Efficacy of botulinum toxin type A against cervical dystonia and muscular hypertonia in persons with severe motor and intellectual disabilities with respiratory problems and/or dysphagia

We administered intramuscular injections of botulinum toxin type A (BTX-A) in 11 persons with cervical dystonia (CD) and muscular hypertonia (MH). All patients had severe motor and intellectual disabilities (SMID). Furthermore, in 10 patients, SMID was accompanied by respiratory problems and/or dysphagia. Three patients received night nasal intermittent positive pressure ventilation and 3 had undergone tracheotomy; 5 patients had upper respiratory problems. Because of these complications, BTX-A dose was gradually increased in those patients until the desired effect was obtained (mean last dose, 6.8 u/kg/dose). All patients were clinically assessed with the Tsui scale before treatment with BTX-A. At 1, 2, 4, and 8 weeks after BTX-A injections, responses to the injections were assessed with the Tsui scale repetitively in all patients. Significant or mild improvements in the Tsui scale scores were observed in 8 patients without any severe adverse effects. In addition, some improvements in respiration and body weight gain were observed. We observed a reduction in the number of oral medications in 10 cases. Administration of BTX-A for the treatment of SMID has numerous benefits, not all of which can be explained by Tsui scale scores. BTX-A is safe and has potential for use in the treatment of CD and MH with respiratory problems and/or dysphagia.     

肌电图引导局部肌肉注射A型肉毒毒素治疗痉挛性斜颈的疗效观察

目的 观察肌电图(EMG)引导局部肌肉注射A型肉毒毒素(BTX-A)治疗痉挛性斜颈(CD)的疗效.方法 应用EMG检查19例CD患者头颈部152块肌肉,针对放松状态下出现的多频群放电位的114块靶肌肉进行BTX-A局部肌肉注射;治疗前后分别采用Tsui量表对病情和疗效进行评估;随访观察疗效持续时间以及不良反应.结果 治疗后EMG发现靶肌肉5块;根据Tsui量表评分,治疗后总有效率第1周为47.3%,第2周为78.9%,第3、4周均为94.7%;随访显示疗效平均保持10个月;不良反应轻微,均在4周内自行缓解.结论 EMG引导局部肌肉注射BTX-A治疗CD安全有效.     

Riluzole therapy in cervical dystonia.

We conducted a 6-week open-label pilot study with blinded video rating of riluzole (50 mg twice a day) in six patients with cervical dystonia (CD) refractory to botulinum toxin A and oral pharmacological treatment. The Tsui rating scale served as primary efficacy measure and improved significantly under riluzole (P = 0.002). In three of six patients, the Tsui score improved by more than 30% with a greater 50% reduction in the head tremor/jerk subscore of the Tsui scale. These data suggest that riluzole may be helpful in a subgroup of patients with disabling CD refractory to other therapies.     

The botulinum toxins in the treatment of cervical dystonia

The use of botulinum toxin to treat cervical dystonia (CD) has dramatically improved the quality of life of patients with this disabling, often painful disease. Two forms of toxins, botulinum toxin type A (BTX-A) and botulinum toxin type B (BTX-B), have each been studied in large multicenter trials in subjects with CD. A study of BTX-A demonstrated improvement of 5.15 to 10.65 degrees in head position using the Cervical Dystonia Severity Scale (CDSS) in those treated with BTX-A (trade name BOTOX) compared with placebo. A study in patients who continued to respond to BTX-A and a similarly designed study in patients who were resistant to BTX-A demonstrated statistical improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in those treated with BTX-B (evaluated as NeuroBloc) compared with placebo. The potential availability of both forms of toxin will allow physicians to offer further treatment options to patients with CD.     

