Evidence map›Paper›PMID 41140053›Full record

SynthesisEuropean journal of neurology2025

Diagnostic and Prognostic Value of Blood and Cerebrospinal Fluid Biomarkers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Kazuki Obara, Daisuke Ito, Christer Nilsson, Shorena Janelidze, Alexander Santillo, Masahisa Katsuno, Niklas Mattsson-Carlgren

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
–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

10 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Review
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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

7 authors.

Kazuki ObaraClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID 0009-0006-5170-9169
Daisuke ItoDepartment of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.ORCID 0000-0002-5037-2289
Christer NilssonDepartment of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden.
Shorena JanelidzeClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Alexander SantilloClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID 0000-0001-9717-0820
Masahisa KatsunoDepartment of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.ORCID 0000-0001-9453-9311
Niklas Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.ORCID 0000-0002-8885-7724

Funding

Elsa Schmitz stiftelse för neurologisk och neurokirurgisk forskningJapan Science and Technology Agency (JST) SPRING JPMJSP2125Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
6 · The paper itself

Abstract

backgroundReliable biomarkers for amyotrophic lateral sclerosis (ALS) are urgently needed due to diagnostic and prognostic challenges. This systematic review and meta-analysis aimed to synthesize recent evidence on the utility of blood and cerebrospinal fluid (CSF) biomarkers for ALS.

methodsWe systematically reviewed studies published from January 1, 2019 to March 25, 2025, that evaluated blood or CSF biomarkers for ALS. Eligible studies reported diagnostic performance, group-level biomarker values, hazard ratios (HRs) for survival, or correlations with functional rating scales or disease progression rates. Study quality was assessed using the QUADAS-2 and QUIPS frameworks. Random-effects models were employed to pool summary receiver operating characteristic (SROC) curves, HRs, standardized mean differences, and correlation coefficients.

resultsWe included 47 studies in the SROC analysis and 27 in the HR analysis, covering 9078 participants (5556 ALS and 3522 controls). Neurofilament light chain (NfL) consistently demonstrated the highest diagnostic accuracy (sensitivity/specificity: 0.81-0.87 vs. ALS mimics) and high prognostic value (pooled HRs: 2.8-4.3) in both blood and CSF. CSF chitinases and the p-tau/t-tau ratio showed moderate utility. Other biomarkers, including interleukins, had limited clinical relevance. Most studies showed moderate to high risk of bias, with methodological heterogeneity and limited transparency.

conclusionsNfL is the most validated biomarker for ALS diagnosis and prognosis, in both blood and CSF. However, its limited accuracy when used alone carries a considerable risk of misclassification. Future studies should adopt prevalence-specific strategies and integrate biomarkers within multimodal frameworks to enhance diagnostic and prognostic precision.

Indexed as

Amyotrophic Lateral SclerosisBiomarkersHumansNeurofilament ProteinsPrognosisBiomarkersneurofilament protein LNeurofilament Proteinsamyotrophic lateral sclerosisbiomarkerdiagnosisdisease progressionneurofilament proteinsprognosissurvival

Identifiers

PMID41140053
PMCPMC12554952

What OpenQuestion holds

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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.