Autoimmune seizures and epilepsy
Christian Geis, … , Francesc Graus, Josep Dalmau
Christian Geis, … , Francesc Graus, Josep Dalmau
Published February 4, 2019
Citation Information: J Clin Invest. 2019;129(3):926-940. https://doi.org/10.1172/JCI125178.
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Review

Autoimmune seizures and epilepsy

Abstract

The rapid expansion in the number of encephalitis disorders associated with autoantibodies against neuronal proteins has led to an incremental increase in use of the term “autoimmune epilepsy,” yet has occurred with limited attention to the physiopathology of each disease and genuine propensity to develop epilepsy. Indeed, most autoimmune encephalitides present with seizures, but the probability of evolving to epilepsy is relatively small. The risk of epilepsy is higher for disorders in which the antigens are intracellular (often T cell–mediated) compared with disorders in which the antigens are on the cell surface (antibody-mediated). Most autoantibodies against neuronal surface antigens show robust effects on the target proteins, resulting in hyperexcitability and impairment of synaptic function and plasticity. Here, we trace the evolution of the concept of autoimmune epilepsy and examine common inflammatory pathways that might lead to epilepsy. Then, we focus on several antibody-mediated encephalitis disorders that associate with seizures and review the synaptic alterations caused by patients’ antibodies, with emphasis on those that have been modeled in animals (e.g., antibodies against NMDA, AMPA receptors, LGI1 protein) or in cultured neurons (e.g., antibodies against the GABAb receptor).

Authors

Christian Geis, Jesus Planagumà, Mar Carreño, Francesc Graus, Josep Dalmau

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Figure 1

Paraneoplastic limbic encephalitis and epilepsy mediated by cytotoxic T cell mechanisms.

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Paraneoplastic limbic encephalitis and epilepsy mediated by cytotoxic T ...
(A) Coronal fluid-attenuated inversion recovery (FLAIR) MRI image showing increased signal and volume of the right amygdala and hippocampus, suggestive of limbic encephalitis, in a patient with a history of seminoma and acute-onset seizures associated with Ma2 paraneoplastic antibodies. (B) Coronal FLAIR image 1 year later, showing atrophy of the right hippocampus and medial temporal lobe sclerosis. (C) Subtraction ictal SPECT coregistered to MRI (SISCOM) showing increased ictal perfusion over the right hippocampus and parahippocampal gyrus during a right temporal lobe seizure with epigastric aura, piloerection, and loss of awareness. (D) Coronal FLAIR image showing resection of the temporal pole and right mesial temporal lobe structures. After surgery, the frequency of the seizures decreased, but they did not resolve (Engel’s class III). (E) Inflammatory infiltrates in the surgical specimen; the section of the tissue was immunostained with TIA-1 antibody, a marker of cytotoxic T cells (shown as brown granular staining). Some TIA-1–positive cells are in close apposition with neurons (arrows). Scale bars: 10 μm. Images reprinted with permission from Carreño et al. (63).