肌电图引导下A型肉毒毒素治疗不同类型痉挛性斜颈的临床研究

目的：探讨A型肉毒毒素（BTX-A）局部注射治疗不同类型原发性痉挛性斜颈的疗效。方法：在肌电图引导下,对24例痉挛性斜颈患者行BTX-A局部肌肉注射,按其临床类型分组比较疗效及不良反应。结果：全部患者治疗后Tsui量表评分均明显下降,混合型改善程度更明显。所有患者均未见严重不良反应。结论：肌电图引导下BTX-A治疗不同类型痉挛性斜颈均有效,且安全。     

偏侧面肌痉挛和良性特发性眼睑痉挛的临床与治疗特点

目的 探讨偏侧面肌痉挛(HFS)和良性特发性眼睑痉挛(BEB)的临床特点、治疗现状以及对A型肉毒毒素(BTX-A)治疗的反应.方法 对2013年4~10月在武汉大学人民医院神经内科门诊就诊的HFS患者和BEB患者进行调查,其中HFS患者110例,BEB患者90例.所有的患者均接受了BTX-A局部注射治疗.注射后2周左右复诊,在每周二下午的专病门诊随访,并记录BTX-A的疗效持续时间.结果(1)入组200例患者中,BTX-A治疗起效时间0~30 d(中位数4 d),疗效持续时间2~128周(中位数16周),总有效率96.9%.HFS患者症状明显好转(完全和明显缓解)占99.3%,BEB患者占90.2%.总的来说,BEB患者的疗效持续时间[(13.6±5.5)周]与HFS患者[(20.3±10.2)周]相比较短.HFS患者所用BTX-A剂量[(53.2±15.8)U]较BEB患者[(74.8±20.2)U]少.(2)BTX-A注射(70.9%)、针灸(68.2%)和口服药(65.5%)是HFS患者曾经选择的最多的非手术治疗方法.针灸和口服药大部分效果不好而自行停用.BTX-A注射(88.9%)、口服药(86.7%)和眼轮匝肌切割术(31.1%)是BEB患者曾经选择的最多的治疗方法,但患者均反映手术无效.结论 HFS和BEB是运动障碍门诊最常见的两种疾病,BTX-A治疗HFS和BEB安全、有效,对HFS效果更好,BEB患者需要更频繁的注射,其面部肌张力障碍的治疗更具挑战性.     

Effects of botulinum toxin therapy for respiratory distress in patients with cervical hypertonia

Botulinum toxin A (BTX-A) therapy has been approved as a first-line therapy for spastic torticollis. However it has been suggested as that its use in patients with respiratory distress should be decided cautiously. We treated 5 patients with abnormal posture, cervical hypertonia and obstructive respiratory distress by BTX-A, and analyzed its efficacy for respiratory distress by their Tsui score and respiratory status after BTX-A therapy. All 5 patients clinically had some degree of dysphagia before BTX-A therapy. Cervical hypertonia and induced abnormal posture were improved in all patients. The youngest patient could control muscle tone after only 2 doses of BTX-A and subsequently maintained a good condition without additional BTX-A. BTX-A therapy can decrease torsion and hyperextension of the upper respiratory tract by reducing cervical hypertonia. Consequently, it may improve respiratory status. On the other hand, mild dysphagia and excessive salivation was noted in one patient for each symptom. It is safe to avoid BTX-A invasion to the anterior muscle of neck and rapid changes in the swallowing pattern.     

The finding and evaluation of EMG-guided BOTOX injection in cervical dystonia

In this prospective study we report the results of EMG-guided BOTOX injections in a total of 15 cervical dystonia (CD) patients. Pre-treatment and post-treatment evaluations included physical examination results, Tsui ratings, and video recording. The dosage of BOTOX injection was determined by the EMG pattern, type of CD, and the degree of muscle hypertrophy. Seven patients underwent injections with and without EMG, and eight patients underwent injections with EMG-guidance only. The results showed that among the patients who underwent EMG-guided BOTOX injection there are: (1) fewer BOTOX-related side effects due to injection of the adequate dose of BOTOX to the accurate site of hyperactive muscles, (2) greater clinical improvement due to confirmation of hyperactivity in muscles in each type of cervical dystonia, (3) a better ability to reduce the amount of oral medication for treatment of muscle pain and spasms. We suggest that the use of EMG-guided BOTOX injections be considered for those CD patients with retrocollis, those who have had a sub-optimal treatment response to non EMG-guided BOTOX injections, and those with increased concern of side effects or a concomitant goal of reducing oral medications.     

