva in one of the patients . CONCLUSION: The application of botulinum toxin A to the submandibular gland is a promising technique to reduce salivary flow rate and probably an alternative in the treatment of drooling in children with cerebral palsy. Curr Opin Neurol Neurosurg, 1992 Jun, 5(3), 301 - 7 The dystonias; Markham CH; The various dystonias have been found in at least five different hereditary backgrounds . The gene responsible for one of the dystonias, idiopathic torsion dystonia (ITD), lies on chromosome 9q32-34, with flanking markers now 1-2 cM apart . Magnetic resonance imaging and computerized tomography (CT) abnormalities in the basal ganglia, especially in the putamen, are found in many secondary dystonias . Botulinum toxin therapy is proving very useful in the treatment of focal dystonias. Clin Geriatr Med, 2001 Nov, 17(4), 769 - 94, vii Lasers and cosmetic dermatologic surgery for aging skin; Rohrer TE; Many topical agents and physical modalities have been used throughout the years to give the face a more youthful appearance . The goal has always been to effectively and consistently rejuvenate the face while minimizing the time of recovery and risk for complications . Because each person is unique, there is no one modality that is best for everyone . This article reviews some of the options available for treating photoaged skin in 2001 . Various lasers (e.g., vascular lesion, pigmented lesion, hair removal, and resurfacing), botulinum A toxin, chemical peels, and various dermal and subcutaneous filler substances all are discussed. Cutis, 2001 Aug, 68(2), 99 - 101 Dermatologic surgery into the next millennium, part II; Warmuth IP et al.; This is the second article in a 4-part series on dermatologic surgery . This section provides detailed information about filling agents and botulinus toxin A . The filling agents discussed here are frequently used in our office . It is emphasized that meticulous technique and patient selection predict a good cosmetic result . To select the right agent, patient safety must be a priority. Neurol Clin, 2001 Aug, 19(3), 681 - 705, vii Dystonia and its disorders; Friedman J et al.; Dystonia is a movement disorder characterized by sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures . The term dystonia does not signify a single disease, but instead describes a symptom and sign that may be part of many disorders with a variety of causes . Dystonia may be classified by age of onset, distribution of symptoms, or by etiology . An increasing number of genetic forms of dystonia have been recognized and the findings have advanced knowledge of underlying neural mechanisms of pathogenesis . Options for treatment of dystonia include pharmacological therapy, botulinum toxin injection, or neurosurgical procedures. J Electromyogr Kinesiol, 2001 Aug, 11(4), 231 - 46 EMG-interference pattern analysis; Finsterer J; The EMG interference pattern, built up of single motor unit action potentials, may be analyzed subjectively, or objectively by computer aided, quantitative methods, like counting of zero-crossings, counting of spikes, amplitude measurements, integration of the area under the curve, decomposition techniques, power spectrum analysis and turn/amplitude analysis . Since the shape of the interference pattern of healthy muscles is dependent on age, sex, force, muscle, temperature, fatigue, fitness level, recording site and surrounding tissue, electrode type, sensitivity, filters, sampling frequency and threshold level, all methods of analyzing the IP have to be standardized . Quantitative methods of analyzing the EMG interference pattern may be used for monitoring botulinum toxin therapy of dystonia and spasticity, quantifying spontaneous activity, assessment of chronic muscle pain, neuro-urological and proctological function, and diagnosing neuromuscular disorders . For diagnostic purposes, the methods favored are those that use needle electrodes and do not require measurement or monitoring of muscle force . The most well-evaluated methods are those using turn/amplitude analysis, like the cloud methods and the peak-ratio analysis . Peak-ratio analysis has the advantage that reference limits are easy to obtain and that its utility is well established and confirmed by several investigations . Overall, automatic methods of EMG interference pattern analysis are powerful tools for diagnostic and non-diagnostic purposes. Br J Dermatol, 2001 Aug, 145(2), 289 - 93 Treatment of focal hyperhidrosis with