Fierro Brigida, Brighina Filippo, D'Amelio Marco, Daniele Ornella, Lupo Innocenzo, Ragonese Paolo, Palermo Antonio, Savettieri Giovanni
Department of Clinical Neurosciences, University of Palermo, Via G. La Loggia, 1, 90129 Palermo, Italy.
Exp Brain Res. 2008 Feb;184(4):521-8. doi: 10.1007/s00221-007-1121-y. Epub 2007 Sep 8.
Dopaminergic drugs and deep brain stimulation restore cortical inhibition in Parkinson disease (PD) patients. High-frequency rTMS was also found to increase cortical inhibition in PD but its therapeutic effect is still controversial. Here we hypothesize that, if dopaminergic drugs reverse to normal cortical excitability in M1, the effect of high-frequency (hf)-rTMS in PD patients could depend on whether they are in a medicated or unmedicated state. The present study aims to explore the lasting effects of sub-threshold hf rTMS trains over M1 on cortical inhibition in patients with "on" and without "off" L-DOPA treatment. Fourteen PD patients were examined twice while "on" and "off" medication. In both conditions, a paired-pulse paradigm was used to evaluate short intracortical inhibition (SICI) and long intracortical inhibition (LICI) that were evaluated before and after hf rTMS trains applied on the motor cortex. The results were compared with those obtained from normal controls. In baseline condition, SICI and LICI were significantly reduced in "off" compared to "on" patients and controls. hf-rTMS over the motor cortex significantly increased SICI and LICI in "off" medication PD patients. Magnetic stimulation proved to be ineffective when the same patients were in "on" state. The results showed that hf-rTMS affected intracortical inhibition (ICI) only in unmedicated patients. By restoring cortical inhibitory circuits dopaminergic drugs, normalize the excitability changes in M1 subsequent to motor rTMS. Whether patients are in a medicated or an unmedicated state would therefore appear to be critical for rTMS effects in PD patients. If a positive correlation exists between increased cortical inhibition and clinical improvement, hf-rTMS during the "off" state could be regarded as a potential add-on treatment to reduce the need of L-dopa and thus delay the adverse effects of its chronic use.
多巴胺能药物和深部脑刺激可恢复帕金森病（PD）患者的皮质抑制。高频重复经颅磁刺激（rTMS）也被发现可增加PD患者的皮质抑制，但其治疗效果仍存在争议。在此我们假设，如果多巴胺能药物使初级运动皮层（M1）的皮质兴奋性恢复正常，那么高频（hf）-rTMS对PD患者的影响可能取决于他们是处于服药状态还是未服药状态。本研究旨在探讨阈下hf rTMS序列对M1进行刺激对接受左旋多巴（L-DOPA）治疗“开”期和“关”期患者皮质抑制的长期影响。14例PD患者在服药“开”期和未服药“关”期各接受了两次检查。在两种状态下，均采用配对脉冲范式来评估短程皮质内抑制（SICI）和长程皮质内抑制（LICI），并在对运动皮层施加hf rTMS序列前后进行评估。将结果与正常对照组的结果进行比较。在基线状态下，与“开”期患者和对照组相比，“关”期患者的SICI和LICI显著降低。对运动皮层进行hf-rTMS可显著增加未服药“关”期PD患者的SICI和LICI。当同一患者处于“开”期时，磁刺激无效。结果表明，hf-rTMS仅对未服药患者的皮质内抑制（ICI）有影响。多巴胺能药物通过恢复皮质抑制回路，使运动rTMS后M1的兴奋性变化恢复正常。因此，患者处于服药状态还是未服药状态似乎对rTMS对PD患者的影响至关重要。如果皮质抑制增加与临床改善之间存在正相关，那么“关”期的hf-rTMS可被视为一种潜在的辅助治疗方法，以减少对L-多巴的需求，从而延缓其长期使用的不良反应。
