title: Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up.
abstract: OBJECTIVE
  This nationwide study gives a detailed description of the clinical features and long-term outcome of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.
  
  
  METHODS
  We collected patients prospectively from October 2013, and retrospectively from samples sent to our laboratory from January 2007. LGI1 antibodies were confirmed with both cell-based assay and immunohistochemistry. Clinical information was obtained in interviews with patients and their relatives and from medical records. Initial MRI and follow-up MRI were revised blindly. Neuropsychological assessment was performed in those patients with follow-up over 2 years.
  
  
  RESULTS
  Annual incidence in the Netherlands was 0.83/million. A total of 34/38 patients had a limbic encephalitis. Subtle focal seizures (66%, autonomic or dyscognitive) and faciobrachial dystonic seizures (FBDS, 47%) mostly occurred before onset of memory disturbance. Later in the disease course, 63% had tonic-clonic seizures. Initial MRI showed hippocampal T2 hyperintensity in 74% of the patients. These lesions evolved regularly into mesial temporal sclerosis (44%). Substantial response to immunotherapy was seen in 80%, with early response of seizures and slow recovery of cognition. At follow-up ≥2 years, most surviving patients reported mild residual cognitive deficit with spatial disorientation. A total of 86% had persistent amnesia for the disease period. Relapses were common (35%) and presented up to 8 years after initial disease. Two-year case fatality rate was 19%.
  
  
  CONCLUSIONS
  Anti-LGI1 encephalitis is a homogenous clinical syndrome, showing early FBDS and other focal seizures with subtle clinical manifestations, followed by memory disturbances. Better recognition will lead to earlier diagnosis, essential for prompt start of treatment. Long-term outcome of surviving patients is mostly favorable, but relapses are common.
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Agnes
authors: A
authors: van Sonderen
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Roland D
authors: RD
authors: Thijs
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Elias C
authors: EC
authors: Coenders
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Lize C
authors: LC
authors: Jiskoot
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Esther
authors: E
authors: Sanchez
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Marienke A A M
authors: MA
authors: de Bruijn
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Marleen H
authors: MH
authors: van Coevorden-Hameete
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Paul W
authors: PW
authors: Wirtz
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Marco W J
authors: MW
authors: Schreurs
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands.
authors: Peter A E
authors: PA
authors: Sillevis Smitt
authors: From the Departments of Neurology (A.v.S., M.A.A.M.d.B., P.A.E.S.S., M.J.T., M.H.v.C.-H.), Neuropsychology (E.C.C., L.C.J.), and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague; Stichting Epilepsie Instellingen Nederland (SEIN) (R.D.T.), Heemstede; Department of Radiology and Nuclear Medicine (E.S.), VU University Medical Center, Amsterdam; and Department of Biology (M.H.v.C.-H.), Division of Cell Biology, Utrecht University, the Netherlands. m.titulaer@erasmusmc.nl.
authors: Maarten J
authors: MJ
authors: Titulaer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000276:immunology* / Q000523:psychology / Q000628:therapy; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins; D020363:Limbic Encephalitis / Q000453:epidemiology* / Q000276:immunology* / Q000523:psychology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011506:Proteins / Q000276:immunology*; D012189:Retrospective Studies; D013577:Syndrome; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins