Marlene Baumann
Autoimmune encephalitis encompasses a range of antibody-mediated neuroinflammatory disorders, with the expansion and emergence of new entities since anti-N-methyl-D-aspartate receptor (anti-NMDAr) encephalitis, the first specific antibody-mediated form, described by Dalmau et al in 2007.1
Autoimmune encephalitis is increasingly recognized as an underlying cause of new acute or recent-onset altered mental status including diverse and profound neuropsychiatric/behavioral symptoms, cognitive deficits, seizures, and movement disorders, among others.2–5
It is speculated that a number of patients are misdiagnosed, at least initially, with a primary psychiatric, neurodegenerative, or viral disease. As such, it is vital for the radiologist to recognize and raise the possibility of autoimmune encephalitis as a diagnostic consideration in the appropriate clinical setting.
Because autoantibody test results and response to therapy are not available at disease onset, the initial diagnostic approach, besides neurologic assessment, includes neuroimaging and other conventional tests such as EEG that are accessible to most clinicians. Early radiologic suspicion is essential to ensure appropriate and timely clinical and lab work-up, including serum/CSF antibody testing, and treatment in order to optimize clinical outcomes. Normal MR imaging does not exclude autoimmune encephalitis, but helps exclude other potential underlying pathologies.2
In this AJNR News Digest, we highlight several recent articles that explore various facets of this topic, ranging from pathophysiology and MR imaging review, to similarities in neuropsychiatric systemic lupus erythematosus (SLE) imaging and treatment response as compared with a subset of patients with striatal NMDAr autoimmune encephalitis, to MR imaging features that could potentially help to differentiate pediatric-onset neuromyelitis optica spectrum disorder (NMOSD) from acute disseminated encephalomyelitis (ADEM).1–3,6–8
Paraneoplastic and nonparaneoplastic are 2 broad categories of antibody-mediated CNS disorders; however, a more clinically relevant classification is based on the location of the antibody-targeted antigen.2 Group I antibodies target intracellular neuronal antigens, are less specific, and are associated with increased irreversible neuronal damage, decreased response to treatment, and an underlying malignancy.2 Group II antibodies target cell-surface antigens, are more specific, and are associated with more favorable neurologic outcomes.2
NMDAr antibody (group II) encephalitis, one of the most common and best-characterized subtypes of autoimmune encephalitis, is classically seen in young adults and children, with a female predominance (female-to-male ratio of around 8:2).2,4 As this subtype is mediated by immunoglobulin G (IgG) antibodies against the GluN1 subunit of the neuronal NMDAr, CSF analysis for the IgG antibody is the only specific diagnostic test. Ovarian teratomas and herpes encephalitis are known triggers of NMDAr autoimmunity, with the former known to be more common in adult women.5 Anti-NMDAr encephalitis has a well-characterized progression of clinical features, and diagnostic criteria for probable and definite disease have been established in the literature.6 Interestingly, pathologic MR imaging findings are often absent,2,3 and MR imaging findings play no role in the aforementioned criteria. Zhang et al reported normal brain MRI findings in half of a cohort of 53 Chinese patients with proven anti-NMDAr encephalitis.6 Other studies have shown the absence of neuroimaging findings on initial presentation (89%) or follow-up imaging (79%).2,9 When abnormal, imaging may show a classic limbic encephalitis pattern; however, wide variation in the extent and distribution of nonrestricting T2-FLAIR-hyperintense lesions, with cases of mild transient cortical enhancement, has been reported.2,3
Autoimmune encephalitis of the striatum is uncommon, reported in 8% of anti-NMDAr cases in one study.1 Antibody-mediated inflammation of the striatum in SLE is also relatively uncommon.1 Kelley et al presented a case series of 5 patients with confirmed SLE and associated anti-double-stranded DNA (anti-dsDNA) antibody; MR brain imaging findings of bilateral nonenhancing, nonrestricting T2-FLAIR signal hyperintensity within the striatum; and positive response to plasmapheresis.1 The MR imaging pattern was nonspecific, but highly suggestive of autoimmune encephalitis in the appropriate clinical setting, and was compared with a companion case of striatal anti-NMDAr encephalitis.1 The case series lends support to the hypothesis in the literature that peripheral antibodies targeting dsDNA enter the central nervous system to cross-react with NMDAr antigens.1