Characteristics and Mechanisms of Aperiodic Alternating Nystagmus

Aperiodic alternating nystagmus (AAN) is defined as spontaneous alternating nystagmus in which the direction of nystagmus reverses repeatedly but the reversals do not occur at a consistent cycle interval and the cycle durations and/or peak slow-phase velocities are irregular. The etiologic distribution of vestibular disorders associated with AAN and the underlying mechanisms remain unclear. This study aimed to identify the clinical characteristics and potential underlying mechanisms of AAN.

We analyzed quantitative eye-movement recordings, audiovestibular test results, and neuroimaging results of 22 patients with AAN, and conducted a systematic review of reported cases of AAN in both peripheral and central vestibular disorders.

The systematic review identified an additional 29 patients with AAN. Peripheral vestibular causes accounted for 32 (62.7%) of all 51 patients, and comprised acute peripheral vestibulopathy (n=16), Ménière's disease (n=9), vestibular schwannoma (n=3), vestibular paroxysmia (n=2), labyrinthine fistula (n=1), and lateral semicircular canal dysplasia (n=1). Central vestibular disorders (19.6%, n=10) comprised acute infarction (n=6) most commonly involving the medulla, brainstem glioma with concurrent cerebellar damage (n=1), traumatic diffuse brain injury (n=2), and adult-onset Alexander disease (n=1). The remaining 17.6% of cases (n=9) had undetermined causes. Compared with peripheral cases, central vestibular disorders were associated with significantly greater duration asymmetry of AAN (p=0.041), higher prevalence of persistent AAN (p=0.037), and more-frequent abnormal ocular motor findings (p<0.001). In contrast, reduced bithermal caloric responses were more prevalent in peripheral than central vestibulopathy (p<0.001).

AAN can result from various peripheral and central vestibular disorders. Greater duration asymmetry, persistence of AAN, and accompanying ocular motor abnormalities can suggest a central origin, whereas reduced bithermal caloric responses may support a peripheral origin.