Cortical Disinhibition Drives Freezing of Gait in Parkinson's Disease and an Exploratory Repetitive Transcranial Magnetic Stimulation Study

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2023-08-30 DOI:10.1002/mds.29595

Huimin Sun MD, Caiting Gan MD, Lina Wang MD, Min Ji MSc, Xingyue Cao MSc, Yongsheng Yuan MD, Heng Zhang MSc, Aidi Shan MSc, Mengxi Gao MSc, Kezhong Zhang MD, PhD

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引用次数: 1

Abstract

Background

Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD).

Objective

The aim was to reveal the mechanisms of “OFF-period” FOG (OFF-FOG) and “levodopa-unresponsive” FOG (ONOFF-FOG) in PD.

Methods

We measured the transcranial magnetic stimulation (TMS) indicators and gait parameters in 21 healthy controls (HCs), 15 PD patients with ONOFF-FOG, 15 PD patients with OFF-FOG, and 15 PD patients without FOG (Non-FOG) in “ON” and “OFF” medication conditions. Difference of TMS indicators in the four groups and two conditions and its correlations with gait parameters were explored. Additionally, we explored the effect of 10 Hz repetitive TMS on gait and TMS indicators in ONOFF-FOG patients.

Results

In “OFF” condition, short interval intracortical inhibition (SICI) exhibited remarkable attenuation in FOG patients (both ONOFF-FOG and OFF-FOG) compared to Non-FOG patients and HCs. The weakening of SICI correlated with impaired gait characteristics in FOG. However, in “ON” condition, SICI in ONOFF-FOG patients reduced compared to OFF-FOG patients. Pharmacological treatment significantly improved SICI and gait in OFF-FOG patients, and high-frequency repetitive TMS distinctly improved gait in ONOFF-FOG patients, accompanied by enhanced SICI.

Conclusions

Motor cortex disinhibition, represented by decreased SICI, is related to FOG in PD. Refractory freezing in ONOFF-FOG patients correlated with the their reduced SICI insensitive to dopaminergic medication. SICI can serve as an indicator of the severity of impaired gait characteristics in FOG and reflect treatments efficacy for FOG in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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皮层去抑制驱动帕金森病的步态冻结和探索性重复经颅磁刺激研究。

背景:参与姿势和步态调节的初级运动皮层功能障碍与帕金森病(PD)的步态冻结(FOG)有关。目的:探讨PD患者“OFF-period”(OFF-FOG)和“ONOFF-FOG”(左旋多巴无反应)的发生机制。方法:在“开”和“关”用药条件下，分别测量21例健康对照(hc)、15例“开”- OFF-FOG PD患者、15例“关”- OFF-FOG PD患者和15例无FOG PD患者(Non-FOG)的经颅磁刺激(TMS)指标和步态参数。探讨四组和两种情况下TMS指标的差异及其与步态参数的相关性。此外，我们还探讨了10hz重复性经颅磁刺激对ONOFF-FOG患者步态和经颅磁刺激指标的影响。结果:在“OFF”状态下，与非FOG患者和hcc相比，FOG患者(包括ONOFF-FOG和OFF-FOG)的短间隔皮质内抑制(SICI)表现出显著的衰减。SICI的减弱与FOG患者的步态特征受损相关。然而，在“ON”状态下，与OFF-FOG患者相比，ONOFF-FOG患者的SICI降低。药物治疗显著改善OFF-FOG患者的SICI和步态，高频重复TMS明显改善ONOFF-FOG患者的步态，并伴有SICI增强。结论:以SICI下降为代表的运动皮质去抑制与PD的FOG有关。ONOFF-FOG患者的难治性冻结与其SICI降低对多巴胺能药物不敏感相关。SICI可作为FOG患者步态特征受损程度的指标，反映PD患者FOG的治疗效果。©2023作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.