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Ciano-Petersen NL, Muñiz-Castrillo S, Villagrán-García M, Farina A, Vogrig A, Wucher V, Duy L, Birzu C, Goncalves D, Flabeau O, Duwicquet C, Benard A, Nicole F, Rogemond V, Picard G, Joubert B, Honnorat J. Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2024; 11:e200260. [PMID: 39388653 PMCID: PMC11474543 DOI: 10.1212/nxi.0000000000200260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 03/29/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND AND OBJECTIVES To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC). METHODS Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; p = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, p = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; p = 0.02). DISCUSSION MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.
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Affiliation(s)
- Nicolás Lundahl Ciano-Petersen
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Sergio Muñiz-Castrillo
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Macarena Villagrán-García
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Antonio Farina
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Alberto Vogrig
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Valentin Wucher
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Le Duy
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Cristina Birzu
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - David Goncalves
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Olivier Flabeau
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Coline Duwicquet
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Adrien Benard
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Fabien Nicole
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Veronique Rogemond
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Geraldine Picard
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Bastien Joubert
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
| | - Jerome Honnorat
- From the French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (N.L.C.-P., S.M.-C., M.V.-G., A.F., V.W., L.D.D., V.R., G.P., B.J., J.H.), Université Claude Bernard Lyon 1, France; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND (N.L.C.-P.); Red Andaluza de Investigación Clínica y Traslacional en Neurología (NeuroRECA) (N.L.C.-P.), Málaga, Spain; Center for Sleep Sciences and Medicine (S.M.-C.), Stanford University, Palo Alto, CA; Department of Neuroscience (A.F.), Psychology, Pharmacology and Child Health. University of Florence, Italy; Clinical Neurology (A.V.), Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC); Department of Medicine (DMED) (A.V.), University of Udine, Udine, Italy; Sorbonne Université (C.B.), Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin; OncoNeuroTox Group (C.B.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris; Immunology Department (D.G., F.N.), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite; Service de Neurologie (O.F.), Centre Hospitalier de la Côte Basque, Bayonne; Department of Neurology (C.D.), University Hospital of Tours; and Service de Neurologie (A.B.), Centre Hospitalo-Universitaire Rennes, France
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Li D, Zong S, Yao Y, Molenaar PC, Damoiseaux JGMC, Li H, Rouhl RPW, Martinez-Martinez P. Anti-GABAB receptor encephalitis: clinical and laboratory characteristics, imaging, treatments and prognosis. Front Immunol 2024; 15:1442733. [PMID: 39445020 PMCID: PMC11496097 DOI: 10.3389/fimmu.2024.1442733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 09/20/2024] [Indexed: 10/25/2024] Open
Abstract
Introduction Anti-GABABR encephalitis is a rare disease reported to be often associated with tumors. The current study aims to summarize the clinical characteristics, imaging features, treatments, outcomes and explore the potential prognosis risk factors of patients with anti-GABABR encephalitis. Methods Patients tested positive for anti-GABABR were retrospective studied from a single medical center in China over a period of 3 years. They were followed up for a maximum period of 18 months. Clinical data were summarized and prognostic factors including demographic characteristics, laboratory tests, and neurological functions were compared between survived and deceased patients at 18 months follow-up. Results Twenty-six patients, 10 females (38.5%) and 16 males (61.5%), diagnosed with anti-GABABR encephalitis were studied. The median age was 58 years. Of the 23 cases with complete clinical data, their main manifestations were epileptic seizures (65%), mental and behavioral abnormalities (52%), and cognitive impairment (48%). 7 (30.4%) cases had tumors: 5 small cell lung cancer (SCLC), 1 rectum adenocarcinoma (moderately differentiated) and 1 esophageal squamous cell carcinoma. MRI showed 5 (22%) cases had T2 FLAIR increased signals in cortex but with different regions affected. One of the two patients scanned for PET-CT showed hypermetabolism in the left temporal lobe region. The disease course ranged from 5 days to 3 years. 2 patients (one had esophageal carcinoma) without immunotherapy and 3 patients (one had SCLC) that did not response to immunotherapy died soon after diagnosis. 18 patients improved after immunotherapy while 3 (all had SCLC) died after relapses. The prevalence of epileptic seizures and malignancies was significantly lower in the survival group than in the deceased group at 18-months follow-up, the same as the admission mRs score. Serum fibrinogen, cerebrospinal fluid immunoglobulin G quotient, and 24-hour intrathecal synthesis rate were significantly lower in the survival groups as well. Conclusions Cortex T2 FLAIR abnormalities were only observed in a small proportion of anti-GABABR encephalitis patients with heterogeneous MRI phenotypes. High mRS score at admission, epileptic seizures and the presence of a tumor indicated a poor prognosis, while the underlying mechanism of the later two factors should be investigated further.
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Affiliation(s)
- Dongrui Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands
| | - Shenghua Zong
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands
- Neuroimmunology Group, KingMed Diagnostic Laboratory, Guangzhou, China
| | - Yaobing Yao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Peter C. Molenaar
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands
| | - Jan G. M. C. Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center (MUMC)+, Maastricht, Netherlands
| | - Hui Li
- Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Rob P. W. Rouhl
- School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands
- Department of Neurology, Maastricht University Medical Center (MUMC +), Maastricht, Netherlands
- Academic Centre for Epileptology Kempenhaeghe/MUMC+, Maastricht, Netherlands
| | - Pilar Martinez-Martinez
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands
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Giorelli M, Liuzzi D, Aniello MS, Altomare S, Tarricone NR. Sequential onset of anti-HU-related paraneoplastic sensory polyneuropathy and limbic encephalitis in pancreatic neuroendocrine tumour: a case report. Acta Neurol Belg 2024; 124:1729-1732. [PMID: 38498265 DOI: 10.1007/s13760-024-02531-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 03/13/2024] [Indexed: 03/20/2024]
Affiliation(s)
- Maurizio Giorelli
- Operative Unit of Neurology, "Dimiccoli" General Hospital, Viale Ippocrate 11, 76121, Barletta, ASL BT, Italy.
| | - Daniele Liuzzi
- Operative Unit of Neurology, "Dimiccoli" General Hospital, Viale Ippocrate 11, 76121, Barletta, ASL BT, Italy
| | - Maria Stella Aniello
- Operative Unit of Neurology, "Dimiccoli" General Hospital, Viale Ippocrate 11, 76121, Barletta, ASL BT, Italy
| | - Sergio Altomare
- Operative Unit of Neurology, "Dimiccoli" General Hospital, Viale Ippocrate 11, 76121, Barletta, ASL BT, Italy
| | - Nunzia Rita Tarricone
- Operative Unit of Clinical Pathology, "Bonomo" Civil Hospital, Andria, ASL BT, Italy
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Dai YL, Xiao L, Pan Z, He GQ, Gao J, Guo X, Huang Z. Anti-Hu antibody associated paraneoplastic neurological syndrome in a child with ganglioneuroblastoma: A rare case report and literature review. Medicine (Baltimore) 2024; 103:e38148. [PMID: 38728479 PMCID: PMC11081564 DOI: 10.1097/md.0000000000038148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 04/16/2024] [Indexed: 05/12/2024] Open
Abstract
RATIONALE Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens. PATIENTS CONCERNS Diagnosis and treatment of Hu-PNS. DIAGNOSES This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination. INTERVENTIONS The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy. OUTCOMES The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence. LESSONS Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.
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Affiliation(s)
- Yi-Ling Dai
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Ling Xiao
- Sichuan University, Chengdu, Sichuan, P.R. China
| | - Zhen Pan
- Sichuan University, Chengdu, Sichuan, P.R. China
| | - Guo-Qian He
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Ju Gao
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Xia Guo
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Zhuo Huang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
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Faure F, Yshii L, Renno T, Coste I, Joubert B, Desestret V, Liblau R, Honnorat J. A Pilot Study to Develop Paraneoplastic Cerebellar Degeneration Mouse Model. CEREBELLUM (LONDON, ENGLAND) 2024; 23:181-196. [PMID: 36729270 DOI: 10.1007/s12311-023-01524-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/20/2023] [Indexed: 02/03/2023]
Abstract
Modeling paraneoplastic neurological diseases to understand the immune mechanisms leading to neuronal death is a major challenge given the rarity and terminal access of patients' autopsies. Here, we present a pilot study aiming at modeling paraneoplastic cerebellar degeneration with Yo autoantibodies (Yo-PCD). Female mice were implanted with an ovarian carcinoma cell line expressing CDR2 and CDR2L, the known antigens recognized by anti-Yo antibodies. To boost the immune response, we also immunized the mice by injecting antigens with diverse adjuvants and immune checkpoint inhibitors. Ataxia and gait instability were assessed in treated mice as well as autoantibody levels, Purkinje cell density, and immune infiltration in the cerebellum. We observed the production of anti-Yo antibodies in the CSF and serum of all immunized mice. Brain immunoreaction varied depending on the site of implantation of the tumor, with subcutaneous administration leading to a massive infiltration of immune cells in the meningeal spaces, choroid plexus, and cerebellar parenchyma. However, we did not observe massive Purkinje cell death nor any motor impairments in any of the experimental groups. Self-sustained neuro-inflammation might require a longer time to build up in our model. Unusual tumor antigen presentation and/or intrinsic, species-specific factors required for pro-inflammatory engagement in the brain may also constitute strong limitations to achieve massive recruitment of antigen-specific T-cells and killing of antigen-expressing neurons in this mouse model.
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Affiliation(s)
- Fabrice Faure
- Synaptopathies and Autoantibodies (SynatAc) Team, Institut NeuroMyoGène (INMG)-MeLis, INSERM U1314, CNRS UMR 5284, Université de Lyon, Université Claude Bernard Lyon 1, 69373, Lyon, France
| | - Lidia Yshii
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, 31024, Toulouse, France
- Department of Immunology, Toulouse University Hospital, 31300, Toulouse, France
- Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000, Louvain, Belgium
- Department of Neurosciences, KU Leuven, 3000, Louvain, Belgium
| | - Toufic Renno
- Cancer Research Centre of Lyon, Université de Lyon, INSERM 1052, CNRS 5286, 69008, Lyon, France
| | - Isabelle Coste
- Cancer Research Centre of Lyon, Université de Lyon, INSERM 1052, CNRS 5286, 69008, Lyon, France
| | - Bastien Joubert
- Synaptopathies and Autoantibodies (SynatAc) Team, Institut NeuroMyoGène (INMG)-MeLis, INSERM U1314, CNRS UMR 5284, Université de Lyon, Université Claude Bernard Lyon 1, 69373, Lyon, France
- French Reference Centre On Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France
| | - Virginie Desestret
- Synaptopathies and Autoantibodies (SynatAc) Team, Institut NeuroMyoGène (INMG)-MeLis, INSERM U1314, CNRS UMR 5284, Université de Lyon, Université Claude Bernard Lyon 1, 69373, Lyon, France
- French Reference Centre On Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France
| | - Roland Liblau
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, 31024, Toulouse, France
- Department of Immunology, Toulouse University Hospital, 31300, Toulouse, France
| | - Jérôme Honnorat
- Synaptopathies and Autoantibodies (SynatAc) Team, Institut NeuroMyoGène (INMG)-MeLis, INSERM U1314, CNRS UMR 5284, Université de Lyon, Université Claude Bernard Lyon 1, 69373, Lyon, France.
