Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period.

Although botulinum toxin A (BTX) has been licensed in Canada for treatment of various movement disorders since 1990, few clinical studies regarding its long-term efficacy and side effects have been reported. We conducted a retrospective analysis of 235 patients who received BTX from our movement disorders clinic over a 10-year period (January 1990 to December 1999). A total of 2,616 treatment cycles (multiple injections) were administered to 235 patients with cervical dystonia (CD), hemifacial spasm (HS), blepharospasm (BP), and other movement disorders. Substantial benefit at 5 years was seen in most patients (90% in BP, 88% in HS, 63% in CD, 100% in jaw closing and lower limb dystonia, and 56% in writer's cramp). Benefit was maintained for up to 10 years in CD, HS, and BP data, with a 75.8% benefit reported. Twenty-eight percent of patients discontinued treatment during the follow-up period due to a variety of reasons. Of these, 9.1% of patients developed primary resistance, and 7.5% of patients secondary resistance. Adverse effects, mostly minor, developed in 27% of patients at any one time, occurring over 4.5% of treatment cycles. These were most frequently reported in blepharospasm (22 of 36 patients in 40 cycles), followed by hemifacial spasm (21 of 70 patients in 46 cycles), and cervical dystonia (17 of 106 in 28 cycles). Only 1.3% of patients discontinued therapy due intolerable adverse effects. The results show that BTX is a safe and effective treatment of various types of movement disorders, and most side effects are well tolerated. Discontinuation for any reason was also low after 5 years. Efficacy was maintained after long periods of treatment with high degree of patient satisfaction.     

Treatment of idiopathic hemifacial spasm with botulinum toxin

Twelve patients with idiopathic hemifacial spasm received treatment with botulinum toxin A over a period of 18 months. Of 76 treatments given, most (94.7%) led to successful relief of eyelid spasms and all treatments were successful for perioral and lower facial muscle spasms. An average dose of 9.3 units of toxin per session was given to produce a mean interval of relief of 10.8 weeks. Blepharoptosis was the only ocular side effect; it was mild, reversible and occurred in 2 patients. However, lower facial palsy was frequent (9 patients); it was mild to moderate in severity but only partially reversible in 8 patients. Dosage for lower facial muscles should therefore be reduced.     

Botulinum toxin in the treatment of lingual movement disorders

Lingual movement disorders are a rare but serious manifestation of neurologic disease, which have the potential to cause significant morbidity. Traditionally, these disorders were treated with pharmacotherapy achieving only limited results. Several case series have demonstrated the effectiveness of Botulinum toxin injection for the management of focal lingual movement disorders; however, apprehension persists regarding intralingual injections due to the risk of dysphagia. Here, we report seven patients with lingual movement disorders treated with intralingual Botox? (Allergan product) injections via a novel superior approach into the genioglossus over a period of 3 to 72 months. All patients experienced a marked improvement in their abnormal tongue movements with no substantial bleeding or dysphagia. Lingual Botulinum toxin injection should be considered a safe and viable treatment option for a variety of disorders affecting the tongue. © 2009 Movement Disorder Society     

Botulinum toxin treatment in patients with focal dystonia and hemifacial spasm. A multicenter study of the Italian Movement Disorder Group

In six Centers belonging to the Italian Movement Disorder Study Group, the efficacy of botulinum toxin treatment was evaluated in an open collaborative study in 251 patients with focal dystonia and hemifacial spasm. The percentage of functional improvement ranged from 66% to 81% in patients with blepharospasm, from 40% to 51% in patients with spasmodic torticollis and from 73% to 81% in those with hemifacial spasm. Good results were also obtained in patients with oromandibular dystonia, laryngeal dystonia and writer's cramp. Side effects were mild and transient. Local botulinum toxin injection is the first choice symptomatic treatment in focal dystonia and hemifacial spasm.

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Sommario In 6 centri facenti parte del Gruppo Italiano per lo Studio dei Disturbi del Movimento è stata valutata l'efficacia della somministrazione di tossina botulinica A in 251 pazienti affetti da distonia focale e da spasmo del facciale. Nei pazienti con blefarospasmo, la percentuale media di miglioramento osservata è compresa tra il 66 e l'81%, mentre nei pazienti con torcicollo varia tra il 40% e il 51%. Nei pazienti affetti da spasmo del facciale la percentuale media di miglioramento è compresa tra il 73% e l'81%. Buoni risultati sono stati ottenuti anche nella terapia di distonie focali meno frequenti, come la distonia oromandibolare e laringea e il crampo dello scrivano. Gli effetti collaterali osservati sono risultati generalmente lievi, locali e transitori. Lo studio conferma quindi l'utilità della tossina botulinica nella terapia sintomatica delle distonie focali e nello spasmo del facciale.

