Effect of botulinum toxin type A on cerebral palsy with upper limb spasticity

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.     

Serial injection of botulinum toxin for muscle imbalance due to regional spasticity in the upper limb

Background and purpose. Three-dimensional movement in the upper limb presents a challenge for functional management of regional spasticity. Potential toxicity of botulinum toxin limits the number of muscles which may be injected in any one session. Serial injection may offer a solution, but carries theoretical risk of development of resistance due to antibody formation. This article reviews a small case series, gathered in a post-acute neuro-rehabilitation setting, to evaluate the use of serial botulinum toxin injection in terms of goal achievement and clinical evidence for toxicity or resistance.

Methods. Nine patients with regional spasticity following acute stroke or brain injury had serial injection of botulinum toxin to muscle groups around the shoulder, elbow and/or wrist. Injection was followed by splinting/physiotherapy as appropriate. Goal attainment scaling was used to assess outcome.

Results. Functional goals achieved were reduction of pain (n = 6/7) associated reaction (n = 4/5) or care needs (n = 5/6), improved gait (n = 2/3) or independence in self-care (n = 2/5). Two ‘golden responder’ cases are presented in detail to demonstrate resolution of symptoms with up to four serial injections of botulinum toxin over a period of up to 6 months. No clinical evidence of toxicity or resistance was seen in any case.

Conclusion. These preliminary findings suggest that serial botulinum toxin injection followed by appropriate physiotherapy/splinting may provide effective treatment for regional spasticity. Resistance has not presented a problem in this post-acute situation, where treatment has not been required beyond a few months. Ongoing evaluation is underway.     

Serial injection of botulinum toxin for muscle imbalance due to regional spasticity in the upper limb

BACKGROUND AND PURPOSE: Three-dimensional movement in the upper limb presents a challenge for functional management of regional spasticity. Potential toxicity of botulinum toxin limits the number of muscles which may be injected in any one session. Serial injection may offer a solution, but carries theoretical risk of development of resistance due to antibody formation. This article reviews a small case series, gathered in a post-acute neuro-rehabilitation setting, to evaluate the use of serial botulinum toxin injection in terms of goal achievement and clinical evidence for toxicity or resistance. METHODS: Nine patients with regional spasticity following acute stroke or brain injury had serial injection of botulinum toxin to muscle groups around the shoulder, elbow and/or wrist. Injection was followed by splinting/physiotherapy as appropriate. Goal attainment scaling was used to assess outcome. RESULTS: Functional goals achieved were reduction of pain (n=6/7) associated reaction (n=4/5) or care needs (n=5/6), improved gait (n=2/3) or independence in self-care (n=2/5). Two 'golden responder' cases are presented in detail to demonstrate resolution of symptoms with up to four serial injections of botulinum toxin over a period of up to 6 months. No clinical evidence of toxicity or resistance was seen in any case. CONCLUSION: These preliminary findings suggest that serial botulinum toxin injection followed by appropriate physiotherapy/splinting may provide effective treatment for regional spasticity. Resistance has not presented a problem in this post-acute situation, where treatment has not been required beyond a few months. Ongoing evaluation is underway.     

超声引导联合电刺激定位注射肉毒毒素治疗脑卒中后上肢痉挛

目的评价超声引导联合电刺激定位注射肉毒毒素(BTX-A)治疗脑卒中后上肢肌痉挛的效果。方法选择脑卒中上肢痉挛患者23例,在超声引导联合电刺激定位引导下,多点注射法将BTX-A注入靶肌。注射后进行常规康复训练。注射前、注射后1、2、4、12周分别采用改良Ashworth评分、腕指关节主动活动度测量、Fug1-Meyer评估表对上肢部分进行疗效评价。结果注射BTX-A后,患者肌张力、腕指关节主动活动度、Fug1-Meyer评估表上肢部分评分均较注射前明显改善(P均<0.05)。结论超声引导联合电刺激定位注射BTX-A治疗脑卒中后上肢肌痉挛,定位准确,治疗效果明显。     

