1)杭州师范大学附属医院认知与脑疾病研究中心,杭州 311121;2)杭州师范大学附属医院神经内科,杭州 311121
浙江省精准精神医学重点实验室开放基金(2025A2)和浙江省自然科学基金(LY23C090002)资助项目。
1)Centre for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 311121, China;2)Department of Neurology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 311121, China
This work was supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry (2025A2) and the Natural Science Foundation of Zhejiang Province (LY23C090002).
马查多-约瑟夫病(Machado-Joseph disease,又称脊髓小脑共济失调3型,spinocerebellar ataxia type 3,SCA3)是全球最常见的常染色体显性遗传性小脑共济失调类型。SCA3具有进行性致残的特征,目前临床仍缺乏有效的疾病修饰疗法。重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)作为一种极具潜力的非侵入性干预手段备受关注,但其临床应用长期受限于刺激方案不统一及治疗机制不明。近期,Chen等发表在Brain Stimulation上的一项里程碑式研究,通过结合高剂量间歇性theta爆发刺激(intermittent theta-burst stimulation,iTBS)与同步经颅磁刺激(transcranial magnetic stimulation,TMS)-脑电图(electroencephalogram,EEG)技术,有效应对了上述挑战。本文对该研究的主要发现进行了深入评述,重点阐述了小脑-皮层抑制(cerebello-cortical inhibition,CBI)功能的恢复是其关键的治疗机制。此外,本文进一步探讨了该研究的广泛意义,提出未来的转化研究应整合加速iTBS(accelerated iTBS,aiTBS)范式、皮层反应测量(cortical response measurements,CRM)及个体化神经导航技术,从而开启共济失调精准神经调控的新纪元。
Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.
韩亚真,周洁,陈宇超,高忠明,车先伟.重塑“小脑抑制”:重复经颅磁刺激治疗马查多-约瑟夫病的机制解析与精准医疗展望[J].生物化学与生物物理进展,2026,53(2):505-510
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