Inghilleri M, Gilio F, Conte A, Frasca V, Marini Bettolo C, Iacovelli E, Gregori B, Prencipe M, Berardelli A
Dipartimento Scienze Neurologiche, Università di Roma La Sapienza, Rome, Italy.
Exp Brain Res. 2006 Oct;174(4):667-72. doi: 10.1007/s00221-006-0506-7. Epub 2006 Aug 5.
Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold intensity progressively increases the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effects of topiramate (TPM) at different doses on cortical excitability variables tested with rTMS. We tested the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight patients before and after treatment with TPM at different doses for chronic neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor threshold) was applied at baseline and during the TPM induction phase (drug intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV 100 mg/day) and total TPM plasma concentrations were measured. The effects on the MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight control subjects. TPM had no effect on the resting motor threshold. Antiepileptic treatment at increasing doses abolished the normal rTMS-induced MEP facilitation. ANOVA showed that this was a dose-related effect. Accordingly, in patients receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP facilitation. TPM left the progressive lengthening of the CSP during the rTMS train unchanged. In control subjects, rTMS applied over repeated sessions elicited a constant increase in MEP size. Our results suggest that TPM modulates the excitatory intracortical interneurons probably by altering rTMS-induced synaptic potentiation. These drug-induced effects are related to TPM doses and plasma concentrations. In conclusion, rTMS may be useful for quantifying the effectiveness of antiepileptic drugs and for assessing individual responses to different drugs but acting through similar mechanisms, thus combining functional neurophysiological information and laboratory data.
以5赫兹频率和阈上强度进行的重复经颅磁刺激（rTMS）会使正常受试者的肌肉诱发电位（MEP）大小逐渐增加，皮质静息期（CSP）持续时间延长。本研究旨在评估不同剂量的托吡酯（TPM）对rTMS测试的皮质兴奋性变量的影响。我们测试了8例慢性神经性疼痛患者在不同剂量TPM治疗前后，局灶性rTMS诱发的MEP大小和CSP持续时间的促进作用。对每位患者，在基线时以及TPM诱导期（药物摄入方案：第1周25毫克/天，第2周50毫克/天，第3周75毫克/天，第4周100毫克/天）应用rTMS（5赫兹频率 - 静息运动阈值的120%），并测量TPM血浆总浓度。在8名对照受试者中测试了重复 sessions 中施加的5赫兹 - rTMS对MEP大小的影响。TPM对静息运动阈值无影响。剂量增加的抗癫痫治疗消除了正常rTMS诱导的MEP促进作用。方差分析表明这是一种剂量相关效应。因此，在接受较高剂量（75和100毫克）TPM的患者中，rTMS未能引发MEP促进作用。TPM使rTMS序列期间CSP的逐渐延长保持不变。在对照受试者中，重复sessions应用rTMS会使MEP大小持续增加。我们的结果表明，TPM可能通过改变rTMS诱导的突触增强来调节兴奋性皮质内中间神经元。这些药物诱导的效应与TPM剂量和血浆浓度有关。总之，rTMS可能有助于量化抗癫痫药物的有效性以及评估个体对不同药物的反应，但通过类似机制起作用，从而将功能性神经生理学信息和实验室数据结合起来。
