Innate and adaptive immunity in human epilepsies

Abstract

SummaryInflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies. Infiltration of lymphocytes is observed in autoimmune epilepsies, especially the classical paraneoplastic encephalitides with antibodies against intracellular tumor antigens. The presence of lymphocytes in the CNS also has been found in focal cerebral dysplasia type 2 and in cortical tubers. Various autoantibodies have been shown to be associated with temporal lobe epilepsy (TLE) and hippocampal sclerosis of unknown etiology, which may be due to the presence of viral DNA. During the last decade, an increasing number of antineuronal autoantibodies directed against membranous epitopes have been discovered and are associated with various neurologic syndromes, including limbic encephalitis. A major challenge in epilepsy is to define biomarkers, which would allow the recognition of patient populations who might benefit from immune‐modulatory therapies. Some peripheral inflammatory markers appear to be differentially expressed in patients with medically controlled and medically refractory and, as such, could be used for diagnostic, prognostic, or therapeutic purposes. Establishing an autoimmune basis in patients with drug‐resistant epilepsy allows for efficacious and targeted immunotherapy. Although current immunotherapies can give great benefit to the correctly identified patient, there are limitations to their efficacy and they may have considerable side effects. Thus the identification of new immunomodulatory compounds remains of utmost importance.

Clinical Management of Epilepsy With Glutamic Acid Decarboxylase Antibody Positivity: The Interplay Between Immunotherapy and Anti-epileptic Drugs

“…Autoimmunity is increasingly being recognized as a cause of epilepsy ( 1 ). Glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibodies have been associated with multiple non-neurological and neurological syndromes including autoimmune epilepsy ( 2 ).…”

Central nervous system lymphatic unit, immunity, and epilepsy: Is there a link?

“…[71][72][73] Here we address the mechanisms F I G U R E 1 Schematic representation of lymphatic flow (light blue) located in the meninges, at the calvarium and cranial fossa (dorsal and ventral side of the cranium). [71][72][73] Here we address the mechanisms F I G U R E 1 Schematic representation of lymphatic flow (light blue) located in the meninges, at the calvarium and cranial fossa (dorsal and ventral side of the cranium).…”

“…The role of adaptive immunity in the pathophysiology of CNS diseases is emerging. [71][72][73] Here we address the mechanisms F I G U R E 1 Schematic representation of lymphatic flow (light blue) located in the meninges, at the calvarium and cranial fossa (dorsal and ventral side of the cranium). A, In the calvarium, MLVs are located along the dural sinuses and the middle meningeal artery (red), as well as along the rostral rhinal vein and the tentorium around the pineal gland.…”

Commentary on Nóbrega‐Jr et al. “Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal antibodies”

“…It is of great interest to identify the underlying etiology of MTLE‐HS (eg, autoimmune), so as to treat patients adequately (eg, immunosuppression) without time delay. Accumulating evidence suggests that autoimmune encephalitis within the limbic system (limbic encephalitis [LE]) is an underestimated and increasing cause of MTLE‐HS . In line with those studies, the study of Nóbrega‐Jr et al questioned the frequency of neuronal antibodies in MTLE‐HS as a parameter to determine which epilepsy patients might retrospectively have had an underlying autoimmune disease etiology and might profit from immunotherapy.…”