Dermatol Surg, 2003 May, 29(5), 557 - 9 Multiple eccrine hidrocystomas: a new therapeutic option with botulinum toxin; Blugerman G et al.; BACKGROUND: Multiple eccrine hidrocystomas are benign cystic lesions that are associated with a chronic course and seasonal variability . Even though in the literature it is presented as a very infrequent pathology, we think this is more a lack of knowledge of the existence of said pathology and the fact that patients confuse it with comedo . OBJECTIVE: To treat multiple eccrine hidrocystomas of the face . RESULTS: We present a case of multiple eccrine hidrocystomas of the face in a cook man . Hidrocystoma is a benign cystic tumor of the sweat glands eccrine or apocrine . Multiple eccrine hidrocystomas are benign cystic lesions that are associated with a chronic course and seasonal variability . They appear like multiple shining small papule . Although a solitary eccrine hidrocystoma can be treated easily with surgical excision, the elimination of multiple lesions is problematic because of their number and location . CONCLUSION: The benefits of BTX-A treatment for multiple eccrine hidrocystomas include ease of application, no risk of scarring, and a good postoperative course . Because of the blockage produced by BTX-A on cholinergic terminals of the parasympathetic system that governs sweat glands secretion, it is suggested that periodic doses of BTX-A are injected in the superficial epidermis in order to treat multiple eccrine hidrocystomas. Dermatol Surg, 2003 May, 29(5), 545 - 8 Botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis: efficacy and duration with repeated treatments; Lowe PL et al.; BACKGROUND: Botulinum toxin type A (BTX-A) has been shown to be effective for the temporary reduction of local hyperhidrosis . OBJECTIVE: To investigate the duration of efficacy of BTX-A with repeat treatments for axillary hyperhidrosis . METHODS: Patients who completed a prior randomized, controlled, parallel-group study comparing BTX-A with vehicle for bilateral primary axillary hyperhidrosis were eligible for this 18-month, open-label, noncomparative, follow-up study . Patients had to request further treatment, fulfill the preceding study inclusion/exclusion criteria, and have spontaneous sweat production that was more than 50% of the baseline value of the previous study . Patients received up to four treatments of intradermal BTX-A (2 mL, 50 U) . All of the 12 patients who were enrolled completed the study . Two of the 12 patients (17%) were previously treated with placebo . RESULTS: In the 18 months of study and follow-up, five patients (42%) required a total of two active injections . Three patients (25%) required a total of three active injections, and four patients (33%) required a total of four active injections . The response rate was 83% (10 of 12) at 4 weeks after the first treatment . The mean percentage change from baseline in overall sweat production was approximately 80% at Week 4 . The mean time between the first and second treatment in this study was just over 29 weeks, with a range of 17.8 to 57.5 weeks . CONCLUSION: BTX-A is an effective repeat treatment for axillary hyperhidrosis giving variable but clinically helpful remission . No clinically relevant changes in vital signs or safety parameters were noted. Dermatol Surg, 2003 May, 29(5), 533 - 8; discussion 538 Diffusion and short-term efficacy of botulinum toxin A after the addition of hyaluronidase and its possible application for the treatment of axillary hyperhidrosis; Goodman G; BACKGROUND: Botulinum toxin adequately treats hyperkinetic facial lines and hyperhidrosis . Higher doses of botulinum toxin appear to enhance efficacy and longevity possibly through greater evenness of diffusion; however, recurrent treatments with higher doses are expensive . OBJECTIVE: To admix botulinum toxin with hyaluronidase and to test whether there is maintenance of efficacy, a spread of effect, and possibly a decrease in required dose compared with botulinum toxin . METHODS: Six patients participated in a double-blinded side-to-side comparison pilot study with photographic analysis for frontalis overactivity and Minor's iodine and gravimetric testing for axillary hyperhidrosis . RESULTS: Initial efficacy of botulinum with admixed hyaluronic acid appeared maintained with possibly increased diffusion when hyaluronic acid is added . No difference was evident on short-term review of patients treated with 50 U of botulinum in one axilla compared with the contralateral side injected with 25 U with admixed hyaluronidase . CONCLUSION: There may be a role for hyaluronic acid in aiding diffusion and decreasing the required dose of botulinum toxin in hyperhidrosis axillaris. Dermatol Surg, 2003 May, 29(5), 530 - 1; discussion 532 Foam during reconstitution does not affect the potency of botulinum toxin type A; Trindade De Almeida AR et al.; BACKGROUND: Among factors that may affect the potency of botulinum toxin A (Botox), it is said that foam, together with bubbles, may cause surface denaturation of the toxin . OBJECTIVE: To determine whether the muscle relaxation effect of Botox is preserved and has the same duration when it is reconstituted in the presence of foam . METHODS: Six female volunteers, aged 42 to 56 years old, were treated for glabellar and periocular wrinkles . Each half of the face was treated with 16 U of Botox divided in four sites: three at the lateral orbital area and one at the medial brow, in the glabellar region . The right side received Botox gently reconstituted with saline to avoid foaming formation . The left side of the face was treated with Botox that was rapidly reconstituted in order to achieve as many bubbles as possible, even with shaking . Blinded observers compared pretreatment and posttreatment photographs and answered assessment-related questions . The results were analyzed clinically and statistically . RESULTS: There was no difference in muscle paralysis between treated sides in all patients, neither in early (15 days) nor late (4 months) follow-up evaluations . CONCLUSION: Botox maintains its potency even in the presence of foaming during the reconstitution process. Dermatol Surg, 2003 May, 29(5), 523 - 9; discussion 529 Multicenter, double-blind study of the efficacy of injections with botulinum toxin type A reconstituted up to six consecutive weeks before application; Hexsel DM et al.; BACKGROUND: It is recommended that botulinum toxin be used immediately or within 2 weeks after its reconstitution because its efficacy might be compromised by prolonged storage . OBJECTIVES: To evaluate the efficacy of botulinum toxin type A (BTX-A) reconstituted over 6 consecutive weeks for the treatment of glabellar frown lines . METHODS: Four vials of BTX-A were reconstituted each of 7 days over a period of 6 weeks, totaling 28 vials, corresponding to seven reconstitution dates . During this period, the BTX-A was stored according to the manufacturer's instructions . On the day after the last reconstitution, all of the reconstituted vials were injected in patients from four dermatologic centers taking part in this study . A total of 88 patients were treated on the same day and were followed every 2 weeks for 4 months . All patients were photographed at all stages . A number of professionals assessed the efficacy of reconstituted BTX-A based on the reduction of the maximum frowning capacity of the treated muscles . RESULTS: Of the 88 patients who were selected, 3 were excluded . Three forms of evaluation were applied, and no statistically significant differences were found in the results presented . CONCLUSION: BTX-A may be applied up to 6 weeks after reconstitution without losing its effectiveness . Other factors, which are probably individual, may influence the response to BTX-A injections. Dermatol Surg, 2003 May, 29(5), 519 - 22; discussion 522 Botulinum toxin type B (MYOBLOC) versus botulinum toxin type A (BOTOX) frontalis study: rate of onset and radius of diffusion; Flynn TC et al.; BACKGROUND: Botulinum toxin types A and B can improve the appearance of facial wrinkles . Differences in the time until onset and the degree of diffusion have been observed anecdotally, but no direct comparative studies have been done . OBJECTIVE: To compare the rate of onset and the radius of diffusion of botulinum toxin types A and B in the rhytides of the forehead . METHODS: Adults with symmetrical moderate to severe forehead wrinkles at full contracture received botulinum toxin type A (BOTOX; 5 U) on one side of the forehead and type B (MYOBLOC; 500 U) on the other side . Photographs taken at rest and full frontalis contracture were analyzed by computer, and a time-lapse motion picture was created . Radius of diffusion and time until full effect were measured . RESULTS: Botulinum toxin type B had a slightly faster onset of action than type A . All patients responded to type B quickly, whereas some had a delayed response to type A . A greater radius of diffusion was consistently observed with botulinum toxin type B, as measured by the greater area of wrinkle reduction at the doses used . CONCLUSIONS: In this comparative study of patients with symmetrical forehead wrinkles, botulinum toxin type B produced a greater area of diffusion and a more rapid onset of action than type A. Dermatol Surg, 2003 May, 29(5), 516 - 8 Botulinum toxin type B for dynamic glabellar rhytides refractory to botulinum toxin type A; Alster TS et al.; BACKGROUND: Botulinum toxin type B (BTX-B; Myobloc) has recently been introduced for the treatment of dynamic rhytides . This serotype is structurally similar to botulinum toxin type A (BTX-A; Botox) and appears to produce equivalent muscular paralysis . Because of the fact that some patients may become resistant to the effects of BTX-A with its continued use or may require large doses of type A to exert adequate muscular paralysis, the use of BTX-B may prove beneficial in these cases . OBJECTIVE: To determine the effect of BTX-B on glabellar rhytides refractory or showing decreased clinical effect to treatment with BTX-A . METHODS: Twenty females (mean age, 43 years) with vertical glabellar rhytides showing decreased or negligible clinical effect to BTX-A were treated with intramuscular injections of BTX-B . Five standardized intramuscular sites (procerus, inferomedial corrugator muscles, superior middle corrugator muscles) received a total dose of 2,500 U . Patients were evaluated at pretreatment and 48 to 72 hours, 1 week, and 2 and 4 months after injection . RESULTS: All glabellar rhytides improved after treatment with BTX-B injections . Peak clinical effect was noted 1 month after treatment, with 50% of peak effect evident at the 2-month follow-up . Near complete dissolution of effect was seen at 4 months after treatment . Side effects were transient and were limited to moderate injectional pain and rare bruising and frontal brow tightness . CONCLUSIONS: BTX-B is an effective treatment modality for glabellar rhytides refractory or exhibiting decreased clinical effect to BTX-A . The duration of effect using the 2,500 U dosing schedule described herein was shorter than that typically achieved after equivalent BTX-A injection. Dermatol Surg, 2003 May, 29(5), 508 - 15 A double-blinded, randomized, placebo-controlled pilot study of the safety and efficacy of Myobloc (botulinum toxin type B)-purified neurotoxin complex for the treatment of crow's feet: a double-blinded, placebo-controlled trial; Baumann L et al.; Crow's feet develop with age and are one of the earliest signs of the normal aging process . Botulinum toxin type A, approved by the Food and Drug Administration for the treatment of glabellar wrinkles in April 2002, has been used off-label to treat facial wrinkles since 1981 . Botulinum toxin type B (BTX-B, Myobloc) was Food and Drug Administration-approved for use in cervical dystonia in the United States in December 2000 and has subsequently been used in an off-label indication to treat facial wrinkles . There are sparse data in the literature evaluating the safety and efficacy of BTX-B for the treatment of facial wrinkles . In this pilot study, participants with moderate or severe crow's feet wrinkles were treated with Myobloc versus placebo . The duration of correction and side effect profile are reported. Dermatol Surg, 2003 May, 29(5), 501 - 7; discussion 507 Prospective open-label study of botulinum toxin type B (Myobloc) at doses of 2,400 and 3,000 U for the treatment of glabellar wrinkles; Sadick NS; BACKGROUND: A previous open-label study evaluated botulinum toxin type B (BTX-B; Myobloc) for the treatment of glabellar wrinkles and showed that it is safe and effective at a dose of 1,800 U . The duration of effect at this dose was approximately 8 weeks, and it was felt that higher doses would result in a longer duration of effect . OBJECTIVE: This is a prospective open-label study to assess the safety, efficacy, and duration of response following BTX-B injection at doses of 2,400 and 3,000 U for the treatment of glabellar frown lines . METHODS: A total of 39 patients were enrolled: 16 patients received 2,400 U . Eighteen patients received 3,000 U, and 5 patients received saline injections (control group) . Doses were divided equally among six sites . RESULTS: All subjects had rapid improvement of interglabellar rhytides, with full response seen within 2 to 3 days . The duration of effect was 9.6 and 10.4 weeks with 2,400 and 3,000 U, respectively . Five subjects (two in the 2,400-U group and three in 3,000-U group) reported adverse events related to the BTX-B injection . Three subjects complained of mild pain at the injection site, and two subjects complained about lid droop/ptosis (one with the occurrence of headache) . CONCLUSIONS: BTX-B injection is safe and effective for the treatment of glabellar wrinkles . It has a very rapid onset of action, and increasing the dose appears to prolong the duration of response . At 3,000 U, the duration of response was 10.4 weeks and was associated with minimal adverse effects . Adverse events were mild and were similar to those seen in previous studies with BTX-A . Additional studies evaluating BTX-B at higher doses