Eleopra R, Tugnoli V, De Grandis D
Department of Neurology, S. Anna Hospital of Ferrara, Italy.
Mov Disord. 1997 Jan;12(1):89-94. doi: 10.1002/mds.870120115.
When botulinum toxin (BT) is administered for the first time at fixed doses, variable clinical responses can be observed in patients with the same form of dystonic disorder. Many factors may contribute to this phenomenon, including the variability rate of absorption of the drug. Animal experimental models (rat diaphragm preparation) have demonstrated an increased absorption of BT in the terminal nerve endings of the muscle under repetitive electrical stimulation, suggesting that "muscle activity" also may play an important role. The aim of our study was to evaluate in humans the role of the muscle activity on the variability of the effect induced by BT type A. Eleven patients with blepharospasm and idiopathic facial hemispasm were studied by using neurophysiologic techniques. In nine patients, both extensor digitorum brevis (EDB) muscles were injected with low (3 IU), fixed doses of type A BT. For the first 24 h after administration of the drug, periodic electrical stimulation of only one EDB was used. The subsequent percentage changes in compound muscle action potential (CMAP) amplitude was calculated at different intervals over a 30-day period. The percentage in the CMAP for the stimulated EDB was compared with that of the contralateral nonstimulated side. We found that the effect of the induced neuromuscular blockade was significantly greater for the stimulated side. In the other two patients, we injected BT in one EDB and the same volume of normal saline solution in the contralateral muscle to assess the stability of the CMAP in untreated muscle over time. We observed that the CMAP was unchanged in the untreated EDB; therefore we concluded that muscle activity plays an important role in the variability of clinical response often seen.
当首次以固定剂量施用肉毒杆菌毒素（BT）时，患有相同形式肌张力障碍疾病的患者可能会出现不同的临床反应。许多因素可能导致这种现象，包括药物吸收的变异性。动物实验模型（大鼠膈肌制备）已证明，在重复电刺激下，肌肉终末神经末梢对BT的吸收增加，这表明“肌肉活动”也可能起重要作用。我们研究的目的是评估人类中肌肉活动对A型BT诱导效应变异性的作用。我们使用神经生理学技术对11例眼睑痉挛和特发性半面痉挛患者进行了研究。在9例患者中，双侧趾短伸肌（EDB）均注射了低剂量（3 IU）的固定剂量A型BT。在给药后的前24小时，仅对一侧EDB进行周期性电刺激。在30天内的不同时间间隔计算复合肌肉动作电位（CMAP）幅度的后续百分比变化。将受刺激EDB的CMAP百分比与对侧未受刺激侧的进行比较。我们发现，受刺激侧诱导的神经肌肉阻滞效果明显更大。在另外2例患者中，我们在一侧EDB注射BT，在对侧肌肉注射相同体积的生理盐水，以评估未治疗肌肉中CMAP随时间的稳定性。我们观察到未治疗的EDB中CMAP没有变化；因此我们得出结论，肌肉活动在常见的临床反应变异性中起重要作用。