     

Treatment of hemifacial spasm with botulinum toxin.

The effectiveness of botulinum toxin injections in 11 patients with hemifacial spasm was investigated in a prospective placebo-controlled blinded study. The patients were treated with four sets of injections to various facial muscles, selected by clinical evaluation. Three injections were with graded doses of toxin and one was with placebo. The order of injections was random and unknown to the patients. Results were scored both subjectively by patient assessment of symptoms and objectively by blinded review of videotapes made one month after each injection. Subjective improvement occurred after 79% of injections with botulinum toxin, regardless of dose of toxin. Only 1 patient improved after placebo. Objective improvement was seen after 84% of injections with botulinum toxin. No patient showed objective improvement after placebo injection. The most frequent side effect was facial weakness, seen after 97% of injections of botulinum toxin. Facial bruising (20%), diplopia (13%), ptosis (7%), and various other mild side effects were seen less frequently. Botulinum toxin appears to be an effective and safe method of therapy for hemifacial spasm.     

The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences.

The increasing use of botulinum toxin type-A, especially for focal dystonia and spasticity has highlighted the issue of secondary non-responsiveness. Within the last few years botulinum toxin type-B (Myobloc/Neurobloc) has become commercially available as an alternative to type-A. This paper discusses our initial experience of botulinum toxin type-B in a total of 63 individuals who attended our botulinum clinic. Thirty-six patients had cervical dystonia and a secondary non-response to type-A toxin. Thirteen of these patients (36%) had a reasonable clinical response to Neurobloc and continue to have injections. The other 23 patients either had no response, or a poor response, or had unacceptable side effects and ceased treatment. A small number of people with blepharospasm, hemifacial spasm and foot dystonia also had a disappointing response to injection. Twenty patients with spasticity were also type-A resistant. Seven of these show some continuing response to type-B, without unacceptable side effects. These findings demonstrate that botulinum toxin type-B has a place in the management of patients who have become non-responsive to type-A, but overall the responses to type-B toxin were disappointing.     

A型肉毒毒素治疗头颈部肌张力障碍的临床观察

目的观察A型肉毒毒素(BTXA)治疗偏侧面肌痉孪、睑痉孪、Meige’s综合征、痉孪性斜颈的疗效。方法治疗组(A组)用BTXA对86例患者进行头颈部肌肉多点注射,对照组(B组)50例根据诊断选用不同的药物或/和针灸、理疗、中医药治疗。观察两组疗效及副作用。结果A组治疗后当日至3d内开始见效,7～15d达高峰,疗效维持2～6月。总有效率为100%,疗效明显高于B组(P<0.001)。BTXA重复注射疗效无下降,1例HFS患者第三次注射产生耐药性,少数患者有轻微的局部副反应,未见全身副作用。B组62%(31例)的患者疗效维持5～15月后减退,需逐渐增加剂量,少数患者出现白细胞减少、肝功能损害、皮疹、共济失调等不良反应。结论A型肉毒毒素局部注射是治疗头颈部肌张力障碍的一种安全、有效、简便的方法。     

Botulinum toxin A injection in the treatment of hemifacial spasm

Introduction – There are conflicting reports concerning the variation in duration of symptoms relief for patients with hemifacial spasm who have undergone several injections of botulinum A toxin (BOTX-A). We present our experience of BOTX-A injections in Taiwanese patients to analyze this issues, and to inspect whether the efficacy of treatment depends on the pre-injection severity. Material and method — From July 1992 to December 1994, 137 patients received injections of BOTX-A. We used objective and subjective score system to evaluate the efficacy and side effects of BOTX-A injection. Results — The overall successful rate of substantial relief of spasm was 88%. The mean duration of response was 20 weeks. Patents with more severe spasm tended to have shorter duration of improvement. The effects of consecutive injections remained fairly constant over the first 4 injections. Conclusion — The BOTX-A injection is an effective and safe treatment for patients with hemifacial spasm and the effect could be sustained over the consecutive injections.     

Botulinum toxin therapy of hemifacial spasm: comparing different therapeutic preparations

Hemifacial spasm (HFS) is characterized by involuntary irregular clonic or tonic movements of the muscles innervated by cranial nerve VII on one side of the face, and is most often a result of vascular compression of the facial nerve at the root exit zone (Muscle and Nerve 1998; 21 :1740). Disability associated with this disorder ranges from social embarrassment to interference with vision resulting from involuntary eye closure. Treatment of HFS most often involves botulinum toxin injections, but may also include medications and surgery. We describe treatment with the three types of botulinum toxin currently commercially available – Botox®, Dysport® and Myobloc®/NeuroBloc®.     

