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).

一名 44 岁女性，抗 YO 副肿瘤性小脑综合征呈阳性且影像学正常，但出现了眼部运动障碍，包括周期性交替性眼球震颤 (PAN)、凝视诱发性眼球震颤 (GEN) 和反跳性眼球震颤 (RN)。在注视期间，存在典型的 PAN，但注视位置的变化会引起 GEN 和 RN 复杂的、随时间变化的振荡。为了阐明这种不寻常的眼球震颤模式的病理生理学，我们开发了介导前庭眼反射和凝视保持的电路正常功能的数学模型，包括它们的适应性机制。模拟表明，我们患者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：减少凝视积分器的时间常数，产生 GEN 和 RN，以及增加前庭速度存储正增益的增益反馈回路，产生 PAN。我们得出的结论是，我们患者的眼球震颤的凝视和时间变化模式可以通过产生典型 PAN 的一个模型和产生典型 GEN 和 RN 的另一种模型的叠加来解释，而不需要在注视保持系统中使用新的振荡器或者两个模型之间更复杂的非线性相互作用。该分析提出了一种在 PAN 等时变眼球震颤的情况下发现凝视诱发和反弹眼球震颤的策略。我们的结果也与当前小脑功能划分的想法一致，用于控制前庭速度存储机制（结节和腹侧悬雍垂）和保持水平凝视稳定（絮球和扁桃体）。