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.

Ultrasonographic Evaluation of Three Approaches for Botulinum Toxin Injection into Tibialis Posterior Muscle in Chronic Stroke Patients with Equinovarus Foot: An Observational Study

Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators.     

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 for the Treatment of Skin Ulcers: A Review Article

The normal biological wound healing process consists of three precisely and highly programmed phases that require optimal conditions including internal and external factors. Any negative factors that disrupt the sequence or time frame of the healing mechanism can result in a non-healing wound or chronic ulcers. Botulinum neurotoxin A (BoNT-A) which is generally known as anti-contraction of muscles has been reported as a successful treatment in various types of chronic ulcers. The aim of this study is to review the outcome of treatment with BoNT-A for chronic skin ulcers. The results demonstrated some positive effects of BoNT-A on chronic ulcers. Ischemic ulcers secondary to Raynaud’s phenomenon seem to be the most promising type of ulcers that have benefited from BoNT-A. The rationale behind using BoNT-A to fasten the wound healing process is also discussed. Further clinical trial studies should be conducted to affirm the efficacy of wound healing using BoNT-A administration.