自己免疫性脳炎における早期診断と早期治療の重要性

抄録

After the discovery of new class of autoantibodies against neuronal cell surface antigens and synaptic proteins (NSA–antibodies), the concept of encephalitis has dramatically changed. Encephalitis can be divided into infectious and autoimmune (non–infectious) groups. Autoimmune encephalitis (AE) may have autoantibodies against intracellular onconeuronal antigens (e.g. Hu, Yo, Ri, CV2/CRMP5, Ma2, amphiphysin) or NSA (e.g. NMDAR, AMAPAR, GABAaR, GABAbR, DPPX). Most of the former antibodies are not pathogenic but are used as a biomarker of classical paraneoplastic neurological syndromes, whereas IgG NSA–antibodies are more likely pathogenic, and the presence of the antibodies implies that patients may respond to immunotherapy. With infectious etiologies in mind previous diagnostic criteria for encephalitis has been made based on fever, mental status changes, inflammatory CSF, and brain MRI and EEG abnormalities ; however, these abnormalities may not be present in patients with NSA antibody–positive AE. Although early initiation of immunotherapy is often emphasized in AE, antibody testing is not readily accessible in most situation, thus initiation of immunotherapy may be delayed. Therefore, 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) with several new diagnostic criteria. A recent study showed that diffuse brain atrophy in anti–NMDAR encephalitis can be reversible and does not imply a poor clinical outcome. In contrast, cerebellar atrophy was irreversible and associated with a poor outcome. First–line immunotherapy can be started depending on the severity of patients with possible AE at early stage while excluding alternative diagnosis, but the second–line immunotherapy should be carefully used after confirming the NMDAR–antibodies in CSF with appropriate testing.

In this lecture, I focus on anti–NMDAR encephalitis and talk about a potential pitfall in clinical diagnosis of the disease.