The variability in the clinical effect induced by botulinum toxin type A: The role of muscle activity in humans
The variability in the clinical effect induced by botulinum toxin type A: The role of muscle activity in humans
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DOI：
10.1002/mds.870120115
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发表时间：
1997-01-01
影响因子：
8.6
通讯作者：
DeGrandis, D
中科院分区：
文献类型：
--
作者：
Eleopra, R;Tugnoli, V;DeGrandis, D
当首次以固定剂量施用肉毒杆菌毒素 (BT) 时，在患有相同形式的肌张力障碍的患者中可以观察到不同的临床反应。许多因素可能导致这种现象，包括药物吸收速率的变化。动物实验模型（大鼠膈肌制备）已证明，在重复电刺激下，肌肉末端神经末梢对 BT 的吸收增加，表明“肌肉活动”也可能发挥重要作用。我们研究的目的是评估人类肌肉活动对 A 型 BT 引起的效应变异性的作用。通过使用神经生理学技术对 11 名患有眼睑痉挛和特发性面肌痉挛的患者进行了研究。在 9 名患者中，双侧趾短伸肌 (EDB) 均注射了低剂量 (3 IU) 固定剂量的 A 型 BT。在给药后的前 24 小时内，仅使用一个 EDB 进行定期电刺激。计算 30 天内不同时间间隔的复合肌肉动作电位 (CMAP) 振幅的后续百分比变化。将受刺激 EDB 的 CMAP 百分比变化与对侧未刺激侧进行比较。我们发现，诱导的神经肌肉阻滞的效果对于受刺激的一侧明显更大。在另外两名患者中，我们在一名 EDB 中注射 BT，并在对侧肌肉中注射相同体积的生理盐水溶液，以评估未经治疗的肌肉中 CMAP 相对于一名患者的稳定性。我们观察到，未经处理的 EDB 中的 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的变异性中起着重要作用。
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 in the 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 change 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 One. 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.