- French Reference Centre On Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France.
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Quinot V, Höftberger R. Pathogenesis and immunopathology of paraneoplastic disorders. HANDBOOK OF CLINICAL NEUROLOGY 2024; 200:33-54. [PMID: 38494287 DOI: 10.1016/b978-0-12-823912-4.00027-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Paraneoplastic neurologic syndromes (PNS) represent a rare group of immune-mediated complications associated with an underlying tumor. Ectopic protein expression in neoplastic cells or an aberrant immune regulation in the course of hematooncologic diseases or thymomas trigger an autoimmune response that may affect any part of the central and/or peripheral nervous system. Recent advances in drug therapies as well as novel animal models and neuropathologic studies have led to further insights on the immune pathomechanisms of PNS. Although the syndromes share common paths in pathogenesis, they may differ in the disease course, prognosis, and therapy targets, depending on the localization and type of antibody epitope. Neuropathologic hallmarks of PNS associated with antibodies directed against intracellular epitopes are characterized by T cell-dominated inflammation, reactive gliosis including microglial nodules, and neuronal degeneration. By contrast, the neuropathology of cell surface antibody-mediated PNS strongly depends on the targeted antigen and varies from B cell/plasma cell-dominated inflammation and well-preserved neurons together with a reduced expression of the target antigen in anti-NMDAR encephalitis to irreversible Purkinje cell loss in anti-P/Q-type VGCC antibody-associated paraneoplastic cerebellar degeneration. The understanding of different pathomechanisms in PNS is important because they strongly correspond with therapy response and prognosis, and should guide treatment decisions.
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Affiliation(s)
- Valérie Quinot
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Romana Höftberger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
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Masciocchi S, Businaro P, Scaranzin S, Morandi C, Franciotta D, Gastaldi M. General features, pathogenesis, and laboratory diagnostics of autoimmune encephalitis. Crit Rev Clin Lab Sci 2024; 61:45-69. [PMID: 37777038 DOI: 10.1080/10408363.2023.2247482] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 08/09/2023] [Indexed: 10/02/2023]
Abstract
Autoimmune encephalitis (AE) is a group of inflammatory conditions that can associate with the presence of antibodies directed to neuronal intracellular, or cell surface antigens. These disorders are increasingly recognized as an important differential diagnosis of infectious encephalitis and of other common neuropsychiatric conditions. Autoantibody diagnostics plays a pivotal role for accurate diagnosis of AE, which is of utmost importance for the prompt recognition and early treatment. Several AE subgroups can be identified, either according to the prominent clinical phenotype, presence of a concomitant tumor, or type of neuronal autoantibody, and recent diagnostic criteria have provided important insights into AE classification. Antibodies to neuronal intracellular antigens typically associate with paraneoplastic neurological syndromes and poor prognosis, whereas antibodies to synaptic/neuronal cell surface antigens characterize many AE subtypes that associate with tumors less frequently, and that are often immunotherapy-responsive. In addition to the general features of AE, we review current knowledge on the pathogenic mechanisms underlying these disorders, focusing mainly on the potential role of neuronal antibodies in the most frequent conditions, and highlight current theories and controversies. Then, we dissect the crucial aspects of the laboratory diagnostics of neuronal antibodies, which represents an actual challenge for both pathologists and neurologists. Indeed, this diagnostics entails technical difficulties, along with particularly interesting novel features and pitfalls. The novelties especially apply to the wide range of assays used, including specific tissue-based and cell-based assays. These assays can be developed in-house, usually in specialized laboratories, or are commercially available. They are widely used in clinical immunology and in clinical chemistry laboratories, with relevant differences in analytic performance. Indeed, several data indicate that in-house assays could perform better than commercial kits, notwithstanding that the former are based on non-standardized protocols. Moreover, they need expertise and laboratory facilities usually unavailable in clinical chemistry laboratories. Together with the data of the literature, we critically evaluate the analytical performance of the in-house vs commercial kit-based approach. Finally, we propose an algorithm aimed at integrating the present strategies of the laboratory diagnostics in AE for the best clinical management of patients with these disorders.
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Affiliation(s)
- Stefano Masciocchi
- Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy
- Department of Brain and Behavioral Sciences, Università degli Studi di Pavia, Pavia, Italy
| | - Pietro Businaro
- Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy
- Department of Brain and Behavioral Sciences, Università degli Studi di Pavia, Pavia, Italy
| | - Silvia Scaranzin
- Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy
| | - Chiara Morandi
- Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy
| | - Diego Franciotta
- Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy
| | - Matteo Gastaldi
- Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy
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Neațu M, Jugurt A, Covaliu A, Davidescu EI, Popescu BO. Autoimmune Encephalitis-A Multifaceted Pathology. Biomedicines 2023; 11:2176. [PMID: 37626673 PMCID: PMC10452276 DOI: 10.3390/biomedicines11082176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/30/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023] Open
Abstract
Autoimmune encephalitis is a complex and multifaceted pathology that involves immune-mediated inflammation of the brain. It is characterized by the body's immune system attacking the brain tissue, leading to a cascade of inflammatory processes. What makes autoimmune encephalitis vast is the wide range of causes, mechanisms, clinical presentations, and diagnostic challenges associated with the condition. The clinical presentations of autoimmune encephalitis are broad and can mimic other neurological disorders, making it a challenging differential diagnosis. This diverse clinical presentation can overlap with other conditions, making it crucial for healthcare professionals to maintain a high level of suspicion for autoimmune encephalitis when evaluating patients. The diagnostic challenges associated with autoimmune encephalitis further contribute to its vastness. Due to the variable nature of the condition, there is no definitive diagnostic test that can confirm autoimmune encephalitis in all cases. In this context, personalized patient management is crucial for achieving favorable outcomes. Each patient's treatment plan should be tailored to their specific clinical presentation, underlying cause, and immune response. Our objective is to raise awareness about the frequent yet underdiagnosed nature of autoimmune encephalitis by sharing five cases we encountered, along with a brief literature review.
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Affiliation(s)
- Monica Neațu
- Department of Clinical Neurosciences, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.N.); (A.J.); (A.C.); (B.O.P.)
- Department of Neurology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Ana Jugurt
- Department of Clinical Neurosciences, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.N.); (A.J.); (A.C.); (B.O.P.)
- Department of Neurology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Anca Covaliu
- Department of Clinical Neurosciences, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.N.); (A.J.); (A.C.); (B.O.P.)
- Department of Neurology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Eugenia Irene Davidescu
- Department of Clinical Neurosciences, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.N.); (A.J.); (A.C.); (B.O.P.)
- Department of Neurology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Bogdan Ovidiu Popescu
- Department of Clinical Neurosciences, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.N.); (A.J.); (A.C.); (B.O.P.)
- Department of Neurology, Colentina Clinical Hospital, 020125 Bucharest, Romania
- Department of Cell Biology, Neurosciences and Experimental Myology, “Victor Babeș” National Institute of Pathology, 050096 Bucharest, Romania
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Gonzalez-Fierro C, Fonte C, Dufourd E, Cazaentre V, Aydin S, Engelhardt B, Caspi RR, Xu B, Martin-Blondel G, Spicer JA, Trapani JA, Bauer J, Liblau RS, Bost C. Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2023; 10:e200117. [PMID: 37080596 PMCID: PMC10119812 DOI: 10.1212/nxi.0000000000200117] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 02/21/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND AND OBJECTIVES Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis. METHODS In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs. RESULTS Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina. DISCUSSION Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.
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Affiliation(s)
- Carmen Gonzalez-Fierro
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Coralie Fonte
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Eloïse Dufourd
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Vincent Cazaentre
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Sidar Aydin
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Britta Engelhardt
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Rachel R Caspi
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Biying Xu
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Guillaume Martin-Blondel
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Julie A Spicer
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Joseph A Trapani
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Jan Bauer
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
| | - Roland S Liblau
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France.
| | - Chloé Bost
- From the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity) (C.G.-F., C.F., E.D., V.C., G.M.-B., R.S.L., C.B.), University of Toulouse, CNRS, INSERM, UPS, France; Theodor Kocher Institute (S.A., B.E.), University of Bern, Switzerland; Laboratory of Immunology (R.R.C., B.X.), National Eye Institute, National Institutes of Health, Bethesda, MD; Department of Infectious and Tropical Diseases (G.M.-B.), Toulouse University Hospital, France; Auckland Cancer Society Research Centre (J.A.S.), Faculty of Medical and Health Sciences, The University of Auckland, New Zealand; Cancer Immunology Program (J.A.T.), Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology (J.A.T.), The University of Melbourne, Parkville, Australia; Department of Neuroimmunology (J.B.), Center for Brain Research, Medical University of Vienna, Austria; and Department of Immunology (R.S.L., C.B.), Toulouse University Hospital, France
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Huang P, Xu M. Four kinds of antibody positive paraneoplastic limbic encephalitis: A rare case report. World J Clin Cases 2023; 11:1586-1592. [PMID: 36926412 PMCID: PMC10012000 DOI: 10.12998/wjcc.v11.i7.1586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/14/2023] [Accepted: 02/15/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes (PNS). 4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis (PLE) have not been reported.
CASE SUMMARY PNS are distant effects of cancer on the nervous system, rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues. If the limbic lobe system of the brain is involved, this will result in PLE. The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic, obscure, and thus easily misdiagnosed or missed. Currently, single- or double-antibody-positive paraneoplastic marginal encephalitis has been reported. However, no cases of three or more-antibody-positive cases have been reported. Here, we report a case of PLE that is anti-collapsing response-mediator protein-5, anti-neuronal nuclear antibody-type 1, anti-aminobutyric acid B receptor, and anti-glutamate deglutase positive, and address relevant literature to improve our understanding of the disease.