are recommended to prolong the duration of response in the treatment of glabellar wrinkles. Dermatol Surg, 2003 May, 29(5), 496 - 500; discussion 500 Botulinum toxin type B (Myobloc); Baumann L et al.; Myobloc, known as Neurobloc in Europe, is a member of the botulinum toxin family . It has been used for a myriad of problems since its approval in the United States in December 2000 . It is currently not approved for cosmetic use but has been used for this purpose . This article reviews what is currently known about botulinum toxin type B and its efficacy and safety. Dermatol Surg, 2003 May, 29(5), 490 - 5; discussion 495 Botulinum toxin A treatment of perioral rhytides; Semchyshyn N et al.; BACKGROUND: Botulinum toxin A is well documented as a useful therapy for smoothing dynamic facial rhytides of the upper face . Most controlled studies have focused on the treatment of glabellar frown lines, horizontal forehead lines, and crow's feet . Reports of botulinum toxin A use in the lower face are few and anecdotal . OBJECTIVE: We present our experience using botulinum toxin A in the lip as a treatment of vertical perioral rhytides, which resulted in the added cosmetic benefits of lip eversion and enhanced lip fullness . METHODS: Eighteen patients were injected with botulinum toxin A into the vertical lip rhytides . The effect of treatment was evaluated at 2 to 3 weeks after procedure . RESULTS: Smoothening of hyperfunctional lines and upper lip fullness/eversion is observed in patients treated with perioral botulinum toxin A injections; 72% of patients continued treatment . CONCLUSIONS: In select patients, perioral botulinum toxin A results in amelioration of perioral rhytides and enhancement of lip fullness and lip eversion. Dermatol Surg, 2003 May, 29(5), 484 - 9 Effects of botulinum toxin type A on bilateral masseteric hypertrophy evaluated with computed tomographic measurement; Kim HJ et al.; BACKGROUND: A paucity of reports exist on the use of botulinum toxin type A injections as an alternative noninvasive treatment for masseteric hypertrophy . OBJECTIVE: To evaluate the effects of botulinum toxin type A on masseteric hypertrophy using computed tomography . METHODS: Percutaneous intramuscular injections of botulinum toxin type A of 30 U per side was carried out in 11 subjects with masseteric hypertrophy . The changes in the masseteric muscle volume before and 12 weeks after injection were evaluated using computed tomography . The changes in the lower facial contours on the photographs were evaluated as excellent, good, fair, and no changes . RESULTS: Nine of the 11 subjects showed a mean reduction of approximately 22% in the masseteric muscle volume . The maximum reduction was 35.4% (range, 8.1% to 35.4%) . Nine subjects showed aesthetically good results with a grade of good or excellent at 12 weeks after treatment . CONCLUSION: Botulinum toxin injections are a noninvasive alternative method for treating masseteric hypertrophy. Dermatol Surg, 2003 May, 29(5), 477 - 83; discussion 483 Botulinum toxin type A treatment for contouring of the lower face; Park MY et al.; BACKGROUND: Since type A botulinum toxin was first reported for the treatment of masseter muscle hypertrophy in 1994, there have been few reports about cosmetic indications for contouring procedures of the lower face with injection of botulinum toxin type A, and this procedure remains unpredictable . OBJECTIVES: This study attempted a quantitative prospective analysis of reduction of masseter muscle hypertrophy after Botox injection, using ultrasound and computerized tomography (CT) scans to analyze the possible use of botulinum toxin type A as a contouring procedure for the lower face . METHODS: Forty-five patients consented to the study and received a contouring procedure of the lower face from November 2001 to April 2002 . Twenty five to 30 U of Botox per side was injected at five to six points into the prominent portions of the mandibular angle . Serial measurements were made of the thickness of the masseter muscle by ultrasound and CT before the injections and at 1 and 3 months thereafter . A quantitative analysis for the masseter thickness changes was performed on just one patient who underwent all ultrasound and CT scans . Statistical analysis of the masseter thickness change was by two-way and multiple comparison analysis . To evaluate clinical long-term effects, the patient's satisfaction with the procedure and any side effects after injections were monitored during 4 to 10 months of follow-up . RESULTS: Among the total of 45 patients, 15 underwent the three ultrasound measurements, and 14 had the three CT measurements . With regard to quantitative analysis of the thickness change to the masseter on both sides of the face according to time points, this was gradually reduced by both the ultrasound and CT measurements during the first 3 months . By ultrasound, the maximum reduction in masseter thickness was seen 1 month after the injections, with a slight increase being observed at 3 months after injection . A continued reduction of masseteric muscle thickness was seen on the CT up to 3 months after injection . In terms of patient satisfaction for up to 10 months of follow-up, the results were as follows: very satisfied, 1; satisfied, 36; slight improvement, 3; no change or dissatisfied, 5 . Main local side effects included masticatory difficulties, muscle aching at injection sites, and speech disturbance . However, these side effects were transitory, usually lasting from 1 to 4 weeks after the injections . CONCLUSIONS: Preliminary results from this study suggest that an injection of Botox resulted in relatively satisfactory clinical effects, although there was only a short-term follow-up . It is suggested that the use of botulinum toxin type A for contouring of the lower face can be established as a simple, predictable, alternative facial contouring procedure without a prolonged recovery time. Dermatol Surg, 2003 May, 29(5), 468 - 76 Aesthetic botulinum A toxin in the mid and lower face and neck; Carruthers J et al.; BACKGROUND: Botulinum toxin type A (BOTOX formulation) is used extensively for smoothing hyperkinetic lines in the upper face . The use of botulinum toxin for aesthetic indications in the mid and lower face and neck is now becoming increasingly popular . OBJECTIVE: To review our current approaches to botulinum toxin treatment for cosmetic indications in the mid and lower face and neck . METHODS: Procedures and outcomes are described for the primary and adjunctive use of botulinum toxin . RESULTS: Cosmetic treatment with botulinum toxin successfully changes the contour of the palebral aperture; smoothes lines, including "bunny" lines, perioral rhytides, and horizontal neck lines; softens creases, including the mental crease and melomental folds; and alleviates facial asymmetry and nasal flare . The doses of botulinum toxin used in the mid and lower face are generally lower than those used in the upper face . Caution must be used in injecting botulinum toxin in the perioral area to avoid an incompetent mouth . CONCLUSION: Botulinum toxin treatment is valuable for aesthetic improvements in the mid and lower face and neck . In some areas, particularly the perioral region, the use of botulinum toxin in combination with other therapeutic modalities provides optimal results. Dermatol Surg, 2003 May, 29(5), 461 - 7 A prospective, double-blind, randomized, parallel- group, dose-ranging study of botulinum toxin type a in female subjects with horizontal forehead rhytides; Carruthers A et al.; BACKGROUND: Botulinum toxin type A is used cosmetically to improve facial lines, but it has not been thoroughly investigated for the treatment of horizontal forehead rhytides . OBJECTIVE: To compare the efficacy and safety of three doses of botulinum toxin type A in females with horizontal forehead rhytides and to establish whether the response rate and the duration of response are dose dependent . METHODS: Fifty-nine female patients with horizontal forehead rhytides scoring 2 (moderate) or 3 (severe) on the facial wrinkle scale (FWS) were randomly assigned to receive 16, 32, or 48 U of botulinum toxin type A (BOTOX, BOTOX Cosmetic; Allergan, Irvine, CA), which was administered to eight injection sites . Half of the dose was administered to the brow depressors and the other half to the elevators . Wrinkle severity was assessed by the investigator and patient using the FWS at baseline, at Weeks 2 and 4, and then every 4 weeks for 48 weeks . RESULTS: Improvements in horizontal rhytides were observed in all dosage groups . Significant dose-response trends were observed for rate of improvement at maximum brow elevation (53% in the 48-U group vs . 15% in the 16-U group at 16 weeks) and rate of relapse to baseline (35% in the 48-U group vs . 75% in the 16-U group at 16 weeks) by a trained observer . CONCLUSION: Higher botulinum toxin type A doses resulted in greater efficacy and longer duration of effect in the reduction of horizontal rhytides. Dermatol Surg, 2003 May, 29(5), 456 - 60 Satisfaction of patients after treatment with botulinum toxin for dynamic facial lines; Sommer B et al.; OBJECTIVE: To gain first evidence on the patient satisfaction after treatment with botulinum toxin type A (BTX-A) and to check for differences in satisfaction with respect to clinical, psychologic, and sociodemographic parameters . METHODS: In this pilot study, 30 patients who had been treated with BTX-A within the last 3 months answered a standardized questionnaire (the Freiburg questionnaire on aesthetic dermatology and cosmetic surgery) . The items assessed were attitudes on beauty and body, satisfaction with treatment outcome, and general quality of life . A prospective study consisting of the same items runs parallel and will be published later . RESULTS: More than 80% of the patients answered that the treatment had been beneficial to them . All patients would recommend treatment completely or mostly . Only a very small part of the patients was moderately stressed by the treatment . CONCLUSION: Injections with BTX-A is a satisfying and well-tolerated treatment of dynamic facial lines for all patients in this pilot study. Dermatol Surg, 2003 May, 29(5), 444 - 9; discussion 449 Development of the Facial Lines Treatment Satisfaction Questionnaire and initial results for botulinum toxin type A-treated patients; Cox SE et al.; BACKGROUND: Botulinum toxin type A treatment is a safe and effective treatment for facial lines . Patient satisfaction with treatment has not yet been systematically measured and reported . OBJECTIVE: To create a valid and reliable questionnaire to assess patient satisfaction with facial line treatment and to assess treatment satisfaction in facial line patients . METHODS: Development of the Facial Line Treatment Satisfaction (FTS) Questionnaire followed the five-step process recommended by the Patient Reported Outcomes Harmonization Committee . RESULTS: One hundred fifty-two pilot test participants received botulinum toxin type A treatment alone or in combination with a minimally invasive facial line treatment and were satisfied or very satisfied with their facial lines treatment . CONCLUSION: The FTS is a valid and reliable 14-item questionnaire that measures an aesthetic patient's satisfaction with facial line treatment . The FTS can be used in clinical practice or clinical trials of facial line treatments . Botulinum toxin type A treatment is associated with high patient satisfaction. Eur J Neurol, 2003 May, 10(3), 313 - 7 Functional improvement in cerebral palsy patients treated with botulinum toxin A injections - preliminary results; Slawek J et al.; Authors report the preliminary results of an open-label, prospective study to evaluate a functional benefit of botulinum toxin type A injections in diparetic cerebral palsy patients, using gross motor function measure (GMFM) score . In a group of 14 children (mean age 3.9 years, range 2-6) treated with Dysport 30 IU/kg, a statistically significant improvement (P < 0.05) was noticed in both simple measurements (Modified Ashworth Scale, Selective Motor Control, Passive Range of Movements, Physician Rating Scale and parental Clinical Global Impression) and complex functions (GMFM dimensions D and E) after 1 and 3 months . However, the simple measurement scores decreased (but not to the baseline) after 3 months; surprisingly, GMFM scores were still increasing (7.7% change after 3 months and 11.3% change after 6 months in nine patients) . These results are in concordance with a few other data published to date . The study may support the concept of persistent functional gain in long-term treatment of spasticity caused by cerebral palsy with botulinum toxin type A. Eur J Neurol, 2003 May, 10(3), 213 - 9 East-west differences in the organization of botulinum toxin use in nine Central European countries; Homann CN et al.; Availability and quality of expensive treatment modalities such as botulinum toxin (BTX) largely depend on organizational aspects such as costs, reimbursement by insurance companies, expertise and facilities for expert training, and the propagation of research . To investigate which determinants influence the organization of BTX' use throughout nine Central European countries (Austria, Croatia, Czech Republic, Germany, Hungary, Italy, Slovakia, Slovenia and Switzerland) we sent out questionnaires to leading BTX experts and consulted data banks of manufacturers and bulletins of international organizations . In Western European countries, there is a tendency for users to organize themselves in formal groups and to concentrate on research whereas the way how BTX is provided is diverse regarding qualifications of specialists and institutions . In the post-communist Eastern European countries, we found a tendency towards a centralized system of reimbursement and BTX treatment seems to be more in the hands of neurologists than any other specialists . Strong correlations were observed between the number of BTX centres, degree of organization of user groups and number of scientific publications, on the one hand, and parameters of healthcare performance and socioeconomic