Immunopsychiatry: an update on autoimmune encephalitis for neuropsychiatrists

ABSTRACT

Introduction

Autoimmune encephalitis (AIE) is a group of immune-mediated inflammatory processes of the brain with marked psychiatric features. Although relatively rare, they might offer difficult differential diagnosis with psychiatric conditions, especially catatonia and psychotic syndromes. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common AIE, presenting with psychiatric syndromes in 90% of cases. The associated psychopathology is complex, pleomorphic, and best characterized when there is involvement of a psychiatrist in the assessment.

Areas covered

This text will review the main aspects of AIE to psychiatrists and/or neuropsychiatrists.

Expert opinion

Immune system dysfunction has been implicated in the pathophysiology of psychiatric symptoms and disorders. The use of diagnostic criteria for possible AIE, especially when specific antibodies of AIE are not available, allows early diagnosis and prompt treatment which are associated with better clinical outcomes. The study of the psychiatric aspects of AIE can broaden our knowledge of the underlying mechanisms of various psychiatric manifestations.

KEYWORDS:

• Immunopsychiatry
• autoimmune encephalitis
• catatonia
• psychopathology
• neuropsychiatry

Article highlights

• The estimated annual incidence of autoimmune encephalitis (AIE) is between 8 and 15 cases per 1.000.000 people per year.

• Firstly described in 2005, anti-NMDAR encephalitis is the most common AIE, with female to male ratio of 4:1 and an average age at onset of 21 years. Psychiatric symptoms are present in approximately 90% of cases. The psychopathology is often polymorphic, with psychosis (45–67%) and catatonia (~30%) being relatively frequent.

• Psychiatric syndromes have been described in other AIE. For instance, they have been reported in 67% of patients with anti-GABA-B encephalitis and 63% of patients with anti-LGI1 encephalitis. Discerning between AIE and primary psychiatric disorders can be a challenging task.

• There are warning signs, or ‘red flags,’ which point to the diagnosis of AIE: presence of a psychotic syndrome with rapid progression (less than 3 months), absence of previously known psychiatric disorder, occurrence of neurological (e.g. seizures) and/or systemic symptoms (e.g. fever), and poor response to standard psychopharmacological strategies.

• There are different immune-based therapies for AIE. First-line strategies consist of steroids, intravenous immunoglobulin, or plasmapheresis. Second-line consists of cyclophosphamide and rituximab. Patients with paraneoplastic AIE need to have the primary tumor removed.

List of abbreviations

ADEMAcute disseminated encephalomyelitis

AIE Autoimmune encephalitis

CSFCerebrospinal fluid

CNS Central nervous system

EEGElectroencephalography

FBDS Faciobrachial dystonic seizures

GABA Gama-aminobutyric acid

HE Hashimoto<apos;>s encephalopathy

HU Neuronal nuclear antibody type I

HSV Herpes simplex virus

LGI1Anti-leucine-rich glioma inactivated 1

MOG Myelin-oligodendrocyte-glycoprotein

MRI Magnetic resonance imaging

NMDAR N-methyl-d-aspartate receptor

PNS Paraneoplastic neurologic syndrome

SARS-CoV-2Severe acute respiratory syndrome coronavirus 2

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.