Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis

Objective To determine the frequency of anti-NMDA receptor encephalitis without detectable serum NMDAR antibodies and to compare the clinical features of these patients with those with NMDAR antibodies in serum and CSF. Methods This is a retrospective assessment of serum antibody status and clinical features of 489 patients with anti-NMDAR encephalitis, defined by the presence of NMDAR antibodies in the CSF, and available paired serum/CSF samples examined at Hospital Clinic-Institut d’Investigacions Biomediques August Pi I Sunyer, Barcelona, between January 2007 and December 2017. NMDAR antibodies were determined with rat brain immunostaining, in-house cell-based assay (CBA), and a commercial CBA. Patients were considered seronegative if NMDAR antibodies were undetectable with the 3 indicated techniques. Results Serum NMDAR antibodies were not detected in 75 of 489 (15%) patients. Compared with the 414 seropositive patients, the seronegative were older (23.5 years [interquartile range (IQR): 17–43] vs 20.5 [IQR: 14–31]; p Conclusions NMDAR antibodies are not detected in the serum of 15% of the patients with anti-NMDAR encephalitis. These patients appear to be older and have milder neurologic symptoms with less frequency of tumors.