帕金森病中运动皮层去抑制与临床运动特征分离：纵向证据

文献信息

中文摘要

背景： 在帕金森病中，运动功能障碍在很大程度上反映了多巴胺依赖的病理生理改变和随时间进展的代偿机制，并且部分可随多巴胺能治疗逆转。我们近期的横断面观察提示，采用经颅磁刺激短间隔皮质内抑制（SICI）评估的原发性运动皮层去抑制与临床运动特征不相关，不随疾病阶段进展，而是与嗅觉功能障碍相关——后者是一种常见的前驱期且非多巴胺依赖的特征。
目的： 我们旨在提供纵向证据，以支持或反对帕金森病中运动皮层去抑制与临床运动特征分离的假说。
方法： 我们在三个队列（总计n=95例患者）中比较SICI：（1）基线和2年随访（n=43），同时进行运动评估和18F-DOPA正电子发射断层扫描（PET）成像（n=24）；（2）左旋多巴给药前后（n=30）；（3）聚焦超声丘脑底核毁损术前后（n=22）。我们还纳入了来自两项既往已发表研究的合并健康对照组（n=75）。应用贝叶斯统计正式评估支持效应存在或不存在的证据。
结果： 与对照组相比，患者的SICI如预期降低，贝叶斯证据为非常强至极强。我们发现有证据表明，皮质去抑制并未随经18F-DOPA PET确认的临床明显疾病进展而加重，也未在临床有效剂量的左旋多巴或丘脑底核毁损术后改善。此外，SICI的变化在各队列中与运动特征的变化不相关。
结论： 这些发现提供了纵向证据，表明帕金森病中运动皮层去抑制在很大程度上与临床运动特征分离。© 2026 International Parkinson and Movement Disorder Society。

英文摘要

BACKGROUND: In Parkinson's disease, motor dysfunction largely reflects dopamine-dependent pathophysiological alterations and compensatory mechanisms that progress over time and are partially reversible with dopaminergic treatment. Our recent cross-sectional observations suggest that disinhibition of the primary motor cortex-assessed with short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation-does not correlate with clinical motor features, does not progress across disease stages, and instead correlates with olfactory dysfunction, a common prodromal and dopamine-independent feature.
OBJECTIVE: We aimed to provide longitudinal evidence for or against the hypothesis that motor cortex disinhibition is dissociated from clinical motor features in Parkinson's disease.
METHODS: We compared SICI across three cohorts (total n = 95 patients): (1) baseline and 2-year follow-up (n = 43), with concurrent motor assessment and 18F-DOPA positron emission tomography (PET) imaging (n = 24); (2) before and after levodopa administration (n = 30); and (3) before and after focused ultrasound subthalamotomy (n = 22). We also included a pooled healthy control group (n = 75) from two previously published studies. Bayesian statistics was applied to formally assess evidence for the presence or the absence of an effect.
RESULTS: SICI was expectedly reduced, with very strong to extreme Bayesian evidence, in patients compared with control subjects. We found evidence that cortical disinhibition did not worsen with clinically evident disease progression confirmed with 18F-DOPA PET and did not improve following a clinically effective dose of levodopa or subthalamotomy. Moreover, changes in SICI did not correlate with changes in motor features across cohorts.
CONCLUSIONS: These findings provide longitudinal evidence that motor cortex disinhibition is largely dissociated from clinical motor features in Parkinson's disease. © 2026 International Parkinson and Movement Disorder Society.