Syndrome and outcome of antibody‐negative limbic encephalitis

F. Graus, D. Escudero, L. Oleaga, J. Bruna, A. Villarejo‐Galende, J. Ballabriga, M. I. Barceló, F. Gilo, S. Popkirov, P. Stourac, J. Dalmau

To report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. Review of clinical records of 163 patients with LE. Immunohistochemistry on rat brain, cultured neurons, and cell-based assays were used to identify neuronal autoantibodies. Patients were included if 1) there was adequate clinical, CSF, and MRI information to classify the syndrome as LE, 2) MRI images were accesible for central review, and 3) serum and CSF were available and confirmed negative for neuronal antibodies. Twelve (7%)/163 LE patients (median age: 62 years; range: 40-79; 9 [75%] male) without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short-term memory leading to hospital admission in a few weeks (median time: 2 weeks; range: 0.5-12). In four patients the short-term memory dysfunction remained as isolated symptom during the entire course of the disease. Seizures, drowsiness, and psychiatric problems were unusual. Four patients had solid tumors (1 lung, 1 esophagus, 2 metastatic cervical adenopathies of unknown primary tumor) and 1 chronic lymphocytic leukemia. CSF showed pleocytosis in 7 (58%) with a median of 13 white blood cells /mm3 (range: 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins, and combinations of both drugs or with rituximab. Clinical improvement occurred in 6 (54%) of 11 assessable patients. Despite the discovery of new antibodies, 7% of LE remains seronegative. Antibody-negative LE is more frequent in older males and usually develops with predominant or isolated short-term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy. This article is protected by copyright. All rights reserved.