Schmerz, 2004 Dec, 18(6), 498 - 505 {Botulinum toxin A in orthopedic pain therapy}; Placzek R et al.; Botulinum toxin A (BTX A) has been used for more than 20 years as a safe and effective treatment for numerous diseases characterized by pathological muscle hypertension . In patients suffering from dystonia or spasticity, it has been observed that use of BTX A results not only in muscle relaxation but also frequently relieves associated pain . This pain relief is often seen earlier and to a much greater extent than the muscular relaxation itself . This has led to extending the use of BTX A to treat various focal pain syndromes . The results of initial studies in specific musculoskeletal pain therapy suggest that BTX A infiltrations are effective in the treatment of chronic, therapy-resistant pain of the shoulder and back region . Furthermore, BTX A has been found to be a less invasive option for the treatment of chronic epicondylitis and similar tendonitis conditions . The healing process following rupture of tendons or muscle transfer operations may be improved . In adults with increased muscle tone and endoprostheses, the targeted relaxation of spastic muscles might increase the lifetime of the implant and diminish aseptic loosening . In children with cerebral palsy, prophylactic treatment of hip luxation appears possible . The doses used in pain therapy are low; if correctly applied, the tolerance and safety are high and the effect lasts for a number of weeks. J Gastrointest Surg, 2004 Dec 1, 8(8), 997 - 1006 The role of botulinum toxin injection and upper esophageal sphincter myotomy in treating oropharyngeal dysphagia; Zaninotto G et al.; The aims of this study were to assess the efficacy and safety of botulinum toxin (BoTox) injection in the cricopharyngeus muscle (CP) and CP myotomy in patients with oropharyngeal dysphagia (OPD) and to identify factors predicting the outcome of these treatments . The study involved patients with persistent OPD despite 2-6 months of rehabilitation, who all underwent clinical evaluation, esophageal manometry, upper gastrointestinal endoscopy, and videofluoroscopy (VFS) . Patients received 5-10 BoTox units injections in the CP, identified by electromyography . Surgical myotomy of the upper esophageal sphincter was performed when dysphagia persisted after two BoTox injections . After treatment, patients were reevaluated with clinical interviews and VFS . The study population included 21 patients (15 mean and 6 women; median age, 68 years), classified into three groups, based on the etiology of their OPD: eight (38%) had central nervous system abnormalities, five (24%) had peripheral nerve disease, and eight (38%) were classified as idiopathic . The median time since the onset of dysphagia was 18 months . Thirteen of 21 patients (62%) needed supplemental/total gastrostomy feeding, and 5 of 21 (24%) had tracheostomy . One patient died, on posttreatment day 7, due to massive aspiration . No other BoTox-related complications were observed . After BoTox injection, dysphagia improved in 9 of 21 (43%) patients . Severely altered VFS findings and CP incoordination or low activity predicted BoTox failure at multivariate analysis . Dysphagia improved in 8 of 11 (72.7%) patients who failed to respond to BoTox and underwent myotomy . A mild impairment of VFS findings and a higher pressure of pharyngeal contractions best predicted response to BoTox with or without myotomy . BoTox injection can be used as the first therapeutic option in patients with OPD: it is safe and simple and relieves dysphagia in 43% of cases . If BoTox fails, CP myotomy can be offered to patients with preserved oral and tongue activity at VFS and an intact bolus propulsion ability on manometry. J Neurochem, 2004 Dec, 91(6), 1461 - 72 Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates; Bade S et al.; Multi-domain bacterial protein toxins are being explored as potential carriers for targeted delivery of biomolecules . Previous approaches employing isolated receptor binding subunits disallow entry into the cytosol . Strategies in which catalytic domains are replaced with cargo molecules are presumably inefficient due to co-operation of domains during the endosomal translocation step . Here, we characterize a novel transport vehicle in which cargo proteins are attached to the amino terminus of the full-length botulinum neurotoxin type D (BoNT/D) . The intrinsic enzymatic activity of the neurotoxin allowed quantification of the efficacy of cargo delivery to the cytosol . Dihydrofolate reductase and BoNT type A (BoNT/A) light chain (LC) were efficiently conveyed into the cytosol, whereas attachment of firefly luciferase or green fluorescent protein drastically reduced the toxicity . Luciferase and BoNT/A LC retained their catalytic activity as evidenced by luciferin conversion or SNAP-25 hydrolysis in the cytosol of synaptosomes, respectively . Conformationally stabilized dihydrofolate reductase as cargo considerably decreased the toxicity indicative for the requirement of partial unfolding of cargo protein and catalytic domain as prerequisite for efficient translocation across the endosomal membrane . Thus, enzymatically inactive clostridial neurotoxins may serve as effective, safe carriers for delivering proteins in functionally active form to the cytosol of neurones. FEBS Lett, 2004 Dec 3, 578(1-2), 121 - 7 Modulation of botulinum neurotoxin A catalytic domain stability by tyrosine phosphorylation; Ibanez C et al.; Botulinum neurotoxin A (BoNT A) is a substrate of the Src family of tyrosine kinases . Here, we report that the BoNT A light chain (LC) is phosphorylated in the tyrosine-71 located at N-terminus . Covalent modification of this residue notably increases the thermal stability of the endopeptidase activity, without affecting its catalytic efficacy . Similarly, mutation of this residue specifically affected the protein stability but not its endopeptidase function . Fusion of the Tat-translocating domain to the N-terminus of the enzyme produced a cell permeable, functional enzyme, as evidenced by immunocytochemistry and by the cleavage of cytosolic SNAP25 in intact PC12 cells . Noteworthy, truncation of cellular SNAP25 was reduced in cells when the Src kinase activity was inhibited with a specific antagonist, implying that tyrosine phosphorylation of BoNT A LC modulates the in vivo proteolytic activity of the neurotoxin . Taken together, these findings substantiate the tenet that tyrosine phosphorylation of BoNT A LC could be an important modulatory strategy of the neurotoxin stability and suggest that the phosphorylated neurotoxin may be a relevant molecule in vivo. Dev Med Child Neurol, 2004 Dec, 46(12), 807 - 11 Efficacy of botulinum toxin A, serial casting, and combined treatment for spastic equinus: a retrospective analysis; Glanzman AM et al.; Botulinum toxin type A (BTX-A), serial casting, and combined treatment for spastic equinus were compared by chart review . Fifty-five patients with diplegia (n=21), hemiplegia (n=17), quadriplegia (n=6), and other diagnoses (n=11) were reviewed . Thirty-one patients had Gross Motor Function Classification System (GMFCS) scores of I or II, 10 had a GMFCS score of III, and eight had GMFCS scores of IV or V (for six there were no available data) . Mean age was 7 years 1 month (SD 4 y 8mo) . The combined group showed a significantly greater increase in passive range of motion (ROM) of the ankle joint in comparison with BTX-A alone (p=0.0002), with a mean of 17 degrees (SD 11.2) versus 5 degrees (SD 6.7), and casting alone showed a significantly greater increase in comparison with BTX-A alone (p=0.0001), with a mean of 15 degrees (SD 4.5) versus 5 degrees (SD 6.7) . With cast number controlled, change in ROM after casting with and without BTX-A was not significantly different (p=0.37) . There was no significant difference between casting with or without BTX-A, and both improved ROM to a greater degree than BTX-A alone . Casting demonstrated a significantly more robust impact on range of motion than BTX-A alone. Plast Reconstr Surg, 2004 Dec, 114(7), 1892 - 902 Temporary management of upper lid ptosis, lid malposition, and eyelid fissure asymmetry with botulinum toxin type A; Fagien S; During the past 10 years the primary focus for the aesthetic use of botulinum toxin has been directed to the treatment of dynamic facial lines . This agent has been shown to be very effective for the improvement of facial shape . The use of botulinum toxin type A for the correction of a variety of presentations of facial asymmetry has also been well established . The general principles regarding the counter-effects of facial muscle protagonists and antagonists and their potential effects on the position of facial soft-tissue regions apply here as well . Twenty-two patients received botulinum toxin type A for the temporary treatment of mild to moderate unilateral upper eyelid ptosis and aesthetic improvement of lower eyelid position, with favorable results . Although commonly related to a rare yet feared adverse consequence from the inappropriate application of botulinum toxin, its application for the treatment of upper eyelid ptosis, eyelid position, and other lid fissure asymmetries for aesthetic improvement is presented. Org Lett, 2004 Dec 9, 6(25), 4783 - 6 Synthesis of a Gln-Phe hydroxy-ethylene dipeptide isostere; Haug BE et al.; {structure: see text} The protected Gln-Phe hydroxyethylene dipeptide isostere 1 was synthesized as a precursor for preparation of potential inhibitors of Botulinum neurotoxin B metalloprotease . The method allows for the synthesis of additional hydroxyethylene dipeptide isosteres such as 2 with functionalized P1 side chains . The isosteres prepared were coupled with a dipeptide to produce protected pseudotetrapeptide derivatives. J Neurophysiol . 2004 Dec 1; {Epub ahead of print} Effect of forelimb use on postnatal development of the forelimb motor representation in primary motor cortex of the cat; Martin JH et al.; In the cat, the motor representation in motor cortex develops between weeks 8-13 . Motor map development is accompanied by a decrease in the current thresholds for evoking movements with a concomitant increase in the number of effective sites, an increase in the distal representation, and the representation of multijoint synergies . In this study we used intracortical microstimulation in anesthetized cats to examine how forelimb motor experiences influence development of map characteristics . To promote skilled movements during weeks 8-13, animals were engaged in daily performance of a prehension task . Forelimb movements were prevented by intramuscular botulinum toxin injection or restraint . To determine if experience-dependent changes were permanent, we examined the map in different animals between 1 week and 1 year after cessation of testing . Promoting forelimb use resulted in an increase in the number of sites from which multiple joint effects were produced by stimulation and the number of joints represented at those sites . The effect was maximal at 1 week after cessation of testing, and became progressively less at 1 month and at 4 months . Preventing limb use resulted in a decreased number of effective sites, an increase in current thresholds for evoking responses, and a decreased representation of joints at multijoint sites . Our findings show that the motor map can respond to novel motor demands as it is forming during development but that it reverts back to one with the properties of a map in a control animal if those demands are not maintained in the animal's behavioral repertoire. Clin Rehabil, 2004 Nov, 18(7), 764 - 6 Treatment of recurrent posterior dislocation of the shoulder in cerebral palsy by injection with botulinum toxin A into the M . subscapularis; de Boer KS et al.; SUBJECTS: A 20-year-old woman, known to have cerebral palsy and a spastic hemiparesis, suffered from frequent (up to 20 times a day) and painful posterior dislocation of the affected shoulder . INTERVENTIONS: For the last two years we have treated her with injections with botulinum toxin A (100 U Botox) in the M . subscapularis . RESULTS: Pain and dislocation rate have improved substantially. Int J Rehabil Res, 2004 Dec, 27(4), 275 - 81 The effect of botulinum toxin type-A injection on spasticity, range of motion and gait patterns in children with spastic diplegic cerebral palsy: an Egyptian study; El-Etribi MA et al.; Spasticity is defined as increased resistance to passive movement, secondary to hyperreflexia after an upper motor neuron lesion . In children with cerebral palsy (CP), it can interfere with mobility and self-care and can contribute to development of fixed myostatic contractures . This study investigated the efficacy of botulinum toxin type-A, a neuromuscular blocking agent that reduces muscle tone, in a variety of neuromuscular disorders, injections in a prospective, 3-month, controlled study involving 40 children with spastic diplegic CP . The patients were divided into two groups: Group 1 (20 patients) entered a botulinum toxin type-A injection+physiotherapy rehabilitation program; Group 2 (20 patients) were given the physiotherapy rehabilitation program only . Patients were assessed at 4, 8 and 12 weeks post-treatment using the Modified Ashworth Scale (MAS), dynamic gait pattern, ankle range-of-motion measurements and quantification of muscle denervation by nerve conduction techniques . The botulinum toxin type-A group demonstrated statistically significantly decreased spasticity, improved gait function and improved range of motion with evidence of partial denervation of the injected muscle compared to the control group . In conclusion, botulinum toxin type-A injections are a well-tolerated, non-surgical technique that can improve overall response to physiotherapy. Acta Chir Belg, 2004 Oct, 104(5), 577 - 80 The treatment of chronic anal fissure with botulinum toxin; Godevenos D et al.; BACKGROUND/AIMS: The aim of this study was to evaluate the effectiveness of botulinum toxin for the treatment of uncomplicated dorsal chronic idiopathic anal fissure . MATERIAL AND METHODS: Forty-five patients who reported post defecatory anal pain since two months or more were given a total of 20U botulinum toxin in the anal sphincter apparatus on both sides as well as below the anal fissure . RESULTS: Thirty-seven patients received a second session