Autoimmune encephalitis (AE) is the most common form of encephalitis of noninfectious etiology and is caused by autoantibodies targeting different neural epitopes. AE classically presents as a syndrome of rapidly progressive encephalopathy with memory deficits, altered mental status and/or psychiatric symptoms.
The three most frequent antibodies are LGI1, GAD65 and NMDA-R. LGI1 causes a limbic encephalitis with epilepsy and cognitive decline as the most prominent clinical features. GAD65 antibodies have been associated with multiple neurological syndromes including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. Anti-NMDA receptor encephalitis is characterized by neuropsychiatric features.
Emphasis should be given to accurate clinical history, examination and supportive paraclinical diagnostic tests such as MRI, inflammatory cerebrospinal fluid parameters and EEG. Usually, AE is characterized by subacute onset (rapid progression of less than three months), working memory deficits (short-term memory loss), altered mental status (altered level of consciousness, lethargy, personality change) and/or psychiatric and neurological symptoms.
Experience from studies on patients with primary psychiatric diseases tested for NMDA-R and other neuronal surface antibodies suggests that the likelihood of identifying clinically relevant antibodies is very low. Consequently, routine antibody testing should not be considered in patients with schizophrenia and other well-defined chronic psychiatric diseases. A review of patients with first episode psychosis tested for NMDA-R and other neuronal surface antibodies showed that about 3% had serum NMDA-R antibodies. In these patients, antibody testing should be considered as this condition can be treated with an appropriate therapy.
Conclusion: Syndrome-based criteria for autoimmune encephalitis are available as part of a diagnostic algorithm to help clinicians navigate differential diagnoses, the choice of antibody testing and the use of other paraclinical diagnostic tests. In clinical practice, a team approach of neurologists and psychiatrists will facilitate the recognition of AE and its best possible treatment.
Orozco E, Valencia-Sanchez C, Britton J, Dubey D, Flanagan EP, Lopez-Chiriboga AS, et al. Autoimmune Encephalitis Criteria in Clinical Practice. Neurol Clin Pract. 2023 Jun;13(3):e200151.
Dalmau J, Graus F. Autoimmune Psychosis. In: Dalmau J, Graus F. Autoimmune Encephalitis and Related Disorders of the Nervous System. Cambridge: Cambridge University Press; 2022. p. 503–26.
