Modeling the interaction among three cerebellar disorders of eye movements: periodic alternating, gaze-evoked and rebound nystagmus.
Modeling the interaction among three cerebellar disorders of eye movements: periodic alternating, gaze-evoked and rebound nystagmus.
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DOI：
10.1007/s10827-021-00790-9
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发表时间：
2021-08
影响因子：
1.2
通讯作者：
中科院分区：
文献类型：
--
作者：
一名44岁女性，抗YO副肿瘤性小脑综合征阳性，成像正常，出现眼部运动障碍，包括周期性交替性眼球震颤（PAN）、凝视诱发性眼球震颤（GEN）和反弹性眼球震颤（RN）。在固定有典型的PAN，但在凝视位置的变化诱发复杂的，随时间变化的振荡GEN和RN。为了揭示这种不寻常的眼球震颤模式的病理生理学，我们开发了一个数学模型，介导前庭眼反射和凝视保持的电路的正常功能，包括其自适应机制。模拟显示，我们病人的所有发现都可以用小脑回路中两个小的、孤立的变化来解释：降低注视保持积分器的时间常数，产生GEN和RN，增加前庭速度存储正反馈回路的增益，产生PAN。我们的结论是，在我们的病人的凝视和随时间变化的模式的眼球震颤，可以占一个模型，产生典型的PAN和另一个模型，产生典型的GEN和RN的叠加，而不需要一个新的振荡器在凝视保持系统或更复杂的，两个模型之间的非线性相互作用。该分析提出了一种策略，用于在时变眼球震颤（如PAN）的情况下发现凝视诱发和反弹性眼球震颤。我们的研究结果也与目前的想法，小脑功能的前庭速度存储机制（结节和腹侧悬雍垂）的控制和保持水平凝视稳定（小叶和扁桃体）的划分是一致的。
A woman, age 44, with a positive anti-YO paraneoplastic cerebellar syndrome and normal imaging developed an ocular motor disorder including periodic alternating nystagmus (PAN), gaze-evoked nystagmus (GEN) and rebound nystagmus (RN). During fixation there was typical PAN but changes in gaze position evoked complex, time-varying oscillations of GEN and RN. To unravel the pathophysiology of this unusual pattern of nystagmus, we developed a mathematical model of normal function of the circuits mediating the vestibular-ocular reflex and gaze-holding including their adaptive mechanisms. Simulations showed that all the findings of our patient could be explained by two, small, isolated changes in cerebellar circuits: reducing the time constant of the gaze-holding integrator, producing GEN and RN, and increasing the gain of the vestibular velocity-storage positive feedback loop, producing PAN. We conclude that the gaze- and time-varying pattern of nystagmus in our patient can be accounted for by superposition of one model that produces typical PAN and another model that produces typical GEN and RN, without requiring a new oscillator in the gaze-holding system or a more complex, nonlinear interaction between the two models. This analysis suggest a strategy for uncovering gaze-evoked and rebound nystagmus in the setting of a time-varying nystagmus such as PAN. Our results are also consistent with current ideas of compartmentalization of cerebellar functions for the control of the vestibular velocity-storage mechanism (nodulus and ventral uvula) and for holding horizontal gaze steady (the flocculus and tonsil).
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