title: Characterisation of a syndrome of autoimmune adult onset focal epilepsy and encephalitis.
abstract: We report a series of patients with a clinical syndrome characterised by the explosive onset in adulthood of recurrent focal seizures of frontotemporal onset and features suggestive of autoimmune encephalitis. We propose that this presentation of "autoimmune adult onset focal epilepsy and encephalitis" is a recognisable clinical syndrome, and provide evidence it may be associated with heterogeneous immunological targets. Between 2008 and 2011 we encountered six patients with new-onset epilepsy in whom we suspected an autoimmune aetiology. We first characterised the clinical, electroencephalographic, cerebrospinal fluid (CSF), imaging, and pathological findings of this syndrome. We subsequently tested them for antibodies against both intracellular and neuronal cell surface antigens. All patients presented with recurrent seizures with focal frontotemporal onset, refractory to multiple anticonvulsants. Four had focal T2-weighted hyperintensities on MRI. CSF mononuclear cells were variably elevated with positive oligoclonal bands in four. Brain biopsy in one patient demonstrated perivascular lymphocytic infiltration. Two were treated with immunosuppression and went on to achieve complete seizure control and return to baseline cognition. Three of four patients who received only pulsed steroids or no treatment had ongoing frequent seizures, with two dying of sudden unexpected death in epilepsy. Subsequently, three had antibodies identified against neuronal cell surface antigens including N-methyl-D-aspartate receptor and leucine-rich glioma inactivated 1. We suggest that patients with such a presentation should be carefully evaluated for a suspected autoimmune aetiology targeting cell surface antigens and have a therapeutic trial of immunosuppression as this may improve their long-term outcome.
authors: Department of Neurology, Westmead Hospital, Westmead, NSW 2145, Australia; Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.
authors: Sudarshini
authors: S
authors: Ramanathan
authors: Department of Neurology, Westmead Hospital, Westmead, NSW 2145, Australia; Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.
authors: Andrew
authors: A
authors: Bleasel
authors: Department of Neurology, Royal North Shore Hospital, St Leonards, NSW, Australia; Northern Clinical School, University of Sydney, Sydney, NSW, Australia.
authors: John
authors: J
authors: Parratt
authors: Macquarie Neurology, Macquarie University Hospital, Macquarie University, NSW, Australia.
authors: Carolyn
authors: C
authors: Orr
authors: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Westmead, NSW, Australia.
authors: Russell C
authors: RC
authors: Dale
authors: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors: Angela
authors: A
authors: Vincent
authors: Department of Neurology, Westmead Hospital, Westmead, NSW 2145, Australia; Westmead Clinical School, University of Sydney, Sydney, NSW, Australia. Electronic address: vfung@usyd.edu.au.
authors: Victor S C
authors: VS
authors: Fung
mesh_terms: D000328:Adult; D001927:Brain Diseases / Q000134:cerebrospinal fluid / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D004569:Electroencephalography; D004660:Encephalitis; D004828:Epilepsies, Partial / Q000134:cerebrospinal fluid / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D005260:Female; D050031:Hashimoto Disease / Q000134:cerebrospinal fluid / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D056747:Immunomodulation; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D043025:Oligoclonal Bands / Q000378:metabolism; D049268:Positron-Emission Tomography; D011506:Proteins / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D043025:Oligoclonal Bands; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Anti-NMDAR encephalitis; Autoimmune encephalitis; Autoimmune epilepsy; Focal seizures; Limbic encephalitis; VGKC encephalitis