Gaze-Evoked and Centripetal Nystagmus in Creutzfeldt-Jakob Disease

This is a 65-year-old woman who experienced a progressive cerebellopathy over several months. Initially, she presented with mild gait imbalance and positional vertigo, and there was only apogeotropic positional nystagmus (more pronounced in supine roll test compared to Dix-Hallpike) with a very slight downbeat component (peak slow phase velocity [SPV] 2-3 degrees/second). In right roll, there was a 16 d/s peak SPV left-beating nystagmus and she was maximally symptomatic in this position. In left roll, there was a -7 d/s peak SPV right-beating nystagmus and she was less symptomatic. Ocular motor and vestibular exams (including head impulse and video head impulse testing) were normal. A presumptive diagnosis of left apogeotropic horizontal canal benign paroxysmal positional vertigo was made, although there was no response to repeated positional maneuvers over one week. Contrast-enhanced MRI was normal with respect to the posterior fossa. Clear gait and limb ataxia were apparent in the following weeks, and a variety of central ocular motor abnormalities developed including dysmetric saccades, impaired smooth pursuit (with relatively spared vestibulo-ocular [VOR] suppression horizontally given loss of the horizontal VOR), fixation-removed downbeat nystagmus, gaze-evoked and rebound nystagmus. Extensive testing looking for infectious, inflammatory and neoplastic disorders was unrevealing. By the second MRI, the thalamic hemispheres were slightly hyperintense on T2-weighted/FLAIR and diffusion weighted imaging (DWI). CSF RT-QuIC and 14-3-3 protein were positive, and CSF T-tau protein was abnormal at >4000, confirming the diagnosis of Creutzfeldt-Jakob disease (CJD). Regarding her gaze-holding function, after sustained lateral gaze for greater than 10 seconds, nystagmus reversed direction from gaze-evoked nystagmus (e.g., in right gaze, slow phase drift toward primary gaze and fast phase back to the right - centrifugal nystagmus) to centripetal nystagmus (e.g., in right gaze, slow phase drift to the right and fast phase back toward primary gaze). Gaze-evoked nystagmus (GEN) is common with cerebellar disease, as is rebound nystagmus. GEN results from impaired function of the neural integrators (nucleus prepositus hypoglossi and medial vestibular nucleus for horizontal gaze-holding and interstitial nucleus of Cajal for vertical and torsional gaze-holding), while the flocculus/paraflocculus helps to improve neural integrator function1. Therefore, horizontal and vertical GEN is commonly seen with cerebellar disease. With GEN, compensatory mechanisms attempt to minimize the slow phase drift back toward primary position, and this compensatory bias will shift the resting position of the eyes peripherally(2). Ideally, this shift in the null region should be balanced with the slow phase drift back to center. Imbalance between compensatory and pathological biases can create its own slow phase drift. In the case of rebound nystagmus, if the patient looks to the right, in an effort to minimize the leftward slow phase drift back toward center, compensatory mechanisms will pull the null region farther out to the right. When the patient looks from right to straight ahead gaze, the now left-beating (rebound) nystagmus is akin to a GEN and continues until the compensatory and pathological biases are in equipoise(1, 2). Likewise, centripetal nystagmus probably also represents a compensatory shift in the null region farther to the right as compared to the actual eye position in right gaze, the result being a rightward slow phase drift followed by a centripetal fast phase. Thus, the appearance of centripetal nystagmus may represent an over-compensation, usually brought on by sustained eccentric gaze(1). In patients with CJD who have cerebellar manifestations, gaze-evoked and rebound nystagmus have been commonly reported, in addition to less common ocular motor signs like periodic alternating nystagmus (not seen in this patient) and centripetal nystagmus(3), although these findings are not specific for the diagnosis of CJD. 1. Buttner U, Grundei T. Gaze-evoked nystagmus and smooth pursuit deficits: their relationship studied in 52 patients. J Neurol 1995;242:384-389. 2. Leech J, Gresty M, Hess K, Rudge P. Gaze failure, drifting eye movements, and centripetal nystagmus in cerebellar disease. Br J Ophthalmol 1977;61:774-781. 3. Helmchen Ch, Buttner U. Centripetal nystagmus in a case of Creutzfeldt-Jacob disease. Neuro-Ophthalmology 1995;15:187-192.