## 3 Results  
Only 9 out of 19 PedMS patients (3 males and 6 females) agreed to this further evaluation after a mean interval of 1.3 \(\pm\) 0.6 SD years from the first exams (baseline demographic and clinical characteristics are summarized in Table 1A); five of them had started Interferon beta-1a (IFN\(\beta\)-1a) treatment in an average of 140 days (range 21-576 days) from the study entry. The neuropsychiatric scores registered at the second time point suggested a trend to deterioration particularly in the domains of attention and information processing speed, visual-spatial memory, executive functioning and expressive language (Table 1B). However, no significant changes of clinical and cognitive abilities were recorded within the observational interval. The multidimensional scaling (MSD) plot of dispersion index between the miRNA expressions of all PedMS subjects at baseline and at follow-up reported a definite separation between T0 and T12 that was due to 13 significantly differentially expressed (DE) miRNAs (adjusted \(p\)-value \(<\) 0.05, absolute log2 fold change \(>\)1) (Table 2; Supplementary Figure S1). Since the clinical features of the examined PedMS patients did not significantly change during the interval, we could not verify whether any of \begin{table}
\begin{tabular}{l c} \hline \hline
**A.** \\ \hline \multicolumn{2}{c}{**PedMS (No. 9)**} & **Mean \(\pm\) SD** \\ \hline \multicolumn{2}{l}{**Age at onset (years)**} & \(14.1\pm 2.1\) \\ \hline \multicolumn{2}{l}{**Disease duration (years)**} & \(2.2\pm 2.0\) \\ \hline \multicolumn{2}{l}{**EDSS**} & \(2.7\pm 0.9\) (range 1.5–4.5) \\ \hline \multicolumn{2}{l}{**FSS**} & \(3.1\pm 2.0\) \\ \hline \multicolumn{2}{l}{**CDI**} & \(5.4\pm 1.8\) \\ \hline \multicolumn{2}{l}{**Schooling (years)**} & \(10.2\pm 2.0\) \\ \hline \multicolumn{2}{l}{**B.**} \\ \hline \multicolumn{2}{l}{**Cognitive Domains and Tests**} & **Baseline** & **Follow-Up** \\  & **(Mean \(\pm\) SD)** & **(Mean \(\pm\) SD)** \\ \hline \multicolumn{2}{l}{**Verbal memory**} \\ \hline \multicolumn{2}{l}{**SRT-LTS**} & \(30.4\pm 12\) & \(30.8\pm 10.8\) \\ \hline \multicolumn{2}{l}{**SRT-CLTR**} & \(22\pm 12.6\) & \(23.6\pm 11.2\) \\ \hline \multicolumn{2}{l}{**SRT-D**} & \(6.7\pm 2.2\) & \(6.8\pm 2.1\) \\ \hline \multicolumn{2}{l}{**Visual-spatial memory**} \\ \hline \multicolumn{2}{l}{**SPART**} & \(21\pm 4.9\) & \(20.6\pm 3.2\) \\ \hline \multicolumn{2}{l}{**SPART-D**} & \(7.3\pm 2.2\) & \(7.1\pm 1.6\) \\ \hline \multicolumn{2}{l}{**Attention, IPS**} \\ \hline \multicolumn{2}{l}{**SDMT**} & \(40.9\pm 7.9\) & \(42.9\pm 8.9\) \\ \hline \multicolumn{2}{l}{**TMT-A**} & \(41.8\pm 12.7\) & \(41.8\pm 11.8\) \\ \hline \multicolumn{2}{l}{**TMT-B**} & \(97.4\pm 46.3\) & \(93.6\pm 45.7\) \\ \hline \multicolumn{2}{l}{**Executive functioning**} \\ \hline \multicolumn{2}{l}{**TOL**} & \(25.4\pm 5.2\) & \(25\pm 4.7\) \\ \hline \multicolumn{2}{l}{**Expressive language**} \\ \hline \multicolumn{2}{l}{**SVFT**} & \(24.6\pm 10.6\) & \(22.6\pm 8.6\) \\ \hline \multicolumn{2}{l}{**PVFT**} & \(15.6\pm 5.7\) & \(17.4\pm 4.9\) \\ \hline \hline \end{tabular} Abbreviations: EDSS = expanded disability status scale: FSS = fatigue severity scale; CDI = children depression inventory; IPS = information processing speed; SRT-LTS = selective reminding test long-term storage; SRT-CLTR = selective reminding test consistent long-term retrieval; SRT-D = selective reminding test—delayed; SPART = spatial recall test; SPART-D= spatial recall test—delayed; SDMT = symbol digit modalities test; TMT = trail making test (TMT-A and TMT-B); TOL = Tower of London test; SVFT = semantic verbal fluency test; PVFT= phonemic verbal fluency test.  
\end{table} 
Table 1: **A:** demographic and clinical features of the investigated pediatric multiple sclerosis (PedMS) patients (at baseline). **B:** Mean scores (\(\pm\) SD) obtained at the neuropsychiatric tests (baseline and follow-up). these miRNAs might be considered as suggestive markers of the disease progression.