A New Cause of Treatment-Responsive Limbic Encephalitis

Abstract & Commentary

By M. Flint Beal, MD, Professor and Chairman, Department of Neurology, Cornell University Medical College, New York, NY. Dr. Beal reports no consultant, stockholder, speaker’s bureau, research, or other relationships related to this field of study.

Synopsis: A new from of limbic encephalitis is reported, characterized by neuropil antibodies. Patients show an excellent response to immunotherapy or tumor resection.

Source: Mayberg HS, et al. Deep Brain Stimulation for Treatment-Resistant Depression. Neuron. 2005;45:651-660.

Limbic encephalitis is a rare paraneoplastic illness characterized by symptoms of severe short term memory loss, or more extensive symptoms with confusion, seizure, and occasional psychosis. Previously, 2 groups of patients have been identified. The first of these include patients who have neuronal antibodies which have been identified as Hu, Ma2, or CV2/CRMP5. These antibodies produce strong immunostaining of hippocampus neurons. These patients usually have underlying tumors. It is associated particularly with small cell lung carcinoma, non-small cell lung carcinoma, testicular tumors, and thymoma. These patients frequently show increased signal in the medial temporal lobe, with T2 MRI imaging. Reposes to treatment, which are either resection of the tumor or immunosuppressants, are rare, except for patients with testicular tumors and Ma2 encephalitis. The clinical course is typically progressive.

A second group of patients was identified who have antibodies to voltage gated potassium channels (VGKC). These patients have antibodies that show mild staining of hippocampal neurons. CSF abnormalities are infrequent. They frequently show hyponatremia. The brain MRI also tends to show increased T2 signal in the medial temporal lobe. They frequently respond to treatment with corticosteroids, intravenous gamma globulin, and plasma exchange. Relapses may occur but are typically treatable.

The present report is that of a new form of limbic encephalitis. The patients had Sera and CSF that contained an antibody that reacted not as in most previously described paraneoplastic syndromes, with the nucleus or cytoplasm, but instead with the neuropil of the hippocampus or the cerebellum. In only one patient was an intracellular antibody identified. Unlike patients who have antibodies against VGKC, 5 of the 6 patients described had tumors. The tumors included a mediastinal teratoma, thymoma, thymic carcinoma, thyroid cancer, and an ovarian teratoma. In addition, they all showed CSF pleocytosis and intrathecal synthesis of the antibody. All, except for the patient who had the intracellular antibody, made a nice recovery with treatment of the tumor, immunosuppression, or both. The patients showed dramatic clinical and neuroimaging responses. Two patients who had neurological relapses improved with further immunotherapy. Brain MRI and PET imaging studies complemented each other in showing temporal lobe abnormalities; however, there was no overlap between the 2 studies in 50% of the patients, suggesting that both studies were needed. The antibody titres decrease or disappear over months.

Commentary

The present report broadens the spectrum of limbic encephalitis. Mayberg and colleagues have identified a new group of patients who show an excellent response to treatment. The nature of the antibodies remains to be determined. The finding of CSF abnormalities, oligoclonal bands, and abnormalities in the hippocampus on MRI and PET imaging suggest the possibility of limbic encephalitis with novel neuropil antibodies. Thorough investigation of these patients in warranted, since they show an excellent response to therapy.