CONCLUSION This article reports on the management of a case of PLE with four positive antibodies, a review of the literature, in order to raise awareness among clinicians.
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Affiliation(s)
- Pan Huang
- Department of Neurology, People’s Hospital of Deyang City, Deyang 618000, Sichuan Province, China
| | - Min Xu
- Department of Neurology, The Second People’s Hospital of Deyang City, Deyang 618000, Sichuan Province, China
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11
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Liang W, Wang Y, Sun W, Li D, Zhang X, Zhu P, Zhu Z, Fang Y. Persistent pain and numbness in the extremities of an adult due to paraneoplastic peripheral neuropathy caused by olfactory neuroblastoma: A case report. Front Neurol 2023; 13:1002076. [PMID: 36698887 PMCID: PMC9868692 DOI: 10.3389/fneur.2022.1002076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 12/09/2022] [Indexed: 01/11/2023] Open
Abstract
Background Paraneoplastic peripheral neuropathy (PPN) caused by olfactory neuroblastoma (ONB) has not yet been reported. Case report We present a rare case of an adult who hospitalized repeatedly over the past 9 months for persistent pain and numbness in the limbs. This patient was initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and treated accordingly, but neurological symptoms did not improve significantly. After this admission, FDG-PET/CT showed focal hypermetabolism of a soft-tissue mass in the nasal cavity, and further lesion biopsy suggested ONB. Combined with positive serum anti-Hu antibody, the diagnosis of PPN associated with ONB was eventually made. Furthermore, the patient's neurological symptoms were relieved after removal of the primary tumor, confirming the accuracy of the diagnosis. Conclusion Our case not only expanded the clinical characteristics of ONB but also highlighted the importance of early and comprehensive tumor screening for the diagnosis of PPN.
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Affiliation(s)
- Wenwen Liang
- Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yanyan Wang
- Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenzhe Sun
- Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Dongrui Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Xiaoping Zhang
- Department of Infection, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Pengcheng Zhu
- Department of Pathology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhou Zhu
- Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Zhou Zhu ✉
| | - Yongkang Fang
- Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China,Yongkang Fang ✉
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Muacevic A, Adler JR, McFarlane SI. Autoimmune Encephalitis With Autoimmune Diabetes: A Case of Horror Autotoxicus. Cureus 2023; 15:e34268. [PMID: 36855486 PMCID: PMC9968443 DOI: 10.7759/cureus.34268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2023] [Indexed: 01/28/2023] Open
Abstract
Diagnosing autoimmune encephalitis relies on clinical, radiological, and serological studies. Several autoantibodies have been implicated and recognized, with dozens of potential targets identified in the past 20 years. Despite that progress, some patients with encephalitis present a diagnostic dilemma with a seronegative status. The presence of other autoimmune diseases in a patient with encephalitis should provide a clue to the autoimmune nature of a developing neurological syndrome (cognitive, psychiatric, behavioral, and catatonia). In this report, we describe the case of a young man with type 1 diabetes mellitus who was diagnosed with seronegative autoimmune encephalitis after presenting with catatonia. We describe the lengthy clinical course, the various therapeutic trials, and his clinical outcome and response to B-cell depleting agent. This study also discusses the potential pathophysiologic pathways, providing a rationale for the diagnostic workup and therapeutic options for autoimmune encephalopathy in this case presentation.
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Tian J, Cao C, Miao R, Wu H, Zhang K, Wang B, Zhou Z, Chen R, Liu X. Single-Center Retrospective Analysis of Paraneoplastic Syndromes with Peripheral Nerve Damage. Brain Sci 2022; 12:1656. [PMID: 36552116 PMCID: PMC9775908 DOI: 10.3390/brainsci12121656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/23/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022] Open
Abstract
There are few clinical and electrophysiological studies on paraneoplastic neurological syndrome (PNS) with peripheral nerve damage, which brings great challenges to clinical identification and diagnosis. We analyzed the clinical and electrophysiological data of twenty-five confirmed PNS cases using peripheral nerve damage patients. The results showed the most common chief complaint was weakness (20/25, 80%), followed by numbness (13/25, 52%). Nineteen patients (76%) exhibited peripheral nervous system lesions prior to occult tumors, and the median time from symptom onset to the diagnosis of a tumor was 4 months. The electrophysiological results revealed a higher rate of abnormal amplitudes than latency or conduction velocity, especially in sensory nerves. Meanwhile, we found that, compared with patients >65 y, patients aged ≤65 y exhibited more chronic onset (p = 0.01) and longer disease duration (p = 0.01), more motor nerve involvements (p = 0.02), more amplitude involvement (p = 0.01), and higher rates of the inability to walk independently at presentation (p = 0.02). The present study construed that weakness and paresthesia are common symptoms in PNS with peripheral nerve damage in some areas, and the electrophysiological results mainly changed in amplitude. Tumor screening in young and middle-aged patients with peripheral neuropathy cannot be ignored.
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Affiliation(s)
- Jing Tian
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Cuifang Cao
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Ruihan Miao
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Haoran Wu
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Kun Zhang
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Binbin Wang
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Zhou Zhou
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Ruomeng Chen
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
| | - Xiaoyun Liu
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China
- Neuroscience Research Center, Medicine and Health Institute, Hebei Medical University, Shijiazhuang 050011, China
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Farina A, Villagrán-García M, Ciano-Petersen NL, Vogrig A, Muñiz-Castrillo S, Taillandier L, Michaud M, Lefilliatre M, Wang A, Lepine Z, Picard G, Wucher V, Dhairi M, Fabien N, Goncalves D, Rogemond V, Joubert B, Honnorat J. Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2022; 10:10/1/e200058. [PMID: 36446613 PMCID: PMC9709718 DOI: 10.1212/nxi.0000000000200058] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/19/2022] [Indexed: 12/02/2022]
Abstract
BACKGROUND AND OBJECTIVES To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere. METHODS Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015-2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018-2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports. RESULTS Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44-76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5-18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab-positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, p = 0.02) and limbic (54% vs 14%, p < 0.01), brainstem (27% vs 5%, p = 0.02), and dorsal root ganglia (45% vs 5%, p < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, p = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, p < 0.01) and higher mortality (91% vs 46%, p < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, p < 0.01) and higher mortality (26%, p < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature. DISCUSSION The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.
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Affiliation(s)
- Antonio Farina
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Macarena Villagrán-García
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Nicolás Lundahl Ciano-Petersen
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Alberto Vogrig
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Sergio Muñiz-Castrillo
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Luc Taillandier
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Maud Michaud
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Mathilde Lefilliatre
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Adrien Wang
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Zoe Lepine
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Géraldine Picard
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Valentin Wucher
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Maroua Dhairi
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Nicole Fabien
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - David Goncalves
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Véronique Rogemond
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Bastien Joubert
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France
| | - Jèrôme Honnorat
- From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Hospices Civils de Lyon, France; MeLiS - UCBL-CNRS UMR 5284 - INSERM U1314 (A.F., M.V.G., N.L.C.-P., A.V., S.M.-C., G.P., V.W., M.D., V.R., B.J., J.H.), Université Claude Bernard Lyon 1, France; Dipartimento di Neuroscienze (A.F.), Psicologia, Area del Farmaco e Salute del Bambino, Università di Firenze, Italia; Unité de Neuro Oncologie (L.T.), Département de Neurologie, Hôpital Central, Nancy Cedex, France; Unité mixte de Recherche 7039 CRAN BioSiS CNRS (L.T.), Faculté de Médecine, Vandoeuvre les Nancy, France; Centre de Référence des Pathologies Neuromusculaires de l'Adulte (Nord-Est-Ile de France) (M.M.), Service de Neurologie, CHU Central Nancy, France; Service de Neurologie (M.L.), CHU Central Caen, France; Service de Neurologie (A.W.), Hôpital Foch, Suresnes, France; Service de Neurologie (Z.L.), Centre Hospitalier de Pau, France; Service d'Immunologie (N.F., D.G.), Hôpital Lyon Sud, Hospices Civils de Lyon Pierre-Bénite, France; and ImmuCare (Immunology Cancer Research) (B.J., J.H.), Institut de Cancérologie, Hospices Civils de Lyon, France.
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15
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Autoimmune Encephalitis: A Physician’s Guide to the Clinical Spectrum Diagnosis and Management. Brain Sci 2022; 12:brainsci12091130. [PMID: 36138865 PMCID: PMC9497072 DOI: 10.3390/brainsci12091130] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/11/2022] [Accepted: 08/15/2022] [Indexed: 11/25/2022] Open
Abstract
The rapidly expanding spectrum of autoimmune encephalitis in the last fifteen years is largely due to ongoing discovery of many neuronal autoantibodies. The diagnosis of autoimmune encephalitis can be challenging due to the wide spectrum of clinical presentations, prevalence of psychiatric features that mimic primary psychiatric illnesses, frequent absence of diagnostic abnormalities on conventional brain MR-imaging, non-specific findings on EEG testing, and the lack of identified IgG class neuronal autoantibodies in blood or CSF in a subgroup of patients. Early recognition and treatment are paramount to improve outcomes and achieve complete recovery from these debilitating, occasionally life threatening, disorders. This review is aimed to provide primary care physicians and hospitalists who, together with neurologist and psychiatrists, are often the first port of call for individuals presenting with new-onset neuropsychiatric symptoms, with up-to-date data and evidence-based approach to the diagnosis and management of individuals with neuropsychiatric disorders of suspected autoimmune origin.
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16
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Passeri M, Matthews E, Kammeyer R, Piquet AL. Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing. Front Neurol 2022; 13:972143. [PMID: 35968301 PMCID: PMC9366192 DOI: 10.3389/fneur.2022.972143] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Myelopathy is an increasingly recognized presentation of many antibody-mediated neuroinflammatory disorders. While specific features of certain autoimmune myelopathies such as aquaporin-4 antibody associated neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are well-characterized, other less commonly seen antibody-associated myelopathies are not as well-defined. These include but are not limited to, Hu/ANNA1, anti-glial fibrillary acidic protein (GFAP), anti-CV2/collapsin response mediator protein (CRMP5), and amphiphysin. Here, we review the mentioned more common antibody mediated myelopathies as well those that as less common, followed by a review of differentials that may mimic these disorders.
