Article Figures & Data
Figures
- Figure 1 sNfL in a control cohort
Data for sNfL vs age in neurologically healthy controls (n = 301). Vertical lines denote the age range covered by the MS cohort. Specific percentiles were calculated from these samples within the MS age range (n = 212) and are shown as horizontal lines with sNfL percentile values in pg/mL. A nonparametric smoothing line (loess) is shown in blue. There is an age dependency of sNfL with lower levels in younger children (CI [0.963, 0.985], p < 0.001) that is not shown for the controls covering the age range of the MS cohort (CI [0.998, 1.026], p = 0.092). Percentiles are not stratified by sex because there was no significant effect on sNfL. sNfL = serum neurofilament light chain.
- Figure 2 Untreated pediatric patients with MS show elevated sNfL levels compared with controls
Untreated patients at baseline (n = 43) reveal elevated sNfL levels compared with controls of the same age range (n = 212; CI [4.732, 6.911], p < 0.001) with a median sNfL of 19.0 pg/mL [11.7, 43.8] vs 4.6 pg/mL [3.5, 6.0]. Data are shown as boxplots with median and interquartile range. sNfL = serum neurofilament light chain.
- Figure 3 sNfL and MRI data
(A) sNfL levels correlate with the number of T2-weighted (T2w) lesions. MRI data vs sNfL levels are shown stratified by the number of T2w lesions. Most MRIs show more than 9 lesions. sNfL levels are strongly correlated with the number of T2w lesions with an average increase in sNfL of 0.6% per lesion (CI [1.001, 1.010], p = 0.015). (B) sNfL levels correlate with the number of contrast-enhancing lesions (CELs). MRI data vs sNfL levels are shown stratified by the number of CELs. Most MRIs do not show CELs. sNfL levels are strongly correlated with the number of CELs with an average increase in sNfL of 9.1% per lesion (CI [1.045, 1.138], p < 0.001). Data are shown as boxplots with median and interquartile range. sNfL = serum neurofilament light chain.
- Figure 4 sNfL during DMT
(A) sNfL levels decrease under DMT with IFN. In the IFN group, patients with IFN treatment show elevated sNfL levels at baseline (median 14.7 pg/mL [9.5, 43.0]). sNfL levels decreased significantly under DMT with IFN already after 6 ± 2 months of treatment (7.9 pg/mL; CI [0.339, 0.603], p < 0.001), but median sNfL levels stays above the 80th percentile of controls during follow-up. (B) sNfL levels decrease after switch from IFN/GA to fingolimod. Patients switching from IFN or GA to fingolimod during follow-up (fingolimod group) mostly had sNfL levels above the 99th percentile of controls before treatment switch. After treatment switch, sNfL levels decreased significantly from 16.5 pg/mL (12.8; 26.7) to 10 pg/mL (9.5; 43.0) after 6 ± 2 months of fingolimod treatment (CI [0.481, 0.701], p < 0.001) but stayed above the 80th percentile of controls during follow-up. All data are shown as boxplots with median and interquartile range. Percentiles of controls are marked by lines. DMT = disease-modifying therapy; GA = glatiramer acetate; IFN = interferon; sNfL = serum neurofilament light chain.
- Figure 5 Individual disease courses demonstrate potential prognostic value of sNfL as a biomarker
(A) Patient 61, IFN group. Diagnosed at age 15.3 years, treatment with IFN, follow-up for 30 months. No relapses and only 1 CEL were detected after 12 months. sNfL levels never dropped below the 90th percentile and only once (after 12 months) below the 99th percentile. (B) Patient 78, IFN group. Diagnosed at age 7.5 years, IFN treatment, follow-up for 105 months. The patient had 1 relapse 6 months after treatment start and after that no clinical or MRI disease activity anymore. sNfL levels were increased before treatment start and dropped under DMT; levels at follow-up were always below the 80th percentile of controls. (C) Patient 14, fingolimod group. Diagnosed at age 7.2 years, initial IFN treatment for 6 years with a relapse rate of 0.5 per year and in the first 3 years each 1 CEL at 3 time points. sNfL levels were always above the 90th percentile apart from 1 measurement after 35 months. After treatment switch to fingolimod after 66 months due to ongoing clinical and MRI disease activity, there was no relapse or cranial CEL during 12 months of follow-up. sNfL levels dropped below the 90th percentile after 6 months and below the 80th percentile after 12 months of fingolimod treatment. (D) Patient 33, fingolimod group. Diagnosed at age 14.3 years, initial IFN treatment. At age 15.6 years, treatment switch to fingolimod due to ongoing clinical and MRI disease activity. Follow-up under treatment with fingolimod was 22 months without any relapse or CEL detection. sNfL levels were elevated at the time point of switch and decreased under fingolimod treatment; levels below the 90th percentile were reached 22 months later. sNfL levels are shown as (x) connected with a broken line, EDSS levels are shown as blue numbers, numbers of CELs are marked with red asterix (*), green lines show the 50th and 90th percentiles of controls, and red arrows (↑) mark relapses. CEL = contrast-enhancing lesion; DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; sNfL = serum neurofilament light chain.
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