C. Elpers

CD8 + T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing

Rasmussen encephalitis (RE) is a rare paediatric epilepsy with uni-hemispheric inflammation and progressive neurological deficits. To elucidate RE immunopathology, we applied T-cell receptor (TCR) sequencing to blood (n=23), cerebrospinal fluid (n=2) and brain biopsies (n=5) of RE patients, and paediatric controls. RE patients present with peripheral CD8+ T-cell expansion and its strength correlates with disease severity. In addition, RE is the only paediatric epilepsy with prominent T-cell expansions in the CNS. Consistently, common clones are shared between RE patients, who also share MHC-I alleles. Public RE clones share Vβ genes and length of the CDR3. Rituximab/natalizumab/basiliximab treatment does not change TCR diversity, stem cell transplantation replaces the TCR repertoire with minimal overlap between donor and recipient, as observed in individual cases. Our study supports the hypothesis of an antigen-specific attack of peripherally expanded CD8+ lymphocytes against CNS structures in RE, which might be ameliorated by restricting access to the CNS.

Predictive Value of CSF Flow Cytometry in Pediatric Multiple Sclerosis

Background: Optic neuritis (ON) is identified as one of the most frequent potential risk factor associated with future multiple sclerosis (MS). In children, conversion to MS after isolated ON is lower than in adults. Here, we aim to identify cerebrospinal fluid (CSF) and peripheral blood (PB) cell composition and cell activation status as potential biomarkers to distinguish children with isolated ON from children at high risk for MS. Methods: Thirty patients were identified with ON (9), clinically isolated syndrome (CIS, 5), or pediatric MS (16) and first compared with age-matched healthy controls (12) and second to adult patients with MS (33), CIS (10), or isolated ON (17). All patients received intravenous cortisone pulse therapy at least 5 days (1,000 mg/d). CSF was taken prior to cortisone therapy. All MS patients were treatment naive. Results: CSF analysis revealed positive oligoclonal bands (OCB) in 15 of 16 MS children; none of the CIS patients show OCBs, whereas 4 of 9 children with ON expose OCBs. FACS analysis demonstrated elevated plasma cells in CSF both in children and adult MS patients and revealed high proportion of CD4+-T-cells in pediatric MS patients compared with childhood isolated ON. In contrast, proportion of CD8+-T-cells in PB in ON patients was elevated compared with the MS cohort. CSF results of children with CIS conduct completely different from that of adults. Conclusion: FACS analysis and T cell activation could be assumed as predictive parameter, distinguishing isolated ON from CIS or pediatric MS. CIS is supposed to show a different clinical disease course in children compared with adults.

A Case Report on Juvenile Neuromyelitis Optica: Early Onset, Long Remission Period, and Atypical Treatment Response

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system and preferentially targets the optic nerves and spinal cord. NMO is rare in children and clinical course of the disease is highly variable as described in studies. Here, we present a case report of a young girl presenting with a rare course of pediatric NMO with an early disease onset at the age of 12 years, a relapse free interval of 4 years, evidence of NMO immunoglobulin G (IgG) and an unusual response against immunosuppressive therapy. The aim of this report is to highlight the potentially long remission period between relapses complicating proper diagnosis despite well defined diagnostic criteria. In addition, we want to encourage the use of rituximab in pediatric NMO, although larger cohorts are warranted to establish B cell depleting therapies in juvenile NMO.