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

Idiopathic/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 treatabl...

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Published in:Neurology : neuroimmunology & neuroinflammation 2024-11, Vol.11 (6), p.e200311
Main Authors: Postuma, Ronald, Vorasoot, Nisa, St Louis, Erik K., Pelletier, Amélie, Lim, Miranda M., Elliott, Jonathan, Gagnon, Jean-Francois, Gan-Or, Ziv, Forsberg, Leah K., Fields, Julie A., Ross, Owen A., Singer, Wolfgang, Huddleston, Daniel E., Bliwise, Donald L., Avidan, Alon Y., Howell, Michael, Schenck, Carlos H., McLeland, Jennifer, Davis, Albert A., Criswell, Susan R., Videnovic, Aleksandar, During, Emmanuel H., Miglis, Mitchell G., Boeve, Bradley F., Ju, Yo-El S., McKeon, Andrew
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Language:English
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Summary:Idiopathic/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.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.Participants 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.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.Of 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
ISSN:2332-7812
2332-7812
DOI:10.1212/NXI.0000000000200311