botulinum toxin type A: long-term follow-up in 61 patients; Schnider P et al.; BACKGROUND: The blocking action of botulinum toxin type A (BTX-A) on cholinergically innervated sweat glands has been used successfully to treat patients with focal hyperhidrosis . OBJECTIVES: To investigate the long-term efficacy and safety of intradermal injections of BTX-A . METHODS: We performed an open-label study in 61 patients treated over a period of 3 years for axillary or palmar hyperhidrosis . A total dose of 400 mU BTX-A (Dysport) was injected into both axillae or 460 mU BTX-A (Dysport) into both palms . The injections were repeated after relapse . Objective quantification of sweat production was performed using digitized ninhydrin-stained sheets . RESULTS: Four weeks after BTX-A treatment the median reduction in sweat production was 71% compared with baseline (P < 0.001) in the axillary group and 42% (P = 0.005) in the palmar group . Subjective assessment of sweat production by the patients using a visual analogue scale (0, no sweating; 100, the most severe sweating) showed a significant reduction in both the axillary (P < 0.001) and palmar groups (P < 0.001) . Secondary disturbances due to focal hyperhidrosis interfering with daily activities were markedly improved in both groups . The median time interval between the sets of injections was 34 weeks for axillary hyperhidrosis and 25 weeks for palmar hyperhidrosis . The treatment of palmar hyperhidrosis was complicated by transient but not disabling weakness of the small hand muscles in nine of 21 patients . CONCLUSIONS: Repeated intradermal injections of BTX-A in patients with axillary and palmar hyperhidrosis are as effective as first treatments. Hosp Med, 2001 Aug, 62(8), 477 - 9 The use of botulinum toxin in ophthalmology; Denniston A et al.; As the diversity of clinical applications for the botulinum neurotoxin continues to grow, exciting developments are occurring in its use around the eye, where indeed its benefits were first recognized . These include use to treat strabismus, eyelid disorders and a number of other ocular conditions. ORL J Otorhinolaryngol Relat Spec, 2001 Sep-Oct, 63(5), 294 - 7 Treatment of gustatory sweating with botulinum toxin: special aspects; Laskawi R et al.; Botulinum toxin treatment is an efficient, well-tolerated technique for patients suffering from gustatory sweating, first described by our group . With the experience gained in recent years we were able to improve on some of our skills in the diagnosis and treatment of gustatory sweating and here we wish to focus on some interesting aspects: (1) the necessity for an exact anamnesis before treatment with botulinum toxin to ensure correct treatment; (2) the advantages of Minor's test in special situations, for example, when sweating occurs in regions of hairy skin, retroauricular, at the back of the auricle and in areas distant from the site of salivary gland surgery; (3) the reduction of pain during treatment using an anesthetic ointment containing lidocaine and prilocaine as active substances; (4) intracutaneous injections in areas anterior to the fascia-protected skin of the lateral face-covering mimetic muscles, and (5) the occasional necessity for short-time reinjection in small areas of persistent sweating . Neurorehabil Neural Repair, 2001, 15(1), 57 - 68 The estimated cost of managing focal spasticity: a physician practice patterns survey; Radensky PW et al.; The purpose of this study was to estimate the overall cost of managing focal spasticity after stroke (CVA) and traumatic brain injury (TBI) and the cost impact of individual treatments . Sixty physicians described management strategies over six treatment visits for four focal spasticity case studies (one upper and one lower extremity case for CVA and TBI) . Mean and median per-case costs were determined across physicians; median per-case costs of physicians who did or did not report use of specific treatments were compared . Mean per-case costs of managing spasticity are as follows: CVA upper, $5,131; CVA lower, $5,384; TBI upper, $14,615; and TBI lower, $13,966 . Median per-case costs for strategies including botulinum toxin type A (BTX-A) were less than those without BTX-A in CVA upper; median costs for strategies including oral baclofen were more than those without baclofen in CVA lower . Fewer total treatments were reported with BTX-A than without; more total treatments were reported with baclofen than without . No individual treatment