Diagnosing autoimmune encephalitis in psychiatry: clinical recommendations and unresolved challenges from the GENERATE network.

Abstract

Psychiatric syndromes can be caused by underlying autoimmune encephalitis (AE). This represents a diagnostic challenge at the interface of psychiatry and neurology. While AE mostly manifests with a combined, complex neuropsychiatric syndrome, some patients with AE may (initially) present with predominant or isolated psychiatric symptoms. These cases can be difficult to classify, and diagnostic approaches vary considerably across clinical settings. This paper from the GErman NEtwork for Research on AuToimmune Encephalitis (GENERATE) provides interdisciplinary expert recommendations from psychiatry and neurology for the diagnostic evaluation of patients with suspected AE as the cause of psychiatric syndromes for psychiatric care settings. It integrates current scientific evidence with practical, empirical considerations from routine clinical care in different healthcare settings. The proposed diagnostic approach to detect psychiatric manifestations of AE emphasizes a rational, stepwise evaluation incorporating clinical assessment, magnetic resonance imaging, electroencephalography, blood testing, cerebrospinal fluid (CSF) analysis, and neuronal/glial antibody testing in serum and CSF. In diagnostically ambiguous individuals, [¹⁸F]fluorodeoxyglucose positron-emission-tomography and advanced antibody testing (e.g., live-cell-based assays) or neuroimaging techniques (e.g., volumetric analysis) may provide additional supportive information. Typical findings and limitations of diagnostic modalities are discussed to facilitate appropriate interpretation and to avoid under-recognition or overdiagnosis. Importantly, these recommendations do not aim to define new disease entities or diagnostic criteria, but rather to support a harmonized and pragmatic diagnostic approach to patients presenting with psychiatric syndromes suspected to be caused by underlying AE. Finally, key unresolved issues in this evolving field of immunopsychiatry are outlined, and promising research strategies are described.