of 25U botulinum toxin injection . Thirty-five patients (78%) presented completely healed anal fissure, while ten needed lateral internal sphincterotomy . All patients were followed up for 8-36 months . Two patients relapsed . CONCLUSION: Local injection of botulinum toxin is a new and safe treatment; however, two sessions of injections are necessary to be effective and long-term follow-up to assess the recurrence rate of fissure is needed to evaluate further this method of treatment . Partial internal lateral sphincterotomy is no more the treatment of choice for chronic anal fissure. Int J Dermatol, 2004 Dec, 43(12), 969 - 71 Treatment of plantar hyperhidrosis with botulinum toxin type A; Vadoud-Seyedi J; BACKGROUND: Hyperhidrosis (excessive, uncontrollable sweating) can be embarrassing and disabling, significantly impacting social and professional performance and quality of life . Treatments aim to reduce sweating, but few are effective, often carrying the risk of significant side-effects . The aims of this study were to evaluate the efficacy and safety of botulinum toxin type A (BTX-A) for plantar hyperhidrosis and to investigate the role of the Dermojet as a potential injection technique . METHODS: Ten adult patients (five men, five women), aged 19-51 years, with severe, previously unresponsive, plantar hyperhidrosis, were recruited to this single-center, open-label, noncomparative study . The hyperhidrotic area of each foot was injected over 15-20 sites without analgesia with 50 U BTX-A + 5 mL sterile saline using a Dermojet . Patients were followed up for 8 months with monthly sweat reduction assessments using Minor's iodine-starch test . Patients provided a treatment self-assessment after completion of follow-up . RESULTS: Within 7 days post-treatment, eight patients reported significantly decreased sweating, and seven patients were symptom free for up to 5 months . Patient self-assessment showed that seven of the 10 patients were satisfied with their treatment . One minor adverse event was reported comprising a temporary localized hematoma (one patient) . CONCLUSIONS: Intracutaneous BTX-A injection using the Dermojet offers a simple, safe, and effective alternative for treatment of plantar hyperhidrosis. J Agric Food Chem, 2004 Dec 1, 52(24), 7187 - 98 Applying combinatorial chemistry and biology to food research; Wong D et al.; In the past decade combinatorial chemistry has become a major focus of research activity in the pharmaceutical industry for accelerating the development of novel therapeutic compounds . The same combinatorial strategies could be applied to a broad spectrum of areas in agricultural and food research, including food safety and nutrition, development of product ingredients, and processing and conversion of natural products . In contrast to "rational design", the combinatorial approach relies on molecular diversity and high-throughput screening . The capability of exploring the structural and functional limits of a vast population of diverse chemical and biochemical molecules makes it possible to expedite the creation and isolation of compounds of desirable and useful properties . Several studies in recent years have demonstrated the utility of combinatorial methods for food research . These include the discovery of synthetic antimicrobial, antioxidative, and aflatoxin-binding peptides, the identification and analysis of unique flavor compounds, the generation of new enzyme inhibitors, the development of therapeutic antibodies for botulinum neurotoxins, the synthesis of unnatural polyketides and carotenoids, and the modification of food enzymes with novel properties . The results of such activities could open a large area of applications with potential benefits to the food industry . This review describes the current techniques of combinatorial chemistry and their applications, with emphasis on examples in food science research. Ann Otol Rhinol Laryngol, 2004 Nov, 113(11), 877 - 86 A new electromyographic definition of laryngeal synkinesis; Maronian NC et al.; Laryngeal synkinesis involves the misdirected reinnervation of an injured recurrent laryngeal nerve to vocal fold abductor and adductor musculature . The resultant laryngeal dyscoordination can cause vocal fold immobility and airway compromise . Although this entity is sometimes considered in the differential diagnosis, it is only demonstrable with laryngeal electromyography (EMG) . We propose a new EMG definition of synkinesis to assist in its identification during workup of vocal fold immobility . A retrospective chart review from 1992 to 1997 in the Voice Disorders Clinic identified 10 patients with laryngeal synkinesis . Five patients had bilateral immobility, and 5 had unilateral immobility . Monopolar EMG was performed on all patients . Fine-wire EMG was performed when monopolar EMG did not elucidate the cause of the immobility . The EMG studies revealed synkinetic reinnervation in all subjects . On the basis of the EMG results, 7 of the 10 patients were treated with botulinum toxin to weaken the undesired reinnervation . Three of the 7 patients had benefit from this therapy . Laryngeal synkinesis should be considered as part of the differential diagnosis of vocal fold immobility . Awake laryngeal EMG is the only method to demonstrate synkinesis of the larynx . The diagnosis of synkinesis is clinically significant in cases of immobility to identify patients who might benefit from botulinum toxin therapy . Additionally, the presence of synkinesis in cases of unilateral immobility may be a contraindication to laryngeal reinnervation procedures . The benefit of botulinum toxin therapy is likely greater in the treatment of bilateral as opposed to unilateral immobility. Altern Lab Anim, 2003 Dec, 31(6), 611 - 5 Botulinum toxin testing in animals: the questions remain unanswered; Balls M; Questions are raised concerning the testing of botulinum toxin in animals, and the British Government's answers to Parliamentary Questions on this issue are reviewed, with an emphasis on the potential for reducing, refining and replacing the animal tests, which can involve substantial severity, and on the responsibility of the Home Office so see that the Three Rs approach is fully applied in this specific case. J Med Assoc Thai, 2004 Oct, 87(10), 1205 - 11 Hemifacial spasm: results of treatment with low dose botulinum toxin injection; Suputtitada A et al.; BACKGROUND: Hemifacial Sapsm (HFS) is a common movement disorder in Thailand . Botulinum toxin type A (BTA) is an effective and safe treatment for this condition . The success of BTA treatment depends on the experience of the clinician . OBJECTIVE: To study the demographic data, efficacy and safety of low dose BTA injection in HFS patients . SETTING: The Spastic and Dystonia Clinic, Department of Rehabilitation Medicine, King Chulalongkorn Memorial Hospital . DESIGN: Open-label, prospective case-series study . PATIENTS: All patients with HFS referred for BTA injection from December 1st, 1995 to November 30th, 2003 . METHOD: Sex, age, side of spasm, onset of symptoms before BTA injection, underlying diseases, sites of BTA injection, dose of each BTA treatment, duration of response, efficacy, and side-effects were analyzed . 3-5 units of BOTOX were intramuscularly injected per site to all muscles that had spasm . After injection, a 20-minute cold compression on the first day was followed by 20-minute warm compression with massage at each injection site per day for 14 days . RESULTS : A total of 112 patients with HFS were treated with 874 BTA treatments . There were 71 females (63.4%) and 41 males (36.6%) . The mean age was 45 years . 75 patients (67%) were affected on the left side . Mean duration of symptoms was 3.4 years . The sites of injection were orbicularis occuli and orbicularis oris muscles in all 874 treatments (100%) . The mean dose of all treatments was 25 units . The mean initial dose was 30.5 units . The mean dose for subsequent injection was 23 units . The mean duration between treatments was 4.7 months . The mean initial duration was 3.5 months . The mean duration for subsequent injection was 4.8 months . The outcomes of treatment assessed at 4 weeks after injection classified as excellent (>80% improvement) were found in 845 treatments (96.7%) . Most treatments had no complication (91.9%) . Ptosis, facial paresis and double vision were mild and transient, lasting 1-4 weeks . There were no long-term complications of BTA treatment in the present series . CONCLUSION: Low dose BTA injection is an effective treatment for hemifacial spasm patients . There was a longer duration of response in subsequent injections and a lower complication rate in the present study when compared to others. J Surg Orthop Adv, 2004 Fall, 13(3), 149 - 55 Effect of botulinum toxin type A on gait of children who are idiopathic toe-walkers; Brunt D et al.; The purpose of this study was to determine the effects of botulinum toxin type A treatment on ankle muscle activity during gait of children who are idiopathic toe-walkers . Five children who were idiopathic toe-walkers with a mean age was 4.34 years participated . Gait of the subjects was evaluated prior to, 20 days following, and 12 months following bilateral botulinum toxin type A injection of the gastrocnemius and soleus muscles . Subjects received physical therapy following the 20-day evaluation . Dependent variables were type of foot contact pattern and duration of swing-phase tibialis anterior activity and onset of stance-phase gastrocnemius relative to ground contact . Prior to treatment 51% of foot contacts were with the toe (heel just off the ground) or were digitigrade, while the remaining contacts were flat foot or heel strike . At approximately 20 days following treatment, only 8% of foot contacts were toe contact or digitigrade . Prior to treatment, mean gastrocnemius onset was 30 ms prior to foot contact and the duration of swing-phase tibialis anterior was only 345 ms . Following treatment (and a more normal foot contact pattern), mean gastrocnemius onset followed ground contact by 36 ms and tibialis anterior duration increased through terminal swing and into the loading response . The posttreatment improvement was maintained at 12-month follow-up . It appears that botulinum toxin type A treatment normalizes the ankle EMG pattern during gait and a more normal foot-strike pattern is obtained . These data are discussed in terms of a neuromotor rationale for the rehabilitation of children who are idiopathic toe-walkers to maintain posttreatment improvements. Can J Ophthalmol, 2004 Oct, 39(6), 639 - 49 Surgery and botulinum toxin in congenital esotropia; Ruiz MF et al.; BACKGROUND: In a previous study we investigated the advantages and drawbacks of early and delayed injection of botulinum toxin as primary treatment of infantile esotropia with nystagmus in abduction (IENA) . We carried out a further study to investigate the role and efficacy of surgery in this condition and to determine the possible effect of previous injection of both medial recti with botulinum toxin in patients requiring a final horizontal surgical correction . METHODS: Review of the records of 44 patients (24 girls and 20 boys) with IENA seen between 1979 and 1998 who had undergone at least one horizontal surgical procedure . The outcomes in the 16 patients who had previously received botulinum toxin were compared with those in the 28 patients for whom surgery was the primary treatment . RESULTS: There was a negative correlation between the pretreatment esotropic angle and age (Pearson's r = -0.45, p < 0.05) . The first visit to a surgical specialist took place very late (mean age 43 months {standard deviation (SD) 39 months}) . Of the 35 children seen during the period in which botulinum toxin was available, 20 (57%) had additional factors inducing unsteadiness of binocular vision (e.g., moderate to severe initial relative amblyopia, initial ametropia) . Administration of 5 units of botulinum toxin before 18 months of age destabilized dissociated vertical deviation . Overall, 39 patients (89%) had a final residual deviation of less than 10 prism dioptres . The first surgical correction was horizontal and vertical-torsional in 30 patients (68%) . A total of 23 patients (52%) required some retreatment (botulinum toxin or surgery or both) . Children treated initially with botulinum toxin had less surgery than those with initial surgery (mean recession or resection 8.9 mm {SD 4.5 mm} vs . 14.2 mm {SD 4.0 mm}) as well as fewer horizontal muscles operated (mean 1.6 {SD 0.6} vs . 