determinants, on the other . Our study suggests that in the nine countries surveyed, organizational aspects of BTX use vary considerably, whilst similarities are based mainly on socioeconomic rather than socio-demographic determinants. Int J Neurosci, 2003 Feb, 113(2), 165 - 77 A new extra-vertebral treatment model for incomplete spinal cord injuries; Krishnan RV; Advances made in recent times in spinal cord injury repair research will soon take us toward a cure in paraplegics . But what are the prospects for quadriplegics? Certain fundamental issues make treatment approaches to quadriplegia different and difficult . Injury at cervical region poses additional problems for any surgical intervention with life-threatening risks of i) endangering respiratory function, ii) cavitation, cysts, and syringomyelia formation extending cephalad to the injury, and iii) mid-lower cervical injuries, lower motor neuron death, and the resultant degeneration of brachial plexus axons would still leave the upper limbs denervated and paralyzed even as treatment procedures might successfully salvage the lower limbs . With these apparently insurmountable impediments in quadriplegic cord repair, it would be wise to turn to alternative treatment strategies . Conventional treatment models since the days of Ralph Gerard (1940) have all used intra-vertebral procedures . We present here a plausible extra-vertebral repair model suitable for incomplete cord injuries at cervical, thoracic, and lumbar levels . The procedure consists of identifying the extent of viable grey-white matter in the injured area and to utilize it efficiently as a "neural tissue bridge." Next, labile state is induced by using botulinum toxin/colchicine (Krishnan, 1983, 1991; Krishnan et al., 2001 a,b) and Ca+ channel blockers in the motorsensory nerve terminals of polisegmentally innervated skeletal muscles that "bridge" the injured cord segments . This would retrogradely induce a redundant state of intra-spinal growth of nerve terminals and new synaptic connections within those viable neural tissues, as well as promote effective relinking of the injured cord ends and enhance motor-sensory recovery. Neurochirurgie, 2003 May, 49(2-3 Pt 2), 408 - 12 {Neurosurgical treatment of spasticity: indications in children}; Hodgkinson I et al.; Today, we have several efficient neurosurgical treatments of spasticity in children with cerebral palsy . A good indication is possible only if a consensus about the goal of the surgery is found between the surgeon, the child and his/her family, and the reeducation team . This goal is not always functional . Clinical examination is not limited to the analytical assessment of spasticity, but must take into account the general and orthopedic state of the child, and his/her functional evolution, cognitive abilities, habits and general environment . The struggle against spasticity is part of a therapeutical programme which extends over several years . It must be considered before muscular contractures . On lower limbs, in the cases of general spasticity, we propose posterior rhizotomy or intrathecal baclofen administration . Posterior rhizotomy is proposed when a more aggressive intervention is preferred for some muscular groups or when the child's general environment does not allow for the medical care imposed by intrathecal administration . In the case of localized spasticity, botulinum toxin injection permits delaying until the child reaches the age for selective neurotomy . On upper limbs, in children with quadriplegia the indication is essentially physical and occupational therapy . We cannot count on the positive side effects of rhizotomy or intrathecal administration of baclofen on the upper limbs . In children with hemiplegia, with localized or global spasticity of the upper limb, botulinum toxin is proposed as the first form of treatment . Neurotomy or rhizotomy can follow toxin, according to the efficacy of the toxin. Neurochirurgie, 2003 May, 49(2-3 Pt 2), 369 - 76 {The medical treatment of overactive bladder}; Beneton C et al.; Overactive bladder, very frequent in neurological disorders, leads to very distressing symptoms such as urgency, frequency and incontinence which may dramatically impair the patient's quality of life . The medical approach is essentially pharmacological but the management of the nociceptive factors must not be neglected . In the mild urinary dysfunctions, bladder training can be advised . The pharmacological treatment aims at reducing the parasympathetic activity or at deafferenting the bladder . The antimuscarinic agents are an essential part of the treatment . Oxybutynin is the most widely used medication but recent agents like tolterodin have a better tolerability . Other drugs can also be used such as desmopressin, flavoxate . New molecules are under experiment (darifenacin) . In case of troublesome side-effects or resistance to oral medications, local treatments are considered . Intravesical oxybutynin has been tried but has a short-lived efficacy . Intravesical instillation of capsaicine or resiniferatoxin blocks C-fibres afferents and leads to clinical and urodynamic improvement . Recently, injections of botulinum-A toxin in the detrusor have been advocated aiming at blocking the transmission of parasympathetic impulse . The first studies report encouraging results . All these local treatments resulting in bladder paresis are recommended for patients performing self-catheterization . Should these treatments fail, other therapeutic approaches are considered such as intrathecal treatment, neuromodulation, before deciding on neurosurgical or urosurgical procedures. Neurochirurgie, 2003 May, 49(2-3 Pt 2), 265 - 70 {Spasticity and botulinum toxin in 2003 . An update}; Feve A; After the spastic foot in cerebral palsy, there are now wider indications for botulinum toxin injections in spasticity . Post stroke upper limb spasticity has been usefully treated by botulinum toxin in several studies, including double blind placebo-controlled studies . Two serotypes and one serotype B are marketed, with various properties . Botulinum toxin has been studied in multiple etiologies of spasticity . In multiple sclerosis, few studies revealed an efficacy in angulations and comfort . In spinal cord injuries, gait and sphincter disorders can be improved . In post stroke spasticity, lower limb angulations are improved, but gait remained difficult to evaluate . In upper limb spasticity, angulation, function and quality of life were improved in double blind, placebo controlled studies . Comparisons of costs and efficacy are made between botulinum toxin and the other antispastic methods. Curr Treat Options Gastroenterol, 2003 Jun, 6(3), 247 - 256 Hirschsprung's Disease; Belknap WM; Hirschsprung's disease (HSCR) is the most common congenital malformation of the enteric nervous system and requires early diagnosis and surgical repair for the best comprehensive outcome . The early diagnosis of this disorder permits the use of primary endorectal pull-through (PERPT), which is now the definitive surgical therapy for HSCR . PERPT has become the preferred method of treatment for HSCR, and large numbers of successfully treated patients have been described in the recent medical literature . The rate of postoperative complications is generally similar to that following a two-stage surgical repair, but PERPT patients may be at a slightly higher risk for Hirschsprung's-associated enterocolitis . Despite recent surgical advances in the treatment of HSCR, a two-stage surgical repair involving a temporary diverting colostomy may still be necessary in up to one third of patients . Candidates for a staged repair include those HSCR patients with long-segment or total colonic disease or when there has been a delay in diagnosis that results in a markedly dilated proximal colon or patient clinical instability . Internal anal sphincter hypertonicity, occurring either as isolated primary anal achalasia or as a postoperative complication, can be successfully managed by either botulinum toxin injections or anal myectomy . The measurement of colonic motility in surgically repaired patients with a long-standing postoperative abnormality of bowel function can identify several distinct motility disorders that are amenable to separate and individualized therapies . The single most important element in the management of HSCR remains the clinical judgement of the surgeon of record, who utilizes all discernible clinical data to elect the manner of surgical repair in a given patient. J Am Coll Surg, 2003 May, 196(5), 698 - 703; discussion 703-5 Impact of minimally invasive surgery on the treatment of esophageal achalasia: a decade of change; Patti MG et al.; BACKGROUND: Twenty years ago an average of 1.5 Heller myotomies were performed per year in our hospital, mostly for patients whose dysphagia did not improve following balloon dilatation or whose esophagus had been perforated during a balloon dilatation . Ten years ago we started using minimally invasive surgery to treat this disease . STUDY DESIGN: This study measures the impact of minimally invasive surgery with regard to the following: the number of patients referred for treatment; the number of patients who came to surgery without previous treatment; and the results of surgical treatment . Between 1991 and 2001, 149 patients had minimally invasive surgery for achalasia: 25 patients (17%) had thoracoscopic Heller myotomy and 124 (84%) had laparoscopic Heller myotomy and Dor fundoplication . Of the 149 patients, 79 patients (53%) had previous treatment (56 patients {71%}, balloon dilatation; 7 patients {9%}, botulinum toxin injection; 16 patients {20%}, both) and 70 patients (43%) had none of these treatments . Mean postoperative followup was 59 +/- 36 months . Patients were divided into two groups: group A, operated on between 1991 and 1995; and group B, operated on between 1996 and 2001 . RESULTS: In the past decade, the number of patients referred for surgery has increased substantially--group A, 48; group B, 101; an increasing proportion of patients were referred for surgery without previous treatment--group A, 38%; group B, 51%; and the outcomes of the operation progressively improved--group A, 87%; group B, 95% . CONCLUSIONS: These data show that the high success rate of laparoscopic Heller myotomy for achalasia has brought a shift in practice; surgery has become the preferred treatment of most gastroenterologists and other referring physicians . This has followed documentation that laparoscopic treatment outperforms balloon dilatation and botulinum toxin injection. J South Orthop Assoc, 2002 Summer, 11(2), 116 - 8 Transient erectile dysfunction associated with intramuscular injection of botulinum toxin type A; Papadonikolakis AS et al.; Autonomic nervous system dysfunction occurs rarely after botulinum toxin type A (BTX-A) intramuscular injections . We report a case of a 23-year-old man with spastic diplegia who had transient erectile dysfunction after intramuscular injection of BTX-A (total dosage, 300 IU, body weight 95 kg) in both hamstring muscles . Some investigators believe that the local spread of the toxin is responsible for autonomic dysfunction, while others believe that the transportation of the toxin to the spinal cord via retrograde flow or via the blood flow after entering the circulation are possible mechanisms of neurologic side effects . On the basis of our case, a retrograde axoplasmic flow to the spinal cord could probably occur because the spinal cord level of hamstring muscles is close to spinal cord levels responsible for erection control. J South Orthop Assoc, 2002 Summer, 11(2), 71 - 9 Cost impact of botulinum toxin use in Medicaid-enrolled children with cerebral palsy; Balkrishnan R et al.; The use of botulinum toxin type A (BTX) in the management of spasticity in childhood cerebral palsy (CP) is increasing . This study examined annual health care service utilization and costs associated with BTX therapy for spastic CP in Medicaid-enrolled children receiving complete health care coverage (1997 to 1999) . We used pair matching as well as recent statistical technique improvements (bootstrap method) to work with limited samples . The introduction of BTX was associated with an increase of approximately $62 per month in prescription costs for the patient . However, these costs were made up by reductions in hospitalization . When each year was examined individually, reimbursements for BTX users were not different from those for pair-matched non-BTX users . These data suggest that BTX therapy does not significantly add to the costs of treating Medicaid-enrolled children with CP. Jpn J Ophthalmol, 2003 Mar-Apr, 47(2), 145 - 50 Passive length-tensile properties of extraocular muscles under botulinum toxin type C; Furuse T et al.; PURPOSE: Passive length-tension of the extraocular muscle was measured after injection of botulinum neurotoxin type C (BoNT-C) to evaluate its chemo-denervation effect . METHODS: BoNT-C was injected unilaterally at 5.0 or 2.5 units in the superior rectus muscle of the albino rabbit . The muscle was separated several times at its original insertion between 3 days to 8 weeks after injection, and the passive length-tension produced by stretching the muscle from its physiologic length was measured . The length-tension curve was analyzed, and the passive load was determined from early components . The compliance was determined by approximating the entire ascending curve by an exponential function . RESULTS: In the 5.0-unit group, the passive load increased significantly 2 weeks after injection but decreased to the level of the control group after 4 weeks and remained at that level until after 8 weeks after injection . In the 2.5-unit group, also, there were changes similar to those in the 5.0-unit group, but the changes were not significant compared to the control group . No significant change was observed in the compliance in either group . CONCLUSIONS: Persistent chemo-denervation effect was not observed in passive length-tension at the doses of BoNT-C used in this study . The increase in the passive load soon after injection was suggested to have been caused by the same mechanism as BoNT-A. Drug Saf, 2003, 26(7), 461 - 81 Benefits and risks of pharmacological treatments for essential tremor; Lyons KE et al.; Essential tremor can cause significant functional disability in some patients . The arms are the most common body part affected and cause the most functional disability . The treatment of essential tremor includes medications, surgical options and other forms of therapy . Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor . Treatment for essential tremor is recommended if the tremor causes functional disability . If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability . The currently available medications can improve tremor in approximately 50% of the patients . If the tremor is disabling, treatment should be initiated with either primidone or propranolol . If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination . If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used . If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit . Other medications that may be helpful include gabapentin or topiramate . If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor . Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used . There are other medications that have been tried in essential tremor and have questionable efficacy . These drugs include carbonic anhydrase inhibitors (e.g . methazolamide), phenobarbital, calcium channel antagonists (e.g . nimodipine), isoniazid, clonidine, clozapine and mirtazapine . If the patient still has disabling tremor after medication trials, surgical options are usually considered . Surgical options include thalamotomy and deep brain stimulation of the thalamus . These surgical options provide adequate tremor control in approximately 90% of the patients . Surgical morbidity and mortality for these procedures is low . Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation . In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures . The use of medication and/or surgery can provide adequate tremor control in the majority of the patients. Ann Otol Rhinol Laryngol, 2003 Apr, 112(4), 334 - 41 Histology of nerves and muscles in adductor spasmodic dysphonia; Chhetri DK et al.; To elucidate the etiology and pathophysiology of spasmodic dysphonia, we examined the adductor branch of the recurrent laryngeal nerve and the lateral cricoarytenoid muscle from 9 consecutive patients with this disorder who were previously treated with botulinum toxin . Histologic examination revealed average muscle fiber diameters ranging from 21 to 57 microm . Botulinum toxin treatment-related muscle atrophy was observed up to 5 months after injection . Endomysial fibrosis was present in all samples . Histochemical analysis in 8 patients revealed type 2 fiber predominance in 7 patients and fiber type grouping in 2 . Type-specific muscle fiber size changes were not present . Nerve samples were examined in plastic sections . In 8 patients the nerves contained homogeneous, large-diameter myelinated nerve fibers and sparse small fibers . One patient had a relatively increased proportion of small myelinated nerve fibers . Overall, the nerve fiber diameter was slightly larger in patients than in controls . These findings may implicate the central nervous system in the pathophysiology of adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol, 2003 Apr, 112(4), 303 - 6 Posterior cricoarytenoid myoplasty with medialization thyroplasty in the management of refractory abductor spasmodic dysphonia; Shaw GY et al.; Of the approximately 100,000 Americans with primary (idiopathic) laryngeal dystonia, 10% to 15% are thought to havethe abductor form . Botulinum A toxin injected into the posterior cricoarytenoid muscle and/or cricothyroid muscle has been employed as the "gold standard" for therapeutic management; however, successful results are significantly less frequent than with injections for the adductor form . This report describes a new phonosurgical procedure, posterior cricoarytenoid myoplasty with medialization thyroplasty, designed for these refractory patients . Posterior cricoarytenoid myoplasty with medialization thyroplasty has been performed on 3 patients with abductor laryngeal dystonia . All patients had failed at least 5 previous botulinum A injections to the posterior cricoarytenoid and cricothyroid muscles . All patients underwent preoperative and 3 postoperative (2 weeks, 3 months, and 1 year) phonatory analyses . Analysis consisted of recording an aloud reading of a standard passage while a blinded trained speech pathologist counted prolonged voiceless consonants . The patients also completed a satisfaction survey at 1 year . The results demonstrated significant, long-lasting, uniform reduction in breathy breaks in all subjects . The participants all judged their symptoms as greatly improved . Bilateral procedures may be necessary, but should be staged to prevent possible airway compromise . When applied appropriately, posterior cricoarytenoid myoplasty with medialization thyroplasty is a viable tool in the management of refractory abductor laryngeal dystonia. FEBS Lett, 2003 May 8, 542(1-3), 132 - 6 VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes; Caccin P et al.; Tetanus and botulinum neurotoxins (TeNT and BoNTs) block neuroexocytosis via specific cleavage and inactivation of SNARE proteins . Such activity is exerted by the N-terminal 50 kDa light chain (L) domain, which is a zinc-dependent endopeptidase . TeNT, BoNT/B, /D, /F and /G cleave vesicle associated membrane protein (VAMP), a protein of the neurotransmitter-containing small synaptic vesicles, at different single peptide bonds . Since the proteolytic activity of these metalloproteases is higher on native VAMP inserted in synaptic vesicles than on recombinant VAMP, we have investigated the influence of liposomes of different lipid composition on this activity . We found that the rate of VAMP cleavage with all neurotoxins tested here is strongly enhanced by negatively charged lipid mixtures . This effect is at least partially due to the binding of the metalloprotease to the lipid membranes, with electrostatic interactions playing an important role. Mol Cell Neurosci, 2003 Apr, 22(4), 454 - 66 Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation; Meunier FA et al.; Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary . Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed . BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE . The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery. Toxicon, 2003 May, 41(6), 691 - 701 Expression, purification, and efficacy of the type A botulinum neurotoxin catalytic domain fused to two translocation domain variants; Jensen MJ et al.; Clostridial neurotoxins are potent inhibitors of synaptic function, with the zinc-dependent proteolytic light chain (LC) portion of the toxin cleaving one of three neural SNARE proteins . In nature, the LC is expressed as a part of a much larger toxin and hemagglutinin complex, protecting it from environmental degradation and preserving its catalytic activity . We developed forms of the LC of type A botulinum neurotoxin (BoNT-A) with parts of the larger toxin gene, for use as reagents in high-throughput assays to screen for potential LC antagonists, to further elucidate the toxin's mechanism of action, and to study immunological responses to the toxin . Three BoNT-A constructs were engineered and expressed: the LC, LC with translocation region (LC+H(n)), and the LC with the belt portion of the translocation region (LC+Belt) . Purification was optimized to a two-step process, with relatively high yields of all three constructs obtained . Activity assays showed all three constructs to be active, with the LC being the most active . Immunogenic protection against native BoNT-A toxin challenge was observed for all three constructs, with the best protection observed with the LC+H(n) and LC+Belt proteins. Curr Pain Headache Rep, 2003 Jun, 7(3), 229 - 34 Is there a role for botulinum toxin in the treatment of migraine? Evers S. In this review, the studies and case reports that are available from reference systems and published congress contributions on the treatment of migraine with botulinum toxin are evaluated . The studies and reports were analyzed with respect to the study design, the efficacy parameters, and the significance of results . One double-blind, placebo-controlled, randomized study with negative (for a 75 U dose of botulinum toxin) and positive (for a 25 U dose of botulinum toxin) evidence of efficacy, one that was a partly positive controlled study (pain intensity, but not attack-frequency improved), and four positive open studies were available . For the acute treatment of migraine with botulinum toxin, only positive case reports were published . As a result of this analysis, there is no sufficient scientific evidence for a treatment recommendation of migraine with botulinum toxin . Further studies are needed for a definite evaluation of subgroups with probable benefit from such a treatment and for the comparison of botulinum toxin with other migraine prophylactic drugs. Kulak Burun Bogaz Ihtis Derg, 2003 Feb, 10(2), 78 - 81 {Successful use of botulinum toxin injection in the treatment of salivary fistula following parotidectomy}; Kizilay A et al.; A twenty-year-old woman underwent right superficial parotidectomy for pleomorphic adenoma . On the 10th postoperative day she presented with a salivary fistula, for which repeated aspirations with pressure dressings were applied for a month . Despite decreases in the salivary fluid volume, reaccumulation persisted . Following aspiration of the salivary fluid, 40 units of botulinum toxin was injected into the pouch . On the second day of injection, the discharge ceased and the pouch disappeared . No side effects were observed and the patient remained symptom-free during four-month follow-up. Arq Neuropsiquiatr, 2003 Mar, 61(1), 115 - 8 Epub 2003 Apr 16. {Bilateral hemifacial spasm: case report}; Machado FC et al.; Bilateral hemifacial spasm (BHS) is a rare focal movement disorder often associated with vascular compression of both facial nerves . The contractions are usually asymmetric and asynchronous . Typically, one side is affected first and there is a long but variable interval for the symptoms on the other side to occur . BHS must be differentiated from other conditions including blefarospasm, facial myokymia, facial tics, oromandibular dystonia, and hemimasticatory spasm . The most successful and non-invasive symtomatic treatment is botulinum toxin injections but microvascular decompression surgery is another therapeutic option . We report the case of a 70 years old man with bilateral hemifacial spasms and present a brief review of the literature. Arq Neuropsiquiatr, 2003 Mar, 61(1), 112 - 4 Epub 2003 Apr 16. A case of primary spinal myoclonus: clinical presentation and possible mechanisms involved; Campos CR et al.; Spinal myoclonus is a rare movement disorder characterized by myoclonic involvement of a group of muscles supplied by a few contiguous segments of the spinal cord . Structural lesions are usually the cause, but in primary spinal myoclonus the etiology remains unknown . We present the case of a 26-year-old woman with cervical spinal myoclonus in which both clinical and electromyographic findings pointed to the segment C1-C3 as the origin of the myoclonus . Laboratorial examinations were normal and no structural lesion was found in magnetic resonance imaging (MRI) . Botulinum toxin type A was injected in infrahyoid muscles and cervical paraspinal musculature . The patient remained free of symptoms for almost five months . The pathophysiology of spinal myoclonus remains speculative, but there is evidence that various possible mechanisms can be involved: loss of inhibitory function of local dorsal horn interneurons, abnormal hyperactivity of local anterior horn neurons, aberrant local axons re-excitations and loss of inhibition from suprasegmentar descending pathways. Arch Phys Med Rehabil, 2003 Mar, 84(3 Suppl 1), S69 - 73; quiz S74-5 Botulinum toxin type A therapy in chronic pain disorders; Lang AM; This self-directed learning module highlights that the underlying problem in many types of muscle pain disorders is a distortion of critical structures that causes functional deficits and pain . An objective of treatment is to reverse this distortion, enabling repair of damaged tissues and strengthening of weakened muscles . Administering botulinum toxin type A (BTX-A; Botox) to reduce muscle tone and overactivity warrants consideration as part of an overall treatment approach that includes physical therapy to help restore normal muscle length and biomechanical balance to improve the prospect of ensuring long-term relief from associated pain . This article specifically focuses on pertinent review articles, results of controlled and open-trial data, and case reports to assess the role of BTX-A treatment in chronic pain disorders . OVERALL LEARNING OBJECTIVE: To review the clinical trial data of the safety and efficacy of BTX-A for the treatment of chronic pain syndromes associated with muscle disorders. Eur J Gastroenterol Hepatol, 2003 May, 15(5), 561 - 4 Pneumothorax complicating botulinum toxin injection in the body of a dilated oesophagus in achalasia; Weusten BL et al.; Botulinum toxin is used for an increasing number of indications in the field of gastroenterology . We report a case in which injection of botulinum toxin in the dilated tubular oesophagus in a patient with achalasia was complicated by a pneumothorax necessitating suction drainage. Radiol Med (Torino), 2003 Jan-Feb, 105(1-2), 69 - 75 Pyriformis muscle syndrome: CT/MR findings in the percutaneous therapy with botulinic toxin; Fanucci E et al.; PURPOSE: The aim of our study was to evaluate the diagnostic capabilities of computed tomography (CT) and magnetic resonance (MR) imaging in pyriformis syndrome (PS) and the long-term outcomes of CT-guided percutaneous treatment with botulinum . PS is a cause of sciatica and disability . The pain is usually increased by muscular contraction, palpation or prolonged