Pediatric Neuromyelitis Optica is clinically distinct from ADEM: Case report of a 9year old girl

Abstract

IntroductionIn Neuromyelitis Optica (NMO), the autoantibodies target the primary water channel Aquaporin 4 (AQP4), resulting in optic neuritis and long spinal cord lesions. Although extensively studied in adults, pediatric case reports have been limited due to rarity, especially in India. Research QuestionHere we report the case of a 9year old female, initially presented with convulsions and seizures, and later confirmed as NMO seropositive. In addition to the clinical features, we further explored the cellular status of AQP4 and the regulation of its transcription via FOXO3a and miRNA 145 after exposure to the patient sera. Material and MethodsCell-Based assays were performed to confirm the presence of AQP4 autoantibodies, followed by live-cell imaging and Western Blots to probe the fates of cellular AQP4 along with Aqp4 transcript and miRNA145 levels. The nuclear presence of FOXO3a was quantified through fractionation and Western Blot. ResultsWe validated via a single pediatric case study that despite the initial presentation of ADEM-like symptoms, she was an AQP4 seropositive NMO patient. After exposure of the patient sera collected after RTX therapy to our NMO working model, established previously for adult patients, we found that the level of AQP4 reduced significantly with a concomitant decline in the FOXO3a nuclear pool. The transcript level of Aqp4 reduced significantly without affecting the miRNA145 level. Discussion and ConclusionPediatric NMO cases in the Indian subcontinent have only been restricted to case reports. Our study identifies the autoantibody status of a single pediatric patient and additionally explores the effect of patient sera on cellular AQP4. Upon exposure to the patient sera, the redistribution of membrane AQP4 and its concurrent cellular loss have been significant. Although it would be premature to conclude from a single case study, post RTX therapy the reduction in Aqp4 transcript level in a FOXO3a-dependent manner provides evidence for a potentially separate, novel pathway contributing to NMOSD in young patients. The role of FOXO3a as a major transcriptional regulator in young patients is novel and could be clinically significant for NMO pathogenesis.