Double-blind, placebo-controlled trial of botulinum toxin injections for the treatment of spasmodic torticollis

We enrolled 55 patients in a double-blind, placebo-controlled, parallel design study of the effectiveness of botulinum toxin (Botox) injections for the treatment of spasmodic torticollis. Patients received a standard series of injections, either placebo or Botox. We determined the sites of injection and dose per muscle by the nature of head deviation. Compared with placebo, Botox produced statistically significant improvement in the severity of torticollis, disability, pain, and degree of head turning. There were no serious side effects. During the double-blind phase, 61% of patients injected with Botox improved; 74% of patients subsequently improved during a later open phase at a higher dose of Botox. Direction of head turning, severity of torticollis, and presence or absence of jerky movements did not significantly influence the response rate. We conclude that Botox is a valuable treatment for spasmodic torticollis.     

Treatment of spasmodic torticollis by local injections of botulinum toxin

Injections of botulinum toxin into the main cervical muscles responsible for abnormal posture and movements in spasmodic torticollis reduced pain and attenuated dystonia for a period of 2 months on average. After several sessions 9 out of 36 patients (25 p. 100) felt they had improved by at least 50 percent, 16 (44 p.100) by 50 to 75 percent, and 6 (17 p. 100) by more than 75 percent. There were six failures.     

Treatment of spasmodic torticollis with local injections of botulinum toxin

Summary Thirty-seven patients with spasmodic torticollis (cervical dystonia) who received repeated local injections of botulinum toxin have been followed up for a mean period of 12.3 (10–29) months, during which time 138 treatment sessions were performed. Mean doses per muscle averaged 320 mouse units (mu; range 160–1000 mu botulinum toxin A prepared by CAMR, Porton Down, UK). Eighty-six per cent of patients experienced significant improvement of posture and 84% of those with pain had relief following the first injection. Muscular patterns of recurrent torticollis were relatively constant and in most patients efficacy was maintained with subsequent injections, while 15% of all follow-up sessions failed. Only 2 of 37 patients were consistent non-responders; 22% and 10% of all sessions were complicated by transient dysphagia and weakness of neck muscles, respectively. It is concluded that local botulinum toxin injections can be a safe and efficaceous long-term treatment of spasmodic torticollis and that optimal doses should be between 200 and 400 mu/muscle.     

Local treatment of spasmodic torticollis with botulinum toxin

Fifteen patients with spasmodic torticollis were treated with local injections of botulinum--A toxin. All the patients were followed for a period of 4 to 7 months. Thirteen out of 15 patients (86%) improved in the amount of sustained movements of torticollis. In six out of 9 patients presenting with pain complete relief was noted. Beneficial effects of botulinum toxin injections lasted from 2 to 3 months, with reproducible efficacy after repeated injections. The most frequent side effect was dysphagia, presented in 10 patients.     

Vestibulo-ocular abnormalities in spasmodic torticollis before and after botulinum toxin injections.

In order to establish whether vestibular abnormalities often found in spasmodic torticollis are secondary to the abnormal head posture, the vestibulo-ocular reflex (VOR) was studied in eight patients before and after correction of head posture with botulinum toxin. Eye movements were recorded in the dark during sinusoidal and velocity step rotation. Four patients showed a significantly asymmetric response, with the slow phase of the VOR more active ipsilateral to the torticollis (chin). Despite significant improvement of the head posture in all patients for up to 10 weeks following treatment, no correction of the vestibular asymmetry occurred. This suggests that the VOR abnormalities are not caused by the head posture itself. We interpret the findings as evidence of primary involvement of the vestibular system in torticollis and we postulate a widespread derangement of the sensory-motor mechanisms controlling head posture in this disease.     

Muscle activity changes in spasmodic torticollis after botulinum toxin treatment

We assessed electromyographic (EMG) activity in neck muscles before and after botulinum toxin injections in 28 patients with spasmodic torticollis (ST) to investigate possible changes in muscle activation after treatment. A six-channel EMG with surface electrodes was used to record activity of sternocleiodomastoid, trapezius and splenius capitis bilaterally. Objective benefit (>25% reduction in Tsui's score) occurred in 22 patients (78%). Of the 168 muscles studied before botulinum toxin injections, 90 presented EMG activity. Sixty-eight of these muscles were injected and a decrease in EMG activity occurred in 44 (65%) of them. A decrease in EMG activity was also detected in 15 (68%) of those which were not injected. On the other hand, 70 of the 78 muscles without pre-botulinum toxin EMG activity were not injected. However, after treatment, EMG activity increased in 37 (52%) of these muscles. These changes involved 18 patients and occurred without concomitant change in the main direction of head deviation despite the improvement observed in most cases. These results suggest that in ST head turning results from an abnormal central motor program which results in non-specific neck muscle activation.     

A pharmacoeconomic evaluation of botulinum toxin in the treatment of spasmodic torticollis

We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo). During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.     