sitting . MATERIAL AND METHODS: Thirty-four patients suffering from PS, suspected on the basis of clinical and electrophysiological criteria and after imaging examinations had excluded other causes of sciatic pain, had positive lidocaine tests and were treated by intramuscular injection of botulinum toxin type A (BTX-A) under CT guidance . MR sequences was performed in nine patients before treatment and after three months to evaluate the extent of muscle denervation . RESULTS: In 30 cases relief of symptoms was obtained after 5-7 days . In four patients insufficient pain relief warranted a second percutaneous treatment which proved clinically successful . No complications or side effects were recorded after BTX-A injection . The MR examination demonstrated a change in signal intensity of the muscle in seven patients due to denervation, whereas in the remaining two cases only atrophy was detected . Larger series are necessary to confirm these preliminary results . CONCLUSIONS: CT-guided BTX-A injection in the pyriformis muscle is an emergent and feasible technique that appears to yield excellent local therapeutic effects without the risk of imprecise injection. CNS Drugs, 2003, 17(6), 373 - 81 Preventative treatment for migraine and tension-type headaches : do drugs having effects on muscle spasm and tone have a role? Freitag FG. Baclofen, tizanidine and botulinum toxin A, agents used to treat disorders of muscle tone, have been studied as potential preventative treatments for migraine, tension-type headache and other related disorders.The most extensive work has been completed with botulinum toxin A . However, there is still a paucity of well controlled, clinical trials with this agent, and overall there have been conflicting and oftentimes equivocal results: studies of its use in migraine headache have suggested efficacy, whereas those of tension-type headache have not shown significant evidence of efficacy . There were few significant adverse events associated with the use of botulinum toxin A in these trials . The mechanism by which botulinum toxin A may work to prevent headache is not clear . Although changes in muscle tone may play a role in the effect of the drug, central mechanisms such as effects on neuropeptides involved in the pathogenesis of migraine may also be relevant . Further clinical trial work is in progress to help determine optimal administration schedules and choice of injection locations with botulinum toxin A for specific headache disorders.There has been limited study of the use of baclofen, an agent that acts centrally via GABA(A) receptors, in migraine and cluster headache, with only two open trials conducted to date . Both of these studies support the use of baclofen in the preventive treatment of headache.Tizanidine, which may have both a peripheral and a central mechanism in the locus ceruleus in migraine headache, has been studied in several clinical trials . Although the primary mechanism of action of this agent is, like clonidine, as an alpha-adrenoceptor agonist, it has little antihypertensive effect . Open trials of tizanidine have shown it to be useful in chronic headache . One well controlled trial, conducted as a follow-up to an open-label trial in the preventive treatment of chronic daily headache, reported tizanidine as having a statistically significant benefit over placebo . Also of interest is its use in conjunction with a long-acting NSAID to aid in the treatment of rebound headache accompanying the discontinuation of overused acute migraine therapies.In conclusion, though limited, the studies suggest the efficacy of botulinum toxin A, baclofen and tizanidine in primary headache disorders. J Hum Ergol (Tokyo), 2000 Dec, 29(1-2), 35 - 52 Innervation zones of the upper and lower limb muscles estimated by using multichannel surface EMG; Saitou K et al.; The distribution of innervation zones was investigated in 3 subjects for 17 muscles and 8 muscle groups in the upper and lower limb, by detecting bi-directional propagation of motor unit action potentials (MUAPs) with the multichannel surface electrode array . Clarification of the distribution of innervation zones depended on the ease in detecting the propagation of MUAPs and the actual scattering of innervation zones, which were closely related with muscle morphology with respect to the arrangements of muscle fibers . In muscles having fibers running parallel to each other, such as the biceps brachii, intrinsic hand muscles, vastus lateralis and medialis, tensor fasciae latae, peronei, soleus, tibialis anterior, and hypothenar muscles in the foot, it was relatively easy to detect the propagating MUAPs, and the innervation zones were distributed in a relatively narrow band around muscle belly . On the other hand, in muscles with a complicated structure including pinnation of muscle fibers, in-series muscle fibers and aponeurotic tissues, such as the deltoid, flexors and extensors in the forearm, rectus femoris, sartorius, hamstrings and gastrocnemius, it was more difficult to detect the propagating MUAPs and to identify the innervation zones, which were widely scattered or distributed in complex configurations . The distribution of the innervation zones clarified in the present study can be used to find the optimal location of electrodes in surface EMG recordings and of stimulus electrodes in the functional and therapeutic electrical stimulations . It may also be useful in motor point biopsy for diagnosis of neuromuscular diseases as well as in the botulinum toxin injection for the treatment of spasticity. Schmerz, 2003 Apr, 17(2), 149 - 65 {Botulinum toxin in specific pain therapy}; Gobel H et al.; Botulinum toxin has been used for therapeutic purposes in medicine for more than 20 years . Its effective use now covers more than 50 conditions in a wide variety of areas . Its medicinal use was initially based on its blockade of neuromuscular and neurosecretory transfers . Its use for conditions in the field of specific pain therapy is currently authorized in Germany for spastic torticollis, blepharospasm, hemifacial spasm, spastic equine gait in cases of idiopathic cerebral paresis, and spasticity of the arm following stroke.New publications suggest that it can usefully be employed for numerous other painful conditions.The modes of action known today are not confined to the blockade of cholinergic innervation.Indeed, there is also evidence that therapeutic effects are mediated through a normalization of muscle spindle activity, retrograde intake into the CNS with modulation of the central neuropeptide function, inhibition of sterile neurogenic inflammation, and normalization of endplate dysfunction . In view of the methodological peculiarities of studies in the field of pain therapy, such as injection techniques, injection sites, blind study techniques, dosage etc., the scientific evidence for its use in a wide variety of pain syndromes is still patchy in many areas.For this reason the use of botulinum toxin for these syndromes is only justified after full use has been made of standard therapeutic methods and evaluation in specialized centers.The possibility of considering botulinum toxin in specific pain therapy contexts is a new option for patients and doctors.However, its use calls for detailed knowledge of functional neuroanatomy and extensive practical experience and expertise. Schmerz, 2003 Apr, 17(2), 117 - 24 {Treatment of phantom pain with botulinum-toxin A . A pilot study}; Kern U et al.; BACKGROUND: Therapy of phantom pain following amputation is still difficult, since pathophysiological mechanisms are not clarified . Botulinum-toxin A never has been used for this issue . We report four successfully treated cases with chronic phantom pain longer than 3 years . METHODS: We injected 100 IU botulinum-toxin A (4x25 IU in 0,5 ml preservative-free saline 0.9%) in four muscle-triggerpoints of the amputation stump of each patient . All triggerpoints were painful to compression before injection, all patients reported referred sensations in the phantom-foot from at least one of them . Controls were performed by questioning and pain-diaries after 1,2 and 5 weeks . RESULTS: In all cases phantom pain was reduced about 60-80%.The three patients, who had pain attacks, reported a dramatically reduction of the number of attacks (about 90%) . In two of them duration of attacks shortened from 120 to 5-10 min and a reduction of pain intensity from VAS 9 to VAS 1 and VAS 9 to VAS 2 was reported . Disorder of sleep disappeared in both affected patients within 2-3 weeks . Three patients,who could move the phantom foot (mental), had a subjective weakness a few days after botulinum-toxin A injection; in one case although injection was performed in the muscles of the femur! CONCLUSIONS: This is the first report of the use of botulinum-toxin A in the treatment of phantom pain . The contribution of the muscles in the cause of phantom pain is unclear and may be local, as a trigger of spinal reflexes or by modulation of "cortical reorganisation" after amputation . Botulinum-toxin A could work analgesic by the relaxation of the stump muscles or by modulation of neuronal transmitters, for example substance P, with an indirect influence of the CNS. Can J Neurol Sci, 2003 Mar, 30 Suppl 1, S34 - 44 New perspectives on dystonia; Langlois M et al.; Dystonia is a syndrome of sustained muscular contractions with numerous underlying etiologies . This review examines the varied phenomenology of dystonias, its evolving classification including recent genetic data as well as its clinical investigation and treatment . Although age of onset, anatomical distribution and family history are key elements of the investigation of dystonia, classification increasingly relies on etiologic and genetic criteria . Physiological abnormalities in striato-cortical circuits are common in dystonia but the pathophysiology is still unclear . In recent years, a great deal has been learned on the more common primary dystonias such as primary torsion dystonia and on dystonia-plus syndromes such as dopamine responsive dystonia . Treatment of dystonia has also evolved and there are now a number of therapeutic agents with clear beneficial effects including anticholinergics, benzodiazepines, and botulinum toxin and there is growing interest in neurofunctional surgery including deep brain stimulation. J AAPOS, 2003 Feb, 7(1), 1 - 6 Extraocular muscle force generation after ricin-mAb35 injection: implications for strabismus treatment; Christiansen SP et al.; PURPOSE: Ricin-mAb35 is an immunotoxin targeted against skeletal muscle . Previously, we have shown that injection of ricin-mAb35 into rabbit extraocular muscle results in long-term muscle loss, and we have proposed this as a potential treatment for strabismus . In this study, we assessed the effects of ricin-mAb35 injection on extraocular muscle force generation . METHODS: Ricin-mAb35, 0.2 microg/kg in a volume of 0.1 mL, was injected into 1 superior rectus muscle in 16 adult rabbits . The contralateral superior rectus was injected with an equal volume of normal saline . Muscle force generation was assessed in vivo at 1, 6, and 12 weeks . Isometric length-tension curves were developed . Single-twitch tension, peak tetanic force generation, and fatigue rate were determined at optimal preload . Data from treated and control muscles were compared with the paired t test . RESULTS: Force generation declined in ricin-mAb35 treated muscles at each postinjection interval . At 12 weeks, mean tetanic tension (200 Hz) in treated muscles was 13.8 mN/cm(3) compared with 27.7 mN/cm(3) in saline-injected controls (P =.02), a reduction of 50% . Single-twitch tension at 12 weeks was reduced 33% compared to controls (P =.04) . Similar effects were noted at 1 and 6 weeks . Fatigue rate was not greater in treated muscles at any postinjection intervals . CONCLUSIONS: Injection of ricin-mAb35 results in sustained weakness in extraocular muscle, although additional studies will be required to determine the duration of physiologic effect . These results confirm our histological analysis and suggest that ricin-mAb35 may be a more long-term alternative to botulinum toxin A for the treatment of strabismus. Neurology, 2003 Apr 8, 60(7), 1186 - 8 Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cervical dystonia; Jankovic J et al.; The authors compared 130 patients treated for cervical dystonia with original botulinum toxin (BTX) type A (Botox; Allergan, Inc., Irvine, CA), 42 of whom were exposed only to the original BTX type A used before 1998 (25 ng protein/100 units), and 119 treated only with the current BTX type A (5 ng of protein/100 units) . Blocking antibodies were detected in 4 of 42 (9.5%) patients treated only with original BTX type A but in none of the 119 patients treated exclusively with current BTX type A (p < 0.004) . The current preparation decreased the risk of antibody formation by a factor of six . The authors conclude that the low risk of antibody formation after current BTX type A treatment is related to lower protein load. J Ind Microbiol Biotechnol, 2003 Apr, 30(4), 210 - 5 Epub 2003 Apr 02. Pichia pastoris fermentation with mixed-feeds of glycerol and methanol: growth kinetics and production improvement; Zhang W et al.; Fed-batch fermentation of a methanol utilization plus (Mut(+)) Pichia pastoris strain typically has a growth phase followed by a production phase (induction phase) . In the growth phase glycerol is usually used as carbon for cell growth while in the production phase methanol serves as both inducer and carbon source for recombinant protein expression . Some researchers employed a mixed glycerol-methanol feeding strategy during the induction phase to improve production, but growth kinetics on glycerol and methanol and the interaction between them were not reported . The objective of this paper is to optimize the mixed feeding strategy based on growth kinetic studies using a Mut(+) Pichia strain, which expresses the heavy-chain fragment C of botulinum neurotoxin serotype C {BoNT/C(Hc)} intracellularly, as a model system . Growth models on glycerol and methanol that describe the relationship