Differentiating anti-IgLON5 disease and Lewy body dementia: a systematic review

Abstract

Background: Anti-IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is an autoimmune encephalitis which, due to its insidious onset, could mimic neurodegenerative disorders, and multiple symptoms overlap with those seen in dementia with Lewy bodies (DLB). We hypothesized that the symptomatology and findings in patients with anti-IgLON5 disease overlapped with that of DLB.

Objectives: To assess the commonality of features in anti-IgLON5 disease and DLB and identify potential red flags for anti-IgLON5 disease in patients undergoing diagnostic evaluation for DLB.

Methods: We searched in MEDLINE, Web of Science, and Embase from inception on December the 8th, 2022 with the search term "IgLON5". We performed a systematic review of case reports and case series of anti-IgLON5 disease, and two reviewers independently extracted data on symptoms and findings. Frequencies of symptoms were compared with consensus criteria for DLB.

Results: We included 57 studies with 127 individual case reports of anti-IgLON5 disease (mean age 63 years at diagnosis, median symptom duration 2 years). Cognitive dysfunction was reported in 45% of cases, REM-sleep behavioral disorder in 15%, and 14% had parkinsonism. Respiratory insufficiency was reported in 37%, and bulbar symptoms in 67%.

Conclusions: We found a significant overlap between anti-IgLON5 disease and DLB. We propose that anti-IgLON5 disease should be considered in young patients with DLB with chorea, gaze palsy, early dysphagia, or prominent respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti-IgLON5 disease.

Keywords: Anti-iglon5 disease; Autoimmune encephalitis; Cognitive dysfunction; Lewy body dementia; Movement disorders.