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Affiliation(s)
- Michlene Passeri
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Elizabeth Matthews
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Ryan Kammeyer
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
- Department of Pediatrics and Neurology, Children's Hospital Anschutz Medical Campus, Aurora, CO, United States
| | - Amanda L. Piquet
- Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
- *Correspondence: Amanda L. Piquet
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17
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[Clinical Value of Autoantibody Prognostic Markers in Tumor Immune Checkpoint
Inhibitor Therapy]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2022; 25:534-540. [PMID: 35899453 PMCID: PMC9346161 DOI: 10.3779/j.issn.1009-3419.2022.101.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Serum autoantibody markers have the advantages of easy specimen acquisition, simple detection technology and dynamic real-time monitoring. With the wide application of immune checkpoint inhibitors in the treatment of malignant tumors, autoantibody markers in predicting tumor immune checkpoint inhibitors efficacy and forecasting irAEs (immune related adverse events) show good prediction of potential. This review mainly focused on the progress of autoantibody markers in the prediction of therapeutic effect and the monitoring of irAE in tumor immunotherapy.
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18
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Hsieh PC, Wu YR. Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders. J Mov Disord 2022; 15:95-105. [PMID: 35670020 PMCID: PMC9171305 DOI: 10.14802/jmd.21077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 04/16/2022] [Accepted: 04/18/2022] [Indexed: 11/24/2022] Open
Abstract
Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection or neoplasm. Certain phenotypes correlate with specific autoantibody-related neurological disorders, such as orofacial-lingual dyskinesia with N-methyl-D-aspartate receptor encephalitis and faciobrachial dystonic seizures with leucine-rich glioma-inactivated protein 1 encephalitis. Early diagnosis and treatment, especially for autoantibodies targeting neuronal surface antigens, can improve prognosis. In contrast, the presence of autoantibodies against intracellular neuronal agents warrants screening for underlying malignancy. However, early clinical diagnosis is challenging because these diseases can be misdiagnosed. In this article, we review the distinctive clinical phenotypes, magnetic resonance imaging findings, and current treatment options for autoimmune-mediated encephalitis.
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Affiliation(s)
- Pei-Chen Hsieh
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Yih-Ru Wu
- Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- Department of Neurology, Chang Gung University, College of Medicine, Taoyuan, Taiwan
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19
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Gastaldi M, Scaranzin S, Pietro B, Lechiara A, Pesce G, Franciotta D, Lorusso L. Paraneoplastic Neurological Syndromes: Transitioning Between the Old and the New. Curr Oncol Rep 2022; 24:1237-1249. [PMID: 35476177 DOI: 10.1007/s11912-022-01279-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE OF REVIEW Paraneoplastic neurological syndromes (PNS) are caused by nervous system-targeting aberrant anti-tumoral immune responses. We review the updated criteria for PNS diagnosis, incorporating novel information on clinical phenotypes, neuronal autoantibodies (Nabs), and tumors. The impact of the oncologic use of immune checkpoint inhibitors (ICI) on PNS occurrence is also addressed. RECENT FINDINGS Clinical phenotypes and Nabs are redefined as "high/intermediate/low" risk, following the frequency of cancer association. Nabs, the diagnostic hallmark of PNS, can target intracellular or surface neuronal proteins, with important prognostic and pathogenic implications. Many novel assays have been incorporated into laboratory diagnostics, that is becoming increasingly complex. ICI fight tumors, but favor autoimmunity, thus increasing the incidence of PNS-like disorders. Overcoming the old PNS criteria, the new ones are centered around the presence of tumor. Clinical presentation, Nabs, and tumor findings are translated in diagnostic scores, providing a useful tool for PNS diagnosis and management.
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Affiliation(s)
- Matteo Gastaldi
- Neuroimmunology Laboratory, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy.
| | - Silvia Scaranzin
- Neuroimmunology Laboratory, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy
| | | | - Anastasia Lechiara
- Autoimmunology Laboratory, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Giampaola Pesce
- Autoimmunology Laboratory, IRCCS Ospedale Policlinico San Martino, Genova, Italy.,Department of Internal Medicine (Dimi), University of Genova, Genova, Italy
| | - Diego Franciotta
- Autoimmunology Laboratory, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Lorenzo Lorusso
- Neurology and Stroke Unit, Neuroscience Department, A.S.S.T.-Lecco, Merate (LC), Italy
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20
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Ball C, Fisicaro R, Morris L, White A, Pacicco T, Raj K, Agarwal A, Lee WC, Yu FF. Brain on fire: an imaging-based review of autoimmune encephalitis. Clin Imaging 2022; 84:1-30. [DOI: 10.1016/j.clinimag.2021.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 11/28/2021] [Accepted: 12/16/2021] [Indexed: 12/28/2022]
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21
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Yin L, Yuan WL, Wu K, Zhang LN, Li QQ. Study on the pro-inflammatory mechanism of the HuD antibody in promoting M1 polarization and paraneoplastic neurological syndrome occurrence. Bioengineered 2022; 13:8029-8037. [PMID: 35294333 PMCID: PMC9161995 DOI: 10.1080/21655979.2022.2051267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Paraneoplastic neurological syndrome (PNS) is a nonmetastatic complication of malignant tumors that may lead to immune-mediated neuronal dysfunction or death. The occurrence of PNS results from the binding of anti-neuronal antibodies to neuronal cell surface antigens or intracellular antigens, which hinders the function of target proteins and promotes cell death. The aim of this study is to research the effect and immune mechanism of the neuronal ELAV-like protein (HuD antibody) on PNS-related syndrome. Neuronal cells were co-cultured with monocyte macrophages with or without HuD antibody. Next, we detected the apoptosis of neuronal cells by flow cytometry. Meantime, macrophage M1/M2 polarization factors and the secretion of inflammatory factors in the co-culture system were also detected by quantitative polymerase chain reaction (qPCR), Western blots and ELISA technologies. The results showed that after adding the HuD antibody in the co-culture system, the apoptosis level of the neuroma cells were significantly increased, and the apoptosis level were not significant changed when co-culture with monocytes without HuD antibody. In addition, the level of factors of M1 macrophages TNF-α, IL-12, TGF-β and IFN-γ increased, while the level of factors of M2 macrophages IL-10, IL-4, and Arg-1 decreased. The outcomes demonstrated that absorption of the HuD antibody by cerebellar neuronal cells could promote the proliferation of M1 macrophages and stimulates macrophages to secrete inflammatory factors, further damage the neuronal cells, eventually resulting in the occurrence of PNS. This finding provided a theoretical basis for the subsequent treatment and prevention of PNS.
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Affiliation(s)
- Liang Yin
- Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Bengbu Anhui, China
| | - Wen-Ling Yuan
- Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Bengbu Anhui, China
| | - Ke Wu
- Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Bengbu Anhui, China
| | - Li-Na Zhang
- Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Bengbu Anhui, China
| | - Qian-Qian Li
- Department of Neurology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Bengbu Anhui, China
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22
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Gutiérrez Pérez C, Lastra Aras E, Gómez Bravo R, Chivato Martín-Falquina I, Cuenca Zarzuela A, Rodríguez Ledesma I, García Girón C. Chronic intestinal pseudo-obstruction: diagnostic and prognostic utility of ANNA-1/Anti-Hu onconeural antibodies. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2022; 114:175-176. [PMID: 34991323 DOI: 10.17235/reed.2021.8521/2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
We propose an algorithm for the early detection of cancer from a case of paraneoplastic syndrome.
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23
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Rizzo A, Santoni M, Mollica V, Logullo F, Rosellini M, Marchetti A, Faloppi L, Battelli N, Massari F. Peripheral neuropathy and headache in cancer patients treated with immunotherapy and immuno-oncology combinations: the MOUSEION-02 study. Expert Opin Drug Metab Toxicol 2022; 17:1455-1466. [PMID: 35029519 DOI: 10.1080/17425255.2021.2029405] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Treatment-related neurotoxicity is a common side effect in cancer patients. However, few data are available regarding the risk of several neurotoxicities in patients treated with immune checkpoint inhibitors. AREAS COVERED The MOUSEION-02 study is an up-to-date meta-analysis aimed at assessing the risk of peripheral neuropathy, peripheral sensory neuropathy, and headache in cancer patients receiving immunotherapy and immuno-oncology combinations. Patients receiving immunotherapy (as monotherapy or in combination with other anticancer agents) showed lower risk of all-grade peripheral neuropathy (RR, 0.50; 95% CI, 0.35-0.70) and all-grade peripheral sensory neuropathy (RR, 0.49; 95% CI, 0.30-0.79). Similarly, in patients treated with immune checkpoint inhibitor monotherapy, we observed lower risk of all-grade peripheral neuropathy (RR, 0.05; 95% CI, 0.03-0.10) and all-grade peripheral sensory neuropathy (RR, 0.11; 95% CI, 0.05-0.23). No differences were observed in terms of all-grade headache. EXPERT OPINION Although the results of this meta-analysis should be interpreted with caution due to several issues, our study draws attention to immunotherapy-related neurotoxicity with the aim of maximizing clinical outcomes of cancer patients experiencing these not uncommon, and yet poorly studied, adverse events.
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Affiliation(s)
- Alessandro Rizzo
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna - Italy
| | | | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna - Italy
| | | | - Matteo Rosellini
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna - Italy
| | - Andrea Marchetti
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna - Italy
| | - Luca Faloppi
- Oncology Unit, Macerata Hospital, Macerata, Italy
| | | | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna - Italy
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24
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Update on Paraneoplastic Cerebellar Degeneration. Brain Sci 2021; 11:brainsci11111414. [PMID: 34827413 PMCID: PMC8615604 DOI: 10.3390/brainsci11111414] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 12/16/2022] Open
Abstract
Purpose of review: To provide an update on paraneoplastic cerebellar degeneration (PCD), the involved antibodies and tumors, as well as management strategies. Recent findings: PCD represents the second most common presentation of the recently established class of immune mediated cerebellar ataxias (IMCAs). Although rare in general, PCD is one of the most frequent paraneoplastic presentations and characterized clinically by a rapidly progressive cerebellar syndrome. In recent years, several antibodies have been described in association with the clinical syndrome related to PCD; their clinical significance, however, has yet to be determined. The 2021 updated diagnostic criteria for paraneoplastic neurologic symptoms help to establish the diagnosis of PCD, direct cancer screening, and to evaluate the presence of these newly identified antibodies. Recognition of the clinical syndrome and prompt identification of a specific antibody are essential for early detection of an underlying malignancy and initiation of an appropriate treatment, which represents the best opportunity to modulate the course of the disease. As clinical symptoms can precede tumor diagnosis by years, co-occurrence of specific symptoms and antibodies should prompt continuous surveillance of the patient. Summary: We provide an in-depth overview on PCD, summarize recent findings related to PCD, and highlight the transformed diagnostic approach.
