A new encephalitis with GABAA receptor antibodies

Abstract

In the past decade, several autoimmune neurological syndromes have been identified. Many of these syndromes, especially those responsive to immunotherapy, involve antibodies to cell-surface antigens, such as the NMDA receptor, LGI1, and the GABAB receptor. 1 Bien CG Vincent A Barnett MH et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012; 135: 1622-1638 Crossref PubMed Scopus (416) Google Scholar , 2 Davis R Dalmau J Autoimmunity, seizures, and status epilepticus. Epilepsia. 2013; 54: 46-49 Crossref PubMed Scopus (63) Google Scholar Detailed investigations have led to the recognition of distinct features that aid in early diagnosis. For example, faciobrachial dystonic seizures—very brief (<3 seconds) contractions of the arm and usually the ipsilateral face—are highly suggestive of the non-paraneoplastic, autoimmune syndrome associated with anti-voltage-gated potassium channel complex antibodies, specifically the anti-LGI1 variant. 3 Irani SR Michell AW Lang B et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011; 69: 892-900 Crossref PubMed Scopus (613) Google Scholar This is a treatable disorder with an excellent prognosis when recognised early. The faciobrachial dystonic seizures usually precede the rest of the syndrome, which consists of hyponatraemia and limbic encephalitis. Treatment with immunotherapy, especially corticosteroids, in the early phase can not only lead to improvement but can prevent the limbic encephalitis. 4 Irani SR Stagg CJ Schott JM et al. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype. Brain. 2013; 136: 3151-3162 Crossref PubMed Scopus (292) Google Scholar Similarly, the clinical features of anti-NMDA receptor encephalitis are quite distinct, with psychiatric presentation, followed by rapid deterioration, including central apnoea requiring ventilatory support, and prominent dyskinesias, often in young women, and often in those with ovarian teratomas. 5 Titulaer MJ McCracken L Gabilondo I et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013; 12: 157-165 Summary Full Text Full Text PDF PubMed Scopus (1857) Google Scholar Extreme delta brushes on EEG might also be suggestive of this syndrome. 6 Schmitt SE Pargeon K Frechette ES Hirsch LJ Dalmau J Friedman D Extreme delta brush: a unique EEG pattern in adults with anti-NMDA receptor encephalitis. Neurology. 2012; 79: 1094-1100 Crossref PubMed Scopus (482) Google Scholar Identification of the antibodies to cell-surface antigens in these syndromes not only suggests good response to immunotherapy but also raises suspicion of specific yet-to-be-detected underlying malignancies—eg, small-cell lung cancer is present in half of patients with limbic encephalitis with GABAB (metabotropic) receptor antibodies. 7 Höftberger R Titulaer MJ Sabater L et al. Encephalitis and GABAB receptor antibodies: novel findings in a new case series of 20 patients. Neurology. 2013; 81: 1500-1506 Crossref PubMed Scopus (313) Google Scholar Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodiesHigh titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. Full-Text PDF