between specific growth rate ( micro ) and specific glycerol/methanol consumption rate ( nu(gly), nu(MeOH)) were established . A mixed feeding strategy with desired micro (gly)/ micro (MeOH) =1, 2, 3, 4 (desired micro (MeOH) set at 0.015 h(-1)) was employed to study growth interactions and their effect on production . The results show that the optimal desired micro (gly)/ micro (MeOH) is around 2 for obtaining the highest BoNT/C(Hc) protein content in cells: about 3 mg/g wet cells. J Urol, 2003 May, 169(5), 1896 - 900 Effect of botulinum toxin A on the autonomic nervous system of the rat lower urinary tract; Smith CP et al.; PURPOSE: The magnitude and duration of the effects of botulinum toxin A on acetylcholine (ACh) and norepinephrine release from the bladder and urethra of rats were measured using a radiochemical method . MATERIALS AND METHODS: Saline (sham treatment) or botulinum toxin A was injected into the bladder (50 microl.) or urethra (30 microl.) in separate groups of animals . The release of 3H-norepinephrine or 14C-choline was measured at 2 time points after injection (5 or 30 days) . RESULTS: The fractional release of ACh in botulinum toxin A treated animals was significantly inhibited at higher frequencies of electrical field stimulation (20 Hz.) but not at lower frequencies (2 Hz.) 5 days after injection . However, ACh release recovered to sham injected values 30 days after toxin injection . No significant differences in the fractional release of norepinephrine from sham injected or botulinum toxin A bladders were observed . In contrast, norepinephrine release from the urethra was inhibited by botulinum toxin A for at least 30 days after injection . Similar to its effect on transmitter release in the bladder, botulinum toxin A inhibited norepinephrine release in the urethra at high (20 Hz.) but not at low (4 Hz.) electrical stimulation frequencies . CONCLUSIONS: These data indicate that the clinical effects of botulinum toxin A on the lower urinary tract may vary depending on the site of injection and level of nerve activity. Cerebrovasc Dis, 2003, 15(4), 289 - 300 A double-blind randomised placebo-controlled evaluation of three doses of botulinum toxin type A (Dysport) in the treatment of spastic equinovarus deformity after stroke; Pittock SJ et al.; BACKGROUND/OBJECTIVES: Calf muscle hypertonicity following stroke may impair walking rehabilitation . The aim of this study was to assess botulinum toxin (Dysport) in post-stroke calf spasticity . METHODS: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients . They were assessed at 4-week intervals over 12 weeks . RESULTS: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo) . Following dysport treatment, there were small but significant (p = 0.0002-0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo . Investigators' and patients' assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant . Sixty-eight patients reported 130 adverse events, with similar numbers in each group . The few severe events recorded were not considered to be treatment-related . CONCLUSION: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids . The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects . Dysport 500 units resulted in some improvements . Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg . Possible reasons why functional improvements in gait parameters were not observed are also discussed . Acta Med Okayama, 2002 Dec, 56(6), 271 - 7 Botulinum toxin treatment of urethral and bladder dysfunction; Yokoyama T et al.; Tremendous excitement has been generated by the use of botulinum toxin for the treatment of various types of urethral and bladder dysfunction over the past several years . Botulinum toxin is the most lethal naturally occurring toxin known to mankind . Why, then, would an urologist want to use this agent to poison the bladder or urethral sphincter? In this review article we will examine the mechanisms underlying the effects of botulinum toxin treatment . We will discuss the current use of this agent within the urologic community and will provide perspectives on future targets of botulinum toxin. J Oral Maxillofac Surg, 2003 Apr, 61(4), 454 - 7 Up-to-date report of botulinum toxin therapy in patients with drooling caused by different etiologies; Ellies M et al.; PURPOSE: In this study, we evaluated the clinical data for patients with drooling caused by various diseases, treated by injection of botulinum toxin A . We also present a controlled follow-up study documenting efficiency, possible adverse events, and duration of the effect of treatment . PATIENTS AND METHODS: Thirteen patients with drooling caused by head and neck carcinoma, neurodegenerative diseases, or stroke received injections of 50 to 65 U botulinum toxin A (Botox; Allergan, Irvine, CA) in both submandibular and both parotid glands under sonographic control . We measured whole salivary flow rate and the salivary analytes of total protein, alpha-amylase, acid phosphatase, kallikrein, and immunoglobulin A at various times before and after injection . The patients were examined for severity of symptoms, including sonographic investigation of cephalic salivary glands . RESULTS: All 13 patients reported a distinct improvement of their symptoms within 2 weeks after toxin injection . Three patients noted a return of high salivation rates after 12 weeks . Duration of toxin effect varied widely between individuals . In general, salivary flow rates dropped sharply within 1 week after injection but had risen again after 12 weeks . Conversely, analyte concentrations increased in the first stages of treatment and later decreased, returning to pretherapy levels . Sonography did not reveal any major changes of salivary gland parenchyma, and side effects were absent . CONCLUSIONS: Local injection of botulinum toxin A into the salivary glands proved to be a dependable therapy for drooling caused by various etiologies, as shown in 13 patients . Adverse events were not seen . The effect of toxin application lasted for about 3 months . To further clarify this aspect, long-term studies are under way . J Formos Med Assoc, 2003 Jan, 102(1), 5 - 11 Botulinum toxin treatment of urethral and bladder dysfunction; Chuang YC et al.; Botulinum toxin (BTX) is the most lethal naturally occurring toxin known to mankind . Injection of BTX into the urethral sphincter or bladder is an effective treatment for lower urinary tract dysfunction . We reviewed the literature on the mechanisms of action and clinical efficacy of BTX treatment in urologic diseases, with a focus on lower urinary tract dysfunction . Injection of BTX is safe and effective in the treatment of detrusor-sphincter dyssynergia, non-neurogenic pelvic floor spasticity, and refractory overactive bladder . Urodynamic assessment after sphincter injection with BTX reveals a decrease of bladder voiding pressure, urethral pressure profile, and post-void residual urine . An increase of the functional bladder capacity and a decrease of the bladder voiding pressure can be seen after bladder injection with BTX . Clinical improvement was found in a moderate percentage of treated patients in most reported series and lasted for 3 to 14 months without significant adverse effects . In addition, BTX-A treatment inhibits afferent-nerve-mediated bladder contraction . This analgesic effect may expand the application of BTX in the localized genitourinary tract pain syndrome, such as interstitial cystitis and prostatodynia . In conclusion, application of BTX is a promising treatment for lower urinary tract dysfunction with profound basic and clinical implications. Curr Med Chem, 2003 Apr, 10(7), 603 - 23 Gastrointestinal smooth muscles and sphincters spasms: treatment with botulinum neurotoxin; Brisinda G et al.; More than fifty years following the discovery that botulinum neurotoxins inhibit neuromuscular transmission, these powerful poisons have become drugs with many indications . First used to treat strabismus, local injections of botulinum neurotoxin are now considered a safe and efficacious treatment for neurological and non-neurological conditions . One of the most recent achievements in the field is the observation that botulinum neurotoxin is a treatment for diseases of the gastrointestinal tract . Botulinum neurotoxin is not only potent in blocking skeletal neuromuscular transmission, but also block cholinergic nerve endings in the autonomic nervous system . The capability to inhibit contraction of smooth muscles of the gastrointestinal tract was first suggested based on in vitro observations and later demonstrated in vivo; it has also been shown that botulinum neurotoxin does not block non adrenergic non cholinergic responses mediated by nitric oxide . This has further promoted the interest to use botulinum neurotoxin as a treatment for overactive smooth muscles and sphincters, such as the lower esophageal sphincter to treat esophageal achalasia, or the internal anal sphincter to treat anal fissure . Information on the anatomical and functional organization of innervation of the gastrointestinal tract is a prerequisite to understand many features of botulinum neurotoxin action on the gut and the effects of injections placed into specific sphincters . This review presents current data on the use of botulinum neurotoxin to treat diseases of the gastrointestinal tract and summarizes recent knowledge on the pathogenesis of disorders of the gut due to a dysfunction of the enteric nervous system. Curr Med Chem, 2003 Apr, 10(7), 593 - 602 NF-kappaB activating scaffold proteins as signaling molecules and putative therapeutic targets; Chariot A et al.; More than fifty years following the discovery that botulinum neurotoxins inhibit neuromuscular transmission, these powerful poisons have become drugs with many indications . First used to treat strabismus, local injections of botulinum neurotoxin are now considered a safe and efficacious treatment for neurological and non-neurological conditions . One of the most recent achievements in the field is the observation that botulinum neurotoxin is a treatment for diseases of the gastrointestinal tract . Botulinum neurotoxin is not only potent in blocking skeletal neuromuscular transmission, but also block cholinergic nerve endings in the autonomic nervous system . The capability to inhibit contraction of smooth muscles of the gastrointestinal tract was first suggested based on in vitro observations and later demonstrated in vivo; it has also been shown that botulinum neurotoxin does not block non adrenergic non cholinergic responses mediated by nitric oxide . This has further promoted the interest to use botulinum neurotoxin as a treatment for overactive smooth muscles and sphincters, such as the lower esophageal sphincter to treat esophageal achalasia, or the internal anal sphincter to treat anal fissure . Information on the anatomical and functional organization of innervation of the gastrointestinal tract is a prerequisite to understand many features of botulinum neurotoxin action on the gut and the effects of injections placed into specific sphincters . This review presents current data on the use of botulinum neurotoxin to treat diseases of the gastrointestinal tract and summarizes recent knowledge on the pathogenesis of disorders of the gut due to a dysfunction of the enteric nervous system. J Laparoendosc Adv Surg Tech A, 2003 Feb, 13(1), 1 - 4 Laparoscopic Heller myotomy with bolstering partial posterior fundoplication for achalasia; Villegas L et al.; BACKGROUND: The ideal antireflux procedure following laparoscopic Heller myotomy for achalasia is controversial . We present a novel laparoscopic technique of partial posterior fundoplication to bolster the myotomy . METHODS: Between August 1998 and March 2002, eight patients (five females and three males; median age, 40 years) underwent a laparoscopic Heller myotomy with bolstering partial posterior fundoplication . Results of barium swallow and manometry studies were consistent with achalasia . Failed medical treatments included balloon dilation, botulinum injection, and calcium channel blockers . RESULTS: The preoperative weight loss was 33 lb (range, 10-50) with a mean duration of symptoms of 29 months (range, 12-72) . Seventy-one percent of the patients had reflux . Myotomy was confirmed with endoscopic guidance . Partial posterior fundoplication was performed with the edges of the myotomy on the right and left sides sutured to the stomach, which covered the myotomy . No conversion was required . In one patient, a perforation was recognized, repaired, and bolstered . The mean operative blood loss was 72 mL (range, 30-150) . The mean operative time was 4 hours . Patients resumed solids at 2.5 days (range, 2-5) . Postoperative complications included subcutaneous emphysema (n = 1), pneumothorax (n = 1), and umbilical port hernia (n = 1) . None of the patients had reflux symptoms at 3 to 18 months of follow-up . CONCLUSION: Laparoscopic Heller myotomy with partial posterior fundoplication is technically feasible and effectively prevents reflux symptoms . Bolstering the myotomy may help heal small esophageal perforations. J Neurochem, 2003 Apr, 85(2), 409 - 21 The sensitivity of catecholamine release to botulinum toxin C1 and E suggests selective targeting of vesicles set into the readily releasable pool; Stigliani S et al.; The impact of syntaxin and SNAP-25 cleavage on {3H}noradrenaline ({3H}NA) and {3H}dopamine ({3H}DA) exocytotic release evoked by different stimuli was studied in superfused rat synaptosomes . The external Ca2+-dependent K+-induced {3H}catecholamine overflows were almost totally abolished by botulinum toxin C1 (BoNT/C1), which hydrolyses syntaxin and SNAP-25, or by botulinum toxin E (BoNT/E), selective for SNAP-25 . BoNT/C1 cleaved 25% of total syntaxin and 40% of SNAP-25; BoNT/E cleaved 40% of SNAP-25 but left syntaxin intact . The GABA uptake-induced releases of {3H}NA and {3H}DA were differentially affected: both toxins blocked the former, dependent on external Ca2+, but not the latter, internal Ca2+-dependent . BoNT/C1 or BoNT/E only slightly reduced the ionomycin-evoked {3H}catecholamine release . More