Elder Christopher, Kerestes Rebecca, Opal Puneet, Marchese Maria, Devinsky Orrin
NYU Grossman School of Medicine and NYU Langone Health, New York, New York, USA.
Department of Psychology, Monash University, Clayton, Victoria, Australia.
Epilepsia. 2025 Jun;66(6):1773-1792. doi: 10.1111/epi.18316. Epub 2025 Mar 13.
The cerebellum, a subcortical structure, is traditionally linked to sensorimotor integration and coordination, although its role in cognition and affective behavior, as well as epilepsy, is increasingly recognized. Cerebellar dysfunction in patients with epilepsy can result from genetic disorders, antiseizure medications, seizures, and seizure-related trauma. Impaired cerebellar function, regardless of cause, can cause ataxia (imbalance, impaired coordination, unsteady gait), tremor, gaze-evoked nystagmus, impaired slow gaze pursuit and saccade accuracy, as well as speech deficits (slurred, scanning, or staccato). We explore how cerebellar dysfunction can contribute to epilepsy, reviewing data on genetic, infectious, and neuroinflammatory disorders. Evidence of cerebellar dysfunction in epilepsy comes from animal studies as well as human neuropathology and structural magnetic resonance imaging (MRI), functional and diffusion tensor MRI, positron emission and single photon emission computerized tomography, and depth electrode electro-encephalography studies. Cerebellar lesions can infrequently cause epilepsy, with focal motor, autonomic, and focal to bilateral tonic-clonic seizures. Antiseizure medication-resistant epilepsy typically presents in infancy or before age 1 year with hemifacial clonic or tonic seizures ipsilateral to the cerebellar mass. Lesions are typically asymmetric benign or low-grade tumors in the floor of the fourth ventricle involving the cerebellar peduncles and extending to the cerebellar hemisphere. Electrical stimulation of the cerebellum has yielded conflicting results on efficacy, although methodological issues confound interpretation. Epilepsy-related comorbidities including cognitive and affective disorders, falls, and sudden unexpected death in epilepsy may also be impacted by cerebellar dysfunction. We discuss how cerebellar dysfunction may drive seizures and how genetic epilepsies, seizures and seizure therapies may drive cerebellar dysfunction, and how our understanding of epilepsy-related comorbidities through basic neuroscience, animals models and patient studies can advance our understanding and improve patient outcomes.
小脑是一种皮质下结构，传统上被认为与感觉运动整合及协调有关，尽管其在认知、情感行为以及癫痫方面的作用正日益受到认可。癫痫患者的小脑功能障碍可由遗传疾病、抗癫痫药物、癫痫发作及与发作相关的创伤引起。无论病因如何，小脑功能受损均可导致共济失调（平衡失调、协调能力受损、步态不稳）、震颤、凝视诱发的眼球震颤、缓慢凝视追踪和扫视准确性受损，以及言语缺陷（含糊不清、断续或急促）。我们探讨小脑功能障碍如何导致癫痫，回顾有关遗传、感染和神经炎症性疾病的数据。癫痫中小脑功能障碍的证据来自动物研究以及人类神经病理学、结构磁共振成像（MRI）、功能和扩散张量MRI、正电子发射断层扫描和单光子发射计算机断层扫描，以及深部电极脑电图研究。小脑病变很少会引发癫痫，表现为局灶性运动性、自主性发作，以及从局灶性发作发展为双侧强直阵挛性发作。抗癫痫药物难治性癫痫通常在婴儿期或1岁之前出现，发作表现为与小脑肿块同侧的半侧面部阵挛或强直性发作。病变通常是第四脑室底部不对称的良性或低度肿瘤，累及小脑脚并延伸至小脑半球。小脑电刺激在疗效方面产生了相互矛盾的结果，尽管方法学问题使解释变得复杂。癫痫相关的合并症，包括认知和情感障碍、跌倒以及癫痫猝死，也可能受到小脑功能障碍的影响。我们讨论小脑功能障碍如何引发癫痫发作，遗传癫痫、癫痫发作及癫痫治疗如何导致小脑功能障碍，以及我们如何通过基础神经科学、动物模型和患者研究对癫痫相关合并症的理解来促进我们的认识并改善患者预后。
