A 72-year-old man presented with longstanding REM sleep behavior disorder, sensory neuropathy, and progressive bulbar symptoms including dysarthria, dysphagia, dyspnea with inspiratory stridor, diplopia, gait instability, stiffness, urinary retention, constipation, and cognitive decline. MRI brain showed midbrain atrophy with nonspecific white matter changes; DaTscan was normal. Neurologic exam revealed supranuclear palsy with impaired upward gaze, apraxia (ideational, ideomotor, and limb-kinetic), axial rigidity, bradykinesia, gait instability, and length-dependent sensory loss. Serum anti-IgLON5 antibodies were positive (1:960), confirmed in CSF; CSF showed 2 WBC, normal protein, and negative oligoclonal bands.

The patient had recurrent hospitalizations for hypercapnic respiratory failure, aspiration pneumonia, and cardiac arrests, requiring tracheostomy and PEG placement. He received IVIG (2 g/kg over 5 days), plasma exchange, and two doses of rituximab. He was later transitioned to biweekly IVIG (1 g/kg every 2 weeks) while rituximab was held due to infection risk. Immunotherapy stabilized disease progression with modest cognitive and functional improvement.

This case highlights the severe, multisystem nature of anti-IgLON5 disease and supports aggressive, individualized immunotherapy. Early recognition is critical to reduce morbidity and mortality, particularly in patients with significant respiratory involvement.