With a combination of autoimmune and neurodegenerative pathophysiology, anti-IgLON5 disease is unique and has a wide range of clinical features. Typical symptoms include sleep disorders, movement disorders, cognitive changes, and bulbar symptoms. We report a patient with anti-IgLON5 disease and electrodiagnostic findings suggestive of a neuromuscular transmission defect.

An elderly gentleman with a remote history of rectal adenocarcinoma presented with a four-year history of progressive limb weakness. He subsequently developed binocular diplopia, dysphagia, and shortness of breath that worsened at the end of the day, along with brief episodes of full body stiffness. Physical exam showed deconjugate gaze with binocular diplopia, proximal limb weakness, length dependent sensory deficits, and hyperreflexia. Acetylcholine receptor (AChR) and muscle specific kinase (MuSK) antibodies and creatine kinase were unremarkable. Electrodiagnostic testing revealed evidence of a peripheral neuropathy and unstable motor unit potentials in the frontalis, deltoid, and trapezius. Repetitive nerve stimulation of the facial and spinal accessory nerves was normal. Single fiber EMG (SFEMG) of the frontalis revealed an elevated mean jitter. Serum and CSF anti-IgLON5 were positive. Worsening gait dysfunction, dysphagia, and limb weakness led to gradual escalation of immunotherapies, which included IV methylprednisolone, IVIG, plasma exchange, and rituximab. The latter led to modest overall improvement.

Anti-IgLON5 disease is a complex entity with a phenotype that is yet to be fully fleshed out. It should be considered in patients with myasthenia gravis-like presentations, negative AChR and MuSK antibodies, and atypical features, such as abnormal movements or hyperreflexia, even in the presence of abnormal SFEMG testing. The etiology of the neurotransmission defect is unclear and future studies are needed to determine if there is true histopathologic or functional changes at the neuromuscular junction.