2.3 {SD 0.6}) . INTERPRETATION: Surgery with or without further interventions is a reasonable approach for IENA with delayed diagnosis and in cases associated with unsteadiness of binocular vision or with nonhorizontal deviations . Initial treatment with botulinum toxin, injected into both medial recti, is effective, reducing the amount of further horizontal surgery and favouring postoperative stability, except in children under 18 months, in whom injection of 5 units induces unbalanced dissociated vertical deviation. Neurology, 2004 Nov 23, 63(10), 1971 - 3 Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke; Gordon MF et al.; The authors evaluated the long-term efficacy and safety of botulinum toxin type A (BTX-A) in poststroke spasticity patients who completed a 12-week placebo-controlled study and received multiple open-label treatments with 200 to 240 U BTX-A for 42 weeks . Significant and sustained improvements were observed for Disability Assessment and Ashworth scores . Adverse events were generally mild . This extension of a double-blind study demonstrates that repeated treatments of BTX-A significantly improve function and tone in spasticity. Arch Dis Child, 2004 Dec, 89(12), 1133 - 7 Botulinum toxin for cerebral palsy; where are we now? Morton RE, Hankinson J, Nicholson J. In this article, the evidence base for botulinum-A treatment acquired in recent years is outlined, and the practicalities involved in providing this service are described . Botulinum-A is relatively new, and possible improvements for the future are considered. Vojnosanit Pregl, 2004 Sep-Oct, 61(5), 531 - 5 {Botulinum toxin A in the treatment of anal fissure}; Stankovic N et al.; BACKGROUND: This paper presents our first experience in the treatment of primary anal fissure by injection of botulinum A toxin into the internal sphincter . METHODS: The study group of the retrospective study included 12 outpatients (8 females and 4 males), mean age 42 (range 18-60) . During the period 2000-2003, after unsuccessful conservative treatment, patients were treated with the injections of botulinum A toxin, 100 units on both sides of the anal fissure laterally into the internal anal sphincter (50 units on either side) . The patients were clinically evaluated 3, 7, and 30 days, and 3 and 6 months after the treatment . RESULTS: Three fissures had healed after a month, and seven after 3 months . Two remained unhealed, but asymptomatic . There was no incontinence of flatus or faeces after 3 months of the treatment . After temporary healing, two fissures relapsed after 6 months, and these patients had the adequate tonus of the anal sphincter muscles . Except for the temporary incontinence, there were neither other side-effects, nor serious complications . CONCLUSION: Injection of botulinum A toxin achieved good results in the treatment of anal fissure . The appropriate use makes this method safe as an alternative to surgical treatment of anal fissure. J Laryngol Otol, 2004 Oct, 118(10), 781 - 5 Botulinum toxin: helpful adjunct to early resolution of laryngeal granulomas; Pham J et al.; Treating laryngopharyngeal reflux is the most accepted treatment for laryngeal granulomas . However, response to this treatment is prolonged and in some cases persistent . The authors hypothesize that this is due to the continuous trauma to the mucoperichondrium from adduction of the vocal folds thus preventing regeneration of healthy mucosa . A prospective study was performed on six patients with laryngeal granulomas failing prolonged laryngopharyngeal reflux treatment, speech therapy, and surgical excisions . Botulinum toxin A was injected into the affected thyroarytenoid to reduce adduction trauma . Video-stroboscopy was used to assess response . A 50 per cent reduction in the size of the granulomas was noted within two weeks with a complete and permanent response within two to eight weeks in five out of six patients . One patient had an obstructing pyogenic granuloma that required excision and recurred after excision but responded to a repeated injection . The addition of a single injection of botulinum toxin A to the standard treatment expeditiously eliminated persistent and recurrent laryngeal granulomas. Curr Opin Otolaryngol Head Neck Surg, 2004 Dec, 12(6), 543 - 8 Contemporary management of spasmodic dysphonia; Sulica L; PURPOSE OF REVIEW: To review current concept in spasmodic dysphonia management . RECENT FINDINGS: The standard of care for spasmodic dysphonia in 2004 remains botulinum toxin chemodenervation for symptomatic management . This is supported by a large body of literature attesting to its efficacy in many different hands, particularly for the adductor form of the disorder . New surgical approaches await the crucial test of time, in view of historical difficulties in achieving long-term benefit via recurrent nerve section, and currently, surgery is best reserved for the rare patient who does not benefit or cannot tolerate botulinum toxin injections . Despite efforts to refine both surgical and botulinum toxin treatment, symptom relief in abductor spasmodic dysphonia and dystonia with tremor remains suboptimal . SUMMARY: Spasmodic dysphonia is a disorder of the central nervous system rather than the larynx, and as in other forms of dystonia, interventions at the end organ have not offered a definitive cure . The pathophysiology underlying dystonia is becoming better understood as a result of discoveries in genetically based forms of the disorder, and this approach is the most promising avenue to a long-term solution. J Neurophysiol, 2004 Dec, 92(6), 3423 - 32 Afferent input modulates neurotrophins and synaptic plasticity in the spinal cord; Gomez-Pinilla F et al.; The effects of eliminating or decreasing neuromuscular activity on the expression of neurotrophins and associated molecules in the spinal cord and subsequent effects on spinal cord plasticity were determined . Spinal cord isolation (SI), which eliminates any supraspinal and peripheral monosynaptic input to the lumbar region but maintains the motoneuron-muscle connectivity, decreased the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNA and protein in the isolated segments . Synapsin I, an important mediator for the effects of BDNF on synaptic plasticity, also was lower in the lumbar region of SI rats . In contrast, the levels of BDNF, synapsin, and growth-associated protein (GAP-43) were increased in the cervical spinal cord enlargement rostral to the isolated region, most likely reflecting an increased use of the forelimbs in the SI rats . GAP-43 levels were also increased in the lumbar spinal cord region, probably associated with compensatory mechanisms related to the deafferentation . In a separate set of experiments, the soleus muscle was paralyzed unilaterally via intramuscular botulinum toxin type A (BTX-A) injection to determine the effects of reducing the propioceptive input, of this normally highly active muscle on neurotrophin expression in the spinal cord . BDNF and synapsin I mRNAs were lower and NT-3 levels were higher in the lumbar hemicord ipsilateral to the BTX-A injection . Combined, these results indicate that the level of supraspinal and muscle afferent input plays an important role in modulating the levels of BDNF and NT-3 in the spinal cord. J Neurol Neurosurg Psychiatry, 2004 Dec, 75(12), 1688 - 91 Factors predicting improvement in motor disability in writer's cramp treated with botulinum toxin; Djebbari R et al.; OBJECTIVE: To identify factors predicting improvement in motor disability in writer's cramp treated with botulinum toxin (BTX) . METHODS: 47 patients with writer's cramp were treated with BTX and were evaluated by the same neurologists at initial referral, after each BTX injection, and when the effect of BTX was maximal at the time of the study . Patients and examiners simultaneously and independently rated the efficacy of BTX injections . Self assessment was a global clinical impression of the impact of treatment on writing quality, writing speed, writing errors, and legibility of handwriting; for objective assessment, the examiners used the Burke-Fahn-Marsden (BFM) scale . RESULTS: On the BFM scale, there was a significant improvement (p<0.0001) in both severity and disability scores . Patients with a pronation/flexion pattern of dystonia showed the best and the most sustained improvement . Primary writing tremor was little improved . There was a correlation between the self assessment score and the Burke-Fahn-Marsden score . Benefit was maintained over time CONCLUSIONS: These results have implications for the identification of patients most likely to benefit from BTX injections. Eur Urol, 2004 Dec, 46(6), 784 - 91 Lack of ultrastructural detrusor changes following endoscopic injection of botulinum toxin type a in overactive neurogenic bladder; Haferkamp A et al.; INTRODUCTION: Endoscopical injections of Botulinum toxin type A into the detrusor muscle are gaining clinical acceptance in the treatment of neurogenic detrusor overactivity . Structural effects of Botulinum toxin type A are only known from studies on striated muscles, where a widespread nerve sprouting occurs temporarily . The aim of this study was to evaluate the ultrastructural effects of Botulinum toxin type A injections on the human detrusor . MATERIAL AND METHODS: 30 detrusor biopsies were obtained from 24 patients with neurogenic detrusor overactivity . Patients were divided into two groups: Group I included 13 biopsies from patients before the first Botulinum toxin type A injection . Group II included 6 biopsies from patients within 3 months after the first injection and 11 biopsies at the time of decreasing efficacy of Botulinum toxin type A . The biopsies were processed by standard procedure for detailed electron microscopic study and evaluated by 2 examiners without prior knowledge of clinical/urodynamic data . RESULTS: No statistically significant detrusor changes have been found concerning muscle cell fascicle structure (p = 0.445), width of intercellular space (p = 0.482) and number/kind of muscle cell junctions (p = 0.443) . A median of 70% of intrinsic axon terminals presented with signs of degeneration in group I, a median of 66% in group II (p = 0.840) . Out of 309 evaluated axon terminals in both groups, 1 sprouting axon was found in group I, 3 sprouting axons in group II (p = 0.864) . Specimen from group I and group II showed only limited collagen deposits within the detrusor . No changes in the ultrastructure of the detrusor have been observed in those biopsies obtained before and after the Botulinum toxin type A injection of the same patient . CONCLUSION: This study verifies our earlier report of severe intrinsic axon degeneration in the detrusor of patients with neurogenic detrusor overactivity . It also shows nearly no structural differences of the detrusor before and after Botulinum toxin type A injections . Contrary to reports of striated muscle, axonal sprouting within the detrusor was very limited after Botulinum toxin type A injections indicating pathophysiologically different reactions to the toxin either between striated muscle and smooth muscle or between different treated diseases. Basic Clin Pharmacol Toxicol, 2004 Nov, 95(5), 215 - 9 Inhibition of the protease activity of the light chain of type A botulinum neurotoxin by aqueous extract from stinging nettle (Urtica dioica) leaf; Gul N et al.; We investigated the inhibitory effect of stinging nettle leaf extract on the protease activity of botulinum neurotoxin type A and B light chains . The nettle leaf infusion was fractionated and HPLC-based enzymatic assays were performed to determine the capacity of each fraction to inhibit the protease activity of botulinum neurotoxin type A and B light chains . Assay results demonstrated that a water-soluble fraction obtained from the nettle leaf infusion inhibited type A, but did not inhibit type B light chain protease activity . The inhibition mode of water soluble fraction against protease activity of type A light chain was analyzed and found to be a non-competitive. Arch Dermatol, 2004 Nov, 140(11), 1351 - 4 Effect of volume and concentration on the diffusion of botulinum exotoxin A; Hsu TS et al.; OBJECTIVE: To investigate whether the volume of solution used to inject equivalent units of botulinum exotoxin A affects the diffusion of toxin and areas of rhytid diminution in the treatment of dynamic forehead lines . DESIGN: Ten volunteers with dynamic forehead lines were included . Each study patient received a single injection at a point 2.5 cm above the orbital rim on either side of the forehead with equivalent units, but in different volumes, of botulinum exotoxin A . The sides of injection were randomized; one side of the patient's forehead was injected first with 5 U of botulinum exotoxin A in 0.25 mL (2 U/0.1 mL) of preserved saline in the midpupillary line, followed by injection of the other side with 5 U in 0.05 mL of preserved saline (2 U/0.02 mL) . There was a 5-fold difference in volume injected . Subjects were evaluated 14 days later for total area affected during visual inspection of the subjects' foreheads during active muscle contraction . SETTING: Private dermatology office . MAIN OUTCOME MEASURE: Visual inspection to measure the area of rhytid effacement in both height and width . RESULTS: The area affected by the botulinum exotoxin A injection was 50% greater in the side with the larger volume in 9 of 10 subjects . The average area affected was 6.05 cm(2) for the injection of the larger volume compared with 4.12 cm(2) for the injection with the smaller volume . The shape of rhytid effacement was oval, rather than round, with the average width longer than the average height . CONCLUSIONS: In this prospective, randomized, controlled study, we found that injection of botulinum exotoxin A in low concentration and higher volume resulted in greater diffusion and a larger affected area . The pattern of toxin spread is altered by muscular contraction in the injected sites . These results show that the dilution has implications on the desired effect of botulinum exotoxin A. Strabismus, 2004 Dec, 12(4), 257 - 60 Does Botulinum toxin have a role in the treatment of small-angle esotropia? Dbo EL, Frcophth JP. A retrospective review of the Toxin Clinic database was carried out over an 18-year period . We identified 68 patients with esotropia of 20 prism dioptres and under who were treated with Botulinum toxin . There were 47 females and 21 males, with a mean age of 34 years (range 11-78 years) . Thirty-two (47%) patients had residual esotropia, 20 (29%) had primary esotropia, 11 (16%) had consecutive esotropia, 4 (6%) had secondary esotropia and 1 (1.5%) had a decompensating esophoria . The mean pre-toxin angle was 16 prism dioptres (range 6-20) . A total of 434 injections were given, with an average of 6 per patient (range 1-36) . Forty-five (66%) patients underwent continued toxin treatment with an interval of 3 to 31 months . Thirteen (19%) patients achieved long-term benefit from only one injection . Seven were unable to demonstrate binocular vision pre-injection but demonstrated it post-injection . Following an initial injection, nine (13%) patients proceeded to surgery . Botulinum toxin was a successful treatment for these patients and was well tolerated, with no side effects . It appears to have a definite role in the treatment of small-angle esotropia. J Cosmet Laser Ther, 2004 Sep, 6(3), 145 - 8 Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing; Yamauchi P et al.; OBJECTIVE: Periorbital aging and lines are a result of intrinsic skin aging, ultraviolet damage, and repetitive action of periorbital muscles . Rejuvenation of this area should therefore be optimized by combining treatments that approach the different causative factors . METHODS: This was a single-center, prospective, randomized, placebo-controlled study comparing the efficacy and safety of combining Botox injections (18 units per area) with ablative laser resurfacing versus laser resurfacing alone without Botox in the treatment of periorbital rhytids . RESULTS: We have concluded a bilateral study comparing the effects of Botox((R)) versus saline placebo injections to the