had a significant impact on median treatment costs in TBI . Physician-reported spasticity management costs are substantial . Despite higher drug costs for BTX-A compared with oral therapies like baclofen, strategies for managing spasticity in CVA that include BTX-A may cost less than those without BTX-A. Anal Biochem, 2001 Sep 1, 296(1), 130 - 7 High-throughput assays for botulinum neurotoxin proteolytic activity: serotypes A, B, D, and F; Schmidt JJ et al.; Botulinum neurotoxins (BoNT) are zinc metalloproteases that cleave and inactivate cellular proteins essential for neurotransmitter release . Because the paralytic effect of BoNT is a consequence of its enzymatic activity, selective inhibitors may be useful as drugs or as tools for further research . To expedite inhibitor discovery, we developed high-throughput, solid-phase protease activity assays for four of the seven BoNT serotypes: A, B, D, and F . Each assay consisted of a cleavable oligopeptide, based on the natural substrate sequence, labeled with fluorescein and covalently attached to maleimide-activated multiwell plates . Solutions of holotoxin or nontoxic catalytic domain of BoNT were incubated in substrate-coated wells, with or without test compounds, followed by transfer and assay of solubilized product in a multiwell fluorometer . Routine toxin concentrations ranged from 10 to 100 ng/ml, but concentrations as low as 2 ng/ml gave reproducible signals . The fluorescence assays were selective, gave very low background readings, and were stable upon prolonged storage . Using the nontoxic catalytic domain of BoNT A, we determined the relative inhibitory potencies of a family of structurally related pseudotripeptide compounds . Unlike previous methods, our assays did not employ antibodies or reverse-phase extraction steps, only well-to-well transfers, and were easily adapted to a high-throughput automated environment . J Neurol, 2001 Jul, 248(7), 572 - 6 The effect of botulinum toxin injections to the calf muscles on freezing of gait in parkinsonism: a pilot study; Giladi N et al.; BACKGROUND: Freezing of gait (FOG) is a common and very disabling parkinsonian symptom, which is poorly understood and responds unsatisfactorily to medical treatment . We recently reported a unique patient with Parkinson's disease (PD) who had significant alleviation of FOG shortly after she was injected with botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al . 1997) . OBJECTIVE: To assess the effect of BTX-A injections into the calf muscles of parkinsonian patients on FOG . METHOD: BTX-A was injected in an open fashion into the calf muscles of 10 parkinsonian patients (age 55-75 years) with FOG as a predominant symptom . Response of FOG was assessed subjectively by the patient from worsening (-1) to marked improvement (+3) . One patient was injected in a single blind fashion with saline or BTX-A after he had an initial good response . RESULTS: Seven patients reported different rates of improvement of FOG severity in 15 out of 17 therapeutic sessions . Four patients (40%) reported marked improvement (+3) of FOG in 5 sessions . Two patients reported no effect in two sessions . The mean duration of improvement was 6 weeks (range 1-12 weeks) with definite deterioration afterwards . The patient who was injected in a single blind fashion did not respond to saline injections but improved significantly with BTX-A treatment . CONCLUSIONS: We observed a clear temporal relationship between BTX-A injections into the calf muscles of parkinsonian patients and improvement of FOG . A double blind placebo controlled prospective study is needed before any conclusions can be drawn about the role of BTX-A injection in FOG. Arch Surg, 2001 Aug, 136(8), 870 - 7 Laparoscopic Heller myotomy and Dor fundoplication for achalasia: analysis of successes and failures; Patti MG et al.; BACKGROUND: In the treatment of achalasia, surgery has been traditionally reserved for patients with residual dysphagia after pneumatic dilatation . The results of laparoscopic Heller myotomy have proven to be so good, however, that most experts now consider surgery the primary treatment . HYPOTHESIS: The outcome of laparoscopic myotomy and fundoplication for achalasia is dictated by technical factors . SETTING: University hospital tertiary care center . DESIGN: Retrospective study . PATIENTS AND METHODS: One hundred two patients with esophageal achalasia underwent laparoscopic Heller myotomy and Dor fundoplication . Fifty-seven