The effect of botulinum toxin injections to the calf muscles on freezing of gait in parkinsonism: a pilot study

Background Freezing of gait (FOG) is a common and very disabling parkinsonian symptom, which is poorly understood and responds unsatisfactorily to medical treatment. We recently reported a unique patient with Parkinson's disease (PD) who had significant alleviation of FOG shortly after she was injected with botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al. 1997). Objective To assess the effect of BTX-A injections into the calf muscles of parkinsonian patients on FOG. Method BTX-A was injected in an open fashion into the calf muscles of 10 parkinsonian patients (age 55–75 years) with FOG as a predominant symptom. Response of FOG was assessed subjectively by the patient from worsening (–1) to marked improvement (+3). One patient was injected in a single blind fashion with saline or BTX-A after he had an initial good response. Results Seven patients reported different rates of improvement of FOG severity in 15 out of 17 therapeutic sessions. Four patients (40%) reported marked improvement (+3) of FOG in 5 sessions. Two patients reported no effect in two sessions. The mean duration of improvement was 6 weeks (range 1–12 weeks) with definite deterioration afterwards. The patient who was injected in a single blind fashion did not respond to saline injections but improved significantly with BTX-A treatment. Conclusions We observed a clear temporal relationship between BTX-A injections into the calf muscles of parkinsonian patients and improvement of FOG. A double blind placebo controlled prospective study is needed before any conclusions can be drawn about the role of BTX-A injection in FOG. Received: 31 August 2000 / Received in revised form: 24 October 2000 / Accepted: 19 January 2001     

Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective,multicentre, randomised,double-blind,placebo-controlled,parallel group study

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score ≥ 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49 %) than placebo (33 %) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42 %) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia. Received: 3 October 2000, Received in revised form: 20 March 2001, Accepted: 2 May 2001     

Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections

The purpose of this study was to analyze the health-related quality of life (HRQL) of patients with cervical dystonia (CD) and the impact of botulinum toxin A (BTX-A) therapy in these patients. The authors recruited 101 patients with CD, all previously treated with BTX-A. Both before and 4 weeks after injection of BTX-A the patients were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), a Visual Analogue Scale for pain (VAS: 0-100%), the Short Form 36 health survey questionnaire (SF-36), and the Montgomery-Asberg Depression Rating Scale (MADRS). A control group of 84 healthy volunteers was also evaluated. The patients? baseline SF-36 scores were worse in all the domains when compared with those of the controls. Depression was found in 47.5% of the patients. Improvements were noticed 4 weeks after the single BTX-A injections in all the SF-36 domains, and in the VAS, TWSTRS and MADRS scores. The TWSTRS results did not correlate with any of the SF-36 subscores. Stepwise backward regression analysis revealed depression as the main predictor of poor HRQL, as well as female sex, poor financial situation, and living alone. On contrary, longer treatment with BTX-A was associated with better scores. Cervical dystonia has a marked impact on HRQL and treatment with BTX-A injections has a beneficial effect, seen both in objective and in subjective measures. Depression in CD patients is a main predictor of worse HRQL.     

肌电图引导下A型肉毒毒素治疗痉挛性斜颈146例临床研究

目的:探讨肌电图引导下A型肉毒毒素局部肌肉注射治疗原发性痉挛性斜颈的疗效。方法:对146例痉挛性斜颈患者在肌电图引导下进行A型肉毒毒素局部肌肉注射,观察其治疗效果以及不良反应。结果:146例痉挛性斜颈患者,治疗后Tsui量表评分明显下降;重复治疗者复发症状减轻,治疗剂量下降,疗效仍良好。所有患者均未见严重不良反应。结论:肌电图引导下A型肉毒毒素局部肌肉注射是一种治疗痉挛性斜颈有效和安全的手段。     

Initial efficacy of intramuscular injection of botulinum toxin type A against cervical dystonia and general muscular hypertonia in persons with severe motor and intellectual disabilities

We introduced an intramuscular injection of botulinum toxin type A (hereafter, BTX-A) in 5 cases of cervical dystonia (CD) with generalized muscular hypertonia (GMH). The patients all had severe motor and intellectual disabilities (SMID). The initial injections (first and second) of BTX-A exerted a focal muscular relaxant effect in all 5 cases. It is interesting that they decreased hypertonia in the lower extremities, which resulted in an improved activity of daily living (ADL) in 4 cases (80%). This fact reveals the involvement of many muscles in regard to CD and GMH, especially in patients with severe cerebral palsy. As for adverse effects, a mild increase of saliva and cough indicated transient misswallowing in 2 cases (40%) and changes in the pattern of head movement and posture in 2 cases (40%). These effects were all mild and did not disturb ADL in any patient. BTX-A is considered to be safer and worthier of trying to decrease complaints related to CD and GMH than we expected. Furthermore, a modified Tsui's score cannot explain the many benefits from BTX-A in the treatment of SMID. For a reliable assessment of BTX-A therapy used to treat CD and GMH, especially in persons with SMID, more expressible and specific assessment methods will need to be established.     

