Glutamatergic autoencephalitides: an emerging field.

Abstract

Autoimmune responses targeting synaptic proteins are associated with a wide range of neurologic symptoms. Among these disorders are those associated with antibodies to ionotropic glutamate receptors, including the NMDAR (N-methyl-D-aspartate receptor) and AMPAR (α-amino-3-hydrozy-5-methyl-4-isoxazolepropionic acid receptor). Patients with anti-NMDAR encephalitis present with psychiatric symptoms, seizures, movement disorders, impaired consciousness, and autonomic derangements; half of patients have an associated ovarian teratoma, and most patients respond to immunosuppressive therapies. Patients' antibodies bind to the amino terminal domain of the NMDAR, and result in loss of NMDARs from synapses with subsequent NMDAR hypofunction. Anti-NMDAR antibodies have now been reported in other neuropsychiatric conditions, including psychosis, dementia, and HSV encephalitis. The pathophysiologic relevance of anti-NMDAR antibodies in these disorders is not yet clear, but their presence may indicate a role for immunotherapy in some patients. Although considerable work remains to be done, our understanding of disorders associated with anti-glutamate receptor antibodies has grown exponentially since they were first described just over 7 years ago, revolutionizing neurology. These antibodies, by interfering with synaptic function, readily link basic science and clinical medicine, and have revealed the impact of sudden but sustained loss of specific neurotransmitter receptors in humans. Improved understanding of their pathophysiology will lead to better treatments for these diseases while providing novel insights regarding the roles of glutamate receptors in learning, memory, and neuropsychiatric disease.