Dysphagia after botulinum toxin injections for spasmodic torticollis: clinical and radiologic findings.

We prospectively evaluated the frequency, severity, and radiologic features of swallowing abnormalities following Botox treatment of spasmodic torticollis. We performed both clinical and radiologic evaluations of swallowing before and following Botox in 18 consecutive cervical dystonia patients receiving their first Botox treatment. Before Botox, 11% of the patients had clinical symptoms of dysphagia and 22% had radiologic signs of a peristaltic abnormality. After Botox, the signs and symptoms of dysphagia in these patients did not change, but an additional 33% developed new dysphagic symptoms and 50% of the patients developed new peristaltic abnormalities by radiologic studies. Complaints of swallowing difficulty were always associated with abnormal radiologic findings. Neither the total Botox dose nor Botox into particular muscles differed between those with dysphagia and those without.     

Botulinum toxin treatment in spasmodic torticollis.

Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial. Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments. Following the controlled trial, treatment with botulinum toxin was continued in an open fashion. A total of 60 patients with torticollis received toxin in a total of 117 treatment periods. The mean follow up period was 8.4 months. In 39 patients with pain there was benefit in 77% of treatment periods. Some improvement in neck posture occurred in 83% of the treatment periods with a mean duration of 12 weeks. Side effects were frequent with dysphagia being the most common (28% of treatment periods). Botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study (400-600 mouse units).     

A pilot study on the use of botulinum toxin in spasmodic torticollis

Dystonic torticollis has been treated with local injections of botulinum toxin in a single blind study of 12 patients. A significant decrease of abnormal movements was recorded, and pain improved. Further studies are desirable to define the optimum dosage and site for injections, and the long term effects of repeated injections.     

Effects of botulinum toxin injections on speech in adductor spasmodic dysphonia

Adductor spasmodic dysphonia involves an overadduction of the vocal folds during speech causing uncontrolled voice and pitch breaks and slow, effortful speech. The disorder is resistant to speech therapy and often recurs following initial benefit from unilateral recurrent laryngeal nerve resection. Botulinum toxin injections into multiple sites of the thyroarytenoid muscle on one side were performed in 16 patients. Speech was recorded prior to injection and three times post-injection. Symptoms were measured by two examiners from speech spectrograms without knowledge of speaker identity or recording session. Significant (p less than or equal to 0.03) reductions in pitch and voice breaks, phonatory aperiodicity, and sentence time occurred only when injections resulted in unilateral vocal fold paralysis. Symptoms returned with the restoration of vocal fold movement, 3 months later. Reduction in speed of swallowing without aspiration was reported in 80% of cases. Although speech volume was reduced, there were no instances of aphonia.     

Botulinum toxin in spasmodic torticollis.

Ten patients with spasmodic torticollis were treated by injection of a total dose of 30 ng of botulinum toxin type A into the affected sternomastoid and posterior cervical muscles. Nine patients reported improvement in head position and control, which was confirmed in seven cases by clinical assessment and "blind" videotape ratings before and 6 weeks after injection. Five patients who had pain reported relief. Seven patients had mild transient dysphagia after injection; two who were given a more concentrated solution of the toxin developed more severe dysphagia, but this also recovered. Other minor transient side effects included weakness of the voice and local pain. The beneficial effects of botulinum toxin injections lasted some 2 to 3 months. A slight reduction in the total dose of toxin injected avoided the main side effects, and this method of treatment appears to offer successful control of head position and pain in the majority of patients with torticollis.     

经颅磁刺激、电刺激与肉毒素治疗痉挛性斜颈的疗效观察

目的本研究应用磁刺激、电刺激三叉神经和A型肉毒素局部注射来治疗痉挛性斜颈患者,并对三种治疗方法进行疗效对比。方法以扭转型为主的60例痉挛性斜颈患者,随机分为经颅磁刺激组20例,电刺激三叉神经组20例,同期肉毒素局部注射组20例。三组年龄及病程比较无统计学差异。结果经颅磁刺激组和电刺激三叉神经组在治疗前后临床分级评分及临床见效时间评定和临床疗效评定方面均优先于同期肉毒素局部注射组(p<0.01),前两者比较无显著差异(p>0.01)。结论采用经颅磁刺激及电刺激三叉神经眼支的方法治疗痉挛性斜颈疗效显著,且其近期疗效优于A型肉毒素局部注射治疗。     

Change in pattern of muscle activity following botulinum toxin injections for torticollis

Twenty patients with torticollis had electromyographic studies of their neck muscles performed before and after a series of local injections of botulinum toxin. The pattern of muscle activity changed after the injections, and this effect persisted even after head position had returned to baseline. Patients who did not experience any clinical benefit from the injections also demonstrated a change in the pattern of muscle activity. These results suggest that the underlying abnormality in torticollis usually involves a general motor program for head position, rather than the activity of individual neck muscles.     