Guidelines for the therapeutic use of botulinum toxin in movement disorders

Since its introduction in the early '80s the use of botulinum toxin has improved the quality of life of the patients affected by movement disorders. Toxin's neuromuscular blocking action allows a symptomatic treatment of those clinical conditions characterised by excessive muscular activity. Although the dosages used are safe and the side-effects are reversible, a correct use of botulinum toxin depends on the knowledge of its clinical pharmacology and of the anatomy of the body segments to be injected. In addition, the treatment of more complex conditions, i.e. laringeal dystonia, imposes an inter-disciplinary approach and specialised injection techniques.In this review, the Italian Study Group on Movement Disorders presents the consensus guidelines for the therapeutic use of botulinum toxin in movement disorders. The main toxin types, their use and administration modalities, and the training guidelines will be presented.

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Sommario Dalla sua introduzione nei primi anni '80, l'uso della tossina botulina ha prodotto un sensibile miglioramento della qualità della vita dei pazienti affetti da disordini del movimento. La sua azione bloccante la trasmissione neuromuscolare ha consentito il trattamento sintomatico di quelle condizioni cliniche caratterizzate da eccessiva attività muscolare. Nonostante la relativa sicurezza dei dosaggi impiegati e l'assenza di effetti collaterali irreversibili l'adeguato uso della tossina botulinica nei disordini del movimento dipende da conoscenze specifiche di farmacologia clinica e di anatomia normale funzionale dei distretti da infiltrare. Inoltre, per il trattamento di patologie più rare o complesse, come ad esempio la disfonia spasmodica, si rendono necessari un approccio interdisciplinare e speciali tecniche di somministrazione.In questo articolo vengono presentate le principali indicazioni alla terapia con tossina botulinica dei disordini del movimento redatte dal Gruppo di Studio per i Disordini del Movimento della S. I. N. Sono inoltre esposti i principali tipi di tossina disponibili sul mercato italiano, le modalità di uso e somministrazione nonché le nozioni di addestramento per il personale medico che intenda attuare tali terapie.

     

Flexor digitorum superficialis: Locations of individual muscle bellies for botulinum toxin injections

Twenty-two Flexor Digitorum Superficialis (FDS) muscles from 18 cadavers were dissected to find the “Optimal Injection Site” (OIS) for botulinum toxin injections to individual bellies of FDS. Coordinates are given as a percentage of the distance along a landmarking line from the medial epicondyle to the pisiform and in millimetres (mm) lateral to it. The OIS were: FDS2: 72%, 14 mm; FDS3: 54%, 17mm; FDS4: 49%, 7mm; FDS5: 76%, 6mm. OIS measurements guide the electromyographer to localize the targeted muscle belly. © 1997 John Wiley and Sons, Inc. Muscle Nerve 20: 1041–1043, 1997     

Botulinum toxin: State of the art

Botulinun neurotoxin (BoNT) has emerged as one of the most multipurpose therapeutic agents in modern medicine with more clinical applications than any other drug currently on the market. Initially developed in the treatment of strabismus and neurologic movement disorders, the use of botulinun neurotoxin has been expanding during the past 3 decades to include the treatment of a variety of ophthalmologic, gastrointestinal, urologic, orthopedic, dermatologic, dental, secretory, painful, cosmetic, and other conditions. In addition to onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin), and RimabotulinumtoxinB (Myobloc or NeuroBloc) there are other novel botulinun neurotoxin products currently in development. With a better understanding of the cellular mechanisms of botulinun neurotoxin and advances in biotechnology, future botulinun neurotoxin products will likely be even more effective and customized to the specific indication and tailored to the needs of the patients. © 2017 International Parkinson and Movement Disorder Society     

Treatment of occupational cramp with botulinum toxin: Diffusion of toxin to adjacent noninjected muscles

Over a 5-year period, 40 patients, 11 with musician's and 29 with writer's cramp, were treated with botulinum toxin A using a precise injection technique in which the hollow-bore electromyography (EMG) needle was positioned by both standard EMG and by muscle twitch evoked by stimulating current passed through it. Moderate to complete improvement in dystonia occurred in 28 patients (70%) after the first injection and in 34 patients (85%) after the second injection with better outcome in nonmusicians than in musicians. Of note, weakness of uninjected muscles, immediately adjacent to those injected, was found in 25/40 patients (63%). The most common patterns of toxin spread were from flexor digitorum sublimis to profundus, extensor carpi radialis to extensor digitorum communis, and extensor indicis proprius to extensor pollicis brevis. Spread to, and weakness of, adjacent uninjected muscles was a major factor contributing to suboptimal outcome in 6/39 (15%) such patients. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 593–598, 1997.     

