Best Clinical Practice in Botulinum Toxin Treatment for Children with Cerebral Palsy

Botulinum toxin A (BoNT-A) is considered a safe and effective therapy for children with cerebral palsy (CP), especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS) of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.     

The long-term efficacy and safety of botulinum toxin in refractory chronic tension-type headache

The objective of this study was to investigate the long-term efficacy and safety of botulinum toxin type-A (BoNT-A) for refractory chronic tension-type headache (CTTH). An open-label, prospective study was carried out in the Department of Neurology of Kirikkale University on 28 patients (8 males, 20 females), mean age 35.6 years, diagnosed with moderate/severe CTTH refractory to preventive medications. Each patient received BoNT-A injections once in pericranial muscles. Efficacy and safety data were analysed for 28 refractory CTTH patients who were receiving concomitant headache prophylactic medications at baseline and during the study. The main outcome parameters were reduction of headache frequency and intensity over 1 year. Both parameters were significantly decreased (p<0.05) by the end of the study. Sixty-four percent of patients reported complete headache relief at the final visit, compared to 7% CTTH persisted. BoNT-A also resulted in significant reductions in analgesic consumption (p<0.05). Adverse effects were transient and local. BoNT-A was found to be an effective and safe treatment for refractory CTTH patients with concomitant headache prophylactic medications, resulting in significant reductions in headache frequency, intensity and analgesic consumption which persisted up to 1 year.     

Comparison Between Steroid and 2 Different Sites of Botulinum Toxin Injection in the Treatment of Lateral Epicondylalgia: A Randomized,Double-Blind,Active Drug-Controlled Pilot Study

Objective

To compare the effects of 2 different injection sites of low doses of botulinum toxin type A with steroid in treating lateral epicondylalgia.

NeuroBloc/Myobloc: Unique features and findings

This review outlines factors that differentiate botulinum toxin serotypes and focuses on the unique features of the commercially available form of BoNT-B (i.e., Myobloc^®/NeuroBloc^®). A series of preclinical studies in Cynomolgus monkeys are reviewed. Each of these studies used electrophysiologic measures of changes in the compound muscle action potential (CMAP) following supramaximal nerve stimulation to evaluate the direct effects of the toxin in the injected muscle, as well as the spread of the effects to non-injected muscles. The results of 14 studies were summarized, including several that compared the effects of equivalent doses of BoNT-A and BoNT-B injected into muscles on the opposite side of the same monkey. There is clear evidence that when equivalent doses of BoNT-A and BoNT-B are assessed, there is greater spread to both nearby and remote non-injected muscles associated with BoNT-A. Similar studies in the mouse model demonstrated that high, but non-lethal, doses of BoNT-A unilaterally injected into the foot resulted in spread of the effects across the midline to the opposite non-treated foot, while there was no evidence of bilateral effects with equivalent unilateral injections of BoNT-B. Finally, this review summarizes a series of studies in the trapezius and gastrocnemius muscles of monkeys demonstrating that when doses producing equivalent initial effects of BoNT-A and BoNT-B are compared, the duration of effects and the time course of recovery are almost identical across toxins.     

肉毒毒素A对大鼠慢性神经源性疼痛中P物质和炎性反应的影响

目的探索肉毒毒素A(Bo NT-A)对慢性神经源性疼痛的镇痛效应和作用机制。方法将大鼠随机分为对照组、假手术组、疼痛模型组(结扎左侧L5、L6脊神经,结扎3 d后于同侧足底皮下注射0.9%氯化钠溶液)、肉毒毒素干预组(结扎左侧L5、L6脊神经,结扎3 d后同侧足底皮下注射Bo NT-A 30 U/kg)。根据处死时间不同将各组分为1 d、3 d和1周(1 w)组。HE染色观察组织形态学变化,免疫组化检测P物质(SP)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)蛋白表达情况,原位杂交及实时定量PCR法测定其基因表达水平。结果 SNL后大鼠脊髓炎性细胞浸润,并随着结扎时间的增长浸润程度加重。与对照组比较,疼痛模型组1 d、3 d和1周时SP、IL-6和TNF-α的蛋白、mRNA表达均显著上升(P0.05);与疼痛模型组比较,肉毒毒素干预组1 d、3 d和1周时SP、IL-6和TNF-α的蛋白、mRNA表达均显著下降(P0.05)。结论 Bo NT-A对慢性神经源性疼痛的镇痛机制可能是通过抑制神经递质SP和炎性介质IL-6、TNF-α的表达实现的。     