precisely, {3H}NA exocytosis induced by ionomycin was sensitive to toxins in the early phase of release but not later . The Ca2+-independent {3H}NA exocytosis evoked by hypertonic sucrose, thought to release from the readily releasable pool (RRP) of vesicles, was significantly reduced by BoNT/C1 . Pre-treating synaptosomes with phorbol-12-myristate-13-acetate, to increase the RRP, enhanced the sensitivity to BoNT/C1 of {3H}NA release elicited by sucrose or ionomycin . Accordingly, cleavage of syntaxin was augmented by the phorbol-ester . To conclude, our results suggest that clostridial toxins selectively target exocytosis involving vesicles set into the RRP. Laryngorhinootologie, 2003 Mar, 82(3), 202 - 13; quiz 214-8 {Botulinum toxin in ENT medicine}; Rohrbach S et al.; In otorhinolaryngology, botulinum toxin is a suitable therapeutic option in the muscular and the autonomic nervous system concerning dysfunctions . Respecting some special aspects, it is an effective treatment for disorders of different etiology with very few side-effects . The positive therapeutic effect is temporarily limited, so that the patients need further treatment . Beside the classical indications like the facial hyperkinesias (i.e . blepharospasms, hemifacial spasm) the treatment of complex dystonias (oromandibular dystonia, laryngeal dystonia, cervical dystonia), gustatory sweating, hypersalivation and crocodile tears is successful . Botulinum toxin is an alternative treatment of tension type headache and migraine . A new indication of botulinum toxin application may lay in the treatment of nasal hypersecretion through the effect on the nasal glands. Clin Oral Investig, 2003 Mar, 7(1), 52 - 5 Epub 2003 Jan 25. Treatment of recurrent temporomandibular joint dislocation with intramuscular botulinum toxin injection; Ziegler CM et al.; Recurrent dislocation of the mandibular condyle poses a difficult problem for affected patients . In the course of time, dislocations often become more frequent and more difficult to avoid . Even with good patient compliance, conservative treatment is often not sufficient . Operative procedures have also been described for the treatment of temporomandibular joint dislocation . However, these interventions are invasive, involving open arthrotomy with possible complications, and cannot safely guarantee a successful outcome . On the other hand, botulinum toxin injections into the lateral pterygoid muscles offer the option of a predictable and prolonged period without renewed dislocation . We present the results of this treatment carried out in 21 patients with recurrent temporomandibular joint dislocation . Four patients were treated following unsuccessful physical therapy and the use of occlusal splints . The remaining 17 patients were treated for a number of conditions resulting in dislocation, including some with senile dementia and mental impairment in whom compliance with conservative measures was poor or completely absent . Injections were given on a 3-month basis in order to have a sustained effect . Within the study period of 6 months to 3 years, only two of the 21 patients suffered further dislocation . There were no side effects recorded as a result of treatment. Mov Disord, 2003 Apr, 18(4), 395 - 402 Reversible reorganisation of the motor cortical representation of the hand in cervical dystonia; Thickbroom GW et al.; Previous work has suggested that there may be a widespread disturbance of motor control mechanisms in patients with cervical dystonia . In the present study, we used transcranial magnetic stimulation to investigate the topography of the corticomotor projection to the abductor pollicis brevis (APB) muscle in 10 subjects with idiopathic torticollis . Threshold-adjusted stimuli were delivered at multiple scalp sites during a low-level voluntary contraction of the APB, and maps were generated of motor evoked potential amplitude versus scalp site . The cortical maps for the APB on the side opposite to the direction of head rotation were displaced laterally or posteriorly in all subjects and reverted to a more normal position after botulinum toxin injection of the cervical muscles in 5 subjects . The findings point to a reversible reorganisation of the corticomotor representation of the hand on the same side as the sternocleidomastoid (SCM) muscle that is involved in producing the dystonia . These results provide further evidence for the involvement of cortical centres and for a more widespread abnormality of motor control mechanisms in focal dystonia . The findings also support the notion that head turning is chiefly mediated by the hemisphere ipsilateral to the direction of the head rotation by means of a corticomotor projection to the contralateral SCM . Clin Neuropharmacol, 2003 Mar-Apr, 26(2), 102 - 8 Treatment of dystonia; Goldman JG et al.; Therapeutic strategies in the treatment of dystonia consist primarily of pharmacologic, surgical, and supportive approaches . Many recent advances have been made in the treatment of dystonia with newer medications, availability of different botulinum toxins, and surgical procedures . However, these treatment modalities all have limiting factors and varying levels of efficacy . Studies range from case reports and open-label trials to double-blind placebo-controlled trials . More research and larger studies are needed to explore these newer medications and surgical techniques for both primary focal and generalized dystonia . Studies in functional outcome and quality of life further support the importance of discovering safe and effective means to treat dystonia . An algorithmic approach may be useful to guide the physician along the various treatment choices. Eur J Neurosci, 2003 Mar, 17(6), 1303 - 5 Syntaxin I modulation of presynaptic calcium channel inactivation revealed by botulinum toxin C1; Stanley EF; The chick ciliary ganglion calyx-type nerve terminal was used to examine voltage-sensitive inactivation of presynaptic N-type Ca2+ channels and to test if this inactivation is modulated by the transmitter release-associated protein syntaxin I . We tested the role of this protein with botulinum toxin C1 (BtC1) which cleaves syntaxin I close to its membrane anchor . The presynaptic Ca2+ current inactivated as two distinct populations with approximately 75% inactivating at a depolarized potential, V1/2 approximately -15 mV, with the remainder inactivating at approximately -75 mV . BtC1 had no detectable effect on the latter component but resulted in a approximately 7 mV positive shift in the V1/2 of the -15 mV inactivating component . These results confirm that the bulk of presynaptic N-type Ca2+ channels are in general resistant to voltage dependent inactivation and provide the first direct evidence that the physiological properties of presynaptic nerve terminal Ca2+ channels are subject to modulation by release site-associated proteins. Neurol India, 2002 Dec, 50 Suppl, S94 - S101 Botulinum toxin in post-stroke spasticity; Borgohain R et al.; Botulinum toxin therapy is useful in the treatment of post stroke spasticity as seen in many clinical studies . This therapy is always done in conjunction with the physiotherapists . Successful use of botulinum toxin in spasticity requires careful patient and dose selection . Residual function of the spastic limb and the condition of the agonist and antagonist muscles must be carefully assessed . This is to ensure that the overall condition of the patient will improve by inducing partial or complete paralysis of one or more muscles . It is important that the antagonist muscle(s) must have a) sufficiently powerful functional control, or b) be capable of hypertrophy and strengthening if allowed to perform through the appropriate range of motion, or c) be acceptable in the flaccid state . No fixed joint deformity should be present . It is important to check that weakening the spastic limb(s) will not further compromise residual function (including gait) . The rationale for the use of botulinum toxin in spasticity is that a velocity-dependant increase in the stretch reflex response in a spastic antagonist muscle may interfere with normal movement in an agonist muscle . However, spasticity may be beneficial in certain situations, eg . leg extension in spasticity may act as a brace in some patients and assist gait . Generally, the side effects associated with botulinum toxin are temporary and well tolerated . The advantages of botulinum toxin are avoidance of anaesthetics, high patient acceptance and persistence of benefit for months . It also facilitates rehabilitation goals, i.e . increased range of motion, ease of hygiene and positioning, and improves quality of life . Its main disadvantage is its high cost. Am J Physiol Gastrointest Liver Physiol, 2003 Aug, 285(2), G291 - 7 Epub 2003 Mar 26. Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle; James AN et al.; Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis . Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle . The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle . Guinea pig pyloric muscle strips were studied in vitro . Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h . ACh (100 microM)-induced contractile responses were determined before and after 6 h . Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS . At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 +/- 9% without affecting ACh-induced contractions . At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 +/- 7% and decreased ACh-induced contraction by 79 +/- 9% . In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility . At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves . At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh. Toxicon, 2003 Mar, 41(4), 475 - 81 Toxicity of botulinum neurotoxins in central nervous system of mice; Luvisetto S et al.; Botulinum neurotoxins (BoNTs) act specifically on cholinergic nerve terminals, where they cause a sustained block of acetylcholine release, and therefore they are powerful tools to study the role of cholinergic neurons in neuronal processes . Peripheral effects of BoNTs are widely documented while central effects have not been studied . Here, we report for the first time on the central toxicity of BoNT serotypes A and B following their direct intracerebroventricular (icv) injection in CD1 mice . The LD50 values were found to be in the range 0.5-1.0 x 10(-6)mg/kg . We recorded the following signs preceding animal death: piloerection and weight decrease appear first, followed by temperature decrease, eyelid closure, loss of sensorimotor reflexes, dehydration, dyspnea . Mice died of heart or respiratory failure . The surviving mice recovered completely within 4-6 days and regained the initial healthy conditions . At sub-lethal doses, the same clinical signs appear in a lighter form and with a longer time course. Dermatol Surg, 2003 Apr, 29(4), 348 - 50; discussion 350-1 Botulinum toxin type B; Sadick NS; BACKGROUND: Botulinum toxin B is an antigenically distinct form of Botulinum toxin which has unique physical and clinical properties that distinguish it from Botulinum toxin A . OBJECTIVE: To describe properties of Botulinum toxin B . METHODS: More rapid onset, greater diffusion characteristics as well as diminished longevity have been identified to date in previous studies . RESULTS: BTX-B is safe and effective . CONCLUSION: The clinical role of this novel neurotoxin in the aesthetic arena is presently evolving. Dermatol Surg, 2003 Apr, 29(4), 340 - 7 Comparison of botulinum toxins A and B in the aesthetic treatment of facial rhytides; Sadick NS et al.; Botulinum toxin injections have become a popular treatment for minimizing or eliminating facial wrinkles . After injection, the toxin acts to paralyze or weaken facial mimetic muscles . Two antigenically distinct serotypes, botulinum toxin type A (BTX-A) and botulinum toxin type B (BTX-B), are currently available . BTX-A is a lyophilized powder preparation requiring reconstitution; BTX-B is a ready-to-use liquid formulation . Both agents produce the same resultant clinical effect (i.e., muscle weakening) . However, in addition to differences with respect to formulation, they are pharmacologically distinct in terms of molecular size, cellular mechanism of action, and species sensitivity . BTX-A has been used for aesthetic purposes for more than 10 years . Clinical studies and observations have shown that it is an effective agent for treating hyperkinetic facial lines . BTX-B was approved for use in cervical dystonia in 2000, but it has been used off-label to treat facial wrinkles as reported in several open-label studies . These preliminary dose-ranging studies have demonstrated that BTX-B is also effective . Both agents are extremely safe nonsurgical modalities for hyperkinetic facial lines . This article reviews the pharmacology and molecular features of BTX-A and BTX-B and highlights some of the key clinical studies that have been published to date with these two agents. Ann Otol Rhinol Laryngol, 2003 Mar, 112(3), 258 - 63 Recovery of swallowing disorders in patients undergoing supracricoid laryngectomy with botulinum toxin therapy; Marchese-Ragona R et al.; In recent decades, functional laryngeal surgery has become a widespread method of treating glottic and supraglottic neoplasms, since it ensures an oncological outcome comparable to that of radical surgery and functional results that are conducive to a good quality of life . The most common postoperative complaints for this type of surgery are swallowing disorders, which can thwart good surgical results, especially when severe . Five supracricoid laryngectomees with swallowing disorders unresolved by speech therapy were treated by percutaneous injection of botulinum toxin under electromyographic control . All patients presented marked improvement in their complaints . A single session of botulinum toxin type A treatment resolved the dysphagia in all cases. Int J Eat Disord, 2003 Apr, 33(3), 356 - 9 Achalasia mimicking prepubertal anorexia nervosa; Richterich A et al.; A 9-year-old girl presents for continuing weight loss of 10 kg over the course of 1 year . Medical history showed three episodes