Yips and other movement disorders in golfers

Golf is a sport that requires perfect motor coordination and a balance between mobility and stability. Golfer's “yips,” an intermittent motor disturbance manifested as transient tremor, jerk, or spasm that primarily occurs when the player is trying to chip or make a putt, is a movement disorder frequently encountered in both amateur and professional golfers. In addition, other movement disorders, such as tremors and dystonia, also can interfere with playing golf. Although the pathophysiology of the yips remains poorly understood, recent studies suggest that it may be a form of a task‐specific, focal dystonia involving the hand and arm. Because task‐specific dystonias and tremors are best treated by botulinum toxin injections, this also may be an effective therapy for the yips. The aim of this article is to systematically review the literature and our own experience with the yips and other movement disorders in golfers. © 2013 Movement Disorder Society     

Hemifacial spasm: Clinical findings and treatment

Hemifacial spasm (HFS) is a peripherally induced movement disorder characterized by involuntary, unilateral, intermittent, irregular, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. We reviewed the clinical features and response to different treatments in 158 patients (61% women) with HFS evaluated at our Movement Disorders Clinic. The mean age at onset was 48.5 ± 14.1 years (range: 15–87) and the mean duration of symptoms was 11.4 ± 8.5 (range: 0.5–53) years. The left side was affected in 56% instances; 5 patients had bilateral HFS. The lower lid was the most common site of the initial involvement followed by cheek and perioral region. Involuntary eye closure which interfered with vision and social embarrassment were the most common complaints. HFS was associated with trigeminal neuralgia in 5.1% of the cases and 5.7% had prior history of Bell's palsy. Although vascular abnormalities, facial nerve injury, and intracranial tumor were responsible for symptoms in some patients, most patients had no apparent etiology. Botulinum toxin type A(BTX-A)injections, used in 110 patients, provided marked to moderate improvement in 95% of patients. Seven of the 25 (28%) patients who had microvascular decompression reported permanent complications and the HFS recurred in 5 (20%). Although occasionally troublesome, HFS is generally a benign disorder that can be treated effectively with either BTX-A or microvascular decompression. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1740–1747, 1998     

原发性与面瘫后面肌痉挛患者面部异常运动A型肉毒毒素的治疗效果对比研究

目的 探讨A型肉毒毒素(botulinum toxin type A,BoNT-A)治疗原发性及面瘫后面肌痉挛患者痉挛及伴随联带运动的疗效差异。方法 选取2009年1月-2018年7月具有联带运动的面瘫后面肌痉挛患者12例,按照1:2配比性别无差异且具有联带运动的原发性面肌痉挛患者24例,分析2组BoNT-A治疗后痉挛严重程度以及伴随联带运动的改善差异。结果 面瘫后及原发性面肌痉挛患者在起效时间[(4.38±2.17)vs.(4.67±4.14)d],维持时间[(3.83±2.94)vs.(4.96±2.48)d],注射剂量[(31.35±12.30)vs.(26.98±8.75)U]方面无明显差异(P>0.05)。原发性面肌痉挛组患者满意度显著较高(84.79±19.81 vs. 64.17±31.54,P<0.05)。2组痉挛改善有效率均高于90%,组间无明显差异(91.67% vs. 95.83%,P>0.05)。2组联带运动均有改善,但无明显差异(83.33% vs. 58.33%,P>0.05)。5个自主动作相关联带运动改善方面仅发现原发性面肌痉挛患者噘嘴引起联带运动的改善有明显差异(P<0.05)。结论 BoNT-A可以显著改善原发性与面瘫后面肌痉挛患者的痉挛严重程度,在联带运动严重程度改善方面有一定疗效。原发性面肌痉挛患者噘嘴引起的联带运动在BoNT-A治疗后显著改善。     

Alteration of central motor excitability in a patient with hemimasticatory spasm after treatment with botulinum toxin injections.

Hemimasticatory spasm (HMS) is a condition characterized by paroxysmal involuntary contraction of masticatory muscles. We performed an electrophysiological investigation of a single patient with HMS to identify any pathophysiological changes associated with the condition. We identified a delayed M wave and jaw jerk on the affected side and an absent masseteric silent period during spasm. Botulinum toxin injections successfully treated the clinical symptoms and resulted in a significant reduction in the excitability of the blink reflex recovery cycle. These data suggest that HMS may be due to ectopic activity in the motor portion of the trigeminal nerve that is capable of inducing changes in the excitability of central reflex pathways. These changes can be altered by successful treatment with botulinum toxin.