Characterize the clinical features and vestibulo-ocular function of patients with anti-glutamic acid decarboxylase 65 (anti-GAD65) associated neurologic disorders who were referred for evaluation from Neuro-ophthalmology or Neurotology.

Anti-GAD65 associated neurologic disorders are rare. The most recognized is Stiff-person syndrome (SPS), but other phenotypes have been described, such as cerebellar ataxia and brainstem manifestations.

Retrospective review of medical records from 1997 to 2018 at Johns Hopkins Hospital revealed 170 patients with diagnosis of SPS or anti-GAD65 associated neurologic disorder, of which eight (4.7%) were referred for neurologic evaluation by Neuro-ophthalmology or Neurotology.  Video-oculography (VOG) was used to analyze ocular motor and vestibular function that was consistent with posterior fossa involvement.

Three patients were referred from Neuro-ophthalmology and five from Neurotology. Symptoms for which patients were initially seen included diplopia, vertigo, and dizziness. Four additionally exhibited ataxia. Average age was 62 years (range: 49-77) and average time to diagnosis was 5.6 years. The majority were male and Caucasian. Four had coexisting autoimmune conditions. None had a paraneoplastic etiology. All had elevated anti-GAD65 antibodies in serum. Six had CSF studies, of which five showed elevated anti-GAD65 antibodies. VOG was performed in seven, with findings of: spontaneous nystagmus (seven, one with fixation and six with it removed), positional nystagmus (five), saccadic pursuit (four), skew deviation (three), hyperventilation induced nystagmus (three), abnormal vestibulo-ocular reflex suppression (three), abnormal head impulse testing (three), and gaze evoked nystagmus with rebound (two). Seven received immunotherapy, all of whom reported functional improvement. Five received symptomatic therapy, four of whom reported functional improvement.

Besides SPS, other phenotypes of anti-GAD65 associated disorders are increasingly recognized. Brainstem abnormalities can be further characterized on VOG. Ocular and vestibular symptoms may prompt initial evaluation by other specialties. Hence, further inter-disciplinary education and collaboration may help increase awareness of these less-recognized symptoms and facilitate earlier diagnosis.