Evidence map›Paper›PMID 41469698›Full record

ArticleJournal of neuroinflammation2025

Longitudinal high-frequency blood biomarkers of axonal injury and astrocytic activation after immune reconstitution in multiple sclerosis.

Hernan Inojosa, Luise Werder, Rocco Haase, Undine Proschmann, Pascal Benkert, Jens Kuhle, Hagen B Huttner, Tjalf Ziemssen, Katja Akgün

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Hernan InojosaDepartment of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.
Luise WerderDepartment of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.
Rocco HaaseDepartment of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.
Undine ProschmannDepartment of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.
Pascal BenkertDepartments of Biomedicine and Clinical Research, Multiple Sclerosis Centre and Research Centre for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland.
Jens KuhleDepartments of Biomedicine and Clinical Research, Multiple Sclerosis Centre and Research Centre for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland.
Hagen B HuttnerDepartment of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.
Tjalf Ziemssen *Department of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany. tjalf.ziemssen@ukdd.de.
Katja Akgün *Department of Neurology, Centre of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, TUD Dresden University of Technology, Fetscherstraße 74, Dresden, 01307, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSerum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) reflect axonal damage and astrocytic injury. Their clinical role in longitudinal real-world monitoring after immune reconstitution therapy (IRT) in multiple sclerosis (MS) remains insufficiently defined. We evaluated longitudinal sNfL and sGFAP dynamics in people with multiple sclerosis (pwMS) treated with alemtuzumab (ATZ) as a model of IRT to determine their prognostic and monitoring value in real-world care.

methodsPwMS initiating ATZ were prospectively followed up every three months for up to five years. sNfL and sGFAP levels were measured using single molecule array (Simoa) and converted to age- and BMI-adjusted Z scores based on healthy control datasets. Longitudinal trajectories were analysed with generalised linear mixed models adjusted for age, sex, and disease duration. Receiver operating characteristic (ROC) analysis with Youden’s index identified optimal cut-offs for disease activity. Logistic and Cox regression models assessed predictive values. Event-related analyses examined biomarker changes around relapses, MRI activity, progression independent of disease activity (PIRA), and retreatment.

resultsEighty-four pwMS (mean age 36.5 ± 9.0 years, 76% female) were included. Baseline sNfL Z scores were significantly higher in males and in those with recent MRI activity or treatment failure. sNfL rose transiently one month after the first ATZ course, declined by month 3, and remained stably reduced thereafter. Youden’s index-derived baseline sNfL Z scores ≥ 0.75 modestly predicted disease activity during year 1 (odds ratio: 5.10, 95% CI 1.79–14.49), and Z scores > 1.0 predicted relapses after the first ATZ course (hazard ratio: 2.96, 95% confidence interval 1.36–6.43, p = 0.006). Compared to matched pwMS without disease activity, event-related analyses showed significant sNfL elevations around relapses (p = 0.004), MRI activity (p = 0.015), and retreatment (p = 0.002). A transient increase was observed in the 6 months before PIRA events, followed by normalization (p = 0.017). sGFAP levels remained overall stable over follow-up (p = 0.677) and showed no predictive value. DISCUSSION: sNfL provided modest predictive and clear monitoring value in pwMS treated with ATZ and may complement individualized follow-up alongside clinical and MRI assessment. In contrast, sGFAP remained overall stable and did not associate with inflammatory events. However, a modest association with subclinical MRI activity was observed, suggesting further research is needed to fully understand the role of sGFAP in monitoring IRT-treated pwMS. These findings support the real-world clinical utility of high-frequency sNfL monitoring for early detection of breakthrough disease activity after IRT.

Indexed as

AstrocytesAxonsGlial Fibrillary Acidic ProteinMultiple SclerosisNeurofilament ProteinsAdultAlemtuzumabBiomarkersFemaleHumansImmunologic FactorsLongitudinal StudiesMaleMiddle AgedAlemtuzumabBiomarkersGlial Fibrillary Acidic ProteinImmunologic Factorsneurofilament protein LNeurofilament ProteinsDisease monitoringGlial fibrillary acidic proteinImmune reconstitution therapyMultiple sclerosisNeurofilament light chain

Identifiers

PMID41469698
PMCPMC12849723

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.