Recent advances in autoimmune encephalitis

Abstract

Since the description of autoimmune encephalitis (AE) associated with N-methyl-D-aspartate receptor antibodies (anti-NMDARE) in 2007, more than 12 other clinical syndromes and antibodies have been reported. In this article, we review recent advances in pathophysiology, genetics, diagnosis pitfalls, and clinical phenotypes of AE associated with cell surface antibodies and anti-GAD associated neurological syndromes. Genetic studies reported human leukocyte antigen (HLA) associations for anti-LGI1, anti-Caspr2, anti-IgLON5, and anti-GAD. Follow-up studies characterized cognitive dysfunction, psychiatric symptoms, sleep disorders, and adaptative behavior dysfunction, mainly for anti-NMDARE. Late-onset anti-NMDARE and anti- GABA-B receptor (GABA-BR) encephalitis patients were described to have worse prognoses and different tumor associations. Additionally, the clinical spectrum of anti-LGI1, anti-AMPAR, anti-CASPR2, and anti-IgLON5 was expanded, comprising new differential diagnoses. The diagnostic criteria for AE were adapted to the pediatric population, and a diagnostic algorithm was proposed, considering potential mimics and misdiagnosis. We also review the limitations of commercial assays for AE and treatment recommendations, as well as clinical scales for short and long-term assessment of AE patients, along with cognitive evaluation.

Figure 1

Clinical spectrum of autoimmune encephalitis. Observe the different clinical phenotypes of each antibody reported.

Figure 2

Abbreviations: ABs, antibodies; ADEM, acute disseminated encephalomyelitis; AE, autoimmune encephalitis; BBE, Bickerstaff brainstem encephalitis; HE, Hashimoto encephalopathy; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance imaging; NMDARE, anti-NMDA receptor encephalitis; PNID, probable neuroinflammatory disorder; SN-AE, seronegative autoimmune encephalitis. Diagnostic algorithm for autoimmune encephalitis (adapted from Van Steenhoven et al. 8 ). Begin the algorithm from the entry criteria of possible AE, then apply the subsequent criteria (MRI demyelination, probable anti-NMDARE, probable anti-LGI1 encephalitis, BBE). Patients with positive Abs are classified as definite AE. In case of negative testing, evaluate thyroid ABs, probable SN-AE criteria, AE mimics (including PNID).