Predictive Value of Cerebrospinal Fluid Flow Cytometry in Pediatric Multiple Sclerosis

Aims: Optic neuritis (ON) in general is identified as one of the most frequent potential risk factors associated with future development of multiple sclerosis (MS). In children, the association between ON and MS seems to be weaker and conversion rate to MS after isolated ON is much 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 exclusive isolated ON from children with high risk for MS.

Methods: A total of 18 patients were identified during July 2011 and October 2014 with either ON or pediatric MS. Overall, six patients presented with isolated ON (five females and one male) and 12 patients with pediatric MS (10 females and 2 males).

Results: ON occurred unilateral in all the patients. Mean age at onset of ON was 12.7 years (range, 8.4–17.2 years). MS initially presented with ON in four patients and four patients showed paresthesia. All patients showed relapsing remitting disease course. Mean age at disease onset was 14.8 years (range, 9.8–17.8 years). All patients received intravenous cortisone pulse therapy over at least 5 days (1,000 mg per day). Lumbar puncture (LP) was done in all cases during the first 2 days after patients were admitted to the hospital. CSF was taken before start of cortisone therapy. All MS patients were treatment naive before LP. CSF analysis revealed positive oligoclonal bands in all the MS patients. FACS analysis demonstrated high proportion of CD4 ± T-cells in pediatric MS patients in comparison to children with isolated ON. In contrast, proportion of CD8 ± T-cells in ON patients was elevated compared with the MS cohort. In comparison to our reference group, both CD4+ and CD8+ T-cells showed enhanced activation status in both the patient groups.

Conclusion: Clinical characteristics of our pediatric ON and MS cohort are comparable to published data. FACS analysis and T cell activation could be assumed as predictive parameter, distinguishing isolated ON from pediatric MS. Therefore, analysis by FACS is recommended in all children suspected of ON or MS. Further investigation is provided to confirm these findings in larger cohorts.

Keywords: pediatric multiple sclerosis, optic neuritis, cerebrospinal fluid, biomarker.