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25
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Gutiérrez Pérez C, Lastra Aras E, Gómez Bravo R, Chivato Martín-Falquina I, Cuenca Zarzuela A, Rodríguez Ledesma I, García Girón C. Chronic intestinal pseudo-obstruction: diagnostic and prognostic utility of ANNA-1/Anti-Hu onconeural antibodies. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021. [PMID: 34470446 DOI: 10.17235/reed.2021.8186/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
A 65-year-old woman who, in the context of dyspepsia and dismotility, was diagnosed with chronic intestinal pseudo-obstruction (CIPO) in small cell lung carcinoma (SCLC). In spite of a remarkable tumor response after the combination of chemotherapy and immunotherapy, an intestinal sepsis led to the patient's sudden death.
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26
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Ahn SJ, Lee HS, Lee WJ, Chu K. Low-dose interleukin-2 as a novel therapeutic option for refractory paraneoplastic neurologic syndrome: a case of chronic relapsing anti-Ma2/Ta paraneoplastic myeloradiculopathy. ENCEPHALITIS 2021; 1:79-84. [PMID: 37469846 PMCID: PMC10295880 DOI: 10.47936/encephalitis.2021.00038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/18/2021] [Accepted: 03/23/2021] [Indexed: 07/21/2023] Open
Abstract
Paraneoplastic neurologic syndromes (PNS) caused by anti-Ma2/Ta antibodies have diverse presentations. Myeloradiculopathy is one anti-Ma2/Ta-associated PNS manifestation. We report the case of a patient with chronic relapsing anti-Ma2/Ta paraneoplastic myeloradiculopathy. The patient was successfully treated with low-dose human recombinant interleukin-2, despite having chronic relapsing symptoms and a refractory response to conventional immunotherapy.
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Affiliation(s)
- Seon-Jae Ahn
- Center for Hospital Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Neurology, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Han-Sang Lee
- Center for Hospital Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Neurology, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Woo-Jin Lee
- Center for Hospital Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Neurology, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kon Chu
- Department of Neurology, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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Salim A, Tapia Rico G, Shaikh A, Brown MP. A systematic review of immune checkpoint inhibitor-related neurological adverse events and association with anti-neuronal autoantibodies. Expert Opin Biol Ther 2021; 21:1237-1251. [PMID: 33645372 DOI: 10.1080/14712598.2021.1897101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Immune checkpoint inhibitors (ICI) therapy has led to a paradigm shift in cancer drug development and in the clinical evaluation of approaches to combination cancer treatment. Dysregulation of the immune system by ICI therapy may also elicit autoimmune phenomena and consequently manifest clinically as immune-related adverse events (irAEs) including neurological irAEs. Areas Covered: The purpose of this review is to explore the role of autoantibodies in the diagnosis and prediction of neurological irAEs and to evaluate their pathogenicity. We searched Pubmed and Embase for neurological irAEs and associated autoantibodies and found 28 patients with central and peripheral neurological irAEs. Of these patients, up to 40% had encephalitis, 34.4% with myasthenia gravis and 22% of patients with peripheral neuropathy and Guillain-Barre Syndrome had autoantibodies. Expert Opinion: Overall, our survey suggested a causal relationship between neurological irAEs and autoantibodies. Detection of autoantibodies may help to diagnose neurological irAEs and inform their clinical management.
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Affiliation(s)
- Ayesha Salim
- Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia
| | - G Tapia Rico
- Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia.,School of Medicine, University of Adelaide, Adelaide, South Australia
| | - A Shaikh
- Gastroenterology and Hepatology Department, Royal Adelaide Hospital, Adelaide, South Australia
| | - M P Brown
- Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia.,School of Medicine, University of Adelaide, Adelaide, South Australia
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28
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Valencia-Sanchez C, Zekeridou A. Paraneoplastic Neurological Syndromes and Beyond Emerging With the Introduction of Immune Checkpoint Inhibitor Cancer Immunotherapy. Front Neurol 2021; 12:642800. [PMID: 33897597 PMCID: PMC8062756 DOI: 10.3389/fneur.2021.642800] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 03/15/2021] [Indexed: 12/19/2022] Open
Abstract
Paraneoplastic neurological syndromes are more commonly seen with malignancies such as small cell lung cancer, thymoma, gynecological malignancies, and breast cancer as well as seminoma. With the introduction of immune checkpoint inhibitor (ICI) cancer immunotherapy we see an increase of autoimmune neurological complications in patients with malignancies not traditionally associated with paraneoplastic neurological syndromes, such as melanoma and renal cell carcinoma. Immune checkpoint inhibitors enhance antitumor immune responses resulting often in immune-related adverse effects that can affect any organ, including the central and peripheral nervous system, neuromuscular junction and muscle. Neurological complications are rare; neuromuscular complications are more common than central nervous system ones but multifocal neurological presentations are often encountered. The vast majority of neurological complications appear within 3 months of ICI initiation, but have been described even after ICI cessation. Neural autoantibody testing reveals autoantibodies in approximately half of the patients with CNS complications. Early suspicion and diagnosis is critical to avoid worsening and improve outcomes. Therapeutic strategies depend on the severity of the symptoms and initially typically involve discontinuation of ICI and high dose steroids. Further immunosuppression might be necessary. Outcomes are dependent on patient's characteristics and clinical presentations.
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Affiliation(s)
- Cristina Valencia-Sanchez
- Departments of Neurology and Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, United States
| | - Anastasia Zekeridou
- Departments of Neurology and Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, United States
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29
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Hurley LC, Levin NK, Chatterjee M, Coles J, Muszkat S, Howarth Z, Dyson G, Tainsky MA. Evaluation of paraneoplastic antigens reveals TRIM21 autoantibodies as biomarker for early detection of ovarian cancer in combination with autoantibodies to NY-ESO-1 and TP53. Cancer Biomark 2020; 27:407-421. [PMID: 32083570 DOI: 10.3233/cbm-190988] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND The majority of ovarian cancer cases are diagnosed at an advanced stage with poor prognosis. This study evaluates autoantibodies against tumor antigens to identify candidate biomarkers for early detection of ovarian cancer in women at increased risk. OBJECTIVE To assess the immunoreactivity of paraneoplastic antigens and tumor associated antigens with high-grade serous ovarian cancer (HGSOC) samples. METHODS Five paraneoplastic antigens along with three tumor-associated antigens were evaluated with HGSOC patient serum samples. Validation screening was performed with n= 164 serum samples consisting of: 50 late stage HGSOC, 14 early stage HGSOC, 50 benign ovarian cyst, and 50 healthy control samples on ELISA and western blot. The four markers TRIM21, NY-ESO-1, TP53, and PAX8 were evaluated on a second validation serum set, n= 150. RESULTS TRIM21 achieved the highest sensitivity in the first validation screening of 33% with 100% specificity. Combining TRIM21 with NY-ESO-1, TP53, and PAX8 provided 67% sensitivity with 94% specificity, and 56% sensitivity at 98% specificity. These four markers resulted in 46% sensitivity with 98% specificity in the second validation cohort; TRIM21 achieved the highest individual sensitivity of 36%. CONCLUSIONS Autoantibodies to TRIM21, NY-ESO-1, and TP53 may complement CA125 in screening of women at genetic risk for ovarian cancer.
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Affiliation(s)
- Laura C Hurley
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Nancy K Levin
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA.,Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA
| | - Madhumita Chatterjee
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA.,Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA
| | - Jasmine Coles
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Shlomo Muszkat
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Zachary Howarth
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA
| | - Gregory Dyson
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA.,Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA
| | - Michael A Tainsky
- Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, USA.,Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI, USA.,Molecular Therapeutics Program, Karmanos Cancer Institute, Detroit, MI, USA
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30
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Lu WC, Xie H, Yuan C, Li JJ, Li ZY, Wu AH. Identification of potential biomarkers and candidate small molecule drugs in glioblastoma. Cancer Cell Int 2020; 20:419. [PMID: 32874133 PMCID: PMC7455906 DOI: 10.1186/s12935-020-01515-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 08/24/2020] [Indexed: 12/18/2022] Open
Abstract
Background and aims Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. Methods Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein–protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database. Results A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM. Conclusions Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.
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Affiliation(s)
- Wei-Cheng Lu
- Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning China
| | - Hui Xie
- Department of Histology and Embryology, College of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning China
| | - Ce Yuan
- Graduate Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, USA
| | - Jin-Jiang Li
- Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang, Liaoning China
| | - Zhao-Yang Li
- Department of Laboratory Animal Center, China Medical University, Shenyang, Liaoning China
| | - An-Hua Wu
- Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning China
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31
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O'Donovan B, Mandel-Brehm C, Vazquez SE, Liu J, Parent AV, Anderson MS, Kassimatis T, Zekeridou A, Hauser SL, Pittock SJ, Chow E, Wilson MR, DeRisi JL. High-resolution epitope mapping of anti-Hu and anti-Yo autoimmunity by programmable phage display. Brain Commun 2020; 2:fcaa059. [PMID: 32954318 PMCID: PMC7425417 DOI: 10.1093/braincomms/fcaa059] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 03/08/2020] [Accepted: 03/12/2020] [Indexed: 12/13/2022] Open
Abstract
Paraneoplastic neurological disorders are immune-mediated diseases understood to manifest as part of a misdirected anti-tumor immune response. Paraneoplastic neurological disorder-associated autoantibodies can assist with diagnosis and enhance our understanding of tumor-associated immune processes. We designed a comprehensive library of 49-amino-acid overlapping peptides spanning the entire human proteome, including all splicing isoforms and computationally predicted coding regions. Using this library, we optimized a phage immunoprecipitation and sequencing protocol with multiple rounds of enrichment to create high-resolution epitope profiles in serum and cerebrospinal fluid (CSF) samples from patients suffering from two common paraneoplastic neurological disorders, the anti-Yo (n = 36 patients) and anti-Hu (n = 44 patients) syndromes. All (100%) anti-Yo patient samples yielded enrichment of peptides from the canonical anti-Yo (CDR2 and CDR2L) antigens, while 38% of anti-Hu patients enriched peptides deriving from the nELAVL (neuronal embryonic lethal abnormal vision like) family of proteins, the anti-Hu autoantigenic target. Among the anti-Hu patient samples that were positive for nELAVL, we noted a restricted region of immunoreactivity. To achieve single amino acid resolution, we designed a novel deep mutational scanning phage library encoding all possible single-point mutants targeting the reactive nELAVL region. This analysis revealed a distinct preference for the degenerate motif, RLDxLL, shared by ELAVL2, 3 and 4. Lastly, phage immunoprecipitation sequencing identified several known autoantigens in these same patient samples, including peptides deriving from the cancer-associated antigens ZIC and SOX families of transcription factors. Overall, this optimized phage immunoprecipitation sequencing library and protocol yielded the high-resolution epitope mapping of the autoantigens targeted in anti-Yo and anti-Hu encephalitis patients to date. The results presented here further demonstrate the utility and high-resolution capability of phage immunoprecipitation sequencing for both basic science and clinical applications and for better understanding the antigenic targets and triggers of paraneoplastic neurological disorders.
