Red flags and symptom overlap in anti‐IgLON5 disease and dementia with Lewy bodies – a systematic review

Abstract

AbstractBackgroundAnti‐IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is a type of autoimmune encephalitis (AE) but unlike other AEs anti‐IgLON5 disease has an insidious onset and prominent tau pathology. Anti‐IgLON5 disease mimics neurodegenerative disorders and multiple symptoms overlap with the second most common cause of neurodegenerative dementia, Dementia with Lewy bodies (DLB). The purpose of this review was to assess the overlap in features between anti‐IgLON5 disease and DLB and to identify potential red flags for anti‐IgLON5 disease in patients undergoing diagnostic evaluation for DLB.MethodWe conducted a systematic review of reports on features of anti‐IgLON5 disease from full‐text articles in MEDLINE, Web of Science, and Embase. The reviewed data was compared to consensus criteria for DLB.ResultWe included 57 studies with a total of 125 cases of anti‐IgLON5 disease. The median age was 61 years at diagnosis, with a median symptom duration of 3.5 years. Ten % (13/113 cases) presented with cognitive dysfunction. REM‐sleep disorder was diagnosed in 43% (17/39 cases), and movement disorders were present in 73% (80/110 cases) of which parkinsonism was identified in 21% (18/85 cases). In 47% (25/59 cases), psychiatric disturbances were reported, and hallucinations were observed in 37% (11/30 cases). Dysautonomia was reported in 56% (42/75 cases). Regarding red flags for anti‐IgLON5 disease, bulbar symptoms were observed in 75% (82/109 cases) and respiratory insufficiency was in 60% (32/66 cases). Brain MRI was normal in 56% (40/72 cases) and routine cerebrospinal fluid examination was normal in 63% (36/57 cases). Anti‐IgLON5 antibodies were positive in serum in all cases, where serum was tested and positive in cerebrospinal fluid in 96% (71/75 cases).ConclusionWe found a significant overlap between symptoms in anti‐IgLON5 disease and DLB including cognitive dysfunction, REM‐sleep disorders, parkinsonism, and an insidious onset over several years. We propose that anti‐IgLON5 disease should be considered in atypical DLB cases with bulbar or respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti‐IgLON5 disease.