A型肉毒毒素治疗脑卒中后上肢痉挛的疗效观察

目的通过向脑卒中上肢痉挛患者注射A型肉毒毒素（BTXA），以探讨A型肉毒毒素对其上肢肌肉痉挛及活动功能的影响。方法共选取32例脑卒中患者，其偏瘫侧上肢屈肌痉挛Ashworth评级为2～3级，将其随机分为治疗组及对照组。治疗组患者选择肱二头肌、前臂屈肌群注射A型肉毒毒素，随后进行康复训练；对照组患者未给予A型肉毒毒素注射，仅单纯进行康复训练。于治疗前、治疗后1周、2周、6周及12周时进行疗效评定。疗效评定指标包括改良Ashworth痉挛量表评分、Fugl—Meyer上肢功能检测及Barthel指数评分。结果治疗组患者治疗后各观察时间点偏瘫侧上肢肌痉挛情况较治疗前明显降低，肌痉挛改善幅度以治疗后第2周时最为显著，随后改善幅度有所减缓，但与治疗前比较，差异仍有统计学意义（P〈0．05），疗效一直持续至治疗后第12周；同时治疗组患者Fugl—Meyer评分、Barthel指数评分也较治疗前明显改善，并且与对照组各相应疗效指标间差异均有统计学意义（P〈0．05）。结论A型肉毒毒素可显著降低脑卒中患者痉挛上肢肌张力，并对改善患肢活动功能及日常生活活动能力具有明显促进作用．其疗效至少持续12周左右。     

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity.

Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000 U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS).

Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500 U and the peak improvement was at week 8 after injection. A dose of 1000 U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication.

Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500 U.     

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity.

Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000?U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS).

Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500?U and the peak improvement was at week 8 after injection. A dose of 1000?U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication.

Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500?U.     

Post stroke hemiplegia: interest of botulinum toxin injection at the upper limb]

OBJECTIVES: To present data about the effect of botulinum toxin injection on the upper limb of stroke patients. METHODS: We used the Medline data bank. Analysis took into account the international classification of functioning and disability. Important technical or pragmatic points were analysed separately. RESULTS: Botulinum toxin reduces spasticity of the injected muscles, with a mean gain of about 1 point on the Ashworth scale in the 4 to 6 weeks post injection, but with a large variability. This is associated to an increase in the passive range of motion, especially at wrist, and at times to a facilitation of active movements, when they are still possible. Improvement in functional tests is observed when fair proximal and distal motricity persists. Reduction in the dependence in daily living activities has not been shown by group studies. Several patients have an improvement in using the hand for blocking and transporting objects, mainly in a facilitating position (pronation, partial wrist flexion). Comfort of patients and caregivers is more regularly improved. Results are partially predictable; improvement in function is observed in patients with fair distal motricity (extension) and low spasticity, and improvement in comfort in those with severe spasticity and low motricity. CONCLUSION: Further studies are required, on one hand for better assessment of distal functional improvement, on the other hand at earlier phases of the disease.     

Dose-dependent response to intramuscular botulinum toxin type A for upper-limb spasticity in patients after a stroke

OBJECTIVE: To test the hypothesis that intramuscular (IM) botulinum toxin type A (BTX) reduces excessive muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke. DESIGN: Randomized, double-blind, placebo-controlled, multicenter, 24-week trial. SETTING: Six academic and 13 private US outpatient medical centers. PARTICIPANTS: Ninety-one patients with a mean age of 60 years (range, 30-79 y). Mean time elapsed from ischemic or hemorrhagic stroke to study enrollment was 25.8 months (range, 0.9-226.9 mo). INTERVENTIONS: Up to 2 treatments of placebo, or 90, 180, or 360U of BTX. Concurrent splinting and physical therapy protocols were permitted, but no changes were allowed during the study. MAIN OUTCOME MEASURES: Wrist, elbow, and finger flexor tone assessed by the Modified Ashworth Scale, physician and patient global assessments, pain, FIM instrument, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Muscle tone decreased more with injections of BTX than with placebo in the wrist flexors at weeks 1, 2, 3, 6, and 9 (P< or =.026); in the elbow flexors at weeks 1, 2, 3, 4, 5, and 9 (P< or =.033); and in the finger flexors at weeks 1 and 3 (P< or =.031). A dose-dependent response was generally observed in tone reduction but not in pain, FIM, or SF-36 measures. CONCLUSIONS: IM BTX reduced muscle tone in a dose-dependent manner in the elbow, wrist, and fingers of patients who experience spasticity after a stroke but did not appear to affect global quality of life or disability.     

Treatment of focal upper limb spasticity with botulinum toxin after stroke. Interest of an individual approach.]

INTRODUCTION: It is now demonstrated that botulinum toxin can improve upper limb spasticity after stroke. OBJECTIVES: This study was designed to assess the efficacy of botulinum toxin on upper limb spasticity with an individual approach. METHODS: Prospective study on 18 patients who had disabling spasticity of upper limb after stroke. For each patient, the treatment's target was fixed preliminary to botulinum toxin injection. Evaluation of efficacy (Ashworth scale and predefined targets) was performed at 1 month and treatment continuation was decided individually. RESULTS: A beneficial effect was reported by most patients when the treatment was aimed at improving comfort or quality of life. In one case, the treatment was designed to improve grasping. In that case, no effect was reported. For three patients, a neurotomy was performed in order to obtain a long lasting effect. For nine patients, repeated injections were decided. For the six other patients, no long-standing treatment was performed. DISCUSSION: This study confirms that botulinum toxin can improve comfort of patients with upper limb spasticity. On the base of our experience, we discussed contribution of botulinum toxin to enhance and optimise strategies for the treatment of focal upper limb spasticity with emphasis on the comparison with selective neurotomy.     

