2023 Volume 40 Issue 3 Pages 368-376
Autoimmune encephalitis (AE) is now defined as a form of encephalitis that occurs as a result of a brain–specific immune response with or without a cancer association, and it usually associates with antibodies against a neuronal, or glial, cell surface antigen (Dalmau and Graus definition 2022).
A variety of neuronal surface (NS) antibodies (NS–Abs) have been identified since 2007. It has been shown that NS–Abs play an important role in the pathophysiology of various neurological and neuropsychiatric disorders, including non–infectious/post–infectious encephalitis, first episode psychosis, epileptic/non–epileptic seizures, demyelinating syndrome, progressive dementia, involuntary movements (orofacial–limb dyskinesias, faciobrachial dystonic seizures, catatonia, rigidity, stiffness, tremors, myoclonus, chorea, stereotypies, oculomotor abnormalities), and non–REM/REM sleep disorder.
In 2016, a practical diagnostic approach to AE was proposed to achieve prompt immunotherapy at 3 levels of evidence for AE (possible, probable, and definite) along with newly proposed diagnostic criteria for possible AE, probable AE, probable and definite anti–NMDAR encephalitis, autoimmune limbic encephalitis, ADEM, and Hashimoto encephalopathy. In patients with new–onset refractory status epilepticus (NORSE), AE with antibodies against NMDAR, LGI1, GABAbR or GABAaR is often considered in the differential diagnosis of secondary NORSE ; however, cryptogenic NORSE is not an AE, rather a heterogeneous group of disorders that presents with NORSE as a condition, in which neuroinflammation or innate immunity–mediated mechanisms have been implicated. C–NORSE score based on the initial clinical assessments is useful for discriminating C–NORSE from secondary one. Neuronal IgM or IgA class antibodies have been described but should not be used as diagnostic markers ; only IgG neural antibodies are considered to have diagnostic significance. Identification of NS–Abs is crucial in making the diagnosis of AE or paraneoplastic syndrome ; however, the testing results using commercial assays (line blots, fixed cell–based assay, or rodent brain immunohistochemistry) should be interpreted with caution when measured with commercial assay alone.
In this lecture, I focus on pitfalls in clinical diagnosis and antibody testing in patients with AE, including recent update.
