Clinical Spectrum of Encephalitis Associated With Antibodies Against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Case Series and Review of the Literature

Importance  The clinical features of autoimmune encephalitis associated with antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR-Abs) remain poorly defined.

Objectives  To describe 7 patients with encephalitis and AMPAR-Abs and to provide a review of the literature on this disease entity.

Design, Setting, and Participants  The setting was the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (Lyon, France), and participants were 7 consecutive patients diagnosed as having encephalitis and AMPAR-Abs between January 1, 2010, and December 1, 2014. Patients’ clinical data were analyzed, with a median follow-up period of 12 months (range, 2-31 months). Relevant articles were identified in the MEDLINE database using the keywords autoimmune encephalitisand AMPA receptor antibodies until February 15, 2015.

Main Outcomes and Measures  Modes of onset, full clinical presentations, and cancer prevalence.

Results  The patients included 4 women and 3 men (median age, 56 years). Four main modes of encephalitis onset were observed, including confusion (3 patients), epileptic (1 patient), amnestic (1 patient), and a severe form of fulminant encephalitis (2 patients). In contrast with previous reports, we observed only 1 patient with seizures. Two patients had cancer (1 lung carcinoma and the other thymic carcinoma). Analysis of the literature identified 35 published cases of encephalitis and AMPAR-Abs, including 18 with clinical data. The same modes of encephalitis onset were observed, including confusion (12 patients), epileptic (1 patient), amnestic (3 patients), and fulminant encephalitis (2 patients). Eleven patients were initially seen with a neoplasm (lung, breast, thymoma, or ovary).

Conclusions and Relevance  The clinical spectrum of AMPAR encephalitis is variable. Cancer was found in 13 of 27 patients (48%) with known cancer status. Most patients are seen with symptoms suggestive of autoimmune limbic encephalitis, although they can be paucisymptomatic or may manifest severe panencephalitis that evolves to a minimally conscious state and diffuse cortical atrophy. Patients suspected of having autoimmune encephalitis should undergo screening for serum and cerebrospinal fluid AMPAR-Abs.

JAMA Neurology 2015