Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis
Bibliographic record
Abstract
Serum neurofilament light chain (NfL) is emerging as an important biomarker in multiple sclerosis (MS). Our objective was to evaluate the prognostic value of serum NfL levels obtained close to the time of MS onset with long-term clinical outcomes. In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset (baseline) with more than 15 years of routine clinical follow-up. Levels of serum NfL were quantified in patients and matched controls using digital immunoassay (SiMoA HD-1 Analyzer, Quanterix). Sixty-seven patients had a median follow-up of 18.9 years (range 15.0-27.0). The median serum NfL level in patient baseline samples was 10.1 pg/mL, 38.5% higher than median levels in 37 controls (7.26 pg/mL, p = 0.004). Baseline NfL level was most helpful as a sensitive predictive marker to rule out progression; patients with levels less 7.62 pg/mL were 4.3 times less likely to develop an EDSS score of ≥ 4 (p = 0.001) and 7.1 times less likely to develop progressive MS (p = 0.054). Patients with the highest NfL levels (3rd-tertile, > 13.2 pg/mL) progressed most rapidly with an EDSS annual rate of 0.16 (p = 0.004), remaining significant after adjustment for sex, age, and disease-modifying treatment (p = 0.022). This study demonstrates that baseline sNfL is associated with long term clinical disease progression. sNfL may be a sensitive marker of subsequent poor clinical outcomes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".