periorbital areas before and following erbium: YAG laser resurfacing of the areas in 33 patients . The results demonstrated that the Botox-treated side with laser resurfacing improved significantly more than the contralateral area treated with saline and laser in diminishing periorbital rhytids as well as textural, pigmentation, and other features of periorbital skin aging . CONCLUSION: This study illustrates the benefits of a combined approach to treating periorbital skin aging. Rev Neurol, 2004 Nov 1-15, 39(9), 826 - 9 {Cervical spinal cord compression in chondrodysplasia punctata: report of two cases}; Pascual-Castroviejo I et al.; AIM: To present two patients with chondrodysplasia punctata and cervical spine compression who had a chronic myelopathy . CASE REPORTS: The patients are a boy who was seen in our service at 13 years of age because of a progressive spastic quadriparesis since infancy and muscle spasm, and a girl, actually 15-year-old, who was studied by us since 2 years of age because of the same problem and moderate mental retardation . Magnetic resonance study disclosed narrowing of the spinal canal at the level of C1-C2 and C5-C6 . Surgical decompression was performed in both cases . The case 2 also received physiotherapy, myorrelaxing medication and botulinum toxin treatments . The case 2 has short stature and intellectual level below normality . CONCLUSION: Chondrodysplasia punctata, that exhibits well defined clinical and radiological manifestations, is a disease that can present spinal cord compression during the first years of life . However, other pathological causes of still unknown origin may contribute to the progressive evolution and lack of recuperation of the problems derived of the spasticity as well as the mental retardation and the short stature. Curr Urol Rep, 2004 Dec, 5(6), 432 - 6 A case for botulinum toxin-A in idiopathic bladder overactivity; Smith CP et al.; Botulinum toxin (BTX) has been shown to be an effective agent in suppressing detrusor overactivity due to neurogenic causes . Similar to results obtained with traditional agents to treat bladder overactivity (ie, antimuscarinic medications), the use of BTX has been extended to patients with idiopathic detrusor overactivity . This article briefly reviews the use of BTX to treat disorders of detrusor overactivity and, based on early clinical and laboratory results, establishes the case for its use as a therapeutic modality to treat idiopathic detrusor overactivity. Br J Dermatol, 2004 Nov, 151(5), 1093 - 5 BOTOX delivery by iontophoresis; Kavanagh GM et al.; We report two patients with severe palmar hyperhidrosis who responded to BOTOX delivered not by injection, the usual method of delivery, but by iontophoresis . The Botulinum molecule has been considered too large for delivery into the skin this way . However, other large peptides, both non-ionic and cationic, have been delivered successfully by this method, so we suspected that BOTOX could in fact be iontophoresed . Our saline-controlled treatment of these two patients with a small iontophoresis unit (Iomed Phoresor II) allowed small volumes of standard BOTOX dilutions to be used, and demonstrates that iontophoresis can indeed deliver BOTOX successfully . This has important therapeutic potential for the large number of patients with focal hyperhidrosis . They may be spared painful injections, and in more severe cases, invasive surgery. J Urol, 2004 Dec, 172(6 Pt 1), 2316 - 20 The effect of botulinum-a toxin on patients with severe urge urinary incontinence; Flynn MK et al.; PURPOSE:: We determined the effect of 150 units of botulinum-A toxin (Botox, Allergan, Irvine, California) on subjects with severe urge urinary incontinence (UUI) . MATERIALS AND METHODS:: This was an open label uncontrolled clinical trial . Subjects were recruited from the female urology and urogynecology clinics at Duke University . Inclusion criteria included evidence of UUI on 3-day bladder diary, a 24-hour pad weight of 100 gm or greater, absent or minimal stress leakage, absent detrusor dysfunction, and a history of failed anticholinergic and physical therapies . Exclusion criteria included evidence of a urinary tract infection, or other correctable or neurological etiology for UUI . The detrusor of each subject was injected with 150 units of botulinum-A toxin . Evaluations were performed at 2 weeks, 6 weeks, 3 months and 6 months after injection . Outcome measures included daily incontinence episodes, Urogenital Distress Inventory and the Incontinence Impact Questionnaire, 24-hour pad weights, daily pad usage and urinalysis at all visits . Urodynamic studies were performed at the 6-week and 3-month visits . RESULTS:: Three subjects had uncomplicated urinary tract infections during followup . No other adverse effects occurred . Statistically and clinically significant decreases greater than 50% were seen in virtually all outcome measures at all visits up to 3 months . Most subjects showed signs of recurrent UUI by 6 months . All subjects reported remarkable subjective improvement in incontinence . No significant changes in maximal cystometric capacity, maximal detrusor pressure, peak flow or post-void residual volumes were seen . CONCLUSIONS:: Botulinum-A toxin can significantly decrease urge urinary incontinence and improve quality of life for 3 months after injection . Additional studies are needed to determine ideal doses, dosing intervals, safety and cost-effectiveness of this therapy. J Comput Assist Tomogr, 2004 Nov-Dec, 28(6), 865 - 9 Sectional neuroanatomy of the face; Goktepe AS et al.; Needle electromyography and the injection procedures of the face are difficult because of the small size and close anatomic relations of the facial structures . Local injections of the face have increased in frequency since the introduction of botulinum toxin . This article intends to provide anatomically accurate schematics of innervation of the muscles of facial expression that can be used to interpret magnetic resonance images of the muscles and nerves . Cross-sectional schematics of the face were drawn as they appear in imaging projections . The relevant cranial and spinal nerves were color coded . The muscles and skin surfaces were labeled and assigned the color of the appropriate nerves . An organized comprehensive map of the motor innervation of the face allows the physician to increase the accuracy and efficacy of interventional procedures . This could also assist the electromyographer in correlating the clinical and electrophysiologic findings with magnetic resonance images. Urology, 2004 Nov, 64(5), 871 - 5; discussion 875 Botulinum toxin a has antinociceptive effects in treating interstitial cystitis; Smith CP et al.; OBJECTIVES: To present clinical evidence with botulinum toxin A (BTX-A) suggesting an antinociceptive role in patients with interstitial cystitis (IC) . Intriguing evidence in a somatic pain model has suggested that BTX-A injection may have an antinociceptive effect on both acute and chronic (inflammatory) pain . METHODS: Thirteen female patients (6 in the United States and 7 in Poland) with IC according to the criteria of the National Institute of Diabetes, Digestive and Kidney Disease were included . Under short general anesthesia or sedation, 100 to 200 U of Dysport (Polish patients) or Botox (U.S . patients) was injected through a cystoscope into 20 to 30 sites submucosally in the trigone and floor of the bladder . Patients were evaluated with the O'Leary-Sant validated IC questionnaire or with voiding charts and a visual analog pain scale 1 month postoperatively and at subsequent 3-month intervals . The Polish patients also underwent pretreatment and post-treatment urodynamic evaluations . RESULTS: Overall, 9 (69%) of 13 patients noted subjective improvement after BTX-A treatment . The Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index mean scores improved by 71% and 69%, respectively (P <0.05) . Daytime frequency, nocturia, and pain by visual analog scale decreased by 44%, 45%, and 79%, respectively (P <0.01) . The first desire to void and maximal cystometric capacity increased by 58% and 57%, respectively (P <0.01) . CONCLUSIONS: Our results suggest that BTX-A has an antinociceptive effect on bladder afferent pathways in patients with IC, producing both symptomatic and functional (ie, urodynamic) improvements. Cranio, 2004 Oct, 22(4), 325 - 9 Treatment of inferior lateral pterygoid muscle dystonia with zolpidem tartrate, botulinum toxin injections, and physical self-regulation procedures: a case report; Vazquez-Delgado E et al.; The following case report depicts the management of a patient suffering with a jaw opening oromandibular dystonia using a combination of botulinum toxin injections, zolpidem, and relaxation procedures . Eventually the botulinum toxin injections were eliminated, and the patient was maintained with only zolpidem and relaxation procedures. Dermatol Online J . 2004 Oct 15;10(2):1. Vibration anesthesia: a noninvasive method of reducing discomfort prior to dermatologic procedures; Smith KC et al.; In some dermatologic and cosmetic procedures, local anesthesia is not sufficient for relieving pain; often patients are averse to injections . We propose vibration anesthesia, the use of vibration delivered with commercially available inexpensive massagers to reduce discomfort . We find the analgesic effect of vibration helpful in minimizing pain in patients undergoing injections of botulinum toxin type A treatment for hyperhidrosis, injection of filler substances such as Restylane and Juvederm, laser therapy for leg veins, nail-fold injections, Q-switched laser treatment of tattoos, incision and drainage of abscesses, and cautery of facial warts, as well as facilitating anesthetic injections for needle-phobic patients . We expect that additional uses will be found as experience with this modality grows . Although the use of vibration anesthesia generally does not eliminate pain completely, it can serve to make the injection or procedure much more tolerable. Aesthetic Plast Surg . 2004 Nov 4; {Epub ahead of print} The Minimal Approach: An Innovation in Facial Cosmetic Procedures; de Maio M; Plastic surgery is a rapidly growing field, particularly the use of less invasive procedures such as biodegradable dermal fillers and botulinum toxin . Aging is a complex process involving two important factors: volume loss throughout the face, and repetitive muscle movements that cause wrinkles and folds . Dermal fillers work by providing support for facial structures, whereas botulinum toxin reduces the mimetic effects . In combination, these products can be used effectively to reshape and rejuvenate the face and neck . Dermal fillers can be used throughout the face to raise the eyebrows, fill the tear trough, reshape the nose, lift the nose tip, fill nasolabial folds and oral comissures, fill the cheeks, raise the cheekbones, reshape the jaw line, and rejuvenate the neck area . This "minimal approach" offers a faster, less painful, and less costly alternative or complement to surgical facelifts . A variety of biodegradable injectable products are currently available, the most common of which are collagen- or hyaluronic acid-based . Using these products in combination takes advantage of their hydrophobic and hydrophilic properties and can provide better and longer-lasting results . The addition of botulinum toxin can further extend the duration of results by reducing the mimetic stress that can break down the polymers . With regular maintenance treatments, the minimal approach using dermal fillers and botulinum toxin can give patients a "whole new look" with a fast and relatively painless lunchtime procedure. J Neural Transm . 2004 Nov 3; {Epub ahead of print} Efficacy and tolerability of a botulinum toxin type A free of complexing proteins (NT 201) compared with commercially available botulinum toxin type A (BOTOX degrees ) in healthy volunteers; Jost WH et al.; Purpose: This randomized controlled trial was performed to compare the novel botulinum toxin type A free of complexing proteins (NT 201) with the marketed preparation BOTOX degrees regarding efficacy and tolerability . Methods: Fourteen healthy volunteers received a single intramuscular injection into the extensor digitorum brevis (EDB) muscle of either 4 units NT 201, or 4 units of BOTOX degrees randomised by foot . Compound muscle action potential (CMAP) measurements were recorded for up to 90 days after injection . Results: Both drugs produced a maximum decline between Day 7 and Day 14 . At Day 90, administration of both drugs resulted in approximately a 40% CMAP decline as compared to baseline . Duration of paralytic effect was comparable in both groups, at all response thresholds tested . Both drugs were well tolerated . Conclusion: The effects of small amounts of NT 201 and BOTOX degrees injected into the EDB muscle are comparable in terms of efficacy, time to onset of action, duration of action, and tolerability. Int J Colorectal Dis . 