Objective:

To investigate vestibular characteristics in patients with anti-glutamic acid decarboxylase 65 (anti-GAD65)-associated neurologic disorders using video head-impulse testing (vHIT) and examine its relationship with cerebellar radiologic markers.

Background:

Anti-GAD65-associated neurologic disorders may present with prominent vestibular and oculomotor (VOM) dysfunction, likely due to involvement of the vestibulocerebellum. vHIT allows for objective assessment of the vestibular system. vHIT patterns in anti-GAD65-associated neurologic disorders have never been reported before.

Design/Methods:

Retrospective review of medical records from 1997 to 2024 identified patients with diagnosis of anti-GAD65-associated neurologic disorders who also completed vHIT. Phenotypes included stiff-person syndrome spectrum disorders (SPSD) and GAD65-positive pure cerebellar ataxia (CA). vHIT parameters included vestibulo-ocular reflex (VOR) gain, and presence of catch-up saccades. A VOR gain <0.7 was considered decreased, and >1.0 increased or hyperactive. Available Brain MRI and FDG-PET scans were analyzed for measurement of cerebellar volume and uptake analysis, respectively.

Results:

A total of 33 out of 228 patients were identified. The majority of patients reported vestibular symptoms (67%) and most common phenotypes were SPS-plus (51%), followed by classic SPS (27%). Median (IQR) titer of GAD65-antibody in serum was 118,939 IU/mL (22,975 - 312,361IU/mL). Eye movement findings localizing to the cerebellum were present in 82% of patients. Mean VOR gain was 1.05±0.19 in classic SPS, 1.13±0.13 in progressive encephalomyelitis with rigidity and myoclonus (PERM), 1.05±0.23 in SPS-plus, and 0.85±0.21 in CA. One-way ANOVA revealed significant difference in mean VOR gain among the various phenotypes;F(3,64)= 3.11, p= .032. VOR gain was increased in 58% of patients, mostly bilaterally. The majority of vHITs did not have presence of catch-up saccades, although two showed a hyperactive VOR with back-up saccades. Brain and PET scan findings are currently being analyzed.

Conclusions:

The vHIT pattern in patients with anti-GAD65-associated neurologic disorders suggest vestibulocerebellar dysfunction. Together with video-oculography findings, it may provide diagnostic clues for these rare disorders.