To describe two patients with anti-IgLON5 disease whose presentations expand the recognized clinical and radiologic phenotype.
Anti-IgLON5 disease is a rare autoimmune neurological disorder with six established phenotypes: sleep disorder, bulbar syndrome, PSP-like syndrome, cognitive decline with chorea, peripheral nervous system involvement, and cerebellar ataxia with tremor. MRI is typically unremarkable, and cancer association has not been established.
We report two patients evaluated at a single academic center with confirmed anti-IgLON5 antibodies and atypical presentations not captured by existing phenotypic classifications.
Patient 1 is a 63-year-old woman who developed subacute visual distortion, impaired depth perception, intermittent diplopia, and severe posture-dependent disequilibrium with migrainous features. Neuro-vestibular testing revealed central positional nystagmus, high VOR gains, saccadic pursuit, and impaired VOR suppression. MRI demonstrated diffuse corpus callosum T2/FLAIR hyperintensities and bilateral oculomotor nerve enhancement. Serum anti-IgLON5 titer was 1:7,680 with CSF positivity and 7 oligoclonal bands. Concurrent breast biopsy revealed invasive ductal carcinoma. She improved after IV methylprednisolone and IVIG, with a fourfold titer decline. Sleep symptoms were absent throughout. Patient 2 is an 81-year-old man with progressive generalized chorea, gait impairment, cognitive decline, and excessive daytime sleepiness over two years. Notably, choreiform movements persisted during sleep, documented on video. Serum anti-IgLON5 CBA was positive with negative IFA. MRI showed only diffuse atrophy. He responded to valbenazine for chorea and IVIG for the underlying disease, later transitioning to rituximab for sustained benefit.
These cases broaden the anti-IgLON5 phenotype. Patient 1 demonstrates a novel ocular-vestibular syndrome with bilateral oculomotor nerve enhancement, corpus callosum involvement, and concurrent malignancy. Patient 2 illustrates sleep-persistent chorea, contrasting with the typical suppression of chorea during sleep. Both cases responded to immunotherapy, supporting early treatment in this evolving disease spectrum.