2004 Oct 30; {Epub ahead of print} Long-term results of botulinum toxin for the treatment of chronic anal fissure: prospective clinical and manometric study; Arroyo A et al.; BACKGROUND . The aim of this prospective trial was to analyse the effectiveness and morbidity of chemical sphincterotomy in the treatment of chronic anal fissure after a 3-year follow-up . METHODS . One hundred consecutive patients with chronic anal fissures were treated by chemical sphincterotomy with 25 U botulinum toxin injected into the internal sphincter . Clinical and manometric results were recorded . RESULTS . No major complications were found; initial incontinence at the 2-month review (6%) spontaneously reversed at 6 months . There was a tendency of progressive recurrence over time, with an overall healing after 3 years of 47% . We found a group of patients with clinical (symptoms longer than 12 months and presence of a sentinel pile before treatment) and manometric factors (persistently elevated mean resting pressure, percentage of time with slow waves, and number of patients or percentage of time with ultra slow waves after treatment) associated with a higher recurrence of anal fissures . CONCLUSION . Since it avoids the greater risk of incontinence associated with surgical sphincterotomy, we recommend the use of botulinum toxin as the first therapeutic approach for patients with chronic anal fissure and risk factors for incontinence; despite the higher rate of recurrence associated with this treatment . In patients with factors related to recurrence, re-injection with higher doses of botulinum toxin or complementary medical-surgical treatment should be considered. J Am Acad Dermatol, 2004 Nov, 51(5), 739 - 45 Sweat gland morphology and periglandular innervation in essential palmar hyperhidrosis before and after treatment with intradermal botulinum toxin; Swartling C et al.; BACKGROUND: Intradermal botulinum toxin (Btx) produces long-lasting relief of focal hyperhidrosis, but its mechanism of action is poorly understood . OBJECTIVE: To study the effect of Btx A on the size and innervation of sweat glands in patients with palmar hyperhidrosis . METHODS: Palmar skin biopsy was performed in 26 hyperhidrotic patients before scheduled Btx treatment and in 11 controls . Twelve of the patients also underwent biopsy 1 to 6 months after the Btx injections . Sweat gland morphology was investigated by light microscopy; the cross-sectional area of the secretory tubule and its lumen was measured by image analysis . Immunofluorescence (IF) with antibodies to the neural markers protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP 43), and to vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP), was used to analyze the periglandular innervation . RESULTS: The gross morphology of the sweat glands was similar in patients and controls, with no significant differences in tubular and luminal areas between the groups . After Btx treatment, the tubular dimensions remained unchanged, but the lumen tended to be smaller ( P = .07) . Around the glands, increased GAP 43 staining indicating sprouting was seen within 3 months after Btx treatment ( P = .016); whereas the PGP 9.5 staining was decreased in most specimens ( P = .09) indicating lack of functional nerve growth . No change in VIP or CGRP immunoreactivity was observed . CONCLUSIONS: The sweat glands appear structurally normal in hyperhidrotic patients before Btx therapy, whereas after therapy the luminal area of the gland is frequently diminished . The IF data GAP 43/PGP 9.5 suggest that Btx therapy induces long-standing functional denervation of the sweat glands, which might explain its anti-transpiratory efficacy. J Bone Joint Surg Am, 2004 Nov, 86-A(11), 2377 - 84 Botulinum toxin as an adjunct to serial casting treatment in children with cerebral palsy; Kay RM et al.; BACKGROUND: Although botulinum toxin A is frequently used to augment serial casting in the treatment of soft-tissue contractures in children with cerebral palsy, its effectiveness for this purpose has not been evaluated . The purpose of the present study was to determine whether botulinum toxin A injection increases the efficacy of serial casting . METHODS: A prospective, randomized trial was undertaken to compare serial casting only with serial casting combined with botulinum toxin A (Botox) injection for the treatment of ankle equinus contractures in twenty-three children with cerebral palsy . Range-of-motion testing, spasticity assessment, and computerized gait analysis were performed as long as twelve months after treatment . RESULTS: There was no difference between the groups with regard to the duration of casting required to correct the equinus contracture . Both groups maintained a significant improvement in passive ankle dorsiflexion throughout the follow-up period, although the group managed with casting and Botox had a significant loss of dorsiflexion when the values at six, nine, and twelve months were compared with the value at three months . Peak dorsiflexion during the stance and swing phases was significantly improved in both groups at three months but only in the group managed with casting alone at twelve months . Plantar flexor spasticity was significantly decreased at three months in both groups, but it was significantly decreased at six, nine, and twelve months only in the group managed with casting alone . Spasticity was significantly greater in the group managed with casting and Botox than it was in the group managed with casting only at six, nine, and twelve months . CONCLUSIONS: The present study demonstrates the efficacy of serial casting in the treatment of equinus contractures in children with cerebral palsy who are able to walk . Contrary to our hypothesis, the addition of botulinum toxin A to a serial casting regimen led to earlier recurrence of spasticity, contracture, and equinus during gait . The results of the present study suggest that botulinum toxin combined with serial casting for the treatment of fixed contractures will lead to a recurrence of plantar flexor spasticity and equinus contracture by six months in this patient population . While previous research has indicated that the injection of botulinum toxin A is superior to casting for the treatment of dynamic equinus, the present study suggests that serial casting alone is preferable for the treatment of fixed equinus contractures in children with cerebral palsy. Facial Plast Surg Clin North Am, 2005 Feb, 13(1), 1 - 10 Complications of botulinum toxin A use in facial rejuvenation; Vartanian AJ et al.; The esthetic application of botulinum toxin type A (Botox) is a safe treatment modality; nevertheless complications can occur as a result of patient-and physician-related factors . Fortunately, adverse effects and undesirable sequelae after Botox injections are temporary . Complications may be more serious in patients who have more severe rhytids (which require more Botox), previous facial plastic surgery (altered anatomy), and those who have pre-existing neuromuscular disease . The physician can reduce complications by using proper injection techniques, appropriate regional Botox dosing, and by being conservative in the overall approach to Botox-mediated facial rejuvenation. Ann Chir Plast Esthet, 2004 Oct, 49(5), 537 - 52 {Botulinum toxin and wrinkles: few side effects and effective combining procedures with other treatments}; Ascher B et al.; Chemical denervation, through the biologic effect of botulinum toxin, provides a very effective, low risk, lasting treatment for hyperkinetic wrinkles, mainly of the upper face . Patients with such rhytides, when treated with surgical myotomies or other alternative medical treatments, are at greater risk and with potentially less lasting results . Botulinum toxin has been widely used for the last 20 years in many areas of medicine . It has been used for 13 years in dermatology and plastic surgery, without important complications or sequellae . Any complications appear to be reversible . In these two specialties, with the minute quantities (units) and volume of material injected, complications are infrequent; some of them are now anecdotal . The only main complication from a cosmetic point of view is blepharoptosis, which is more and more rare . Because of a better anatomical knowledge of the affected muscles, and our improved technique, risks are greatly reduced . In our two latest multicenter studies on glabellar wrinkles, between 2002 and 2004, we saw no blepharoptosis . Conversely, in case of dynamic wrinkles associated with muscle, fat, and skin relapse, and/or deep furrows, only surgical procedures and/or other surface treatments are effective . Botulinum toxin injections are not meant to replace upper, mid, or mandibular face and neck lifts; indeed, botulinum toxin injections may optimize results from these surgical procedures . These injections play a fundamental process in producing long lasting results . The current and future evolution, in cosmetic surgery, is toward full achieved, but focused, natural, and minimally invasive surgical procedures in combination with effective and minimal risk techniques such as the botulinum toxin injections . To optimize the effect of the medical procedures, botulinum toxin should be injected three weeks before surgery . In addition botulinum toxin injections may optimize and prolong the effect of the surface procedures, as lasers, peels and fillers . This medicosurgical combination is one of the examples that best describes the evolution of plastic and aesthetic surgery in 2004. Ann Chir Plast Esthet, 2004 Oct, 49(5), 527 - 36 {Functional facial analysis after botulin on toxin injection}; Le Louarn C; As usual, the face at rest is analysed before btx injection . But the interest of the analysis of the face dynamically, in a functional way, with the help of the palpation, is demonstrated . A key point is to decide to favor the high position of the highbrow more than to totally fade the frontal wrinkles . To perform this, a new functional segmentation of the frontalis muscle is described . The role of the procerus muscle as antagonist of the frontalis muscle, inferior medial part, is explained . To elevate the medium third of the eyebrow, the lateral part of the corrugator muscle is injected with a specific technique . This technique decreases the risk of weakening the overlying frontalis muscle and the underlying levator palpebrae muscle . To achieve a higher elevation of the eyebrow tail, and to totally fade the upper and medium crow's foot, different points of injection on the lateral orbital rim are described, without the risk of migration to the oculo motor muscles . Fading the tear trough with the injection of the superior malar part of the orbicularis oculi muscle is explained . Thanks to the use of the functional analysis of the face and to the comprehension of the fabulous possibilities of the botulinum toxin A, it is now justified to switch from a "ready to wear" way of injection to a "haute couture" way, that is to say adapted to each patient. Ann Chir Plast Esthet, 2004 Oct, 49(5), 521 - 6 {Frontal muscular balance and botulinum toxin}; Belhaouari L et al.; A good knowledge of the anatomy of the muscles of upper third of the face and their function, a good understanding of the famous Frontal Muscular Balance, to consider the anatomic and histological modifications induced by ageing in the cutaneous layer and the muscular function of the underlying "peaucier muscles", are essential for a better approach and for an easy and safe use of botulinum toxin, remarkable product, and for avoiding its operator-dependent risks. Mund Kiefer Gesichtschir, 2004 Nov, 8(6), 369 - 75 Epub 2004 Nov. {Botulinum toxin for treatment of gustatory sweating . A prospective randomized study}; Nolte D et al.; BACKGROUND: Botulinum toxin A has meanwhile become a proven method for treatment of gustatory sweating (focal hyperhidrosis, Frey's syndrome) . Clear-cut recommendations regarding dosage of botulinum toxin A in Frey's syndrome are currently not available . The aim of this prospective randomized study therefore was to investigate botulinum toxin A with respect to its efficacy in Frey's syndrome, the ideal dose yielding maximal duration of the effect, and patient contentedness as well as unwanted side effects in patients of the Clinic of OMF Surgery at the Ruhr-University of Bochum . PATIENTS AND METHOD: Twenty patients suffering from severe Frey's syndrome as a result of operations of the parotid gland were examined with the starch iodine test according to Minor . The gustatory skin areas were re-examined after intracutaneous injection of botulinum toxin A for up to 1 year . The patients ( n=20) were randomly assigned to two different treatment groups (group I: 2 MU/cm(2), n=10; group II: 3 MU/cm(2), n=10) . RESULTS: Mean sweating skin areas in the two treatment groups ranged between 39+/-9 and 32+/-12 cm(2), respectively . A single injection of 3 MU botulinum toxin A resulted in a nearly complete blockade of gustatory sweating for the observation period of 1 year . In the group treated with 2 MU botulinum toxin A, 44% of the total gustatory skin areas were still sweating, thus necessitating a second injection of botulinum toxin A in these patients . CONCLUSION: Intracutaneous injection of botulinum toxin A represents a highly effective and minimally invasive procedure for the treatment of Frey's syndrome . This study shows for the first time that a dosage of 3 MU/cm(2) of botulinum toxin A achieves a complete and reliable blockade of gustatory sweating lasting for at least 12 months . This dose may therefore be recommended for treatment of this syndrome. Obstet Gynecol, 2004 Nov, 104(5 Pt 1), 922 - 5 Botulinum toxin in the treatment of refractory vaginismus; Ghazizadeh S et al.; OBJECTIVE: To investigate the efficacy of botulinum toxin injection to treat women with moderate and severe vaginismus . METHODS: Twenty-four women referred to our clinic from February 2002 to February 2004 (mean age 25 years; range 19-34 years) with third- to fourth-degree vaginismus were recruited for this study . These women had previous unsuccessful treatments . Botulinum toxin (150-400 mIU) was injected into the puborectalis muscles in 3 sites on each side of the vagina . RESULTS: Twenty-three patients (95.8%) had vaginal examinations 1 week postoperatively that showed little or no vaginismus, 18 (75%) achieved satisfactory intercourse after the first injection, 4 (16.7%) had mild pain, 1 was cured after a second injection, 1 patient refused vaginal examination and did not attempt to have coitus, and another had no coitus as a result of her husband's secondary impotence . The women were followed up for a mean of 12.3 months (range 2-24 months), and there were no cases of recurrence . CONCLUSION: In refractory cases of vaginismus when conventional therapies have failed, local injection of botulinum toxin can be considered . LEVEL OF EVIDENCE: III. Acta Orthop Scand, 2004 Oct, 75(5), 630 - 3 Selective botulinum toxin injection in the treatment of recurrent deformity following surgical correction of club foot: a preliminary report of 3 children; Mitchell PD et al.; Management of a child with club foot deformity that recurs after an apparently successful posteromedial soft tissue release remains a challenge . Revision surgery is often attempted, but this carries a high risk of significant scarring or neurovascular complications . We have treated 3 children (3 feet) with relapsed club foot and fixed deformities, using Botulinum toxin A (BTX-A) injection into muscle groups clinically thought to be responsible for recurrent deformity, followed by moulded plaster casts . Two cases have maintained a good foot position with an minimum follow-up of 