IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study

Ronald Postuma, Nisa Vorasoot, Erik K. St Louis, Amélie Pelletier, Miranda M. Lim, Jonathan Elliott, Jean Francois Gagnon, Ziv Gan-Or, Leah K. Forsberg, Julie A. Fields, Owen A. Ross, Wolfgang Singer, Daniel E. Huddleston, Donald L. Bliwise, Alon Y. Avidan, Michael Howell, Carlos H. Schenck, Jennifer Mcleland, Albert A. Davis, Susan R. CriswellAleksandar Videnovic, Emmanuel H. During, Mitchell G. Miglis, Bradley F. Boeve, Yo El S. Ju, Andrew Mckeon

Research output: Contribution to journalArticlepeer-review

Abstract

Background and ObjectivesIdiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.MethodsParticipants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5.ResultsOf 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease.DiscussionOur finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings.

Original languageEnglish
Article numbere200311
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume11
Issue number6
DOIs
StatePublished - Sep 13 2024

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