Objective:

We report a novel presentation of IgLON5-associated neurological disease with possible paraneoplastic phenomena, expanding the clinical phenotypic spectrum of this disorder.

Background:

Anti-IgLON5-associated neurological disease is characterized by neuroinflammatory and neurodegenerative features. Autopsies from advanced cases reveal phospho-tau accumulation in the hypothalamus and brainstem. Clinical features include sleep and movement disorders, bulbar symptoms, dysautonomia and motor neuron disease-like phenotypes. Overlap with progressive supranuclear palsy (PSP-like) is also seen.

Design/Methods:

A fifty-one-year-old man in general good health presented with deficits in visual fields, visual acuity and color vision. Funduscopic examination demonstrated bilateral optic disc edema confirmed by magnetic resonance imaging. Slit-lamp exam demonstrated granular-appearing optic discs and hemorrhagic telangiectasias. Treatment with high-dose steroids with taper was initiated. Early cessation of steroids caused symptom recurrence. New onset disabling orthostatic intolerance, daytime somnolence, sleep apnea, and twitching while sleeping were noted.

Results:

Repeat brain imaging demonstrated partial resolution of optic disc edema. Cerebrospinal fluid evaluation demonstrated normal opening pressure and glucose, 4 nucleated cells, elevated protein (82 mg/dl), and negative neuroinfectious work-up. Cytology showed rare lymphocytes and monocytes. IgLON5 antibodies were identified (1:8 titer). Whole-body PET scan demonstrated FDG-avid lesions in a testicle, with ultrasound demonstrating hypoechogenicity suggestive of infection/trauma vs burned-out tumor, representing a potential paraneoplastic etiology. His treatment regimen was escalated to monthly intravenous Cyclophosphamide infusions over 6 months.

Conclusions:

This patient presented with recurrent bilateral optic neuritis, evolving to develop sleep apnea, daytime hypersomnolence, and involuntary nocturnal movements. IgLON5 antibodies were detected in cerebrospinal fluid. Symptomatic response to immunosuppressive therapy, with symptom relapse on pausing immunosuppression was noted. While oculomotor abnormalities are reported in the disorder, this is a novel presentation of CNII involvement in a patient with IgLON5 antibodies. As understanding of IgLON-5 disease evolves, a low threshold for diagnostic suspicion is emphasized, as treatment may prevent irreversible neuronal damage and subsequent neurodegeneration.