18 months, and one other is also doing well having had a tibialis anterior tendon transfer as well as the BTX-A therapy . In our limited experience, targeted BTX-A injection with plaster casting has been safe, and may obviate the need for major revision surgery in a proportion of cases with recurrent club foot deformity following previous posteromedial soft tissue release. Semin Ophthalmol, 2003 Dec, 18(4), 200 - 4 Treatment of headache with botulinum toxin administration; Gruener G et al.; Botulinum toxin has been increasingly applied to the treatment of a wide variety of neurological disorders . Its application to headache disorders, and specifically those classified as migraine or tension-type, followed the observation of its effectiveness in decreasing pain . Studies that have primarily used botulinum toxin type A, but with varying dose regimens and sites of administration, have since observed its beneficial effects and in those subjects, headaches have lessened in their frequency or severity . However, questions that have primarily concerned dose and sites of administration have since arisen and clear guidelines for botulinum toxin use in headache disorders have yet to be developed. J Obstet Gynaecol, 2000, 20(3), 300 - 2 Vaginismus: results of treatment with botulin toxin; El-Sibai AS; In view of the long-term therapy necessary to cure vaginismus and specially persistent cases, we considered using botulin toxin (BT) injections for the treatment of such cases . Eight women (mean age 26.6 +/- 1.2 years) with vaginismus were treated with BT . Another five women with vaginismus, matching the eight patients in age, acted as controls . The patients in the study group were injected with BT (25 IU diluted in 1 ml saline) into each of the two bulbospongiosus muscles . Control patients were injected with saline . Mean follow-up was 10.2 +/- 3.3 months . All the patients injected with BT improved . The couples could achieve satisfactory intromission . No patient was in need of re-injection and there was no recurrence during the follow-up period . Control subjects did not improve with the saline injection into the bulbospongiosus muscle . In conclusion, BT injection effected cure in all of the vaginismus patients with no complications or recurrence . The technique is simple, easy, cost-effective, not time-consuming and can be achieved on an outpatient basis. Curr Pain Headache Rep, 2004 Dec, 8(6), 484 - 8 Alternative therapies for tension-type headache; Lenaerts ME; Treatment of tension-type headache remains very challenging . In addition to conventional therapies, alternative methods such as physical therapy, acupuncture, and botulinum toxin have been studied . In this article, recent literature is reviewed and discussed and challenges for the evaluation of these approaches are considered . Although the clinical evidence is still incomplete, certain treatments are promising and the active ongoing research hopefully will soon yield more answers . Of note, the specific issue of psychologic therapy is dealt with elsewhere in this issue. Plast Reconstr Surg, 2004 Nov, 114(6 Suppl), 1S - 22S Consensus recommendations on the use of botulinum toxin type a in facial aesthetics; Carruthers J et al.; The use of botulinum toxin type A for facial enhancement is the most common cosmetic procedure currently undertaken in the United States . Overall clinical and study experience with botulinum toxin type A treatment for facial enhancement has confirmed that it is effective and safe in both the short and long term . Nevertheless, consistent guidelines representing the consensus of experts for aesthetic treatments of areas other than glabellar lines have not been published . Therefore, a panel of experts on the aesthetic uses of Botox Cosmetic (botulinum toxin type A; Allergan, Inc., Irvine, Calif.) was convened to develop consensus guidelines . This publication comprises the recommendations of this panel and provides guidelines on general issues, such as the importance of the aesthetic evaluation and individualization of treatment, reconstitution and handling of the botulinum toxin type A, procedural considerations, dosing and injection-site variables, and patient selection and counseling . In addition, specific considerations and recommendations are provided by treatment area, including glabellar lines, horizontal forehead lines, "crow's feet," "bunny lines" (downward radiating lines on the sides of nose), the perioral area, the dimpled chin, and platysmal bands . The review of each area encompasses the relevant anatomy, specifics on injection locations and techniques, starting doses (total and per injection point), the influence of other variables, such as gender, and assessment and retreatment issues . Factors unique to each area are presented, and the discussion of each treatment area concludes with a review of key elements that can increase the likelihood of a successful outcome . Summary tables are provided throughout. Wien Klin Wochenschr, 2001, 113 Suppl 4, 42 - 4 {Reimbursement strategies for botulinum toxin type A in Austria}; Diez J et al.; In the last two decades, botulinum toxin A (BtxA) has become the treatment of choice for spasmodic torticollis, blepharospasm and hemifacial spasm . Since 1999 Dysport and Botox are approved in Austria for the treatment of these indications . BtxA is applied in the hospital (out- and in-patient clinics) and by specialists (especially neurologists) in private practices . Complete reimbursement of the costs by the health insurance is provided only if the treatment has taken place in the specialist's private practice . The costs of BtxA application in the hospital are partially covered by the so called "LKF points" (Austrian system for reimbursement of costs in the hospital) or by the flat rate fee for out-patients . Approval for other indications for BtxA is expected in the next years, therefore appropriate cost reimbursement for BtxA is of immense importance . Different reimbursement systems are discussed in the following article . It seems useful to adopt approved procedures in special situations, such as reimbursement for the ambulatory application of chemotherapy and Betainterferon in Austria . The appropriate reimbursement system has to consider the indication and documentation of Btx-treatments as well as the qualification of the Btx-user. Wien Klin Wochenschr, 2001, 113 Suppl 4, 36 - 41 {Botulinum toxin in the treatment of focal hyperhidrosis}; Schnider P et al.; INTRODUCTION: Botulinum A toxin (BTX-A) acts primarily at peripheral cholinergic synapses, inhibiting the release of acetylcholine . Initially it has been used to block the neuromuscular junction in focal dystonic and spastic syndromes . Recently there has been suggestions for potential clinical indications in non-muscular diseases where cholinergic terminals play a role . GUSTATORY SWEATING: In 1995 physicians reported a long-lasting anhidrotic effect of intracutaneous BTX-A injections in patients suffering from gustatory sweating (Frey's syndrome) . Consequently, a number of clinical studies demonstrated good efficacy of intradermal injections of botulinumtoxin in patients with focal hyperhidrosis . FOCAL HYPERHIDROSIS OF THE PALMS AND AXILLAE: Focal hyperhidrosis is usually confined to the palms and axillae . Excessive sweating may be a social handicap and an occupational hazard . The management of focal hyperhidrosis remains controversial . Topical antiperspirants are only effective in very mild cases . Iontophoresis with tap water or anticholinergic drugs is messy and time consuming with only short-lived effect . Sympathectomy, the cornerstone of surgical management, is usually effective in palmar hyperhidrosis . Complications of this technique include surgical risks, postoperative and cosmetic problems and compensatory hyperhidrosis . AXILLARY HYPERHIDROSIS: Several studies confirmed that intracutaneous injections of botulinum toxin are useful in the majority of patients with axillary hyperhidrosis resistant to conventional treatment . In axillary hyperhidrosis total doses are ranging from 200-400 mU Dysport or from 80 to 130 mU Botox to reach a good clinical response . Injections are usually well tolerated and no serious side-effects have been observed . The mean duration of anhidrotic effect ranges between 3 and 9 weeks . PALMAR HYPERHIDROSIS: The use of botulinumtoxin in patients with palmar hyperhidrosis is rather difficult . The therapeutic window is smaller because injections are complicated by transient weakness of the small hand-muscles . Furthermore the injections at the palms are painful which can be overcomed by application of local anaesthetics or the blockade of the ulnar and median nerves . The duration of anhidrotic effect ranges from 20 to 50 weeks . CONCLUSION: Intracutaneous injections of botulinum-toxin should be offered to patients with focal hyperhidrosis of the palms and axillae causing serious social, psychologic and occupational problems, resistant to other conventional treatment options. Wien Klin Wochenschr, 2001, 113 Suppl 4, 30 - 5 {Botulinum toxin type A in the treatment plan for cerebral palsy}; Strobl W; Over the past decade a number of placebo-controlled studies have confirmed that intramuscular injections of botulinum toxin A (BTX A) has antispastic effects . Cerebral palsy is among the most frequent disorders of the growing locomotor apparatus during childhood . Weakness as well as spasticity due to lack of selective neuronal control causes functional impairment and additional mechanisms of compensation, retardation of motor development, secondary deformities of muscles and soft tissues due to a failure of muscle growth, subluxation/dislocation of joints, early osteoarthritis, and pain . Prevention of this vicious circle has to be the main goal of caring for children with spasticity . Quality of life in children with cerebral palsy can be improved by support of their daily living motor activities . Increased muscle tone can be reduced by physical exercises, by individually adapted orthoses, walkers, and wheelchairs, by manual therapy, serial casting and in certain cases by systemic drugs or by multiple-stage surgical procedures . BTX A can be used to enable these treatment possibilities or to increase their effect . In our clinical study (BTX A in 114 patients in 19952/2000) we found no major side effects . Weakness, pain or swelling occurred temporarily . Indications for the use of BTX A are pain, functional impairment, severe cosmetic problems, as well as prevention of secondary contractures, deformities, and dislocations caused by increased muscle tone . We consider the selection of patients for the use of BTX A and the development of a goal-orientated treatment plan by multidisciplinary team approach as the most important steps . Prerequisites are exact statomotoric and dynamic physical examinations, and standardised movement analysis . 3-D-gait analysis and dynamic electromyography is used in cases where functional improvement of gait is the goal of BTX A-treatment. Wien Klin Wochenschr, 2001, 113 Suppl 4, 25 - 9 {Treatment of the spastic drop foot with botulinum toxin type A in adult patients}; Voller B et al.; Spastic drop foot can be managed by physical measures, local pharmacological agents, oral anti-spastic drugs and surgical procedures . Recent studies have documented the clear effect of botulinum toxin type A (BTX-A) in the treatment of the spastic drop foot, particularly by reducing the resistance against passive movement and increasing the range of motion . Functional benefit and pain reduction have also been observed . The use of BTX-A is safe and free of serious side effects . Individual realistic treatment goals must be defined by the rehabilitation team before the treatment . Possible purposes of the treatment are the achievement of a straight foot to allow weight bearing or application of an orthosis and to reduce the premature activation of the calf muscles during gait . Other treatment goals are the facilitation of nursing care, as well as physical and occupational therapy . BTX-A injections can reduce pain, and prevent pressure ulcers or surgical interventions . Early physiotherapy or occupational therapy may increase the treatment effect of BTX-A . Close cooperation between the neurologist, physiotherapist, occupational therapist, nursing staff and other multidisciplinary rehabilitation team members is essential to maximize the benefit for the patients. Wien Klin Wochenschr, 2001, 113 Suppl 4, 16 - 9 {Botulinum toxin type A treatment of upper limb spasticity}; Wissel M et al.; In recent years, local injections with Botulinum toxin type A (BtxA) have become the treatment of choice for dystonia . However, several studies have demonstrated its efficacy and safety in the treatment of focal spasticity as well . These studies have shown efficacy and safety in upper limb spasticity treatment at a total dose between 500 and 1500 units of Dysport per injection session . While injections in upper arm muscles are easily administered without EMG-guidance, we recommend EMG-guidance for lower arm and finger muscles . In addition to functional improvement, BtxA treatment may also be considered for the following reasons: treatment of spasticity associated pain or painful muscle spasms, improved hygiene, facilitation of care, prevention of skin breakdown, and improved positioning of the upper limb . The definition of a realistic treatment goal, in agreement with the patient, as well as adjunctive physiotherapy are prerequisites for a successful BtxA treatment . Dose recommendations are given in Table 1. Wien Klin Wochenschr, 2001, 113 Suppl 4, 6 - 10 {Treatment of focal dystonia with botulinum toxin A}; Sojer M et al.; Local injections with Botulinum toxin A (BtxA) are safe and effective in the treatment of focal dystonia . In cervical dystonia and blepharospasm, BtxA injections have become the treatment of choice . However, good results have also been reported with oromandibular dystonia, spasmodic dysphonia and writer's cramp . In cervical dystonia, muscles for injection are selected by clinical presentation or in complex forms with EMG guidance . Several studies have shown that 500 units Dysport are safe and effective in the treatment of cervical dystonia . In blepharospasm, injections are performed in the periorbital part of the orbicularis oculi muscle with good results