Louis Elan D, Lenka Abhishek
Division of Movement Disorders, Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA.
Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA.
Tremor Other Hyperkinet Mov (N Y). 2017 Jul 13;7:473. doi: 10.7916/D8FF40RX. eCollection 2017.
Although essential tremor (ET) is the most common tremor disorder, its pathogenesis is not fully understood. The traditional model of ET, proposed in the early 1970s, posited that the inferior olivary nucleus (ION) was the prime generator of tremor in ET and that ET is a disorder of electrophysiological derangement, much like epilepsy. This article comprehensively reviews the origin and basis of this model, its merits and problems, and discusses whether it is time to lay this model to rest.
A PubMed search was performed in March 2017 to identify articles for this review.
The olivary model gains support from the recognition of neurons with pacemaker property in the ION and the harmaline-induced tremor models (as the ION is the prime target of harmaline). However, the olivary model is problematic, as neurons with pacemaker property are not specific to the ION and the harmaline model does not completely represent the human disease ET. In addition, a large number of neuroimaging studies in ET have not detected structural or functional changes in the ION; rather, abnormalities have been reported in structures related to the cerebello-thalamo-cortical network. Moreover, a post-mortem study of microscopic changes in the ION did not detect any differences between ET cases and controls.
The olivary model largely remains a physiological construct. Numerous observations have cast considerable doubt as to the validity of this model in ET. Given the limitations of the model, we conclude that it is time now to lay this model to rest.
尽管特发性震颤（ET）是最常见的震颤疾病，但其发病机制尚未完全明确。20世纪70年代初提出的ET传统模型认为，下橄榄核（ION）是ET震颤的主要起源部位，且ET是一种电生理紊乱疾病，与癫痫非常相似。本文全面回顾了该模型的起源和基础、其优点和问题，并探讨是否到了摒弃该模型的时候。
2017年3月进行了PubMed检索，以确定用于本综述的文章。
橄榄核模型得到了ION中具有起搏器特性的神经元的发现以及 harmaline 诱导的震颤模型（因为ION是 harmaline 的主要靶点）的支持。然而，橄榄核模型存在问题，因为具有起搏器特性的神经元并非ION所特有，且 harmaline 模型并不能完全代表人类疾病ET。此外，大量关于ET的神经影像学研究未检测到ION的结构或功能变化；相反，在与小脑 - 丘脑 - 皮质网络相关的结构中报告了异常。而且，一项关于ION微观变化的尸检研究未发现ET病例与对照组之间存在任何差异。
橄榄核模型在很大程度上仍然是一种生理学构想。众多观察结果对该模型在ET中的有效性提出了相当大的质疑。鉴于该模型的局限性，我们得出结论，现在是摒弃该模型的时候了。
