Association of Molecular Biomarkers With Disease Prognosis and Brain Volume in RRMS Patients
Ayça Simay Ersöz1, Ali Bayram3, Ece Akbayır4, Murat Baykara2, Duygu Özkan Yaşargün1, Erdem Tuzun3, Recai Turkoglu1
1Neurology, 2Radiology, Haydarpaşa Numune Training and Research Hospital, 3Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, 4Department of Neuroscience, Atlas University
Objective:
This study aimed to investigate the relationship between baseline biomarker levels(Neurofilament Light Chain(NfL); Brain-Derived Neurotrophic Factor(BDNF); Runt-Related Transcription Factor 1(RUNX1);and Neurogranin(NRGN))measured at the time of diagnosis and disease activity,prognosis,and brain volume measurements at follow-up in patients with relapsing-remitting multiple sclerosis(RRMS).
Background:

MS is a heterogeneus disease,therefore it is important to determine the role of biomarkers measured at the time of diagnosis in predicting disease progression.

Design/Methods:

Thirty-three patients with RRMS were included in this study.Cerebrospinal fluid(CSF) and serum samples obtained at the time of diagnosis were analyzed for NfL,BDNF,RUNX1, and NRGN levels using enzyme-linked immunosorbent assay(ELISA).At the end of the follow-up period, white matter and cortical volumes were quantified on cranial MRI scans using the FreeSurfer software.

Results:

In RRMS patients, baseline CSF NfL levels showed a significant positive correlation with the number of relapses during the early follow-up period(first two years) after biomarker sampling(p=0.018).Patients who developed confirmed disability progression(CDP) during follow-up had significantly lower baseline CSF BDNF levels(p=0.001),with a cut-off value of 222.6 pg/mL.Baseline CSF BDNF levels were significantly negatively correlated with the number of relapses within the first two years,annualized relapse rate,and number of relapses within the first five years(p=0.048;p=0.012;p= 0.018).

Baseline CSF NfL levels had a statistically significant negative association with total white matter volume at follow-up(p=0.006),whereas baseline RUNX1 levels showed a positive association with total white matter volume(B=26.993;p=0.018).Moreover, patients who did not meet the NEDA-3 criteria at the second year exhibited significantly lower left and right cerebral white matter volumes compared with those who achieved NEDA-3(p=0.007;p=0.012).

Conclusions:
This study demonstrates that baseline CSF NfL and BDNF levels in MS patients have prognostic value not only in reflecting existing neuroaxonal injury but also in predicting future disease course and brain volume outcomes. Achieving early and effective disease control,as indicated by NEDA-3 status,has a significant impact on white matter volumes at follow-up.
10.1212/WNL.0000000000215383
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