Cervical dystonia: Improved treatment response to botulinum toxin after referral to a tertiary centre and the use of polymyography

RationaleCervical dystonia is the most common form of (primary) dystonia. The first line of treatment for cervical dystonia is intramuscular injections with botulinum toxin. To optimise the response to botulinum toxin proper muscles selection is required. Pre-treatment polymyographic EMG in addition to clinical evaluation is hypothesised to be a good tool to improve muscle selection and treatment outcome.ObjectiveTo determine the efficacy of botulinum toxin treatment after adjacent polymyographic EMG in cervical dystonia patients referred to our tertiary referral centre with an unsatisfactory response to botulinum toxin treatment elsewhere.MethodsWe performed a retrospective analysis of 40 consecutive second opinion cervical dystonia patients. Standard polymyographic EMG was performed before treatment. We retrieved the Tsui scores and subjective evaluations from the first visit, after 12 weeks and after one year of treatment. In addition, we assessed the final outcome of treatment in our centre based on the records and asked the patients for their personal opinion about the effect of referral to our centre on their treatment response.ResultsAfter one year of treatment there was a significant improvement on both the Tsui scores (p < 0.01) and the subjective treatment evaluation (p < 0.001.) On their last visit 60% of the patients still continued treatment with a reasonable to good response.ConclusionA substantial amount of CD patients with an unsatisfactory response to botulinum toxin improved after polymyography and subsequent treatment with botulinum toxin in a tertiary referral centre.     

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.     

Hemifacial spasm non-motor and motor-related symptoms and their response to botulinum toxin therapy

Hemifacial spasm (HFS) is a chronic movement disorder which presents as clonic and/or tonic facial muscle contractions frequently accompanied by many other sensory (visual or auditory disturbances, pain), motor (facial weakness, trismus, bruxism, dysarthria) and/or autonomic (lacrimation, salivation) symptoms. The aim of the study was to assess the occurrence of HFS non-motor and motor-related symptoms and their responsiveness to botulinum toxin type A (BTX-A) therapy. 56 HFS patients were included in the open-label design study. Patients were examined three times: before BTX-A injection, and 2 and 12 weeks later. The occurrence of non-motor and motor-related symptoms was assessed by a special questionnaire, and the severity of HFS was rated by the Clinical Global Impression-Severity scale (CGI-S) and depression symptoms by the Beck Depression Inventory (BDI). Over 81% of the patients before BTX-A therapy reported HFS non-motor and motor-related symptoms. Almost 50% of the patients reported more than three symptoms. The most frequent symptoms were: tearing (44.5%), eye irritation (39.3%), facial paraesthesia (26.8%) and hearing of a “clicking” sound (25.0%). 2 weeks after BTX-A injection 75% of the patients did not report any symptoms and 20% reported only one or two. 3 months later the number of symptoms had increased again, with 57% of patients reporting at least one. The number of HFS non-motor and other symptoms did not correlate with the patients’ age, disease duration and the presence of neuro-vascular conflict, but were positively correlated with the CGI-S and BDI scores. This study showed that muscle contractions in HFS patients are commonly accompanied by non-motor and other motor-related symptoms and most of them are reduced following BTX-A treatment.     

A型肉毒毒素注射联合肌肉乙醇阻滞治疗痉挛性斜颈的疗效观察

目的 观察A型肉毒毒素(BTX-A)注射联合肌肉乙醇阻滞治疗痉挛性斜颈(ST)的疗效.方法 43例ST患者随机分为联合治疗组(14例)和对照组(29例),两组均给予BTX-A注射,联合治疗组同时进行肌肉乙醇阻滞治疗.在治疗前后分别进行Tsui评分以评估疗效.结果 治疗后Tsui评分联合治疗组[(3.02±3.29)分...     

