TY - JOUR
T1 - IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder
T2 - A Multicenter Study
AU - Postuma, Ronald
AU - Vorasoot, Nisa
AU - St Louis, Erik K.
AU - Pelletier, Amélie
AU - Lim, Miranda M.
AU - Elliott, Jonathan
AU - Gagnon, Jean Francois
AU - Gan-Or, Ziv
AU - Forsberg, Leah K.
AU - Fields, Julie A.
AU - Ross, Owen A.
AU - Singer, Wolfgang
AU - Huddleston, Daniel E.
AU - Bliwise, Donald L.
AU - Avidan, Alon Y.
AU - Howell, Michael
AU - Schenck, Carlos H.
AU - Mcleland, Jennifer
AU - Davis, Albert A.
AU - Criswell, Susan R.
AU - Videnovic, Aleksandar
AU - During, Emmanuel H.
AU - Miglis, Mitchell G.
AU - Boeve, Bradley F.
AU - Ju, Yo El S.
AU - Mckeon, Andrew
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2024/9/13
Y1 - 2024/9/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85204916923&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000200311
DO - 10.1212/NXI.0000000000200311
M3 - Article
C2 - 39270144
AN - SCOPUS:85204916923
SN - 2332-7812
VL - 11
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 6
M1 - e200311
ER -