A Review of the Clinical and Polysomnographic Features of Sleep Disturbances in Patients With Anti‐IgLON5 Disease

This scoping review aims to synthesise prevailing scientific evidence on the sleep‐related manifestations of anti‐IgLON5 disease to identify distinctive sleep and/or polysomnographic patterns which may facilitate diagnosis. A systematic search was conducted to identify studies from 2014 to 2023 which included patients with sleep disturbances and immunohistochemically‐proven anti‐IgLON5 disease. Eligible studies included clinical trials, observational studies, and case series that contained descriptions of their sleep disturbances and/or polysomnographic features. Data on their clinical features, polysomnographic findings, and non‐sleep‐related symptoms were extracted and analysed. 55 cases from eight reports were analysed. Median age at onset was 61.8 years, with a 2‐year median delay to diagnosis. Sleep apnea (97.4%), parasomnia (61.5%), insomnia (41.0%), and daytime sleepiness (41.0%) were the most prevalent disturbances, of which two‐thirds exhibited multiple sleep disorders within the same patient. Most patients had co‐existing non‐sleep‐related features at the initial stages of evaluation, such as bulbar dysfunction (80%), dysautonomia (50.9%), and cognitive impairment (45.5%). Polysomnography ( n = 26) mostly showed the non‐specific features of reduced total sleep time, low sleep efficiency, increased arousal index, and elevated apnea‐hypopnea index in affected patients. Diagnosis of anti‐IgLON5 disease remains challenging. The diagnostic significance of undifferentiated non‐rapid eye movement and poorly‐structured N2 remains unproven. Polysomnographic anomalies were often non‐specific, and their evolution as with disease progression was difficult to discern without longitudinal polysomnography data. Regardless, anti‐IgLON5 disease should be strongly considered in patients with multiple sleep disorders and the above‐mentioned polysomnographic abnormalities, especially when accompanied by neurological anomalies.