Erdem Tüzün1, Josep Dalmau. 1. Division of Neuro-Oncology, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract
BACKGROUND AND OBJECTIVE: Recent studies suggest that a substantial number of patients with autoimmune limbic encephalitis may improve if properly diagnosed and treated. This is due, in part, to the increasing recognition of disorders that associate with antibodies to neuronal cell membrane antigens. This review focuses in these disorders, framed in a clinically useful immunologic classification of limbic encephalitis. REVIEW SUMMARY: Patients with limbic encephalitis usually present with rapidly progressive short-term memory deficits, psychiatric symptoms, and seizures. After excluding viral and systemic autoimmune disorders, many patients with limbic encephalitis (paraneoplastic or not) have cerebrospinal fluid inflammatory findings, EEG or MRI abnormalities in the temporal lobes, and antineuronal antibodies. These antibodies are directed against 2 broad categories of antigens: (1) intracellular or classic paraneoplastic antigens, including Hu, Ma2, CV2/CRMP5, and amphiphysin among others, and (2) cell membrane antigens, including voltage-gated potassium channels, N-methyl-D-aspartate receptor, and others expressed in the neuropil of hippocampus and cerebellum (pending characterization). Whereas the disorders related to the first category of antibodies associate with cancer (lung, testis and other), prominent brain infiltrates of cytotoxic T-cells, and limited response to treatment, the disorders related to the second category of antibodies associate less frequently with cancer (thymoma, teratoma), seem to be antibody-mediated, and respond significantly better to immunotherapy. CONCLUSIONS: Once considered an extremely rare disorder, almost always related to cancer, and refractory to treatment, limbic encephalitis is now regarded as a relatively frequent disorder, often unrelated to cancer, and with clinical-immunologic variants that respond to treatment.
BACKGROUND AND OBJECTIVE: Recent studies suggest that a substantial number of patients with autoimmune limbic encephalitis may improve if properly diagnosed and treated. This is due, in part, to the increasing recognition of disorders that associate with antibodies to neuronal cell membrane antigens. This review focuses in these disorders, framed in a clinically useful immunologic classification of limbic encephalitis. REVIEW SUMMARY:Patients with limbic encephalitis usually present with rapidly progressive short-term memory deficits, psychiatric symptoms, and seizures. After excluding viral and systemic autoimmune disorders, many patients with limbic encephalitis (paraneoplastic or not) have cerebrospinal fluid inflammatory findings, EEG or MRI abnormalities in the temporal lobes, and antineuronal antibodies. These antibodies are directed against 2 broad categories of antigens: (1) intracellular or classic paraneoplastic antigens, including Hu, Ma2, CV2/CRMP5, and amphiphysin among others, and (2) cell membrane antigens, including voltage-gated potassium channels, N-methyl-D-aspartate receptor, and others expressed in the neuropil of hippocampus and cerebellum (pending characterization). Whereas the disorders related to the first category of antibodies associate with cancer (lung, testis and other), prominent brain infiltrates of cytotoxic T-cells, and limited response to treatment, the disorders related to the second category of antibodies associate less frequently with cancer (thymoma, teratoma), seem to be antibody-mediated, and respond significantly better to immunotherapy. CONCLUSIONS: Once considered an extremely rare disorder, almost always related to cancer, and refractory to treatment, limbic encephalitis is now regarded as a relatively frequent disorder, often unrelated to cancer, and with clinical-immunologic variants that respond to treatment.