Pharmacologic reversal of cortical hyperexcitability in patients with ALS
Pharmacologic reversal of cortical hyperexcitability in patients with ALS
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DOI：
10.1212/wnl.54.1.58
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发表时间：
2000-01-11
期刊：
影响因子：
9.9
通讯作者：
Bernardi, G
中科院分区：
文献类型：
--
作者：
Caramia, MD;Palmieri, MG;Bernardi, G
目的：通过给予促进GABA能传递的药物逆转ALS患者异常皮质内兴奋性的特征。背景资料：经颅磁刺激（TMS）揭示了ALS患者的皮层抑制异常，沉默期减少，以及通常在成对TMS下发生的皮层内抑制的缺失。抑制传递障碍可能在ALS的病理生理过程中起一定作用。方法：采用成对TMS，刺激间隔16 ms，对16例ALS患者进行了研究。该方案包括：（1）配对TMS的“无药物”特征;（2）摄入地西泮（3.5 mg）后30分钟的配对TRIS;（3）加巴喷丁（GBP）（600 mg/天）或利鲁唑（50 mg/天2次）治疗3周后的配对TMS。结果：ALS患者的皮质内抑制消失，这种异常情况可通过地西泮或GBP持续治疗逆转。我们还注意到，地西泮和GBP后，单一刺激的运动诱发电位振幅增加（p < 0.01）。结论：ALS患者的过度兴奋的药理学逆转的证明，使一个潜在的重大贡献，了解疾病的病理生理学，迄今为止一直逃避一个有效的治愈。
Objective: To reverse the profile of abnormal intracortical excitability in patients with ALS by administering drugs that promote GABAergic transmission. Background: Transcranial magnetic stimulation (TMS) has revealed abnormalities of cortical inhibition in ALS, a reduction of the silent period, and the absence of intracortical inhibition normally occurring in response to paired TMS. Impaired inhibitory transmission could play a role in the physiopathology of this illness, Methods: Using paired TMS with conditioning stimuli from 1-to-6-msec-interstimulus intervals, we investigated 16 patients with ALS. The protocol included: (1) the "drug-free" profile of paired TMS; (2) paired TRIS 30 minutes after the intake of diazepam (3.5 mg); (3) paired TMS after 3 weeks' treatment with gabapentin (GBP) (600 mg/day) or riluzole (50 mg/twice a day). Results: Intracortical inhibition is lost in patients with ALS, and this abnormal profile is reversed by diazepam or sustained treatment with GBP. We also noted that motor-evoked potential amplitudes to single stimuli increased (p < 0.01) after diazepam and GBP. Conclusions: The demonstration of pharmacologic reversal of hyperexcitability in patients with ALS makes a potentially significant contribution toward understanding the pathophysiology of a disease that has so far eluded an effective cure.