A型肉毒毒素局部注射治疗脑卒中后上肢屈肌痉挛

目的:探讨A型肉毒毒素局部注射治疗脑卒中后上肢屈肌痉挛的疗效。方法:选择12例脑卒中后遗症期的患者,均有偏瘫侧上肢屈肌张力明显增高,改良的Ashworth量表评分Ⅱ～Ⅲ级,肘关节活动范围受限,影响患者日常生活能力。根据患者的具体情况,使用不同剂量的肉毒毒素(100～150单位)稀释后分6～8点患侧肱二头肌局部注射,在注射后2,4,12周时,分别进行痉挛和关节活动范围的再评估,进行比较。结果:A型肉毒毒素局部注射治疗后2,4,12周患者肱二头肌痉挛程度分别为1.7±0.6,1.4±0.4,1.6±0.5均较注射前2.6±0.8显著改善(P<0.05)。患者的关节主动、被动活动范围在注射2,4,12周后较注射前亦有显著增加,分别为(124.2±14.6)°,(126.8±10.5)°,(123.8±7.6)°和(108.6±12.1)°,(107.4±13.2)°,(103.2±8.6)°(P<0.05)。结论:A型肉毒毒素局部注射治疗脑卒中后上肢屈肌痉挛具有较好的疗效。     

香丹穴位注射治疗脑卒中偏瘫后上肢痉挛的临床研究

目的：研究香丹穴位注射治疗脑卒中偏瘫后上肢痉挛的临床疗效。方法：56例脑卒中偏瘫后伴上肢痉挛的患者随机分成两组：治疗组28例，采用穴位注射香丹，配合常规康复训练；对照组28例，仅进行常规康复训练。采用修改的Ashworth痉挛评价表对两组患者治疗前后痉挛程度进行评定。结果；治疗组治愈率为29％，总有效率为100％；对照组治愈率为11％，总有效率为25％，两组疗效具有非常显著性差异（P＜0．01）。结论：配合香丹穴位注射治疗脑卒中偏瘫后上肢痉挛具有比单纯常规康复训练更佳的疗效。     

Botuloscope: 1-year follow-up of upper limb post-stroke spasticity treated with botulinum toxin

BackgroundBotuloscope is a cohort study supported by a French public grant and aiming to evaluate a 1-year treatment of the post-stroke spastic upper limb with botulinum toxin type A (BoNT-A) in terms of individual satisfaction with respect to personalized goals and quality of life.MethodsThis was an open-label prospective, multicentric study (11 French centres) that followed 330 adults [mean (SD) age 53.7 (13.7) years] over 1 year; participants had ranked 5 therapeutic goals at inclusion [mean (SD) 5.1 (7.3) years post-stroke], had severe hemiparesis [median motricity index (MI) 40 (Q1–Q3 24 to 60)], and were assessed at inclusion (M0) and at month 3 (M3) and M12. Outcome criteria were: spasticity, range of motion, pain [visual analog scale (VAS)], motor function [Modified Ashworth Scale (MAS)] and activities (MI; Frenchay Arm Test), and overall satisfaction with the achievement of each goal (VAS) and quality of life (Reintegration to Normal Life Index). Criteria at M0 and M12 were compared. Adverse effects were also collected, as were medication changes.ResultsThe primary goal was comfort and activities for 63% of participants and motor function for 36%. Participants underwent a mean of 2.4 injection sessions, 19% causing adverse effects. The greatest spasticity attenuation occurred with wrist flexors (median decrease in MAS −2 [Q1–Q3; −2 to −1], P < 10⁻³). Fewer individuals took oral anti-spastic drugs (56% at M12 vs 50% at M0; P < 10⁻²). Range of motion increased by 16°, on average (13 to 19; P < 10⁻³) for wrist extension. Pain prevalence decreases at rest (29% at M0 vs. 19% at M12; P < 10⁻⁴) and during mobilization (64% vs. 43%; P < 10⁻⁴), and fewer participants took analgesics (25% vs. 17%; P < 10⁻³). Satisfaction was high for the goals “hand hygiene” and “pain release” and moderate for “improvement in upper limb function”. However, function was more improved for participants who selected this goal as the first priority than others (P < 10⁻²). Overall, 22% had the goal “improving gait and balance”, which was reasonably achieved at M12. Quality of life improved markedly [median 8 (4 to 11) vs. 6 (3 to 10); P < 10⁻⁴]. Prevalence of complete dissatisfaction with the first objective was 10% to 15%.ConclusionThis is the first long-term follow-up of BoNT-A treatment for upper limb spasticity involving a large cohort independent of industry. Quality of life was improved by treating upper limb spasticity with BoNT-A, even at 5 years post-stroke. Personalizing objectives of the treatment amplified its efficacy. BoNT-A was a powerful analgesic when pain was spasticity-related. Treating the spastic upper limb also improved balance and gait abilities.     