Treatment of idiopathic spasmodic torticollis with botulinum toxin A: a double-blind study on twenty-three patients

In a double-blind, placebo-controlled study, 23 patients suffering from intractable spasmodic torticollis (ST) were given successively either botulinum toxin A (BTA) or normal saline by intramuscular injections in the affected muscles. Evaluation was carried out by three blinded observers, using a clinical and video assessment of the severity of torticollis, employing a scoring system described by Tsui (1). Patients were also asked to subjectively comment on changes in the amount of pain and on changes in the activities of daily living (ADL). BTA was proven to be superior on all forms of assessment to placebo, and these results were statistically significant. Side effects mainly consisted of pain at the injection site. Tiredness occurred at equal frequency with BTA and placebo. No serious or systemic side effects were noted. Botulinum toxin is a safe, effective and relatively simple treatment for spasmodic torticollis.     

Effects of botulinum toxin type A on vibration induced facilitation of motor evoked potentials in spasmodic torticollis

BACKGROUND AND AIMS: It has not been clarified if botulinum toxin (BTX) injection leads to muscle spindle dysfunction in man. This study aimed to test the hypothesis that BTX application reduces the facilitation of a magnetic evoked response (MEP). METHODS: We used the vibration induced facilitation of an MEP of the sternocleidomastoid muscle (SCM) as a surrogate marker for muscle spindle function in 20 healthy subjects and 10 patients with idiopathic rotational torticollis in whom BTX was injected unilaterally. RESULTS: The increase in the amplitude and area of the MEPs in the clinically not affected and untreated SCM of the patients did not differ significantly from the controls. At baseline, the vibration induced increase in the affected SCM of the patients was significantly lower than in the control group. Six weeks after BTX application, the observed facilitation decreased significantly (amplitude and area: p<0.001) when compared with baseline values. Twelve weeks after BTX application, facilitation showed an increase in the values of the amplitude (p<0.001), but not of the area when compared with the six week examination. CONCLUSIONS: We demonstrated that the vibration induced MEP facilitation in the SCM of patients with torticollis significantly decreased six weeks after BTX application and again increased after 12 weeks in part when looking at MEP amplitude. This observation is suggestive of denervation and reinnervation of the muscle spindles after BTX injection.     

微创手术治疗痉挛性斜颈

目的探讨痉挛性斜颈的微创手术治疗方法。方法通过详尽的术前检查和定位诊断,制定个性化的手术方案治疗8例痉挛性斜颈,并评价其疗效。结果4例扭转型和2例侧倾型患者痊愈,2例后仰型患者好转。结论术前详细的临床和影像学检查,神经阻滞试验明确诊断,术中神经电生理监测引导,个性化手术方案可有效治疗痉挛性斜颈,而且可以减少正常神经功能的破坏。     

Botulinum toxin F in the treatment of torticollis clinically resistant to botulinum toxin A.

Two reports have shown a Japanese preparation of botulinum toxin type F (BTX-F) to be an effective alternative for patients with torticollis who develop clinical resistance to botulinum toxin type A (BTX-A). A group of patients with torticollis, comprising five secondary non-responders and one primary non-responder, were treated with a preparation of BTX-F produced in the UK (Speywood Pharmaceuticals). A low dose of BTX-F (220 mouse units (MU) in total) was given into clinically affected neck muscles, followed six weeks later by an injection of a total of 520 MU. Antibodies to BTX-A (mouse protection assay) were present in all secondary non-responders but not in the primary non-responder. No patients developed atrophy after injection of Dysport BTX-A (40 MU) into the left extensor digitorum brevis muscle whereas pronounced atrophy occurred in all patients after injection of 40 MU of BTX-F into the right extensor digitorum brevis muscle. Three patients improved subjectively after treatment with 220 MU BTX-F and five (all secondary non-responders) after the subsequent dose of 520 MU (two considerably), with reduced Tsui scores, but group scores were only significantly changed after the higher dose. The primary non-responder remained unchanged after both doses of BTX-F. One patient reported mild dysphagia with 520 MU BTX-F. Mean duration of improvement with 520 MU BTX-F was five (range 4-6)weeks. Thus BTX-F provides benefit for BTX-A non-responders with few side effects but for a shorter period than BTX-A, possibly due to relative underdosing. As with BTX-A, biological sensitivity to BTX-F does not necessarily predict a clinical response.     

Writer's cramp: treatment with botulinum toxin injections

Twelve patients with writer's cramp were treated with injections of botulinum toxin. The overactive muscles were identified by clinical observation of the subjects while they were writing. Repeated injections were given at 2-week intervals until the optimal response was obtained. Eleven patients reported some benefit, which was considered by seven to be significant. Eight of the 10 patients who had pain reported moderate to significant relief. Five patients had local complications, consisting of disabling weakness of target or neighbouring muscles. These preliminary results suggest that this treatment can be successfully applied to many patients with writer's cramp without performing complex electromyographic recordings while the patients are writing.