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Affiliation(s)
- Brian O'Donovan
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Caleigh Mandel-Brehm
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Sara E Vazquez
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Jamin Liu
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.,UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA 94158, USA
| | - Audrey V Parent
- Department of Medicine, Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Mark S Anderson
- Department of Medicine, Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Travis Kassimatis
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Anastasia Zekeridou
- Department of Neurology, Mayo Clinic, Rochester, MN 55902, USA.,Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55902, USA
| | - Stephen L Hauser
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.,Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Sean J Pittock
- Department of Neurology, Mayo Clinic, Rochester, MN 55902, USA.,Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55902, USA
| | - Eric Chow
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Michael R Wilson
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.,Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA
| | - Joseph L DeRisi
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.,Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA 94158, USA
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32
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Vogrig A, Muñiz-Castrillo S, Desestret V, Joubert B, Honnorat J. Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Ther Adv Neurol Disord 2020; 13:1756286420932797. [PMID: 32636932 PMCID: PMC7318829 DOI: 10.1177/1756286420932797] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 05/17/2020] [Indexed: 12/14/2022] Open
Abstract
Paraneoplastic neurological syndromes (PNSs) are rare complications of systemic cancers that can affect all parts of the central and/or peripheral nervous system. A body of experimental and clinical data has demonstrated that the pathogenesis of PNSs is immune-mediated. Nevertheless, the mechanisms leading to immune tolerance breakdown in these conditions remain to be elucidated. Despite their rarity, PNSs offer a unique perspective to understand the complex interplay between cancer immunity, effect of immune checkpoint inhibitors (ICIs), and mechanisms underlying the attack of neurons in antibody-mediated neurological disorders, with potentially relevant therapeutic implications. In particular, it is reported that ICI treatment can unleash PNSs and that the immunopathological features of PNS-related tumors are distinctive, showing prominent tumor-infiltrating lymphocytes and germinal center reactions. Intriguingly, similar pathological substrates have gained further attention as potential biomarkers of ICI-sensitivity and oncological prognosis. Moreover, the genetic analysis of PNS-associated tumors has revealed specific molecular signatures and mutations in genes encoding onconeural proteins, leading to the production of highly immunogenic neoantigens. Other than PNSs, autoimmune encephalitides (AEs) comprise a recently described group of disorders characterized by prominent neuropsychiatric symptoms, diverse antibody spectrum, and less tight association with cancer. Other triggering factors seem to be involved in AEs. Recent data have shed light on the importance of preceding infections (in particular, herpes simplex virus encephalitis) in inducing neurological autoimmune disorders in susceptible individuals (those with a selective deficiency in the innate immune system). In addition, in some AEs (e.g. LGI1-antibody encephalitis) an association with specific host-related factors [e.g., human leukocyte antigen (HLA)] was clearly demonstrated. We provide herein a comprehensive review of the most recent findings in the field of PNSs and AEs, with particular focus on their triggering factors and immunopathogenesis.
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Affiliation(s)
- Alberto Vogrig
- French Reference Center for Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France
- SynatAc Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France
- University Claude Bernard Lyon 1, Université de Lyon, Lyon, France
| | - Sergio Muñiz-Castrillo
- French Reference Center for Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France
- SynatAc Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France
- University Claude Bernard Lyon 1, Université de Lyon, Lyon, France
| | - Virginie Desestret
- French Reference Center for Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France
- SynatAc Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France
- University Claude Bernard Lyon 1, Université de Lyon, Lyon, France
| | - Bastien Joubert
- French Reference Center for Paraneoplastic Neurological Syndromes, Hospices Civils de Lyon, Hospital for Neurology and Neurosurgery Pierre Wertheimer, Lyon, France
- SynatAc Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France
- University Claude Bernard Lyon 1, Université de Lyon, Lyon, France
| | - Jérôme Honnorat
- Centre de Référence National pour les Syndromes Neurologiques Paranéoplasiques, Hôpital Neurologique, 59 Boulevard Pinel, Bron Cedex, 69677, France
- SynatAc Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France
- University Claude Bernard Lyon 1, Université de Lyon, Lyon, France
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33
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Kato R, Aoyama N, Mizutani S, Warabi M, Kasamatsu T, Hujigasaki H. [A case of paraneoplastic sensory neuronopathy with anti-Hu antibody associated with large cell neuroendocrine carcinoma of the endometrium]. Rinsho Shinkeigaku 2020; 60:441-445. [PMID: 32435048 DOI: 10.5692/clinicalneurol.60.cn-001393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
An 81-year-old woman was admitted to our hospital due to paresthesia of the extremities and difficulty in walking for three months. She underwent a total hysterectomy and bilateral salpingo-oophorectomy for large cell neuroendocrine carcinoma (LCNEC) of the endometrium seven months before the admission. The serum levels of neuron specific enolase (NSE) reduced after the surgery. She showed numbness of her limbs, disturbance of vibration, areflexia and autonomic dysfunction. Nerve conduction studies showed sensory dominant sensory neuronopathy. CT scan of her abdomen and pelvis revealed the recurrence of LCNEC of the endometrium. The serum levels of NSE was elevated and anti-Hu antibody was also positive. Other laboratory test, including autoantibodies were unremarkable. We diagnosed her as paraneoplastic sensory neuronopathy associated with postoperative recurrence of LCNEC of the endometrium. Here we show a clinical picture of anti-Hu positive paraneoplastic neurological syndrome with LCNEC of the endometrium.
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Affiliation(s)
- Rina Kato
- Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital
| | - Naoto Aoyama
- Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital
| | - Saneyuki Mizutani
- Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital
| | - Masahiro Warabi
- Department of Pathology, Tokyo Metropolitan Bokutoh Hospital
| | - Takahiro Kasamatsu
- Department of Obstetrics and Gynecology, Tokyo Metropolitan Bokutoh Hospital
| | - Hiroto Hujigasaki
- Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital
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34
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van Coevorden-Hameete MH, de Bruijn MAAM, de Graaff E, Bastiaansen DAEM, Schreurs MWJ, Demmers JAA, Ramberger M, Hulsenboom ESP, Nagtzaam MMP, Boukhrissi S, Veldink JH, Verschuuren JJGM, Hoogenraad CC, Sillevis Smitt PAE, Titulaer MJ. The expanded clinical spectrum of anti-GABABR encephalitis and added value of KCTD16 autoantibodies. Brain 2020; 142:1631-1643. [PMID: 31009048 PMCID: PMC6536844 DOI: 10.1093/brain/awz094] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 01/29/2019] [Accepted: 02/16/2019] [Indexed: 11/27/2022] Open
Abstract
In this study we report the clinical features of 32 patients with gamma aminobutyric acid B receptor (GABABR) antibodies, identify additional autoantibodies in patients with anti-GABABR encephalitis that mark the presence of an underlying small cell lung carcinoma and optimize laboratory methods for the detection of GABABR antibodies. Patients (n = 3225) were tested for the presence of GABABR antibodies using cell-based assay, immunohistochemistry and live hippocampal neurons. Clinical data were obtained retrospectively. Potassium channel tetramerization domain-containing (KCTD)16 antibodies were identified by immunoprecipitation, mass spectrometry analysis and cell-based assays. KCTD16 antibodies were identified in 23/32 patients with anti-GABABR encephalitis, and in 1/26 patients with small cell lung carcinoma and Hu antibodies, but not in 329 healthy subjects and disease controls. Of the anti-GABABR encephalitis patients that were screened sufficiently, 18/19 (95%) patients with KCTD16 antibodies had a tumour versus 3/9 (33%) anti-GABABR encephalitis patients without KCTD16 antibodies (P = 0.001). In most cases this was a small cell lung carcinoma. Patients had cognitive or behavioural changes (97%) and prominent seizures (90%). Thirteen patients developed a refractory status epilepticus with intensive care unit admittance (42%). Strikingly, 4/32 patients had a rapidly progressive dementia. The addition of KCTD16 to the GABABR cell-based assay improved sensitivity of the in-house fixed cell-based assay, without loss of specificity. Twenty-two of 26 patients improved (partially) to immunotherapy or chemotherapy. Anti-GABABR encephalitis is a limbic encephalitis with prominent, severe seizures, but patients can also present with rapidly progressive dementia. The co-occurrence of KCTD16 antibodies points towards a paraneoplastic origin. The addition of KCTD16 improves the sensitivity of the cell-based assay.
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Affiliation(s)
- Marleen H van Coevorden-Hameete
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands.,Department of Biology, Division of Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, CH, Utrecht, The Netherlands
| | - Marienke A A M de Bruijn
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Esther de Graaff
- Department of Biology, Division of Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, CH, Utrecht, The Netherlands
| | | | - Marco W J Schreurs
- Department of Immunology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Jeroen A A Demmers
- Department of Biochemistry, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Melanie Ramberger
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Esther S P Hulsenboom
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Mariska M P Nagtzaam
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Sanae Boukhrissi
- Department of Immunology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Jan H Veldink
- Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, CX, Utrecht, The Netherlands
| | - Jan J G M Verschuuren
- Department of Neurology, Leiden University Medical Center, Albinusdreef 2, ZA, Leiden, The Netherlands
| | - Casper C Hoogenraad
- Department of Biology, Division of Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, CH, Utrecht, The Netherlands
| | - Peter A E Sillevis Smitt
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
| | - Maarten J Titulaer
- Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 40, GD, Rotterdam, The Netherlands
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35
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Neuroinflammation in CNS diseases: Molecular mechanisms and the therapeutic potential of plant derived bioactive molecules. PHARMANUTRITION 2020. [DOI: 10.1016/j.phanu.2020.100176] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Raibagkar P, Ho D, Gunturu KS, Srinivasan J. Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature. J Neuroimmunol 2020; 341:577184. [PMID: 32058173 DOI: 10.1016/j.jneuroim.2020.577184] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 01/28/2020] [Accepted: 02/01/2020] [Indexed: 12/18/2022]
Abstract
We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment. The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.
