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

Ronald Postuma1, Nisa Vorasoot1, Erik K St Louis1

  • 1From the Montreal Neurological Institute and Department of Neurology and Neurosurgery (R.P.), Montréal, McGill University; Center for Advanced Research in Sleep Medicine (R.P., A.P., J.-F.G.), Hôpital du Sacré-Coeur de Montréal; Research Institute of the McGill University Health Centre (R.P., A.P., Z.G.-O.), Montreal, Quebec, Canada; Neurology and Medicine (N.V., L.K.F., J.A.F., O.A.R., W.S., B.F.B., A.M.), Mayo Clinic, Rochester, MN; Division of Neurology (N.V., E.K.S.L.), Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand; Department of Neurology (M.M.L., J.E.), Oregon Health & Science University; Department of Behavioral Neuroscience (M.M.L.); Department of Pulmonary and Critical Care Medicine; Oregon Institute of Occupational Health Sciences; Mental Illness Research Education and Clinical Center (M.M.L.); Neurology; National Center for Rehabilitative Auditory Research; Research Service (M.M.L., J.E.), VA Portland Health Care System, OR; Département of Psychology (J.-F.G.), Université du Québec à Montréal; Department of Human Genetics (Z.G.-O.), McGill University, Montréal, Québec, Canada; Neurology (D.E.H., D.L.B.), Emory University, Atlanta, GA; Neurology (A.Y.A.), Sleep Disorders Center, University of California, Los Angeles; Minnesota Regional Sleep Disorders Center (M.H., C.H.S.), and Departments of Psychiatry, Hennepin County Medical Center, and University of Minnesota Medical School; Minnesota Regional Sleep Disorders Center (M.H.), Hennepin County Medical Center, Minneapolis, MN; Washington University School of Medicine (J.M., A.A.D., Y.-E.S.J.), Saint Louis, MO; Barrow Neurological Institute (S.R.C.), Phoenix, AZ; Movement Disorders Unit (A.V.), Division of Sleep Medicine, Massachusetts General Hospital; Neurological Clinical Research Institute (A.V.), Harvard Medical School, Boston, MA; Psychiatry and Behavioral Sciences (E.H.D., M.G.M.), Stanford University, Redwood City, CA; Neurology and Neurological Sciences (E.H.D., M.G.M.), Stanford University, Palo Alto, CA; and Neurology (E.H.D.), Mt. Sinai School of Medicine, New York.

Neurology(R) Neuroimmunology & Neuroinflammation
|September 13, 2024
PubMed
Summary

Nearly 1% of individuals with idiopathic REM sleep behavior disorder (iRBD) tested positive for IGLON5 autoantibodies, suggesting a link to treatable autoimmune conditions. This finding has significant clinical implications for diagnosing and managing iRBD patients.

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Area of Science:

  • Neurology
  • Immunology

Background:

  • Idiopathic REM sleep behavior disorder (iRBD) is often linked to neurodegenerative diseases like Parkinson's.
  • Increasing evidence suggests RBD can also be an early sign of treatable autoimmune conditions, such as IGLON5 syndrome.

Purpose of the Study:

  • To determine the frequency of specific autoantibodies in a large cohort of patients diagnosed with iRBD.
  • To assess the potential for autoimmune disorders presenting as iRBD.

Main Methods:

  • 339 participants with polysomnography-confirmed iRBD, without parkinsonism or dementia, were included.
  • Plasma samples were screened for IGLON5, DPPX, LGI1, and CASPR2 autoantibodies using cell-based assays.
  • Positive or equivocal results were confirmed with repeat testing and tissue-based immunofluorescence assays for IGLON5.

Main Results:

  • Three participants (0.9%) showed confirmed IGLON5 autoantibodies.
  • One additional participant had a low-titer CASPR2 autoantibody.
  • Symptoms in positive cases included dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms.

Conclusions:

  • Approximately 1% of iRBD patients may have a serious, potentially treatable autoimmune syndrome.
  • Routine autoantibody testing, particularly for IGLON5-IgG, warrants consideration in iRBD diagnosis.
  • Balancing testing costs, benefits, and potential false-positive effects is crucial for implementation.