Expanding clinical spectrum from Hashimoto's encephalopathy to anti-NAE antibody-associated disorders (NAEAD)

Using proteomic analysis, we identified anti-NAE antibodies (autoantibodies against NH₂-terminal of alpha-enolase) as a diagnostic marker for Hashimoto's encephalopathy (HE). As cases of HE with serum anti-NAE antibodies accumulated, the clinical spectrum of HE with anti-NAE antibodies became expanded. In addition, it is now known that antibodies can be detected in other diseases that differ from conventional HE. We recently reported the detection of anti-NAE antibodies in patients with a clinical diagnosis of multiple system atrophy or corticobasal syndrome. These findings suggest that anti-NAE antibodies indicate an immune mechanism in the pathogenesis of neurodegenerative diseases. We propose a novel disease concept for anti-NAE antibody-associated disorders (NAEAD). The clinical spectrum of NAEAD is not limited to HE but is a broad spectrum that partially shares several autoimmune neurological diseases, including autoimmune acute encephalopathy, autoimmune cerebellar ataxia, and autoimmune psychosis, and even extends to immune-associated neurodegenerative diseases.