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Affiliation(s)
- Pooja Raibagkar
- Division of Neurology, Lahey Hospital & Medical Center, Burlington, MA, United States of America; Tufts University School of Medicine, Boston, MA, United States of America.
| | - Doreen Ho
- Division of Neurology, Lahey Hospital & Medical Center, Burlington, MA, United States of America; Tufts University School of Medicine, Boston, MA, United States of America
| | - Krishna S Gunturu
- Tufts University School of Medicine, Boston, MA, United States of America; Division of Oncology, Lahey Hospital & Medical Center, Burlington, MA, United States of America
| | - Jayashri Srinivasan
- Division of Neurology, Lahey Hospital & Medical Center, Burlington, MA, United States of America; Tufts University School of Medicine, Boston, MA, United States of America
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37
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Mundt S, Greter M, Flügel A, Becher B. The CNS Immune Landscape from the Viewpoint of a T Cell. Trends Neurosci 2019; 42:667-679. [DOI: 10.1016/j.tins.2019.07.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/25/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023]
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38
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Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol 2019; 16:535-548. [DOI: 10.1038/s41571-019-0194-4] [Citation(s) in RCA: 129] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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18F-Flurodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) findings in children with encephalitis and comparison to conventional imaging. Eur J Nucl Med Mol Imaging 2019; 46:1309-1324. [DOI: 10.1007/s00259-019-04302-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 02/28/2019] [Indexed: 12/24/2022]
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Macher S, Zimprich F, De Simoni D, Höftberger R, Rommer PS. Management of Autoimmune Encephalitis: An Observational Monocentric Study of 38 Patients. Front Immunol 2018; 9:2708. [PMID: 30524441 PMCID: PMC6262885 DOI: 10.3389/fimmu.2018.02708] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 11/01/2018] [Indexed: 12/30/2022] Open
Abstract
Over the last years the clinical picture of autoimmune encephalitis has gained importance in neurology. The broad field of symptoms and syndromes poses a great challenge in diagnosis for clinicians. Early diagnosis and the initiation of the appropriate treatment is the most relevant step in the management of the patients. Over the last years advances in neuroimmunology have elucidated pathophysiological basis and improved treatment concepts. In this monocentric study we compare demographics, diagnostics, treatment options and outcomes with knowledge from literature. We present 38 patients suffering from autoimmune encephalitis. Antibodies were detected against NMDAR and LGI1 in seven patients, against GAD in 6 patients) one patient had coexisting antibodies against GABAA and GABAB), against CASPR2, IGLON5, YO, Glycine in 3 patients, against Ma-2 in 2 patients, against CV2 and AMPAR in 1 patient; two patients were diagnosed with hashimoto encephalitis with antibodies against TPO/TG. First, we compare baseline data of patients who were consecutively diagnosed with autoimmune encephalitis from a retrospective view. Further, we discuss when to stop immunosuppressive therapy since how long treatment should be performed after clinical stabilization or an acute relapse is still a matter of debate. Our experiences are comparable with data from literature. However, in contrary to other experts in the field we stop treatment and monitor patients very closely after tumor removal and after rehabilitation from first attack.
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Affiliation(s)
- Stefan Macher
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | | | - Desiree De Simoni
- Institute of Neurology, Medical University of Vienna, Vienna, Austria
| | - Romana Höftberger
- Institute of Neurology, Medical University of Vienna, Vienna, Austria
| | - Paulus S Rommer
- Department of Neurology, Medical University of Vienna, Vienna, Austria
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Birnbaum J, Hoke A, Lalji A, Calabresi P, Bhargava P, Casciola-Rosen L. Brief Report: Anti-Calponin 3 Autoantibodies: A Newly Identified Specificity in Patients With Sjögren's Syndrome. Arthritis Rheumatol 2018; 70:1610-1616. [PMID: 29749720 DOI: 10.1002/art.40550] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Accepted: 05/01/2018] [Indexed: 11/12/2022]
Abstract
OBJECTIVE Autoantibodies are clinically useful for phenotyping patients across the spectrum of autoimmune rheumatic diseases. Using serum from a patient with Sjögren's syndrome (SS), we detected a new specificity by immunoblotting. This study was undertaken to identify this autoantibody and to evaluate its disease specificity. METHODS A prominent 40-kd band was detected when immunoblotting was performed using SS patient serum and lysate from rat dorsal root ganglia (DRGs). Using 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing, the autoantigen was identified as calponin 3. Anti-calponin 3 antibodies were evaluated in sera from patients with primary SS (n = 209), patients with systemic lupus erythematosus (SLE; n = 138), patients with myositis (n = 138), patients with multiple sclerosis (MS; n = 44), and healthy controls (n = 46) by enzyme-linked immunosorbent assay. Expression of calponin 3 was assessed by immunohistochemistry. RESULTS Calponin 3 was identified as a new autoantigen. Anti-calponin 3 antibodies were detected in 23 (11.0%) of the 209 SS patients, 12 (8.7%) of the 138 SLE patients, 7 (5.1%) of the 138 myositis patients, 3 (6.8%) of the 44 MS patients, and 1 (2.2%) of the 46 healthy controls. Among SS patients, the frequency of anti-calponin 3 antibodies was highest in those with neuropathies (7 [17.9%] of 39). In this subset, the frequency of anti-calponin 3 antibodies differed significantly from that in the control group (P = 0.02). Calponin 3 was expressed primarily in rat DRG perineuronal satellite cells but not neurons. CONCLUSION Calponin 3 is a novel autoantigen. Antibodies against this protein are found in SS and associate with the subset of patients experiencing neuropathies. Intriguingly, we found that calponin 3 is expressed in DRG perineuronal satellite cells, suggesting that these may be a target in SS.
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Affiliation(s)
| | - Ahmet Hoke
- Johns Hopkins University, Baltimore, Maryland
| | - Aliya Lalji
- Johns Hopkins University, Baltimore, Maryland
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Abstract
PURPOSE OF REVIEW This article describes the methods of diagnosis and management of the sensory-predominant polyneuropathies. To simplify the approach to this category of patients, sensory-predominant polyneuropathies are divided broadly into either small fiber (or pain-predominant) neuropathies and large fiber (or ataxia-predominant) neuropathies, of which the sensory neuronopathies (dorsal root ganglionopathies) are highlighted. RECENT FINDINGS Physicians can now easily perform skin biopsies in their offices, allowing access to the gold standard pathologic diagnostic tool for small fiber neuropathies. Additional diagnostic techniques, such as corneal confocal microscopy, are emerging. Recently, small fiber neuropathies have been associated with a broader spectrum of diseases, including fibromyalgia, sodium channel mutations, and voltage-gated potassium channel antibody autoimmune disease. SUMMARY Despite advances in diagnosing small fiber neuropathies and sensory neuronopathies, many of these neuropathies remain refractory to treatment. In select cases, early identification and treatment may result in better outcomes. "Idiopathic" should be a diagnosis of exclusion and a thorough investigation for treatable causes pursued.
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Ravanidis S, Kattan FG, Doxakis E. Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors. Int J Mol Sci 2018; 19:ijms19082280. [PMID: 30081499 PMCID: PMC6121432 DOI: 10.3390/ijms19082280] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 07/26/2018] [Accepted: 07/31/2018] [Indexed: 12/13/2022] Open
Abstract
The timing, dosage and location of gene expression are fundamental determinants of brain architectural complexity. In neurons, this is, primarily, achieved by specific sets of trans-acting RNA-binding proteins (RBPs) and their associated factors that bind to specific cis elements throughout the RNA sequence to regulate splicing, polyadenylation, stability, transport and localized translation at both axons and dendrites. Not surprisingly, misregulation of RBP expression or disruption of its function due to mutations or sequestration into nuclear or cytoplasmic inclusions have been linked to the pathogenesis of several neuropsychiatric and neurodegenerative disorders such as fragile-X syndrome, autism spectrum disorders, spinal muscular atrophy, amyotrophic lateral sclerosis and frontotemporal dementia. This review discusses the roles of Pumilio, Staufen, IGF2BP, FMRP, Sam68, CPEB, NOVA, ELAVL, SMN, TDP43, FUS, TAF15, and TIA1/TIAR in RNA metabolism by analyzing their specific molecular and cellular function, the neurological symptoms associated with their perturbation, and their axodendritic transport/localization along with their target mRNAs as part of larger macromolecular complexes termed ribonucleoprotein (RNP) granules.
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Affiliation(s)
- Stylianos Ravanidis
- Basic Sciences Division I, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece.
| | - Fedon-Giasin Kattan
- Basic Sciences Division I, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece.
| | - Epaminondas Doxakis
- Basic Sciences Division I, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece.
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Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Iduronate-2-Sulfatase in Rhesus Macaques. MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT 2018; 10:68-78. [PMID: 30073178 PMCID: PMC6070702 DOI: 10.1016/j.omtm.2018.06.004] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 06/07/2018] [Indexed: 11/21/2022]
Abstract
Hunter syndrome is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. The severe form of this progressive, systemic, and neurodegenerative disease results in loss of cognitive skills and early death. Several clinical trials are evaluating adeno-associated virus 9 for the treatment of neurodegenerative diseases using systemic or intrathecal lumbar administration. In large animals, administration via suboccipital puncture gives better brain transduction than lumbar administration. Here, we conducted a good laboratory practice-compliant investigational new drug-enabling study to determine the safety of suboccipital adeno-associated virus 9 gene transfer of human iduronate-2-sulfatase into nonhuman primates. Thirteen rhesus macaques received vehicle or one of two doses of vector with or without immunosuppression. We assessed in-life safety and immune responses. Animals were euthanized 90 days post-administration and sampled for histopathology and biodistribution. The procedure was well tolerated in all animals. Minimal mononuclear cerebrospinal fluid pleocytosis occurred in some animals. Asymptomatic minimal-to-moderate toxicity to some dorsal root ganglia sensory neurons and their associated axons occurred in all vector-treated animals. This study supports the clinical development of suboccipital adeno-associated virus 9 delivery for severe Hunter syndrome and highlights a potential toxicity that warrants monitoring in first-in-human studies.
