Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients

Abstract

Objective: To report the clinical features of 20 pediatric patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Study design: Review of clinical data, long-term follow-up, and immunologic studies performed in a single center in Spain in the last 4 years.

Results: The median age of the patients was 13 years (range, 8 months-18 years), 70% were female. In 12 patients (60%), the initial symptoms were neurologic, usually dyskinesias or seizures, and in the other 40% psychiatric. One month into the disease, all patients had involuntary movements and alterations of behavior and speech. All patients received steroids, intravenous immunoglobulin or plasma exchange, and 7 rituximab or cyclophosphamide. With a median follow up of 17.5 months, 85% had substantial recovery, 10% moderate or severe deficits, and 1 died. Three patients had previous episodes compatible with anti-NMDAR encephalitis, 2 of them with additional relapses after the diagnosis of the disorder. Ovarian teratoma was identified in 2 patients, 1 at onset of encephalitis and the other 1 year later. Two novel observations (1 patient each) include, the identification of an electroencephalographic pattern ("extreme delta brush") considered characteristic of this disorder, and the development of anti-NMDAR encephalitis as post herpes simplex encephalitis choreoathetosis.

Conclusions: The initial symptoms of pediatric anti-NMDAR encephalitis vary from those of the adults (more neurologic and less psychiatric in children), the development of a mono-symptomatic illness is extremely rare (except in relapses), and most patients respond to treatment. Our study suggests a link between post herpes simplex encephalitis choreoathetosis and anti-NMDAR encephalitis.

Figure 1

Symptoms at presentation and during the first month of the disease. A, The initial symptoms of each patient are shown in panel; every radial segment represents one patient. The percentages assist to determine the percentage of patients with a specific symptom or combination of symptoms, each symptom coded with a different color. Patients > 12 years-old are shown in the section with white background, and those ≤ 12 in the section with grey background. Behavioral dysfunction included agitation and aggression (4 patients), psychosis, delusional thoughts, and hallucinations (3), nonspecific behavioral disturbance (3), anxiety (2), stereotyped behavior and obsessions (1), and negativism and autolytic thoughts (1). B, The symptoms during the first month of the disease; patients are represented in the same order as in A.

Figure 3

MRI findings in a patient who developed herpes simplex encephalitis (HSE) followed by anti-NMDAR encephalitis. A–D, The MRI findings during the first week of HSE. A-C, Increased T2-FLAIR signal was demonstrated in the right medial temporal lobe, right insula, posterior basal ganglia, and bilateral opercular regions, and D, increased signal in diffusion weighted images (DWI) . E–H, The MRI obtained during admission for anti-NMDAR encephalitis, one month after HSE onset, showed no additional changes other than the interval evolution of areas of encephalomalacia in opercular regions and hippocampal atrophy.