Hyperactive Otolith-Ocular Reflex During Heat Tilt (Rabbit's Eye Sign) In Anti-Ma2 Rhombencephalitis

Otolith-ocular reflex (OOR) (contralateral ocular torsion [ocular counter-roll, OCR] and skew deviation [upward deviation of the lowermost eye and/or downward deviation of the uppermost eye]), helps to maintain eye position and stabilize fixation in response to head and/or body tilt in the roll plane. While prominent in lateral-eyed animals, OOR is vestigial in humans, indicating the frontal-eyed system has evolved to inhibit this reflex. We show that OOR can be released under pathological conditions. We describe a patient with anti-Ma2-associated rhombencephalitis manifesting with hyperactive OOR, suggesting cerebellar inhibition failure over OOR brainstem machinery. A 38-year-old male presented with a 6-month history of vertical binocular diplopia exclusively elicited during head tilt to the sides, and difficulty looking down. During head tilts, there was marked OCR in both eyes and prominent hyperdeviation of the lowermost eye. There was additional supranuclear vertical saccadic palsy. Brain MRI showed mild midbrain atrophy. There were high titers of anti-Ma2 antibodies both in serum and CSF, linked to the presence of a mediastinal seminoma. Treatment with anti-inflammatory drugs was ineffective, and tumor-directed therapy was further planned. Hyperactive otolith-ocular reflex (rabbit's eye sign) is a unique finding in humans. Its presence warrants the investigation of cerebellar/brainstem disease.