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Paraneoplastische cerebelläre Degeneration (PCD) – eine interdisziplinäre Herausforderung in der Neurologie, Onkologie und Palliativmedizin. Wien Med Wochenschr 2018; 168:193-198. [DOI: 10.1007/s10354-018-0624-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 01/25/2018] [Indexed: 10/18/2022]
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Li J, Lin W. Various clinical features of patients with anti-Hu associated paraneoplastic neurological syndromes: An observational study. Medicine (Baltimore) 2018; 97:e0649. [PMID: 29718880 PMCID: PMC6392975 DOI: 10.1097/md.0000000000010649] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
To describe and analyze the clinical features and prognosis of patients with anti-Hu associated paraneoplastic neurological syndromes (PNS).The symptoms, MRI findings, cerebrospinal fluid (CSF) changes, electroencephalogram (EEG) characteristics and prognoses of 9 well-diagnosed anti-Hu associated PNS patients were analyzed.The study enrolled 6 female and 3 male patients. Three patients presented with vertigo and 6 patients exhibited a depressed mood, numbness of the lower limbs, generalized pains, seizures, mental disturbances, and a temporary unilateral hand tremor on initial presentation. Three patients presented with MRI abnormalities localized in the mesial temporal lobe and the thalamus. Abnormal interictal EEG readings were observed in all 5 patients who underwent EEG study. Four patients were found lung cancer (3 during hospitalization, 1 during follow-up). Seven patients were treated with immunotherapy and improved in symptoms. Three patients died during follow-up (2 with lung cancer).The clinical manifestation of anti-Hu associated PNS is diverse and multifocal. EEG may be more sensitive than MRI for early diagnosis of PNS. Long-term follow-up for patients with CT-negative anti-Hu associated PNS is necessary.
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Miao S, Liao S, Li H, Niu B, Hu H, Qian Y, Guo H, Cao B. Retrospective study of paraneoplastic neurological syndromes in a Chinese Han population from Shandong, East China. Int J Neurosci 2018; 128:821-827. [PMID: 29355452 DOI: 10.1080/00207454.2018.1430693] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVE To analyze the clinical features, diagnostic strategies and therapeutic methods associated with paraneoplastic neurological syndromes. METHODS A retrospective study of paraneoplastic neurological syndromes was performed at a single center in Shandong, East China. The medical records and follow-up data of 28 patients were intensively reviewed between February 2011 and December 2014. RESULTS Twenty-four (85.7%) patients experienced subacute or chronic onset of disease, and the most common symptoms reported were mild myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous system lesions prior to occult tumors, and the median time frame between paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15 weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic encephalitis were the three most common neurological syndromes reported. Elevated serum tumor markers were observed in 44.0% of patients, while 40.7% of patients were positive for onconeural antibodies. Tumors were detected in 21 (75.0%) patients after repeated whole-body screening, and lung carcinomas were the most common primary tumor detected. Seventeen patients received anti-tumor or immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these patients. CONCLUSIONS In the majority of paraneoplastic neurological syndromes patients, the onset of disease is subacute or chronic with mild clinical symptoms. Nervous system lesions usually occur prior to occult tumors with complicated and various clinical manifestations. Neither tumor markers nor onconeural antibodies exhibit a high rate of occurrence, while repeated whole-body screening is helpful in identifying occult tumors. Early diagnosis and treatment are crucial to these patients.
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Affiliation(s)
- Shuai Miao
- a Department of Neurology , Graduate School of the Second Military Medical University , Shanghai , China.,b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
| | - Shaohua Liao
- a Department of Neurology , Graduate School of the Second Military Medical University , Shanghai , China.,b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
| | - Heng Li
- c Department of Neurology, Shandong Provincial Qianfoshan Hospital , Shandong University , Jinan , China
| | - Bing Niu
- b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
| | - Huaiqiang Hu
- b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
| | - Ying Qian
- a Department of Neurology , Graduate School of the Second Military Medical University , Shanghai , China.,b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
| | - Hongwei Guo
- a Department of Neurology , Graduate School of the Second Military Medical University , Shanghai , China.,b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
| | - Bingzhen Cao
- b Department of Neurology , General Hospital of Jinan Military Command , Jinan , China
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Abstract
Paraneoplastic and autoimmune encephalitis comprise a group of immune-mediated disorders that are associated with different immune effector mechanisms. Classic paraneoplastic neurologic syndromes are triggered by an antitumor immune response. The disease is considered to result from a T-cell response; in addition, patients harbour high titers of autoantibodies against intracellular antigens that are considered as epiphenomenon but are useful diagnostic markers. Neuropathology consists of T-cell-dominated inflammation, marked neuronal loss, and microglial activation with upregulation of HLA-DR. In the last decade, an increasing number of diseases associated with autoantibodies against neuronal surface antigens have been described. There is strong evidence that these autoantibodies are pathogenic and the associated syndromes are generally termed as antineuronal autoimmune encephalitis. Patients typically present with limbic, multifocal, or diffuse encephalitis and respond to immunotherapy. Neuropathologic descriptions are restricted to few biopsy and autopsy specimens and show mild inflammatory infiltrates and microglial activation, together with reduced expression of the respective target antigens, immunoglobulin deposits, and a variable degree of complement activation. Other putative autoimmune disorders of the central nervous system include, among others, Rasmussen encephalitis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), acute cerebellitis, Susac syndrome, and Hashimoto encephalitis. While pathologic studies suggest an immune-mediated disease for Rasmussen encephalitis, CLIPPERS, acute cerebellitis, and Susac syndrome, neuropathologic descriptions of Hashimoto encephalitis are rare and the pathogenesis deserves further study.
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Affiliation(s)
- Romana Höftberger
- Institute of Neurology, Medical University of Vienna, Vienna, Austria
| | - Hans Lassmann
- Center for Brain Research, Medical University of Vienna, Vienna, Austria.
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Yshii LM, Gebauer CM, Pignolet B, Mauré E, Quériault C, Pierau M, Saito H, Suzuki N, Brunner-Weinzierl M, Bauer J, Liblau R. CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model. Brain 2017; 139:2923-2934. [PMID: 27604307 DOI: 10.1093/brain/aww225] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 07/21/2016] [Indexed: 12/17/2022] Open
Abstract
CTLA4 is an inhibitory regulator of immune responses. Therapeutic CTLA4 blockade enhances T cell responses against cancer and provides striking clinical results against advanced melanoma. However, this therapy is associated with immune-related adverse events. Paraneoplastic neurologic disorders are immune-mediated neurological diseases that develop in the setting of malignancy. The target onconeural antigens are expressed physiologically by neurons, and aberrantly by certain tumour cells. These tumour-associated antigens can be presented to T cells, generating an antigen-specific immune response that leads to autoimmunity within the nervous system. To investigate the risk to develop paraneoplastic neurologic disorder after CTLA4 blockade, we generated a mouse model of paraneoplastic neurologic disorder that expresses a neo -self antigen both in Purkinje neurons and in implanted breast tumour cells. Immune checkpoint therapy with anti-CTLA4 monoclonal antibody in this mouse model elicited antigen-specific T cell migration into the cerebellum, and significant neuroinflammation and paraneoplastic neurologic disorder developed only after anti-CTLA4 monoclonal antibody treatment. Moreover, our data strongly suggest that CD8 + T cells play a final effector role by killing the Purkinje neurons. Taken together, we recommend heightened caution when using CTLA4 blockade in patients with gynaecological cancers, or malignancies of neuroectodermal origin, such as small cell lung cancer, as such treatment may promote paraneoplastic neurologic disorders.
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Affiliation(s)
- Lidia M Yshii
- INSERM UMR U1043 - CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, 31300, France.,Department of Pharmacology, Institute of Biomedical Sciences I, University of São Paulo, 05508-900, Brazil
| | - Christina M Gebauer
- INSERM UMR U1043 - CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, 31300, France
| | - Béatrice Pignolet
- INSERM UMR U1043 - CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, 31300, France.,Department of Clinical Neurosciences, Toulouse University Hospital, 31059, France
| | - Emilie Mauré
- INSERM UMR U1043 - CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, 31300, France
| | - Clémence Quériault
- INSERM UMR U1043 - CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, 31300, France
| | - Mandy Pierau
- Department of Experimental Paediatrics, University Hospital, Otto-von-Guericke University Magdeburg, 39120, Germany
| | - Hiromitsu Saito
- Department of Animal Genomics, Functional Genomics Institute, Mie University Life Science Research Center, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Noboru Suzuki
- Department of Animal Genomics, Functional Genomics Institute, Mie University Life Science Research Center, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Monika Brunner-Weinzierl
- Department of Experimental Paediatrics, University Hospital, Otto-von-Guericke University Magdeburg, 39120, Germany
| | - Jan Bauer
- Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, A-1090, Austria
| | - Roland Liblau
- INSERM UMR U1043 - CNRS U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, 31300, France
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Yshii LM, Hohlfeld R, Liblau RS. Inflammatory CNS disease caused by immune checkpoint inhibitors: status and perspectives. Nat Rev Neurol 2017; 13:755-763. [PMID: 29104289 DOI: 10.1038/nrneurol.2017.144] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cancer treatment strategies based on immune stimulation have recently entered the clinical arena, with unprecedented success. Immune checkpoint inhibitors (ICIs) work by indiscriminately promoting immune responses, which target tumour-associated antigens or tumour-specific mutations. However, the augmented immune response, most notably the T cell response, can cause either direct neurotoxicity or, more commonly, indirect neurotoxic effects through systemic or local inflammatory mechanisms or autoimmune mechanisms. Consequently, patients treated with ICIs are susceptible to CNS disease, including paraneoplastic neurological syndromes, encephalitis, multiple sclerosis and hypophysitis. In this Opinion article, we introduce the mechanisms of action of ICIs and review their adverse effects on the CNS. We highlight the importance of early detection of these neurotoxic effects, which should be distinguished from brain metastasis, and the need for early detection of neurotoxicity. It is crucial that physicians are well informed of these neurological adverse effects, given the anticipated increase in the use of immunotherapies to treat cancer.
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Affiliation(s)
- Lidia M Yshii
- INSERM U1043 - CNRS UMR 5282, Centre de Physiopathologie Toulouse-Purpan, Purpan Hospital, Place du Docteur Baylac TSA 40031, 31059 Toulouse Cedex 9, France
| | - Reinhard Hohlfeld
- Institute of Clinical Neuroimmunology, Biomedical Centre and University Hospital, Ludwig Maximilian University, Munich 80539, Germany, and Munich Cluster for Systems Neurology (SyNergy), Munich D-81377, Germany
| | - Roland S Liblau
- INSERM U1043 - CNRS UMR 5282, Centre de Physiopathologie Toulouse-Purpan, Purpan Hospital, Place du Docteur Baylac TSA 40031, 31059 Toulouse Cedex 9, France, and the Department of Immunology, Hôpital Rangueil, 1, Avenue du Professeur Jean Poulhès - TSA 50032 - 31059 Toulouse Cedex 9, France
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