of pneumonia requiring hospital admission in the 6 months before presentation and 4 months of weekly psychotherapy for anorexia nervosa . A thorough history of eating behavior and a review of systems revealed not only typical aspects of prepubertal anorexia nervosa but also vomiting at night while asleep, difficulty drinking liquids, epigastric pain, and a frequent experience of "a lump in the throat"; these symptoms were not suggestive of a diagnosis of anorexia nervosa but rather of esophageal achalasia . The patient was transferred to the Department of Pediatrics, and a diagnosis of esophageal achalasia was made by chest x-ray and barium swallow . After dilatation and botulinum toxin application, the patient regained weight easily and was discharged in stable condition . In this case, esophageal achalasia mimicked prepubertal anorexia nervosa . Am J Ophthalmol, 2003 Apr, 135(4), 427 - 31 Botulinum A toxin injection for restrictive myopathy of thyroid-related orbitopathy: effects on intraocular pressure; Kikkawa DO et al.; PURPOSE: To study the effect of extraocular muscle injections of botulinum A toxin on intraocular pressure in patients with thyroid-related orbitopathy . DESIGN: Retrospective observational case series . METHODS: The medical records of eight consecutive patients with restrictive myopathy secondary to thyroid related orbitopathy (TRO) who underwent botulinum A toxin injection from December 1997 to December 1998 were reviewed and analyzed retrospectively . All patients were seen at the University of California, San Diego (UCSD) Thyroid Eye Center, a university-based tertiary referral center . The main outcome measure was intraocular pressure (IOP) readings taken before and after injection in both primary gaze and upgaze (involving one eye in seven of the patients and both eyes in one patient) . Intraocular pressure readings were measured by an unmasked physician using a Goldmann applanation tonometer . RESULTS: A statistically significant decrease in IOP in upgaze was noted 2 to 6 weeks following botulinum A toxin injection and in both fields of gaze (primary and upgaze) after 2 to 4 months . The mean IOP before injection was 21.4 +/- 3.0 mm Hg in primary gaze and 29.9 +/- 9.7 mm Hg in upgaze . The mean IOP, following injection at 2 to 6 weeks, was 19.2 +/- 4.2 mm Hg (P <.095) in primary gaze and 25.1 +/- 5.9 mm Hg (P <.023) in upgaze . At 2 to 4 months following injection, the mean IOP was 19.3 +/- 3.9 mm Hg (P <.044) in primary gaze and 27.7 +/- 8.5 mm Hg (P <.024) in upgaze . Six patients indicated improved ocular deviation, which was associated with a lowering of IOP . Two patients indicated no change in IOP or strabismic deviation following botulinum A toxin injection . CONCLUSIONS: Botulinum A toxin injections cause a secondary effect to lower IOP in patients with restrictive strabismus associated with thyroid-related orbitopathy. Am J Phys Med Rehabil, 2003 Apr, 82(4), 284 - 9 Effect of botulinum toxin type A on cerebral palsy with upper limb spasticity; Yang TF et al.; OBJECTIVE: The objective of this study was to investigate the effects of botulinum toxin type A injections in reducing upper limb muscular spasticity and in improving motor function in children with cerebral palsy . DESIGN: Fifteen children with spastic cerebral palsy who were undergoing regular physical and occupational therapy were enrolled . Botulinum toxin type A injections in clinically indicated target muscle groups were administered after the children had received 3 mo of therapy . A follow-up study was carried out at 6 wk and 12 wk, respectively, after the botulinum toxin type A injections . The main outcome measurements included the Modified Ashworth Scale, the upper limb Physician's Rating Scale, the Bruininks-Oseretsky Test of Motor Proficiency, and the self-care domain of the Pediatric Evaluation of Disability Inventory . RESULTS: The reduction of spasticity in the treated muscle groups differed significantly between the control period and both study periods . Improvements on the Physician's Rating Scale score during the study period also differed significantly as compared with improvements during the control period . There was a significant difference in the improvement of fine motor skills, as measured with Bruininks-Oseretsky Test of Motor Proficiency, between the control period and both study periods . Improvements in self-care capability differed significantly between the control period and 12 wk after botulinum toxin type A treatment, but not between the control period and at 6 wk after treatment . Muscle strength of grasp and pinch did not differ significantly between the control and the study period . Distribution of body parts involvement, disease severity, and function in daily living activities had no significant correlation with functional improvement after the treatment . CONCLUSIONS: Our findings support the premise that botulinum toxin type A injections are effective in reducing upper limb spasticity and in improving movement pattern and fine motor function of patients with spastic cerebral palsy . A reduction in caregivers' burden and improved quality of life were demonstrated through the study period. Clin Ter, 2002 Nov-Dec, 153(6), 403 - 19 {Neurogenic dysphagia: physiology, physiopathology and rehabilitative treatment}; Patti F et al.; Swallowing is both a voluntary than a reflex function . It consist in transporting feeding from mouth to the stomach . Swallowing function occurs with very frequency during the day and needs complex neuromuscular coordination . Several neurologic diseases determine swallowing disorders . Dysphagia, is the difficulty in swallowing . In slight disorders, swallowing function is sufficiently compensated, symptoms are few or absent . Sometimes the patient is able to compensate and obtains a safe deglutition . Rehabilitation of swallowing disorders is based on the assessment of all symptoms and troubles causing dysphagia and on the improvement of the specific disabilities . Rehabilitation is aimed to make patient able for a safe oral feeding . We can use classic specific physiotherapy, compensatory movements of head and neck, electrostimulation, and the chemical myotomia by botulinum toxin injection. Urology, 2003 Mar, 61(3), 550 - 4 Effect of botulinum a toxin in the treatment of voiding dysfunction due to detrusor underactivity; Kuo HC; OBJECTIVES: To investigate the effects of botulinum A toxin in treating patients with voiding dysfunction due to detrusor underactivity . METHODS: Twenty patients with chronic urinary retention (n = 13) or severe dysuria (n = 7) received 50 U of botulinum A toxin by urethral injection . The clinical effects, obstructive symptom score, quality-of-life index, and urodynamics were compared at baseline and after treatment . RESULTS: Of the 4 males and 16 females (age range 14 to 86 years) with voiding dysfunction (cauda equina lesion in 5, dysfunctional voiding in 5, peripheral neuropathy in 6, and detrusor failure of unknown origin in 4), 18 (90%) were treated satisfactorily . Among these patients, the mean quality-of-life score decreased significantly from 5.68 +/- 0.67 to 1.16 +/- 1.61 . The median voiding pressure (56.5 +/- 41.2 versus 39.0 +/- 38.4 cm H(2)O) decreased significantly, as did the maximal urethral closure pressure (65.5 +/- 38.1 versus 50 +/- 32.1 cm H(2)O) and residual urine volume (300 +/- 189.1 versus 50 +/- 153.6 mL) at 2 weeks after treatment and remained stationary for 3 months . The subjective maximal effect was achieved within 1 to 2 weeks . In 7 patients, the indwelling catheters were removed, and in 4 patients who performed clean intermittent self-catheterization, the frequency decreased or it was discontinued . The other 7 patients with difficult urination had significant improvement in the obstructive symptom score (18 +/- 3.3 versus 7 +/- 4.5, P = 0.000) . CONCLUSIONS: Botulinum A toxin at a dose of 50 U was effective in reducing urethral sphincter resistance among our patients with detrusor underactivity and difficult urination. Arch Phys Med Rehabil, 2003 Mar, 84(3), 444 - 54 Changes in movement characteristics of the spastic upper extremity after botulinum toxin injection; Hurvitz EA et al.; OBJECTIVE: To examine the longitudinal effects of botulinum toxin injection on movement characteristics of the spastic upper extremity in children by using motor control testing (MCT) techniques and standard clinical measures . DESIGN: Open-label clinical trial . SETTING: Motor control laboratory at an academic medical center . PARTICIPANTS: A convenience sample of 9 subjects (5 boys, 4 girls; age range, 7-16 y) with cerebral injury (stroke or cerebral palsy) and asymmetric upper-extremity function because of spasticity . Eight subjects had right-sided involvement . INTERVENTIONS: Botulinum toxin injection to the involved upper extremity, involving elbow, wrist, and finger flexors, depending on clinical presentation . MAIN OUTCOME MEASURES: Clinical measures included range of motion (ROM), the Ashworth Scale, FIM trade mark instrument, Pediatric Evaluation of Disability Inventory, portions of the Bruininks-Oseretsky Test of Motor Proficiency, and the Purdue pegboard . MCT consisted of visually guided reaching, bilateral finger-to-nose movements, hand tapping, and isometric pinch force tasks . Kinematic assessments were made before and at 2, 4, 6, 12, 18, and 24 weeks after botulinum toxin injection . RESULTS: All subjects had increased ROM and decreased Ashworth values throughout the testing period . In motor control tasks, improvement typically occurred earlier in the least complex movements, such as hand tapping, with 6 of 9 subjects showing a maximum, although transient, unilateral tapping speed by 6 weeks . A similar time course was observed for pinch force tasks . Improvement in more complex, forward-reaching tasks occurred much later (week 12 or later) or did not occur at all . As with the hand tasks, improved reach performance declined toward the end of the testing period . All subject showed minimal or no improvement in bilateral finger-to-nose movements . Neither maximum changes in ROM or Ashworth values correlated with improvements in functional elbow extension during sit and reach tasks, with 3 subjects with normal active ROM showing late onset or no change in reach . CONCLUSIONS: Although botulinum toxin reduced tone and increased ROM of the spastic upper extremity, the time course and degree of motor improvement appears to depend on the complexity of the task . Future research should focus on the value of adjunct therapy, such as task-specific training, in addition to botulinum toxin treatments to facilitate functional improvement of the spastic upper extremity . Clin Ther, 2003 Jan, 25(1), 298 - 308 Quality-of-life assessment in patients with hyperhidrosis before and after treatment with botulinum toxin: results of an open-label study; Campanati A et al.; BACKGROUND: Patients with hyperhidrosis, a disorder characterized by increased sweat production, experience substantial functional and emotional problems . Botulinum toxin type A (BTX-A) has been shown to be useful in the treatment of hyperhidrosis; however, few studies have considered the effects of treatment on patients' quality of life (QOL) . OBJECTIVES: The objectives of this study were to assess QOL in patients with focal hyperhidrosis; to investigate whether the impairment in QOL in these patients is related to the type of hyperhidrosis or the number of sites involved; and to compare the changes in QOL and the response to BTX-A treatment in patients with axillary and palmar hyperhidrosis . METHODS: Patients with focal primary hyperhidrosis of the axillae, palms, and soles who had experienced decreased QOL and whose condition had not responded to conventional topical and physical therapies were included in this open-label study . Patients completed a self-administered Dermatology Life Quality Index (DLQI) questionnaire before and 2 weeks after treatment with BTX-A . RESULTS: All 41 patients had experienced a decrease in QOL as measured by the DLQI . The impairement in QOL was not dependent on the number or types of sites involved . Treatment with BTX-A led to improvement in QOL in all patients, with the median DLQI score decreasing (ie, improving) significantly from pretreatment level (P < 0.001) . The improvement in QOL and response to treatment were similar in patients with axillary and palmar hyperhidrosis . CONCLUSIONS: Further studies with a longer follow-up period are needed to assess the long-term effects of BTX-A; however, preliminary data from the present study suggest that BTX-A improves QOL in patients with focal hyperhidrosis, independent of the presenting clinical picture. J Comp Neurol, 2003 Apr 21, 459(1), 25 - 43 Heterogeneous expression of SNAP-25 and synaptic vesicle proteins by central and peripheral inputs to sympathetic neurons; Gibbins IL et al.; Neurons in prevertebral sympathetic ganglia receive convergent synaptic inputs from peripheral enteric neurons in addition to inputs from spinal preganglionic neurons . Although all inputs are functionally cholinergic, inputs from these two sources have distinctive neurochemical and functional profiles . We used multiple-labeling immunofluorescence, quantitative confocal microscopy, ultrastructural immunocytochemistry, and intracellular electrophysiologic recordings to examine whether populations of inputs to the guinea pig coeliac ganglion express different levels of synaptic proteins that could influence synaptic strength . Boutons of enteric intestinofugal inputs, identified by immunoreactivity to vasoactive intestinal peptide, showed considerable heterogeneity in their immunoreactivity to synaptosome-associated protein of 25 kDa (SNAP-25), synapsin, synaptophysin, choline acetyltransferase, and vesicular acetylcholine transporter . Mean levels of immunoreactivity to these proteins were significantly lower in terminals of intestinofugal inputs compared with terminals of spinal preganglionic inputs . Nevertheless, many boutons with undetectable levels of SNAP-25 immunoreactivity formed morphologically normal synapses with target neurons . Treatment