Pediatric anti-NMDA receptor encephalitis is seasonal

Abstract

In the majority of pediatric anti-N-methyl-d-aspartate receptor encephalitis (NMDARe) cases, the underlying cause of antibody production and subsequent disease remains unknown. We aimed to characterize this poorly understood population, investigating epidemiological factors potentially related to disease etiology, particularly season of onset. In this retrospective case review study, we analyzed data from the 29 pediatric subjects with anti-NMDAR antibodies and found that symptoms were first reported in the warm months of April-September in 78% of non-tumor-related NMDARe (NT-NMDARe) cases. These findings support further investigation into a possible seasonal trigger of NT-NMDARe.

Figure 1

Seasonal onset of NMDARe and graded long-term recovery. (A) Patients without tumors (NT-NMDARe) were more likely to have symptom onset in the summer (gray) compared to T-NMDARe (black). (B) Outcome information was collected from the last follow-up encounter with neurology or oncology. Patients were stratified into three categories: limited recovery, substantial recovery, and full recovery. Patients without tumors (NT-NMDARe) (grey bars) and T-NMDARe (black bars) are shown. NMDARe, N-methyl-d-aspartate receptor encephalitis.

Figure 2

Laboratory testing of serum or CSF from patients with NMDARe upon presentation. Bars are divided as follows: dark grey bars = NT-NMDARe positive results, light grey = NT-NMDARe negative/normal results, white bars = T-NMDARe positive results, and black = T-NMDARe negative/normal results. Three of the 13 tested had evidence of prior EBV infection (IgM-IgG+), 2/10 mycoplasma IgM-IgG+ (PCR negative), 1/3 parvovirus B19 IgM-IgG+ (PCR negative), and 1/7 Adenovirus PCR+ of respiratory sample (negative CSF PCR). RPR, rapid plasma reagin (for syphilis); CEV, California encephalitis virus; CMV, cytomegalovirus; EEEV, Eastern equine encephalitis virus; EBV, Epstein–Barr virus; HHV-6, human herpesvirus-6; HIV, human immunodeficiency virus; HSV, herpes simplex virus; St. Louis EV, St. Louis encephalitis virus; RRP, rapid respiratory panel (respiratory syncytial virus, influenza A and B, parainfluenza viruses 1, 2, and 3, adenovirus, rhinovirus, and human metapneumovirus by sputum sample PCR), VZV, varicella zoster virus; WNV, West Nile virus; WEEV, Western equine encephalitis virus; ANA, antinuclear antibody; ASO, antistreptolysin antibodies; OCB, oligoclonal bands. NMDARe, N-methyl-d-aspartate receptor encephalitis.