不同时点A型肉毒毒素干预对脊髓损伤大鼠腓肠肌病理特征影响的研究

目的:探讨在不同时间点进行A型肉毒毒素(BoNT-A)注射干预对脊髓损伤(SCI)大鼠肌张力(MAS)、运动功能状态(BBB)及腓肠肌(GM)病理特征的影响,进而寻找BoNT-A干预痉挛最佳时间的理论依据。方法:48只SD雄性大鼠被随机分配至Nor-Contrl组、12周-Contrl组、NS干预组和BT干预组。NS/BT干预组按干预时间又分设3个亚组(2周-NS亚组、2周-BT亚组、4周-NS亚组、4周-BT亚组、8周-NS亚组、8周-BT亚组)。Nor-Contrl组和12周-Contrl组大鼠不予注射药物;BT/NS干预组,按上述时间点分别给予BoNT-A/生理盐水注射大鼠右GM。肌张力评估采用MAS评估,运动功能采用BBB评分。GM标本进行肌重测量及蛋白电泳分析(MyHC)。结果:与12周-Contrl组相比,BT干预组大鼠GM肌重明显下降(P≤0.05)。与12周-Contrl组相比,干预组大鼠MAS及BBB结果差异无显著性意义(P0.05)。BT干预组中不同亚组大鼠GM的MyHC分型占比较Nor-Contrl组及12周-Contrl组间的差异均有显著性意义(P≤0.05);且随着干预时间点不同,BT干预组大鼠GM的MyHC分型占比亦不同。结论:BoNT-A注射干预导致受注射的GM肌重及肌重/体质量比显著下降,萎缩明显;对受试大鼠MAS及BBB无明显影响;早期注射较后期注射更易引起GM发生MyHC构型改变。     

Botulinum toxin type-A and plaster cast treatment in children with upper brachial plexus palsy

Summary

BACKGROUND AND PURPOSE: Electrical stimulation, physical therapy and occupational therapy remain the main treatment for children with upper brachial plexus palsy (UBPP), when surgery has been excluded. A pilot study was undertaken to investigate whether botulinum toxin type A (BoNT-A) and plaster casting, as adjunct to the physical therapy, decreased muscle contracture and improved the position and function of the impaired arm. METHOD: Twenty-two children (mean age 5.6 +/- 3.4 years) with mild UBPP who previously underwent serial cast treatment, unsuccessfully, were enrolled. Neurological impairment and functional status were quantified using Medical Research Council (MRC) and Mallet scales and the Nine-Hole Peg Test (NHPT). Elbow extension was measured using a goniometer. Biceps brachii, brachialis, pronator teres and pectoralis major muscles were injected with 22 units kg(-1) BoNT-A (Dysport, Ipsen). After injection, the treated arm was fixed with a plaster cast and progressively lengthened over 14 days. The cast was maintained for 30 days. Assessments of elbow extension, MRC, Mallet Scale and NHPT were made at baseline, 3, 6 and 12 months. RESULTS: After BoNT-A injection, children had significant improvement of active elbow extension (15.5 degrees +/- 17.1 at 12 months after injection, compared with 42.0 degrees +/- 10.4 at baseline; p < 0.001). NPHT scores improved significantly over the 12 months (51.1 +/- 21.8 seconds compared with 56.7 +/- 19.3 seconds at baseline, p < 0.01). MRC and Mallet scale scores of the paretic muscles were unchanged. CONCLUSION: The children showed a reduction in muscular contracture and improvements of the arm position and elbow extension. The data support the use of BoNT-A and plaster casting as an adjunct to physical therapy, in the treatment of children with mild UBPP.