patients had been previously treated by pneumatic dilatation or botulinum toxin . The design of the operation involved a 7-cm myotomy, which extended 1.5 cm onto the gastric wall, and a Dor fundoplication . Esophagrams, esophageal manometric findings, and video records of the procedure were analyzed to determine the technical factors that contributed to the clinical success or failure of the operation . MAIN OUTCOME MEASURE: Swallowing status . RESULTS: In 91 (89%) of the 102 patients, good or excellent results were obtained after the first operation . A second operation was performed in 5 patients to either lengthen the myotomy (3 patients) or take down the fundoplication (2 patients) . Dysphagia resolved in 4 of these patients . The remaining 6 patients were treated by pneumatic dilatation, but dysphagia improved in only 1 . At the conclusion of treatment, excellent or good results had been obtained in 96 (94%) of the 102 patients . CONCLUSIONS: These data show that a Heller myotomy was unsuccessful in patients with an esophageal stricture; a short myotomy and a constricting Dor fundoplication were the avoidable causes of residual dysphagia; a second operation, but not pneumatic dilatation, was able to correct most failures; and that the identified technical flaws were eliminated from the last half of the patients in the series. J Biol Chem, 2001 Oct 19, 276(42), 39469 - 75 Epub 2001 Aug 14. Erythropoietin receptor-mediated inhibition of exocytotic glutamate release confers neuroprotection during chemical ischemia; Kawakami M et al.; Erythropoietin (EPO) reduced Ca(2+)-induced glutamate (Glu) release from cultured cerebellar granule neurons . Inhibition was also produced by EPO mimetic peptide 1 (EMP1), a small synthetic peptide agonist of EPO receptor (EPO-R), but not by iEMP1, an inactive analogue of EMP1 . EPO and EMP1 induced autophosphorylation of Janus kinase 2 (JAK2), a tyrosine kinase that associates with EPO-R . Furthermore, genistein, but not genistin, antagonized both the phosphorylation of JAK2 and the suppression of Glu release induced by EPO and EMP1 . During chemical ischemia, substantial amounts of Glu were released from cultured cerebellar and hippocampal neurons by at least two distinct mechanisms . In the early phase, Glu release occurred by exocytosis of synaptic vesicle contents, because it was abolished by botulinum type B neurotoxin (BoNT/B) . In contrast, the later phase of Glu release mainly involved a BoNT/B-insensitive non-exocytotic pathway . EMP1 inhibited Glu release only during the early exocytotic phase . A 20-min exposure of hippocampal slices to chemical ischemia induced neuronal cell death, especially in the CA1 region and the dentate gyrus, which was suppressed by EMP1 but not iEMP1 . However, EMP1 did not attenuate neuronal cell death induced by exogenously applied Glu . These results suggest that activation of EPO-R suppresses ischemic cell death by inhibiting the exocytosis of Glu. Prescrire Int, 2001 Feb, 10(51), 12 - 4 Botulinum toxin type A and dynamic equinus in children with cerebral palsy: new indication . Better than repeat casts; Ca(2+) influx and cAMP elevation overcame botulinum toxin A but not tetanus toxin inhibition of insulin exocytosis; Department of Medicine, University of Toronto, Toronto M5S 1A8, Ontario, Canada M5G 1X8Previous reports showed that cleavage of vesicle-associated membrane protein-2 (VAMP-2) and synaptosomal-associated protein of 25 kDa (SNAP-25) by clostridial neurotoxins in permeabilized insulin-secreting beta-cells inhibited Ca(2+)-evoked insulin secretion . In these reports, the soluble N-ethylmaleimide-sensitive factor attachment protein target receptor proteins might have formed complexes, which preclude full accessibility of the putative sites for neurotoxin cleavage . In this work, VAMP-2 and SNAP-25 were effectively cleaved before they formed toxin-insensitive complexes by transient transfection of insulinoma HIT or INS-1 cells with tetanus toxin (TeTx) or botulinum neurotoxin A (BoNT/A), as shown by immunoblotting and immunofluorescence microscopy . This resulted in an inhibition of Ca(2+) (glucose or KCl)-evoked insulin release proportionate to the transfection efficiency (40-50%) and an accumulation of insulin granules . With the use of patch-clamp capacitance measurements, Ca(2+)-evoked exocytosis by membrane depolarization to -10 mV was abolished by TeTx (6% of control) but only moderately inhibited by BoNT/A (30% of control) . Depolarization to 0 