Six major groups of symptoms of anti-NMDAR encephalitis include, 1) abnormal behaviour or cognitive dysfunction (BCD), 2) speech dysfunction (SD), 3) seizures, 4) movement disorders (MD), 5) decreased level of consciousness (DC), and 6) autonomic dysfunction or central hypoventilation (AD/CH). According to recently published criteria, a definite diagnosis of anti-NMDAR encephalitis can be made with one or more of the 6 major groups of symptoms in association with IgG GluN1-antibodies (NMDAR-antibodies) in CSF. The frequency of clinically atypical cases associated with these antibodies is unclear.

To report atypical clinical manifestations associated with NMDA receptor (NMDAR) antibodies.

We reviewed the clinical information of 43 patients (median age 27 years [12-51 years], 33 [76.7%] female) with NMDAR-antibodies in CSF and/or serum detected with cell-based assays and rat brain immunohistochemistry. Typical cases were defined as those with 4 or more of the 6 major groups of symptoms, while atypical cases as those with 3 or less.

In the 43 patients, the median number of major groups of symptoms were 6 (range, 0-6): BCD (n=40), seizures (n=37), SD (n=35), DC (n=35), MD (n=34) and AD/CH (n=30). The clinical features were divided into 2 groups: typical (n=34 patients) and atypical (n=9, 20.9%). Comparison of both groups showed no difference in age of onset, gender, prodromal fever or headache, CSF pleocytosis, oligoclonal bands, or tumor association; however, ventilatory support was less frequently used in atypical cases (1/9 vs 25/34, p=0.0012). The symptoms in atypical cases included isolated seizures (n=3, 1 with MOG-antibodies), isolated psychosis (n=2), multifocal demyelinating syndrome (n=2), meningoencephalitis with leptomeningeal enhancement (n=1, with MOG-antibodies), and autoimmune post-herpes simplex encephalitis (n=1).

In this cohort, 3 of 43 (7%) patients with NMDAR-antibodies, including 2 with multifocal demyelination and 1 meningoencephalitis with overlapping MOG-antibodies, showed atypical clinical features not included in the criteria of anti-NMDAR encephalitis.