Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA.
J Neurophysiol. 2011 Jun;105(6):3034-41. doi: 10.1152/jn.00721.2010. Epub 2011 Apr 6.
Experimental animal models have suggested that the modulation of the amplitude and direction of vestibular reflexes are important functions of the vestibulocerebellum and contribute to the control of gaze and balance. These critical vestibular functions have been infrequently quantified in human cerebellar disease. In 13 subjects with ataxia telangiectasia (A-T), a disease associated with profound cerebellar cortical degeneration, we found abnormalities of several key vestibular reflexes. The vestibuloocular reflex (VOR) was measured by eye movement responses to changes in head rotation. The vestibulocollic reflex (VCR) was assessed with cervical vestibular-evoked myogenic potentials (cVEMPs), in which auditory clicks led to electromyographic activity of the sternocleidomastoid muscle. The VOR gain (eye velocity/head velocity) was increased in all subjects with A-T. An increase of the VCR, paralleling that of the VOR, was indirectly suggested by an increase in cVEMP amplitude. In A-T subjects, alignment of the axis of eye rotation was not with that of head rotation. Subjects with A-T thus manifested VOR cross-coupling, abnormal eye movements directed along axes orthogonal to that of head rotation. Degeneration of the Purkinje neurons in the vestibulocerebellum probably underlie these deficits. This study offers insights into how the vestibulocerebellum functions in healthy humans. It may also be of value to the design of treatment trials as a surrogate biomarker of cerebellar function that does not require controlling for motivation or occult changes in motor strategy on the part of experimental subjects.
实验动物模型表明，前庭反射幅度和方向的调节是前庭小脑的重要功能，有助于眼球运动和平衡的控制。这些关键的前庭功能在人类小脑疾病中很少被量化。在 13 名共济失调毛细血管扩张症（A-T）患者中，该疾病与严重的小脑皮质变性有关，我们发现了几种关键前庭反射的异常。前庭眼反射（VOR）通过眼球运动对头部旋转变化的反应来测量。前庭颈肌反射（VCR）通过颈前庭诱发肌源性电位（cVEMPs）评估，其中听觉点击导致胸锁乳突肌的肌电图活动。所有 A-T 患者的 VOR 增益（眼球速度/头部速度）均增加。VCR 的增加，与 VOR 的增加平行，间接提示 cVEMP 幅度的增加。在 A-T 患者中，眼球旋转轴的对准与头部旋转轴的对准不同。因此，A-T 患者表现出 VOR 交叉耦合，异常眼球运动沿与头部旋转轴正交的轴定向。前庭小脑中的浦肯野神经元的退化可能是这些缺陷的基础。这项研究深入了解了前庭小脑在健康人类中的功能。作为一种替代生物标志物，它也可能对治疗试验的设计有价值，因为它不需要控制实验对象的动机或运动策略的隐匿性变化。