mV to maximize Ca(2+) influx partially overcame BoNT/A (50% of control) but not TeTx inhibition . Of note, cAMP activation potentiated Ca(2+)-evoked secretion by 129% in control cells but only 55% in BoNT/A-transfected cells and had negligible effects in TeTx-transfected cells . These results indicate that, whereas VAMP-2 is absolutely necessary for insulin exocytosis, the effects of SNAP-25 depletion on exocytosis, perhaps on insulin granule pool priming or mobilization steps, could be partially reversed by higher levels of Ca(2+) or cAMP potentiation. Infect Immun, 2001 Sep, 69(9), 5709 - 15 Candidate vaccine against botulinum neurotoxin serotype A derived from a Venezuelan equine encephalitis virus vector system; Lee JS et al.; A candidate vaccine against botulinum neurotoxin serotype A (BoNT/A) was developed by using a Venezuelan equine encephalitis (VEE) virus replicon vector . This vaccine vector is composed of a self-replicating RNA containing all of the VEE nonstructural genes and cis-acting elements and also a heterologous immunogen gene placed downstream of the subgenomic 26S promoter in place of the viral structural genes . In this study, the nontoxic 50-kDa carboxy-terminal fragment (H(C)) of the BoNT/A heavy chain was cloned into the replicon vector (H(C)-replicon) . Cotransfection of BHK cells in vitro with the H(C)-replicon and two helper RNA molecules, the latter encoding all of the VEE structural proteins, resulted in the assembly and release of propagation-deficient, H(C) VEE replicon particles (H(C)-VRP) . Cells infected with H(C)-VRP efficiently expressed this protein when analyzed by either immunofluorescence or by Western blot . To evaluate the immunogenicity of H(C)-VRP, mice were vaccinated with various doses of H(C)-VRP at different intervals . Mice inoculated subcutaneously with H(C)-VRP were protected from an intraperitoneal challenge of up to 100,000 50% lethal dose units of BoNT/A . Protection correlated directly with serum enzyme-linked immunosorbent assay titers to BoNT/A . The duration of the immunity achieved was tested at 6 months and at 1 year postvaccination, and mice challenged at these times remained refractory to challenge with BoNT/A. J Neurol, 2001 Jun, 248(6), 478 - 82 Clinical characteristics of the geste antagoniste in cervical dystonia; Muller J et al.; The geste antagoniste (moving an arm to the face or head) is a well-known clinical feature in cervical dystonia (CD) to alleviate the abnormal posture . The clinical phenomenology of these manoeuvres has not so far been assessed systematically . Fifty patients with idiopathic CD aware of at least one geste antagoniste (60% women, mean age at onset 44.1 years, mean disease duration 7.5 years) were subjected to a standardized investigation including a semiquantitative clinical rating scale and polymyographic recordings of six cervical muscles . Twenty-seven patients (54%) demonstrated more than one geste antagoniste (range 2-5) . A clinically significant (> or = 30%) reduction of head deviation was observed in 41 patients (82 %) . Dystonic head posture improved by a mean of 60 % along all planes by the geste manoeuvre with a complete cessation of head oscillations in nine of 33 patients (27 %) with phasic CD . No significant laterality of the "geste-arm" or the facial target area was found . The duration of geste-effects depended significantly on disease duration and determined the patient's self-rating of the benefit of the manoeuvre . EMG-polygraphy revealed two types of geste-induced polymyographic changes: a decrease in recruitment density and amplitude in at least one dystonic muscle (66%), and an increased tonic muscle activation in the remaining patients . The remarkable efficacy of the geste antagoniste and the considerable variety in performance, duration, and EMG-pattern of these manoeuvres warrant further investigation of the therapeutic use of sensorimotor stimulation, in particular for those CD patients who experience limited or no effect from botulinum toxin therapy. Arch Facial Plast Surg, 2001 Jul-Sep, 3(3), 165 - 9 Effect of botulinum toxin pretreatment on laser resurfacing results: a prospective, randomized, blinded trial; Zimbler MS et al.; BACKGROUND: Facial laser resurfacing and chemodenervation with botulinum toxin type A are used independently as means of nonsurgical facial rejuvenation . Recent reports in the literature have described combining these 2 therapies, claiming improved and longer-lasting laser resurfacing