特发性 REM 睡眠行为障碍中 IGLON5 频率：一项多中心研究。
IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.
机构信息
From 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.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2024 Nov;11(6):e200311. doi: 10.1212/NXI.0000000000200311. Epub 2024 Sep 13.
BACKGROUND AND OBJECTIVES
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.
METHODS
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.
RESULTS
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 disease.
DISCUSSION
Our 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.
TRIAL REGISTRATION INFORMATION
NCT03623672.
背景与目的
特发性/孤立性快速眼动睡眠行为障碍（iRBD）与神经退行性突触核蛋白病如帕金森病、路易体痴呆和多系统萎缩密切相关。然而，越来越多的报告显示，RBD 是严重且可治疗的自身免疫综合征的表现特征，特别是 IGLON5。本研究的目的是调查大量 iRBD 患者中自身抗体的频率。
方法
参与者纳入北美前驱突触核蛋白病队列，接受多导睡眠图确认的 iRBD 检查，无帕金森病和痴呆。使用基于血浆 IgG 的细胞测定法系统筛查 IGLON5、DPPX、LGI1 和 CASPR2 等自身抗体。阳性或可疑结果通过重复测试和 IGLON5 的组织间接免疫荧光测定法确认。
结果
在分析的 339 个样本中，有 3 名（0.9%）患者在细胞测定法中证实存在 IGLON5 自身抗体阳性，该结果通过组织测定法得到确认。另一名患者仅在细胞测定法中表现出 CASPR2 低滴度阳性（临床确定性较低）。这些病例表现出各种症状，包括梦境行为、认知下降、自主神经功能障碍和运动症状。在 1 例 IGLON5 病例和 1 例 CASPR2 病例中，病情进展提示为典型的突触核蛋白病，这表明结果可能是偶然的。然而，有 2 名 IGLON5 患者在临床怀疑之前死亡，其最终的临床图像高度提示自身免疫性疾病。
讨论
我们发现，在一个大型 iRBD 队列中，近 1%的患者可能患有严重但潜在可治疗的自身抗体综合征，这具有重要的临床意义。特别是，这就提出了一个问题，即对于 iRBD 患者，是否应该广泛实施针对 IGLON-5-IgG 的自身抗体检测，考虑到自身免疫性疾病的诊断困难、对治疗的反应以及疾病快速进展的可能性。然而，任何常规检测方案还必须考虑成本和假阳性结果的潜在不利影响。
试验注册信息
NCT03623672。
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