for 12-14 weeks . The most frequently employed starting dose is 120 units Dysport per eye, divided in three periorbital injection sites . In case of levator inhibition, the pretarsal part of the orbicularis oculi muscle should be injected in a lower dose . EMG guidance is not necessary . By contrast, BtxA treatment of spasmodic dysphonia and writer's cramp require EMG-guided injections in order to avoid side-effects . Dose recommendations for the various types of dystonia are given in the text . In up to 5% of patients with dystonia, the development of neutralising antibodies is reported following repetitive injections with BtxA . Patients with antibodies had a shorter interval between injections, more "boosters", a higher dose per 3-month interval, and a higher total dose injected . In case of neutralizing antibodies against the A toxin, the treatment with Botulinum toxin B (Neurobloc) is a possible alternative. Wien Klin Wochenschr, 2001, 113 Suppl 4, 2 - 5 {Pharmacology of botulinum neurotoxin type A}; Bigalke H; The efficacies and potencies of Dysport and Botox, botulinum neurotoxin type A complexes approved for therapy, were investigated under various conditions . Conditions for maximal expression of biological activities of both commercial products were explored in vitro in the phrenic nerve-hemidiaphragm preparation whilst conditions for optimal distribution of Dysport were tested in vivo in a double blind trial involving volunteers, using the foot Muscles extensor digitorum brevis . Whilst Dysport and Botox expressed the same potency in vitro when albumin was added, their potencies markedly departed from each other when the products were reconstituted as recommended by the manufacturer . The biological availability of Dysport could be enhanced in vivo by (1) lowering its concentration, (2) supplementing with albumin and (3) increasing the injection volume . Thus, Dysport can be recovered more efficiently by deviating from the manufacturer's recommendations allowing a more economical use of Dysport. J Inherit Metab Dis, 2004, 27(6), 911 - 5 Management of movement disorders in glutaryl-CoA dehydrogenase deficiency: anticholinergic drugs and botulinum toxin as additional therapeutic options; Burlina AP et al.; Glutaric aciduria type I is an inborn error of metabolism due to the deficiency of glutaryl-CoA dehydrogenase, an enzyme responsible for the catabolism of lysine, hydroxylysine and tryptophan . The most important neurological symptoms include dyskinesia and dystonia, which can be focal, segmental or generalized . Treatment of the extrapyramidal syndrome is often unsatisfactory . We report our experience in the treatment of generalized and focal dystonia with anticholinergic drugs and botulinum toxin type A, respectively . Both therapies proved beneficial. Neurology, 2004 Oct 26, 63(8), 1371 - 5 Botulinum toxin effect on salivary flow rate in children with cerebral palsy; Jongerius PH et al.; OBJECTIVE: To investigate the effectiveness of botulinum neurotoxin (BoNT) type A in reducing salivary flow rate in children with cerebral palsy (CP) with severe drooling . METHODS: During a controlled clinical trial, single-dose BoNT injections into the submandibular salivary glands were compared with scopolamine treatment . Forty-five school-aged children were included . Salivary flow rates from all major glands were obtained at baseline and compared with measurements during the interventions . Basic statistics consisted of analysis of difference scores . RESULTS: Compared with baseline, the mean decrease in submandibular flow was 25% during scopolamine and 42% following BoNT injections . The difference scores were significant with maximum reductions 2, 4, and 8 weeks following BoNT . Of all children, 95% responded during scopolamine . Response rates for BoNT were significantly lower and varied from 69% at 2 weeks to 49% at 24 weeks after injection (the end of the study) . Four patients discontinued scopolamine therapy because of side effects . Only incidentally mild side effects were reported from BoNT . CONCLUSIONS: Intraglandular BoNT injections significantly reduce salivary flow rate in the majority of drooling CP children, demonstrating high response rates up to 24 weeks . The procedure is simple to perform, effective, and safe when ultrasound guidance is used . The anticholinergic effect of BoNT exceeds that of scopolamine . As anticholinergic drugs are frequently contraindicated because of side effects, BoNT injections offer an alternative in the treatment of drooling. J Pediatr Orthop, 2004 Nov-Dec, 24(6), 629 - 33 Results of zone II flexor tendon repair in children younger than age 6 years: botulinum toxin type A administration eased cooperation during the rehabilitation and improved outcome; Tuzuner S et al.; The inability of young children with a zone II flexor tendon repair to cooperate in postoperative care and rehabilitation may represent a high risk for medical and surgical complications . To forestall that risk, botulinum toxin type A (2.5 U/kg, 7 U/kg) injection was used during surgery to induce forearm flexor muscle relaxation in seven children under 6 years old with zone 2 flexor tendon repairs . Patients received a controlled passive motion regimen after surgery . Results were evaluated on the basis of the acquisition of muscle tone and active finger movements, total range of motion of affected joints, postoperative grip strength, muscle atrophy, and phalangeal length . In this prospective clinical study, the mean follow-up was 18 months . All the children had good and excellent results based on the Strickland criteria . As for postoperative complications, one patient had bowstring and another had poor finger sensibility and first web space contracture that required Z-plasty . The selective use of botulinum toxin type A to weaken the targeted muscles generated a sufficient reduction in spontaneous activity of the fingers, permitting an improved rehabilitation program . Botulinum toxin type A administration could be an effective form of therapy, serving as an alternative or adjunct to conventional rehabilitation modalities in these children. Restor Neurol Neurosci, 2004, 22(3-5), 359 - 69 Recovery of gait and other motor functions after stroke: novel physical and pharmacological treatment strategies; Hesse S; The gait-lab at Klinik Berlin developed and evaluated novel physical and pharmacological strategies promoting the repetitive practise of hemiparetic gait in line with the slogan: who wants to relearn walking, has to walk . Areas of research are treadmill training with partial body weight support, enabling wheelchair-bound subjects to repetitively practice gait, the electromechanical gait trainer GT I reducing the effort on the therapists as compared to the manually assisted locomotor therapy, and the future HapticWalker which will allow the additional practise of stair climbing up and down and of perturbations . Further means to promote gait practice after stroke was the application of botulinum toxin A for the treatment of lower limb spasticity and the early use of walking aids . New areas of research are also the study of D-Amphetamine, which failed to promote motor recovery in acute stroke patients as compared to placebo, and the development of a computerized arm trainer, Bi-Manu-T rack, for the bilateral treatment of patients with a severe upper limb paresis. Expert Opin Investig Drugs, 2004 Nov, 13(11), 1437 - 43 The analgesic potential of clostridial neurotoxin derivatives; Foster KA; Botulinum neurotoxins are the most potent acute lethal toxins known, and yet for the last two decades they, and in particular serotype A, have found increasing use in the clinical treatment of diseases or conditions involving neuromuscular or autonomic neuronal transmission . The neurotoxins work by inhibiting the release of acetylcholine from peripheral cholinergic nerve terminals . More recently, the effects on non-cholinergic pathways have been identified, and this has led to an increase in the diseases and syndromes for which botulinum neurotoxins have been found to have clinical utility . In particular, botulinum neurotoxins have been demonstrated to potentially benefit a range of chronic pain syndromes . With the description in the last decade of the biochemical basis of neurotoxin action and the tertiary structure of the toxin molecule, the possibility of designing novel agents utilising selected aspects of toxin function has arisen . This possibility has been pursued in the context of pain relief with the description of a novel hybrid protein derived from botulinum neurotoxin type A, LH(N)/A-ECL, able to selectively target nociceptive afferent neurons and inhibit the release of neurotransmitters involved in pain transmission . This novel derivative of botulinum neurotoxin type A demonstrates prolonged analgesic activity in vivo . This review will consider the evidence for the analgesic properties of the botulinum neurotoxins and their suitability as the basis for novel therapeutic proteins . The general concept of deriving novel therapeutic molecules from the neurotoxins will also be considered. Cochrane Database Syst Rev . 2004 Oct 18;(4):CD003469. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy; Wasiak J et al.; BACKGROUND: Cerebral palsy (CP) is a central nervous system deficit resulting from a non-progressive lesion in the developing brain . Although the brain lesions are static, the movement disorders that arise are not unchanging and are characterised by atypical muscle tone, posture and movement (Rang 1990) . The spastic motor type is the most common form of CP and its conventional therapeutic management may include splinting/casting, passive stretching, facilitation of posture and movement, spasticity-reducing medication and surgery . More recently, health care professionals have begun to use botulinum toxin A (BtA) as an adjunct to interventions in an attempt to reduce muscle tone and spasticity to improve function OBJECTIVES: To assess the effectiveness of intramuscular BtA injections as an adjunct to managing the upper limb in children with spastic CP . SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1966 to March Week 3 2004), EMBASE (1980 to 2003 Week 16) and CINAHL (1982 to Week 3 March 2004) . SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing intramuscular BtA injections into any muscle group of the upper limb with placebo, no treatment or other interventions . DATA COLLECTION AND ANALYSIS: Two authors using standardised forms extracted the data independently . Each trial was assessed for internal validity with differences resolved by discussion . Data was extracted and entered into RevMan 4.2.3 . MAIN RESULTS: Two trials met the inclusion criteria, each having short-term follow up, a small number of subjects and using a single set of injections.The study by Corry 1997 compared BtA with an injection of normal saline and found promising results in elbow extension, elbow and wrist muscle tone . At three months, encouraging results for wrist muscle tone and grasp and release were noted . The trial reported median change, range of changes and the difference in these measures between groups . The study by Fehlings 2000 compared BtA with no intervention . When data were analysed no treatment effect was found for quality of upper limb function, passive range of motion, muscle tone, grip strength or self-care ability . REVIEWERS' CONCLUSIONS: This systematic review has not found sufficient evidence to support or refute the use of intramuscular injections of BtA as an adjunct to managing the upper limb in children with spastic cerebral palsy . Only one of the two identified RCTs reported some promising results in support of reduced muscle tone following BtA injections . Further research incorporating larger sample sizes, rigorous methodology, measurement of upper limb function and functional outcomes is essential. Br J Ophthalmol, 2004 Nov, 88(11), 1403 - 8 Reduction of ocular muscle power by splitting of the rectus muscle I: biomechanics; Haslwanter T et al.; BACKGROUND/AIM: Based on mechanical considerations, the authors have developed a new approach to weakening oculomotor muscles . They present the biomechanical considerations that have encouraged them to explore this approach, and compare it with existing surgical techniques . Results of application to patients are given in the companion paper, and do not require an analytical understanding of the underlying mechanics . METHODS: Using a simple biomechanical model for the oculomotor system and vector component analysis, the eye position dependent torque exerted by extraocular muscles on the eyeball was investigated . This model was applied to the healthy eye, as well as to different surgical procedures (Cuppers' Fadenoperation, Y-split muscle recessions, botulinum toxin, and simple muscle recessions) . CONCLUSION: These investigations suggest that a Y-split muscle recession is a simple and efficient way to weaken ocular rectus muscles . Compared to alternative surgical procedures, undesired radial forces that can lead to post-surgical complications can be kept to a minimum . The authors further speculate that their good results may in part be because of possible preservation of proprioceptive inputs from the insertion of the extraocular muscle. J Neurol Neurosurg Psychiatry, 2004 Nov, 75(11), 1558 - 61 The beneficial antispasticity effect of botulinum toxin type A is maintained after repeated treatment cycles; Bakheit AM et al.; OBJECTIVE: To study the efficacy, safety, and incidence of BtxA antibody formation with repeated treatments with BtxA in post-stroke upper limb muscle spasticity . METHODS: The study was a prospective open label trial . Patients with established post-stroke upper limb spasticity received 1000 units of BtxA (Dysport) into five muscles of the affected arm on study entry . Treatment was repeated every 12, 16, or 20 weeks as clinically indicated . Each patient received a total of three treatment cycles . Efficacy of treatment was assessed using the Modified Ashworth Scale . Patients were assessed on study entry and on week 4 and 12 of each treatment cycle for all safety and efficacy parameters . Blood samples for BtxA antibody assay were taken at baseline and on completion of the trial . RESULTS: Fifty one patients were recruited and 41 of them completed the study . Improvement from the