results . To date, no scientific investigation has been undertaken to prove or disprove this theory . DESIGN: Institutional review board-approved, prospective, randomized, blinded study at university-affiliated outpatient cosmetic surgery offices . INTERVENTION: Patients had one side of their face injected, at specific anatomic subsites (crow's feet, horizontal forehead furrows, and glabellar frown lines), with botulinum toxin 1 week before laser resurfacing . After receiving an injection, patients underwent cutaneous laser exfoliation on both sides of the face with either a carbon dioxide or an erbium dual-mode laser . MAIN OUTCOME MEASURES: Patients' injected (experimental) and noninjected (control) sides were compared after laser resurfacing . Follow-up was documented at 6 weeks, 3 months, and 6 months after laser resurfacing . Subjective evaluation, based on a visual analog scale, was performed in person by a blinded observer . Furthermore, a blinded panel of 3 expert judges (1 facial plastic surgeon, 1 oculoplastic surgeon, and 1 cosmetic dermatologist) graded 35-mm photographs taken during postoperative follow-up visits . RESULTS: Ten female patients were enrolled in the study . A 2-tailed t test showed that all sites that were pretreated with botulinum toxin showed statistically significant improvement (P< or =.05) over the nontreated side, with the crow's feet region showing the greatest improvement . Comparing results between the carbon dioxide and erbium lasers did not result in any statistically significant differences . CONCLUSIONS: Hyperdynamic facial lines, pretreated with botulinum toxin before laser resurfacing, heal in a smoother rhytid-diminished fashion . These results were clinically most significant in the crow's feet region . We recommend pretreatment of movement-associated rhytides with botulinum toxin before laser resurfacing . For optimum results, we further recommend continued maintenance therapy with botulinum toxin postoperatively. Funct Neurol, 2001 Apr-Jun, 16(2), 135 - 41 The position of the head in space: a kinematic analysis in patients with cervical dystonia treated with botulinum toxin; Albani G et al.; Many instruments have been employed in recent years in order to quantify the posture and motion of the head in normal and pathological subjects . Evaluations of this type present many difficulties related to the influence of individual and external factors and to the accuracy of the system used . In patients with cervical dystonia (CD) the only rating scales currently used are semi-quantitative and subjective . More precise information on disease severity and response to the treatment is needed . Posture and motion of the head were evaluated by means of ELITE motion analyser (BTS, Milan, Italy) in 6 patients with the left laterocollis form of CD undergoing treatment with botulinum toxin (BTX) . The method emerged as very useful for the quantification of the therapeutic response (which was more marked in motion than in posture) . We found an inverse relationship between the degree of motion improvement and the restriction of motion before treatment. Dermatol Surg, 2001 Aug, 27(8), 703 - 8 Botulinum-A toxin treatment of the lower eyelid improves infraorbital rhytides and widens the eye; Flynn TC et al.; Botulinum-A exotoxin (BTX-A) can be used cosmetically to improve rhytides, particularly of the upper one-third of the face . In this study, fifteen women had BTX-A (BOTOX, Allergan, Inc.) injected into the orbicularis oculi muscle . One lower eyelid received two units just subdermally in the midpupillary line three millimeters below the ciliary margin . The opposite periocular area received two units BTX-A in the lower eyelid with 12 units BTX-A injected into the lateral orbital ("crow's foot") area . Three injections of four units each were placed 1.5 cm from the lateral canthus, each 1 cm apart . Patients and physicians independently evaluated the degree of improvement (grade 0 = no improvement, grade 1 = mild improvement, grade 2 = moderate improvement, and grade 3 = dramatic improvement) . An independent photographic analysis was performed . Patients reported a grade of 0.73 when two units were injected alone into the lower lid, and a grade of 1.9 when the lower eyelid and the lateral orbital areas were injected . Physician assessment was grade 0.7 with injection of the eyelid alone and grade 1.8 with injection of the lower eyelid and lateral orbital area . Single investigator photographic