Autoimmune encephalitis

Encephalitis causes mental status changes (depressed or altered level of consciousness, lethargy, personality change) associated with fever, seizures, focal neurological deficits, CSF pleocytosis, EEG abnormalities, and variable neuroimaging findings. Some patients with this clinical profile have viral encephalitis and a few have infections by other agents, including Bartonella, Chlamydia, Mycoplasma pneumonia, and other. However, even when PCR, bacterial and viral cultures, serology, and other tests are done, no viral or other pathogen is identified in a significant proportion of patients. Many of these PCR- and culture-negative patients turn out to have autoimmune encephalitis. Most cases of autoimmune encephalitis are caused by antibodies against neural antigens located on the cell membrane.

The most common autoimmune encephalitis is anti-NMDA receptor (NMDAR) encephalitis, which, in some studies, is more frequent than HSV and other viral encephalitides. It is characterized clinically by psychiatric features, memory disturbance, speech disorder, seizures, dyskinesias, decreased level of consciousness, autonomic instability, and hypoventilation. The MRI may show cortical and subcortical signal abnormalities in about 50% of cases and the CSF shows lymphocytic pleocytosis, elevated protein, and oligoclonal bands. Brain biopsies, done in a few cases, show mild nonspecific changes including perivascular lymphocytes and microglial activation.

Anti-NMDAR encephalitis is most frequent in young females with ovarian, mediastinal, and other teratomas, but males with testicular and other teratomas and both sexes with other tumors or without evidence of a tumor may be affected. These tumors contain neural elements not previously encountered by the immune system and exposed to it because there is no blood-brain barrier. Antibodies generated as a result of this sensitization cross the blood-brain barrier and attach to the NMDAR on the neuronal membrane. This leads to decrease of the NMDAR in GABAergic and glutamatergic synapses and increase of extracellular glutamate which causes the symptoms. Treatment consists of steroids, intravenous immunoglobulin, and plasma exchange. Some cases of anti-NMDAR encephalitis follow HSV or other viral encephalitis, suggesting that antibodies to NMDAR arise following disruption of brain and the blood-brain barrier during the primary infection. Anti-NMDAR encephalitis is the prototype of other, less frequent autoimmune encephalitides caused by neuronal surface antibodies.

Another autoimmune encephalitis is limbic encephalitis which presents with confusion, aberrant behavior, memory dysfunction, and seizures, and is associated with abnormal MRI signal in the medial temporal lobes. Limbic encephalitis occurs also as a paraneoplastic syndrome, in which case it is associated with intracytopasmic antibodies.

Another probably immunologically-mediated encephalitis is Rasmussen encephalitis, a rare condition that affects mostly children and young adults. Rasmussen encephalitis is characterized clinically by progressive, drug-resistant focal epilepsy, hemiplegia, and cognitive decline and pathologically by cortical inflammation, neuronal loss, and gliosis confined to one cerebral hemisphere. The inflammation consists exclusively of T-lymphocytes and microgial activation with neuronophagia and microgial nodules. Advanced stages show neuronal loss, gliosis and cortical cavitation. The pathology involves primarily the cerebral cortex and may be focal such that areas of severe cortical damage are bordered by normal brain. Hemispherectomy, which is the only cure for the seizures, has provided abundant material for pathological analysis. Neuronal damage in Rasmussen encephalitis is thought to be mediated by T-cell cytotoxicity and microglial activation. The role of CNS autoantibodies, if any, is unclear.

An autoimmune disorder caused by antibodies to GFAP (autoimmune GFAP astrocytopathy) has been described recently. It is characterized clinically by symptoms of meningitis, encephalitis and myelopathy and pathologically by lymphocytic or, rarely, granulomatous inflammation. About 25% of patients have a coexisting neoplasm, most commonly an ovarian carcinoma. The MRI shows linear perivascular enhancement radiating around the ventricles. GFAP antibodies are present in the CSF.

Updated: March, 2024

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