Tilton Ann H
Department of Neurology, Section of Child Neurology, Louisiana State University Health Science Center, New Orleans, LA, USA.
J Child Neurol. 2003 Sep;18 Suppl 1:S50-66. doi: 10.1177/0883073803018001S0701.
Neuromuscular blockade via injection of alcohol, phenol, or botulinum toxin reduces the tone of overactive muscles in order to restore the appropriate balance between agonists and antagonists. Such a restoration allows improved stretch and increased resting length and can reduce the likelihood of contracture. Alcohol or phenol, injected onto the motor nerve, denatures proteins and promotes axonal degeneration. The onset of action is within hours, whereas the duration of action is variable, ranging from 2 weeks to 6 months and beyond. The advantages of alcohol or phenol chemodenervation lie in their low cost and lack of antigenicity. The disadvantages include the technical difficulty of the injections and significant risk for pain as a result of treatment. Botulinum toxins, purified forms of Clostridium botulinum exotoxins, are injected directly into muscle, where they cleave one or more vesicle fusion proteins, thus blocking release of acetylcholine at the neuromuscular junction. Three commercial products--two of serotype A and one of B--are available. Each differs in its unit potency, side effects, and duration of action. On average, botulinum toxin has a clinical onset of action approximately 12 to 72 hours after injection, with a peak effect at 1 to 3 weeks. Effects then plateau for 1 to 2 months, with patients often requiring reinjection approximately every 3 months. Side effects may include local discomfort at the site of the injection and excessive weakness of the injected or nearby muscles, although more distant effects may occur. Antibody formation is a significant clinical concern and eventually obviates treatment benefit in approximately 5% of patients. Switching serotypes may be effective, at least temporarily. Consensus dosing guidelines have been developed and are presented within. Numerous studies have suggested that botulinum toxin has a role in the care of children with spasticity or dystonia related to cerebral palsy, and may improve equinus, gait, upper extremity use, comfort, and care. Evidence of functional improvement remains equivocal in the severely impaired child; however, there is evidence for improvement in less impaired children. The optimal candidate for injectable neuromuscular blockade is one who has a limited number of muscles that need treatment, who does not have fixed contracture, and who retains selective motor control. The ultimate goal of treatment for the hypertonic child is to maximize function, comfort, and independence. Hypertonia is only one aspect of the upper motoneuron syndrome, which includes both positive and negative symptoms. The treatment program, in which chemodenervation is only one tool, requires a multidisciplinary evaluation and individualized plan to address the whole patient.
通过注射酒精、苯酚或肉毒杆菌毒素进行神经肌肉阻滞可降低过度活跃肌肉的张力，以恢复主动肌与拮抗肌之间的适当平衡。这种平衡的恢复可改善伸展能力，增加静息长度，并可降低挛缩的可能性。将酒精或苯酚注射到运动神经上会使蛋白质变性并促进轴突退变。起效时间在数小时内，而作用持续时间则各不相同，从2周至6个月甚至更长。酒精或苯酚化学去神经支配的优点在于成本低且无抗原性。缺点包括注射技术难度大以及治疗后有明显的疼痛风险。肉毒杆菌毒素是肉毒杆菌外毒素的纯化形式，直接注射到肌肉中，在那里它们会切割一种或多种囊泡融合蛋白，从而阻断神经肌肉接头处乙酰胆碱的释放。有三种商业产品可供使用，两种为A型血清型，一种为B型血清型。每种产品在单位效力、副作用和作用持续时间方面都有所不同。平均而言，肉毒杆菌毒素在注射后约12至72小时出现临床起效，1至3周达到峰值效应。然后效应平稳1至2个月，患者通常大约每3个月需要再次注射。副作用可能包括注射部位的局部不适以及注射肌肉或附近肌肉过度无力，尽管可能会出现更远处的影响。抗体形成是一个重要的临床问题，最终会使约5%的患者治疗益处消失。更换血清型可能有效，至少是暂时有效。已制定了共识给药指南并在文中列出。大量研究表明，肉毒杆菌毒素在治疗与脑瘫相关的痉挛或肌张力障碍儿童中发挥作用，并可能改善马蹄足、步态、上肢使用、舒适度和护理情况。在严重受损儿童中，功能改善的证据仍不明确；然而，在受损较轻的儿童中有改善的证据。可注射神经肌肉阻滞的最佳候选者是需要治疗的肌肉数量有限、没有固定挛缩且保留选择性运动控制的患者。高张力儿童治疗的最终目标是使功能、舒适度和独立性最大化。高张力只是上运动神经元综合征的一个方面，该综合征包括阳性和阴性症状。化学去神经支配只是其中一种手段的治疗方案需要多学科评估和个体化计划来全面治疗患者。