analysis demonstrated that 40% of the subjects who had injection of the lower eyelid alone had an increased palpebral aperture (IPA), while 86% of the subjects who had injection of the lower eyelid and lateral orbital area had an IPA . Subjects receiving two units alone had an average 0.5 mm IPA and a mean 1.3 mm IPA at full smile . Concomitant treatment of the lateral orbital area produced a mean 1.8 mm IPA at rest and a mean 2.9 mm IPA at full smile . The results were more notable in the Asian eye . Two units of BTX-A injected into the lower eyelid orbicularis oculi muscle improves infraorbital wrinkles, particularly when used in combination with BTX-A treatment of the lateral orbital area. Acta Neurol Scand, 2001 Aug, 104(2), 110 - 2 Gabapentin in the treatment of hemifacial spasm; Daniele O et al.; OBJECTIVES: To evaluate the efficacy of gabapentin in the treatment of hemifacial spasm . MATERIAL AND METHODS: Twenty-three patients with hemifacial spasm not suitable for surgery or therapy with botulinum toxin were treated with gabapentin . The main efficacy parameter was the percentage of spasm reduction . RESULTS: A clinically significant reduction of spasms was obtained by 16 patients . CONCLUSION: Gabapentin was effective and safe in reducing hemifacial spasm in 16 out 23 (69.6%) patients. Rev Med Suisse Romande, 2001 Jun, 121(6), 471 - 4 {Current indications for the treatment with botulin toxin}; Kohler A et al.; Botulinum toxin is more and more frequently used as a therapeutic agent . The toxin blocks selectively and reversibly the neuromuscular junction, causing a muscle relaxation . Indications are mainly muscular hypercontraction, such as dystonia, blepharospasm, focal spasticity, strabismus or tics . The range of action extend to focal hyperhydrosis, palmar, axillary or plantar . It seems now that some painful syndrome such as migraine or tension headache may benefit from toxin injections . Esthetic indications constitute an extension to the pure medical indications. Hepatogastroenterology, 2001 Jul-Aug, 48(40), 977 - 9 Topical nitrates and the higher doses of botulinum toxin for chronic anal fissure; Madalinski MH et al.; BACKGROUND/AIMS: Combined BT-A (botulinum toxin A) therapy and local application of nitrates can be more effective than BT-A alone for chronic anal fissure treatment, but so far the optimal dose of BT-A is not known . The aim of our study was to learn if BT-A doses higher than those used so far could change the outcome of fissure treatment . METHODOLOGY: We enrolled 14 consecutive patients suffering from idiopathic chronic anal fissure who did not respond to previous local treatment of nitric oxide donor and subsequent BT-A therapy (25 U of Botox) . They were offered a local nitroglycerin treatment . In failure cases patients received the greater doses of BT-A (50 U of Botox) . RESULTS: In all 11 patients with chronic anal fissure who applied nitroglycerin after BT-A injection, an effect on the internal anal sphincter relaxation was observed but fissure healing after topical nitroglycerin occurred only in 1 case . Of 13 patients with chronic anal fissure who received 50 U of BT-A no healing was reported in 6 cases . One male from this group received a greater dose (100 U of Botox) and then the fissure healed . CONCLUSIONS: The effect of topical nitrates on internal anal sphincter relaxation after botulinum toxin injection is not the last line for nonsurgical treatment of chronic anal fissure . Always we ought to consider using the next greater dose of BT-A before surgical treatment. Restor Neurol Neurosci, 2000, 17(1), 1 - 8 Lower limb muscle activity in ambulatory children with cerebral palsy before and after the treatment with Botulinum toxin A; Hesse S et al.; Purpose: The study investigated the effect of Botulinum toxin A on the gait and lower limb muscle activity of ambulatory CP children . Methods: 19 spastic diplegic and 4 left hemiparetic CP children were injected with a mean dose of 23.5 units of Botulinum toxin A/kg body weight into the gastrocnemius and hamstring muscles . Muscle tone and gait analysis including the kinesiological electromyogram of the shank and thigh muscles were assessed before and four weeks after injection and compared with the help of a multivariate analysis (p < 0.05) . Results: Botulinum toxin A caused a definite reduction of plantarflexor, knee and hip hypertonia in 21 children, resulting in a more plantar grade and erect gait in 17 children four weeks after injection . Gait analysis showed a statistically significant improvement in peak ankle dorsi-flexion and knee extension during stance, and the length of the force point of action under both feet increased . Electromyography revealed sig-nificantly less co-contraction of the lower leg muscles, due to a more phasic instead of a tonic activity of the tibialis anterior muscle, and an improved activation pattern of the left rectus and biceps femoris muscles . Conclusions: The present study demonstrated that the injection of Botulinum toxin A resulted in a more mature muscle activation pattern of CP children . Most of the children walked more plantigrade and erect, the functional gait parameters, however, did not change. Parkinsonism Relat Disord, 2001 Oct, 8(2), 109 - 21 Dystonia and parkinsonism; Jankovic J et al.; Parkinsonism and dystonia may coexist in a number of neurodegenerative, genetic, toxic, and metabolic disorders and as a result of structural lesions in the basal ganglia . Parkinson's disease (PD) and the 'Parkinson-plus' syndromes (PPS) account for the majority of patients with the parkinsonism-dystonia combination . Dystonia, particularly when it involves the foot, may be the presenting sign of PD or PPS and these disorders should be suspected when adults present with isolated foot dystonia . Young age, female gender, and long disease duration are risk factors for PD-related dystonia, but dystonia in patients with PD is usually related to levodopa therapy . The mechanism of dystonia in PD is not well understood and the management is often challenging because levodopa and other dopaminergic agents may either improve or worsen dystonia . Other therapeutic strategies include oral medications (baclofen, anticholinergics and benzodiazepines), local injections of botulinum toxin, intrathecal baclofen, and surgical lesions or high frequency stimulation of the thalamus, globus pallidus, or subthalamus. J Neurosci, 2001 Aug 15, 21(16), 6058 - 68 Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking; Lan JY et al.; Regulation of neuronal NMDA receptors (NMDARs) by group I metabotropic glutamate receptors (mGluRs) is known to play a critical role in synaptic transmission . The molecular mechanisms underlying mGluR1-mediated potentiation of NMDARs are as yet unclear . The present study shows that in Xenopus oocytes expressing recombinant receptors, activation of mGluR1 potentiates NMDA channel activity by recruitment of new channels to the plasma membrane via regulated exocytosis . Activation of mGluR1alpha induced (1) an increase in channel number times channel open probability, with no change in mean open time, unitary conductance, or reversal potential; (2) an increase in charge transfer in the presence of NMDA and the open channel blocker MK-801, indicating an increased number of functional NMDARs in the cell membrane; and (3) increased NR1 surface expression, as indicated by cell surface Western blots and immunofluorescence . Botulinum neurotoxin A or expression of a dominant negative mutant of synaptosomal associated protein of 25 kDa molelcular mass (SNAP-25) greatly reduced mGluR1alpha-mediated potentiation, indicating that receptor trafficking occurs via a SNAP-25-mediated form of soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor-dependent exocytosis . Because group I mGluRs are localized to the perisynaptic region in juxtaposition to synaptic NMDARs at glutamatergic synapses in the hippocampus, mGluR-mediated insertion of NMDARs may play a role in synaptic transmission and plasticity, including long-term potentiation. HNO, 2001 Jul, 49(7), 548 - 52 {Botulinum toxin type A-induced "rebalancing" in bilateral vocal cord paralysis?}; Ptok M et al.; BACKGROUND: Upper airway obstruction due to bilateral vocal cord paralysis in an 80-year-old female patient was successfully relieved by injection of botulinum toxin A (BTA) into the laryngeal adductor muscles . The patient achieved satisfactory airway ventilation . Spirograms obtained preoperatively and postoperatively documented improved peak flow rates and 1-s forced expiratory volume values . Voice quality was breathy after the injection; however, neither aspiration nor dysphagia developed . Surprisingly, the maximum phonation time increased . PATIENTS AND METHODS: During a follow-up check 4 months later, the patient still reported less dyspnea although the vocal cords were closer together than initially after the injection . The decrease in dyspnea as reported by the patien