An underlying immune basis is emerging in an increasing number of epileptic and encephalopathic syndromes. The immunopathological mechanisms may be categorized into antibody-mediated, T-cell cytotoxicity, and microglia-induced degeneration. The immune basis in
Rasmussen syndrome is thought to be T-cell mediated.
Antibodies to extracellular and intracellular
epitopes are implicated in limbic and other encephalitides, characterized by
seizures,
movement disorder,
sleep disorder, obtundation,
psychosis,
mutism, and other psychiatric symptoms. Extracellular
antibodies are directed at cell-surface-expressed neuronal or glial
proteins:
glutamate receptors (N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid),
voltage-gated potassium channel complex (contactin-associated-
protein 2 [CASPR2],
contactin-2 and leucin-rich,
glioma-inactivated 1 [LGI1]), and γ-
aminobutyric acid (
GABA) receptors (GABABR and GABAAR).
Antibodies to intracellular
antigens are less commonly seen (for example,
glutamic acid decarboxylase). Diseases caused by
antibodies to cell-surface-expressed
antigens are better expected to respond to immune treatments than to those where the presumed mechanism is T-cell driven.
Antibodies to the
folate receptor FR1 are a cause of primary cerebral
folate deficiency. Febrile
infection-related
epilepsy syndrome (FIRES) may also have an immune basis, although this is yet to be proven. For all these
epilepsies, the best treatment and the long-term outcomes are not yet clear.