Agnes van Sonderen1, Helena Ariño1, Mar Petit-Pedrol1, Frank Leypoldt1, Peter Körtvélyessy1, Klaus-Peter Wandinger1, Eric Lancaster1, Paul W Wirtz1, Marco W J Schreurs1, Peter A E Sillevis Smitt1, Francesc Graus1, Josep Dalmau1, Maarten J Titulaer2. 1. From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 2. From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. m.titulaer@erasmusmc.nl.
Abstract
OBJECTIVE: To report a large cohort of patients with antibodies against contactin-associated protein-like 2 (Caspr2) and provide the clinical spectrum of this disorder. METHODS: Serum and CSF samples were assessed at 2 neuroimmunology centers in Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were confirmed with 2 independent techniques, including brain immunohistochemistry and cell-based assay. Clinical information was obtained by the authors or provided by treating physicians after patients' informed consent. RESULTS: Median age at symptom onset was 66 years. Of 38 patients, 34 were male. Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent syndromes included limbic encephalitis (42%) and Morvan syndrome (29%). Seventy-seven percent of the patients had ≥3 of the following symptoms: encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or weight loss. A tumor, mostly thymoma, occurred in 19% of the patients. Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients and 25% had clinical relapses. CONCLUSIONS: Caspr2 antibodies associate with a treatable disorder that predominantly affects elderly men. The resulting syndrome may vary among patients but it usually includes a set of well-established symptoms. Recognition of this spectrum of symptoms and consideration of the protracted clinical course are important for early diagnosis of this disorder. Prompt immunotherapy and tumor therapy (if needed) often result in improvement.
OBJECTIVE: To report a large cohort of patients with antibodies against contactin-associated protein-like 2 (Caspr2) and provide the clinical spectrum of this disorder. METHODS: Serum and CSF samples were assessed at 2 neuroimmunology centers in Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were confirmed with 2 independent techniques, including brain immunohistochemistry and cell-based assay. Clinical information was obtained by the authors or provided by treating physicians after patients' informed consent. RESULTS: Median age at symptom onset was 66 years. Of 38 patients, 34 were male. Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent syndromes included limbic encephalitis (42%) and Morvan syndrome (29%). Seventy-seven percent of the patients had ≥3 of the following symptoms: encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or weight loss. A tumor, mostly thymoma, occurred in 19% of the patients. Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients and 25% had clinical relapses. CONCLUSIONS:Caspr2 antibodies associate with a treatable disorder that predominantly affects elderly men. The resulting syndrome may vary among patients but it usually includes a set of well-established symptoms. Recognition of this spectrum of symptoms and consideration of the protracted clinical course are important for early diagnosis of this disorder. Prompt immunotherapy and tumor therapy (if needed) often result in improvement.
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