悬吊推拿运动对脑卒中恢复期上肢痉挛的效果

目的 探讨悬吊推拿运动对脑卒中恢复期上肢痉挛的作用。     

表面肌电在脑卒中肘关节痉挛评价中的意义

目的 采用肌电积分值（IEMG）对脑卒中偏瘫患者的肘关节屈肌（肱二头肌）痉挛进行量化评定，并建立与改良Ashworth分级相对应的肌电积分值量化区间。方法 参照改良Ashworth分级标准将90例受试者进行分组，其中0级20例、Ⅰ级16例、Ⅰ16例、Ⅱ级20例、Ⅲ级18例。记录上述受试者在肘关节持续被动屈伸时肱二头肌表面肌电积分值的变化并进行统计分析。结果 受试者各Ashworth分级所对应的肌电积分值范围如下，Ashworth分级为0级对应1．3-12．Ⅰ（6．7±5．4）νV·s；Ⅰ级对应4．6-12．3（8．5±3．9）μV·s：Ⅰ级对应15．3—28．4（21．8±6．6）μV·s；Ⅱ级对应37．2—68．9（53．1±15．6）μV·s；Ⅲ级对应82．3—144．1（113．2±30．9）μV·s。除Ashworth分级为0级与Ⅰ级所对应的IEMG范围有重叠，IEMG均数间差异无统计学意义（P〉0．05）外，其它各Ashworth分级所对应的IEMG范围均无重叠，IEMG均数间差异均有统计学意义（P〈0．05）。结论肌电积分值可对除Ashworth分级为Ⅰ级以外的脑卒中偏瘫患者肘关节屈肌痉挛进行客观评定及量化分级。     

A型肉毒毒素对意识障碍患者上肢严重肌痉挛的应用价值

目的:探讨A型肉毒毒素局部注射在治疗意识障碍患者上肢严重肌痉挛的应用价值。方法:18例意识障碍患者上肢严重肌痉挛,应用A型肉毒毒素局部注射痉挛肌肉,以改良Ashworth量表(MAS)比较上肢肌张力在治疗前和治疗后1周、4周、12周改善程度,同时以照料者主观评价三项护理任务(穿衣、清洁手掌及剪指甲)完成的难易程度来评定临床功能性目标改善程度。结果:注射A型肉毒毒素治疗后上肢肌痉挛程度明显减轻,屈肘肌MAS评分在治疗前与治疗后1周、4周及12周相比差异有显著性意义(4.17±0.39;2.39±0.99;2.04±0.98;2.0±1.04;P<0.01)。屈掌指肌改良Ashworth量表评分在治疗前与治疗后1周、4周及12周相比差异有显著性意义(4.0;2.22±0.83;1.89±0.78;2.0±0.87,P<0.01)。照料者主观评价任务评分在治疗前(穿衣0.83±0.39,清洁手掌剪指甲1.0)与治疗后1周(分别为2.52±0.95,2.56±0.88),4周(分别为2.78±0.95,2.78±1.09),12周(分别为2.96±0.93,2.67±1.12)相比差异有显著性意义(P<0.01)。所有患者没有发现明显不良反应。结论:局部注射A型肉毒毒素能有效缓解意识障碍患者的上肢肌痉挛,便于患者的护理和卫生,减少相关并发症发生,有利于患者的康复,具有一定的临床应用价值。     

Botulinum toxin type A treatment of upper limb spasticity

In recent years, local injections with Botulinum toxin type A (BtxA) have become the treatment of choice for dystonia. However, several studies have demonstrated its efficacy and safety in the treatment of focal spasticity as well. These studies have shown efficacy and safety in upper limb spasticity treatment at a total dose between 500 and 1500 units of Dysport per injection session. While injections in upper arm muscles are easily administered without EMG-guidance, we recommend EMG-guidance for lower arm and finger muscles. In addition to functional improvement, BtxA treatment may also be considered for the following reasons: treatment of spasticity associated pain or painful muscle spasms, improved hygiene, facilitation of care, prevention of skin breakdown, and improved positioning of the upper limb. The definition of a realistic treatment goal, in agreement with the patient, as well as adjunctive physiotherapy are prerequisites for a successful BtxA treatment. Dose recommendations are given in Table 1.