Evidence map›Paper›PMID 41428098›Full record

SynthesisJournal of neurology2025

Serum and cerebrospinal fluid biomarkers as predictors of cognitive impairment in multiple sclerosis: a systematic review of longitudinal studies.

Giovanni Restuccia, Carla Susinna, Giulia Marafioti, Carmela Rifici, Giangaetano D'Aleo, Edoardo Sessa, Serena Silvestro, Angelo Quartarone, Viviana Lo Buono

Abstract readSystematic Review
In one paragraph

Synthesis in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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.

Giovanni RestucciaIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Carla SusinnaIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy. carla.susinna@irccsme.it.ORCID http://orcid.org/0009-0008-2507-6606
Giulia MarafiotiIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Carmela RificiIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Giangaetano D'AleoIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Edoardo SessaIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Serena SilvestroIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Angelo QuartaroneIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Viviana Lo BuonoIRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, characterized by inflammation, demyelination, gliosis, and neuronal loss. Cognitive disorders are part of the clinical presentation, as well as in the early stages, with a prevalence rate ranging from 40 to 65% and are strictly associated with poor quality of life. In recent years, advances in the field of molecular biomarkers have contributed to improving the accuracy of cognitive diagnosis and to identifying subjects at risk of developing cognitive disorders. By focusing on longitudinal studies, this review aims to elucidate the temporal dynamics and potential predictive value of CSF and serum biomarkers in identifying cognitive decline and monitoring disease progression in MS.

methodsA systematic review was conducted using the PRISMA guidelines. 827 studies were identified by searching PubMed, Scopus, and Web of Science between July and August 2025. After screening, 8 studies fulfilled the eligibility criteria and were included.

resultsNfL showed heterogeneous results: some studies identified it as a feasible biomarker able to predict cognitive decline, while others did not. GFAP did not show significant correlations. Parvalbumin was longitudinally associated with poorer cognition and greater fatigue. Specific microRNAs (miR-126.3p, miR-9p) were associated with processing speed decline. Higher BDNF levels were linked to cognitive improvement. Other biomarkers (OPN, IL-6, CHI3L1, CXCL13) provided insufficient evidence.

conclusionsFindings add interesting contributions to the complex picture of the pathophysiology underpinning cognitive decline in MS. The most promising direction is the shift toward blood-based biomarkers, due to their minimally invasive nature and potential for clinical applicability, which may enable clinicians to anticipate, monitor, and potentially modify the cognitive trajectory of people living with MS.

Indexed as

Cognitive DysfunctionMultiple SclerosisBiomarkersDisease ProgressionHumansLongitudinal StudiesBiomarkersCognitionCognitive impairmentMolecular biomarkersMultiple sclerosisNeurofilament light chainSystematic review

Identifiers

PMID41428098
PMCPMC12722371

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Registered trials

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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 OpenQuestion graph.