Evidence map›Paper›PMID 40664781›Full record

SynthesisJournal of neurology2025

Environmental risk factors for multiple sclerosis: a comprehensive systematic review and meta-analysis.

Bruno Kusznir Vitturi, Maria Cellerino, Daniele Boccia, Emmanuelle Leray, Jorge Correale, Ruth Dobson, Ingrid van der Mei, Kazuo Fujihara, Matilde Inglese

Abstract readSystematic ReviewMeta-Analysis
PubMed Full text at PMC Publisher
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 21 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 3 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

21 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Smoking and disability outcomes in multiple sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  7. B-cell targeting strategies for the treatment of multiple sclerosis: from non-cellular therapies to CAR-engineered cell therapies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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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

9 authors.

Bruno Kusznir VitturiDepartment of Neurology, University Hospital Schleswig-Holstein, Campus Kiel and Kiel University, Arnold-Heller-Str 3, 24105, Kiel, Germany. z_azul@hotmail.com.ORCID http://orcid.org/0000-0002-2821-9042
Maria CellerinoDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Daniele BocciaDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Emmanuelle LerayUMR 6051, EHESP, CNRS, Inserm, ARENES, RSMS U 1309, Rennes University, Rennes, France.
Jorge CorrealeDepartment of Neurology, of Biological Chemistry and Biophysics, Fleni, Institute, CONICET/University of Buenos Aires, Buenos Aires, Argentina.
Ruth DobsonCentre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, EC1M 6BQ, UK.
Ingrid van der MeiMenzies Institute of Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia.
Kazuo FujiharaDepartment of Multiple Sclerosis Therapeutics, School of Medicine and Multiple Sclerosis and Neuromyelitis Optica Center, Fukushima Medical University, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Japan.
Matilde IngleseDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health (DINOGMI), University of Genoa, Genoa, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesMultiple sclerosis (MS) is a demyelinating disease of the central nervous system. Its etiology may involve both genetic and environmental factors, including vitamin D levels, body mass index, infections, and smoking. This is the first comprehensive systematic review with meta-analysis that synthesizes and explore the role of many environmental risk factors in the etiology of MS.

methodsA systematic search of MEDLINE, SciVerse ScienceDirect and Web of Science were conducted for any original peer-reviewed article that included adult subjects diagnosed with and without MS that were exposed to any environmental risk factor. We did not set any time restrictions. Data were extracted and the quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies. All the information was synthesized qualitatively and quantitatively (meta-analysis). We used the random-effects model based on the binomial distribution to calculate the pooled effects sizes (ES) regarding the risk of developing MS according to each potential risk factor.

resultsOne-hundred thirty-two publications met all the eligibility criteria and were included in the review. Overall, 109,626 people with MS and 16,724,390 controls from 38 countries were included in the review. A total of 42 environmental risk factors were investigated as potential risk factors for MS. Among the various statistically significant associations, the pooled ES revealed a direct association between serological evidence of contact with EBV (ES = 1.96, 95% CI = 1.53-2.51), herpes virus type 6 (HHV-6) (ES = 2.84, 95% CI = 2.08-3.89) and varicella-zoster virus (ES = 1.33, 95% CI = 1.08-1.63) and the occurrence of MS. Similarly, smoking was associated with a greater likelihood of having MS (ES = 1.43, 95% CI = 1.27-1.61). Vitamin D levels at any time were negatively associated with the proportion of cases of MS and had a moderate pooled ES (g = - 0.48, 95% CI = - 0.88-0.09). Adult BMI was not associated with MS. DISCUSSION: This review furnishes a broad and detailed overview of the potential environmental risk factors associated with MS. Our findings hold notable implications for public health policies, clinical practices, and the focus of future research.

Indexed as

Environmental ExposureMultiple SclerosisHumansRisk FactorsDemyelinating diseasesenvironmentalmultiple sclerosisneuroepidemiologyrisk factors

Identifiers

PMID40664781
PMCPMC12263771

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.