cycle one baseline was observed in all the outcome measures . Mild to moderately severe treatment related adverse events were reported in 24% of cases . There were no serious adverse events . No BtxA antibodies were detected . CONCLUSION: BtxA at a dose of 1000 units Dysport was efficacious in the symptomatic treatment of post-stroke upper limb spasticity . The study suggests that this effect can be maintained with repeated injections for up to at least three treatment cycles, with duration of effect per cycle of between 12 and 20 weeks . BtxA was safe in the dose used in this study and did not induce the formation of detectable levels of neutralising BtxA antibodies. J Neurol Neurosurg Psychiatry, 2004 Nov, 75(11), 1547 - 51 Does reducing spasticity translate into functional benefit? An exploratory meta-analysis; Francis HP et al.; BACKGROUND: Spasticity and loss of function in an affected arm are common after stroke . Although botulinum toxin is used to reduce spasticity, its functional benefits are less easily demonstrated . This paper reports an exploratory meta-analysis to investigate the relationship between reduced arm spasticity and improved arm function . METHOD: Individual data from stroke patients in two randomised controlled trials of intra-muscular botulinum toxin were pooled . The Modified Ashworth Scale (elbow, wrist, fingers) was used to calculate a "Composite Spasticity Index" . Data from the arm section of the Barthel Activities of Daily Living Index (dressing, grooming, and feeding) and three subjective measures (putting arm through sleeve, cleaning palm, cutting fingernails) were summed to give a "Composite Functional Index" . Change scores and the time of maximum change were also calculated . RESULTS: Maximum changes in both composite measures occurred concurrently in 47 patients . In 26 patients the improvement in spasticity preceded the improvement in function with 18 showing the reverse . There was a definite relationship between the maximum change in spasticity and the maximum change in arm function, independent of treatment (rho = -0.2822, p = 0.0008, n = 137) . There was a clear relationship between the changes in spasticity and in arm function in patients treated with botulinum toxin (Dysport) at 500 or 1000 units (rho = -0.5679, p = 0.0090, n = 22; rho = -0.4430, p = 0.0018, n = 47), but not in those treated with placebo or 1500 units . CONCLUSIONS: Using a targeted meta-analytic approach, it is possible to demonstrate that reducing spasticity in the arm is associated with a significant improvement in arm function. J Neurol Neurosurg Psychiatry, 2004 Nov, 75(11), 1541 - 6 Effects of botulinum toxin type A on vibration induced facilitation of motor evoked potentials in spasmodic torticollis; Urban PP et al.; BACKGROUND AND AIMS: It has not been clarified if botulinum toxin (BTX) injection leads to muscle spindle dysfunction in man . This study aimed to test the hypothesis that BTX application reduces the facilitation of a magnetic evoked response (MEP) . METHODS: We used the vibration induced facilitation of an MEP of the sternocleidomastoid muscle (SCM) as a surrogate marker for muscle spindle function in 20 healthy subjects and 10 patients with idiopathic rotational torticollis in whom BTX was injected unilaterally . RESULTS: The increase in the amplitude and area of the MEPs in the clinically not affected and untreated SCM of the patients did not differ significantly from the controls . At baseline, the vibration induced increase in the affected SCM of the patients was significantly lower than in the control group . Six weeks after BTX application, the observed facilitation decreased significantly (amplitude and area: p<0.001) when compared with baseline values . Twelve weeks after BTX application, facilitation showed an increase in the values of the amplitude (p<0.001), but not of the area when compared with the six week examination . CONCLUSIONS: We demonstrated that the vibration induced MEP facilitation in the SCM of patients with torticollis significantly decreased six weeks after BTX application and again increased after 12 weeks in part when looking at MEP amplitude . This observation is suggestive of denervation and reinnervation of the muscle spindles after BTX injection. Am J Ophthalmol, 2004 Oct, 138(4), 654 - 5 Lidocaine tape (Penles) reduces the pain of botulinum toxin injection for Meige syndrome; Onguchi T et al.; PURPOSE: To evaluate the efficacy of lidocaine tape in reducing pain during botulinum toxin injection . DESIGN: Randomized double-blind study . METHOD: Six men and four women with a diagnosis of Meige syndrome undergoing botulinum toxin injection were recruited.Lidocaine tape was applied to the eyelid skin of a randomly selected eye and placebo tape to the other eye . Pain during botulinum toxin injection was evaluated subjectively by a visual analogue scale . Side effects were also monitored . RESULTS: Mean subjective pain both on puncturing skin and on injection in the lidocaine group was significantly lower than that in the placebo group . Nine of 10 patients found lidocaine tape to be more effective than placebo tape in reducing pain during injection . CONCLUSIONS: Lidocaine tape is a simple and convenient method of reducing pain during botulinum toxin injection . This method is recommended for patients reluctant to receive this treatment because of pain during injection. J Pediatr Surg, 2004 Oct, 39(10), 1458 - 62 Persistent obstructive symptoms after surgery for Hirschsprung's disease: development of a diagnostic and therapeutic algorithm; Langer JC; BACKGROUND: Although most children with Hirschsprung's disease (HD) do well after pull-through surgery, some continue to have persistent obstructive symptoms that may lead to significant morbidity . The author's goal was to develop an organized algorithm for the workup and ultimate management of these symptoms . METHODS: All children referred to the author with severe obstructive symptoms after a pull-through for HD were evaluated using an algorithm based on 5 potential etiologies, and appropriate therapeutic interventions were instituted . RESULTS: A total of 49 children were evaluated over 7 years . Mechanical obstruction was found using rectal examination and barium enema in 7, of which, 2 had resection of a Duhamel spur, and 5 had a repeat pull-through (after failed dilatation) . Rectal biopsy results showed aganglionosis in 10, of whom, 8 underwent repeat pull-through, and 2 refused further surgery . Abnormal intestinal motility or intestinal neuronal dysplasia was found proximal to the aganglionic segment in 10 children using colonic and small bowel manometry or laparoscopic biopsies; 4 of these had additional colon resected and repeat pull-through, and 6 were treated with a bowel management routine, cecostomy, or stoma formation . Internal sphincter achalasia was felt to be the primary cause of symptoms in 14, and all were treated with intrasphincteric botulinum toxin . Eight were found not to fall into any of the above groups and were treated medically for presumed functional megacolon; 2 of these ultimately had a colostomy . CONCLUSIONS: An organized approach to the diagnosis and management of obstructive symptoms in a child after a pull-through for HD permits accurate diagnosis and effective treatment in the majority of cases. Zentralbl Chir, 2004 Oct, 129(5), 381 - 6 {Laparoscopic heller cardiomyotomy either combined with a Dor or Toupet procedure in the treatment of achalasia}; Schulz HG et al.; INTRODUCTION: The treatment of achalasia has undergone a dramatic evolution over the past ten years with the introduction of advanced laparoscopic techniques beside the use of balloon dilatation and injections of botulinumtoxin . With the introduction of the laparoscopic Heller cardiomyotomy the question was raised again whether and if so which antireflux measures are meaningful in combination with the cardiomyotomy . PATIENTS AND METHOD: Since 1998, 51 patients underwent laparoscopic cardiomyotomy in the surgical department of the Marienhospital Herne, Ruhr University Bochum . To prevent postoperative gastroesophageal reflux we performed a Dor fundoplication in 13 patients and a Toupet fundoplication in 38 patients . The mean period of observations was 17 months (3-45 months) . All patients were evaluated through a symptoms score . 16 patients could be clinically and objectively followed-up . RESULTS: The mean operation time was 170 min . (80-290 min) . The intraoperative complications were 8 mucosal disruptions without further morbidity and 1 pneumothorax . Postoperative complications were 1 scarring restenosis and 1 wrap dislocation . Improvement of symptoms was reported in 94.2 % of patients with good or excellent results . In 5.8 % of patients symptoms of reflux were claimed . There was no significant difference in results between Dor- and Toupet-fundoplication . CONCLUSION: Laparoscopic Heller cardiomyotomy with either a Dor or Toupet fundoplication are equivalent with respect to short- and middle-term outcome and efficient procedures with low rate of morbidity and mortality in the treatment of achalasia . A long-term observation period is necessary for determining which type of fundoplication has to be performed particularly regarding restenosis and reflux rate. EMBO Rep, 2004 Nov, 5(11), 1090 - 5 A molecular basis underlying differences in the toxicity of botulinum serotypes A and E; Bajohrs M et al.; Botulinum neurotoxins (BoNTs) block neurotransmitter release through their specific proteolysis of the proteins responsible for vesicle exocytosis . Paradoxically, two serotypes of BoNTs, A and E, cleave the same molecule, synaptosome-associated protein with relative molecular mass 25K (SNAP-25), and yet they cause synaptic blockade with very different properties . Here we compared the action of BoNTs A and E on the plasma membrane fusion machinery composed of syntaxin and SNAP-25 . We now show that the BoNT/A-cleaved SNAP-25 maintains its association with two syntaxin isoforms in vitro, which is mirrored by retention of SNAP-25 on the plasma membrane in vivo . In contrast, BoNT/E severely compromises the ability of SNAP-25 to bind the plasma membrane syntaxin isoforms, leading to dissociation of SNAP-25 . The distinct properties of botulinum intoxication, therefore, can result from the ability of shortened SNAP-25 to maintain its association with syntaxins-in the case of BoNT/A poisoning resulting in unproductive syntaxin/SNAP-25 complexes that impede vesicle exocytosis. Nihon Shinkei Seishin Yakurigaku Zasshi, 2004 Aug, 24(4), 165 - 70 {Methodological consideration in studying the exocytosis mechanisms using microdialysis}; Okada M et al.; Microdialysis has become an effective and frequently used technique to study the extracellular levels of monoamine, i.e . dopamine, serotonin and norepinephrine in the central nervous system . However, the detailed exocytosis mechanisms of monoamine using microdialysis has remained to be clarified . The present report introduces methods for administration of voltage-sensitive calcium channel (VSCC) inhibitors and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) inhibitors to clarify the mechanisms of monoamine exocytosis using in vivo microdialysis . The N-type and P-type VSCCs are inhibited by perfusion with omega-conotoxin GVIA and omega-agatoxin IVA, respectively; however, their diffusion rate from internal to external spaces of the microdialysis probe is lower than 1% . Unlike VSCC inhibitors, SNAP-25, synaptobrevin and syntaxin can be cleavaed with botulinum toxin type A, B and C, respectively . These toxins (with molecular weights over 500,000) bind specifically to the presynaptic membrane via the heavy chain, while the light chain enters the cytosol, where it displays zinc-endopeptidase activity directed to proteins of the neuroexocytosis apparatus . Therefore, to prevent SNARE activity, botulinum toxins are microinjected . These two methods, perfusion with VSCC inhibitors and microinjection with botulinum toxins, can contribute to the clarification of the mechanisms of monoaminergic exocytosis. Eur Neurol, 2004, 52(3), 132 - 5 Epub 2004. Antibody-induced failure of botulinum toxin type B therapy in de novo patients; Dressler D et al.; Botulinum toxin type B (BT-B) therapy failure due to formation of botulinum toxin type B antibodies (BT-B-AB) has only been reported in patients with botulinum toxin type A antibodies (BT-A-AB) . We are reporting BT-B-AB-induced therapy failure in 2 patients with no previous exposure to botulinum toxin . In patient 1 complete therapy failure occurred after a single exposure to 14,400 mouse units (MU) BT-B (NeuroBloc) . The mouse diaphragm assay (MDA) revealed a BT-B-AB titre in excess of 10 mU/ml . Doubling the BT-B dose did not elicit any effects . Application of 360 MU BT-A (Botox) produced the original therapeutic effect, but the second BT-A application was followed by partial and the third by complete therapy failure . Doubling the BT-A dose did not elicit any effects . MDA testing showed a BT-A-AB titre in excess of 10 mU/ml . In patient 2 a single exposure to 7,200 MU BT-B lead to a complete therapy failure . MDA testing revealed a BT-B-AB titre in excess of 10 mU/ml . Doubling the BT-B dose did not elicit any effects . Application of 180 MU BT-A (Botox) produced the original response on 3 consecutive applications . Antibody formation can occur after a single exposure to botulinum toxin . However, this is highly unusual . Since therapy failure occurred after the first-ever botulinum toxin exposure, short intervals between injections and use of booster injections can be excluded as causes for BT-B-AB formation in both patients . A more likely cause may be the substantially higher amount of antigenic protein administered in BT-B therapy compared to BT-A therapy . Further studies are necessary to compare the incidence of antibody formation in BT-B and BT-A therapy . 2004 S . Karger AG, Basel. Skin Res Technol, 2004 Nov, 10(4), 207 - 14 In vivo determination of skin surface topography using an optical 3D device; Jacobi U et al.; BACKGROUND/PURPOSE: Topography of the skin surface is a mirror of the functional skin status . Therefore, its evaluation is of great interest for dermatological research . In the present study, a new optical measuring system was applied to evaluate human skin surface topography in vivo