Botulinum toxin type A treatment of cerebral palsy: an integrated approach

We have applied a multilevel approach to the management of spasticity associated with cerebral palsy (CP). All of the following factors are important in forming an integrated strategy for botulinum toxin type A (BTX-A) therapy: the timing of injections, patient selection, multilevel BTX-A treatment, optimal dosage and injection technique, follow-up treatment and objective measurements of functional outcome. Data on all these factors are presented here. CP patients had a mean age of 6.5 years (n = 315), and the dose of BTX-A (BOTOX®) ranged from 2 to 29 U/kg body weight ( n = 156). The combination of muscles injected in our multilevel approach differed for patients with diplegia, hemiplegia and quadriplegia: patients with hemiplegia received injections in the gastrocnemius and medial hamstrings; this combination was extended to the adductors for patients with diplegia and quadriplegia ( n = 156). For patients with quadriplegia, muscles in a three-level (gastrocnemius, medial hamstrings, adductors and iliopsoas) or two-level (excluding the gastrocnemius) combination were also frequently injected. The duration of effect of BTX-A treatment was mainly determined by follow-up treatment consisting of: serial casting, day and night orthoses and physiotherapy. No major side effects of BTX-A were reported. This integrated approach appears to prolong the duration of BTX-A treatment, resulting in a duration of about 1 year between injections.     

Celiac disease as a possible cause for low serum ferritin in patients with restless legs syndrome

ObjectiveTo describe celiac disease (CD) as a possible cause for low serum ferritin in patients with restless legs syndrome (RLS).BackgroundLow iron stores have been found to be a risk factor for RLS with serum ferritin levels less than 45–50 ng/mL associated with increased severity of RLS. It has become routine clinical practice to test serum ferritin in the initial assessment of RLS. CD is a common genetic disorder that can cause iron deficiency.MethodsConsecutive case series of four patients with RLS and serum ferritin below 25 ng/mL, who had positive screening tests for celiac disease.ResultsWe report four patients who had serum ferritin <12 ng/mL and positive screening tests for CD. All had CD confirmed by duodenal biopsy and response to a gluten-free diet. RLS symptoms improved in all four, with two able to discontinue RLS medication and two responding without medication.ConclusionsIn patients with RLS and low serum ferritin who do not have an obvious cause for iron deficiency, we suggest looking for CD by simple, inexpensive serologic testing. Diagnosis and treatment of CD is likely to improve the outcome for RLS, as well as identify individuals who are at risk for the significant long-term complications of CD.     

Fast voluntary neck movements in patients with cervical dystonia: a kinematic study before and after therapy with botulinum toxin type A.

OBJECTIVE: To study fast voluntary neck movements in patients with cervical dystonia (CD) before and after therapy with botulinum toxin type-A (BTX-A). METHODS: A selected sample of 15 patients with CD (with prevalent torticollis) and 13 age-matched control subjects performed both right and left rotational, and flexion and extension neck movements as fast as possible. Movements were recorded with a motion analysis system (SMART, BTS). Movement time, angular amplitude, and peak angular velocity were analyzed. In patients, rotational neck movements were pooled as "pro-dystonic" (toward the dystonic side) and "anti-dystonic" (toward the non-dystonic side). Results obtained in patients before BTX-A treatment were compared with those of control subjects. The effect of BTX-A treatment was evaluated by comparing movement performance before and after treatment. RESULTS: Before receiving BTX-A, patients performed pro- and anti-dystonic movements with lower peak angular velocity than control subjects. Pro-dystonic movements had a reduced angular amplitude. Anti-dystonic movements showed an abnormally long movement time. Flexion and extension movements required longer movement times, but the other kinematic variables were normal. After BTX-A injections, pro-dystonic movement amplitude and anti-dystonic movement peak angular velocity increased, whereas flexion and extension movements remained unchanged. CONCLUSIONS: Before BTX-A injection patients with CD perform fast voluntary neck movements abnormally and BTX-A injections improved their peak velocity and amplitude. SIGNIFICANCE: Kinematic studies can detect specific neck movement disturbance in patients with CD, and can quantify both the severity of clinical picture and the effect of BTX-A injections in these patients.