Fatigue and Multiple Sclerosis: A Global Look at How Common It Really Is

Table of Contents

• Key Points
• Background: Why Fatigue in MS Matters
• How the Researchers Conducted the Study
• The Main Finding: 59.1% Global Prevalence
• Who Is Most Affected? Key Patient Groups
• How Fatigue Was Measured — and Why the Scale Matters
• Fatigue Around the World and by Income Level
• What Drives the Differences Between Studies?
• Meta-Regression: Pinpointing the Sources of Variation
• Study Quality and Risk of Bias
• What This Means for Patients
• Limitations: What the Study Could Not Prove
• Recommendations for Patients and Clinicians
• Frequently Asked Questions
• Source Information

Key Points

• In a review of 69 studies of 44,468 people with MS in 27 countries, pooled global fatigue prevalence was 59.1% — about 6 in 10.
• Fatigue prevalence was higher in women, older patients, those with greater disability, longer MS duration, and less education.
• The fatigue questionnaire used explained 46.4% of variation between studies — the largest single source of differing estimates.
• Pooled prevalence fell from 64.4% in 2000–2009 to 51% in 2020–2023, possibly reflecting better diagnosis, treatment, and non-drug management.
• No medication convincingly treats MS fatigue; physical activity, dietary changes, and cognitive behavioral therapy can help.

Background: Why Fatigue in MS Matters

Multiple sclerosis (MS) is a long-term, inflammatory, demyelinating disease — meaning the immune system attacks the protective coating around nerves — that affects the central nervous system (the brain and spinal cord). It is one of the most common causes of disability not caused by injury among young adults.

The number of people with MS is rising. Between the 2013 and 2020 editions of the Atlas of MS, reported prevalence increased in every World Health Organization (WHO) region. Today, about 2.8 million people worldwide have MS. Rates are highest in the WHO European Region (EUR) and the Region of the Americas (AMR), and lowest in the WHO African Region (AFR) and the Western Pacific Region (WPR).

MS comes in three main forms, defined by disease activity and clinical course:

• Relapsing–remitting MS (RRMS) — flares of symptoms followed by recovery periods.
• Secondary progressive MS (SPMS) — a steady worsening that often follows years of RRMS.
• Primary progressive MS (PPMS) — gradual worsening from the start, without distinct relapses.

About 85% of people with MS are first diagnosed with RRMS, and many later develop SPMS, with or without occasional relapses on top of the steady decline.

Symptoms vary widely and include spasticity (muscle stiffness), pain, fatigue, bladder and bowel problems, walking difficulties, mood changes, and sleep disorders. Among these, fatigue is one of the most common and most burdensome.

Researchers define MS-related fatigue as "a significant lack of physical and/or mental energy, perceived by the individual or caregiver, that interferes with normal and desired activities." It can appear at any stage of the disease. Crucially, it differs from ordinary tiredness: it is disabling and does not improve with rest or sleep.

Doctors divide MS fatigue into two categories to help guide treatment. Primary fatigue is considered specific to MS. It appears without an obvious trigger and results directly from the disease's underlying disease processes. Secondary fatigue has identifiable causes — sleep problems, mood disorders such as anxiety and depression, side effects of disease-modifying treatments (DMTs, drugs that slow MS), and reduced physical activity. The exact biology behind MS-related fatigue remains unknown.

Fatigue has serious real-world consequences. It is a leading driver of poor health-related quality of life and unemployment among people with MS. It is also a major predictor of claims for social benefits such as sick leave and disability pensions. That makes fatigue one of the most urgent problems in MS care.

Currently, no pharmacological treatment (medication) convincingly treats MS-related fatigue. Non-drug approaches — physical activity, dietary changes, and cognitive behavioral therapy — can help. Because these options and MS care in general have improved, the prevalence of fatigue may be shifting over time. More than a dozen fatigue questionnaires exist. The most commonly used and recommended questionnaires are the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), and the Fatigue Scale for Motor and Cognitive Functions (FSMC). These tools measure different aspects of fatigue and use different cut-off values.

This is the core problem the new study set out to solve. Individual studies have reported fatigue prevalence ranging from 28.4% to 88.2%. An earlier systematic literature review of 12 studies reported rates from 36.5% to 78%. Until now, there was no global consensus on how common MS-related fatigue truly is.

How the Researchers Conducted the Study

The team registered their protocol in PROSPERO (an international database of systematic review plans, number CRD42024499139) and followed PRISMA guidelines, the standard reporting checklist for this type of research.

They searched eight major databases: PubMed, EMBASE, Cochrane Library, Web of Science, PsycINFO, CINAHL, the China National Knowledge Infrastructure (CNKI), and Wanfang. The search covered both English and Chinese studies published since 2000 and was completed on January 31, 2024. A research librarian helped build the search strategy.

Studies had to meet strict criteria to be included:

1. Observational original research — cross-sectional, cohort, or case–control designs.
2. Participants aged 17 years or older with an MS diagnosis, confirmed by a clinician or self-report using the Poser or McDonald criteria.
3. Full-text publication in a peer-reviewed journal.
4. Use of a validated fatigue scale with a defined cut-off value indicating clinically significant fatigue.

Studies were excluded if they included only patients with clinically isolated syndrome or inpatients. Studies were excluded if fatigue was an inclusion criterion, if the sample was smaller than 100 people, if data were insufficient to calculate prevalence, or if data were duplicated.

Two investigators independently screened all records and extracted data using a pilot-tested data sheet. Disagreements were resolved by consensus, with a designated author making final decisions. For each study, the team recorded the publication year, design, sample size, patient source, survey year, country, diagnostic criteria, patient age, sex distribution, MS duration, and MS phenotype. The team also recorded the Expanded Disability Status Scale (EDSS) score (a standard 0–10 measure of MS disability), education level, fatigue cases, fatigue scale, and cut-off value.

Quality was assessed with two standard tools. The Agency for Healthcare Research and Quality (AHRQ) checklist (11 items) was used for cross-sectional studies, scoring 0–3 as low quality, 4–7 as moderate, and 8–11 as high. The Newcastle–Ottawa Scale (NOS) was used for case–control and cohort studies; scores of 7–9 stars meant low risk of bias, 5–6 moderate, and fewer than 4 high.

For the statistics, the team used R software (version 4.2.3) with the "meta" package. Because the studies differed from one another, they used a random-effects model to pool prevalence estimates with 95% confidence intervals (95% CI, the range likely to contain the true value). They applied the Freeman–Tukey transformation to correct for skewed raw proportions. Heterogeneity — how much the studies disagreed with each other — was measured with the Cochrane Q statistic and the I² test, where I² of 75% or higher signals considerable heterogeneity. They also ran subgroup analyses, meta-regression, and a sensitivity analysis that removed studies one at a time to check whether results stayed stable. Statistical significance was set at p < 0.05.

The Main Finding: 59.1% Global Prevalence

The search produced 7,258 records. After removing duplicates, the team assessed 4,838 titles and abstracts, screened 446 full-text articles, and ultimately included 69 studies.

Those 69 studies included 44,468 people with MS. The average study had 644 participants, with a range from 100 to 9,077. Mean patient age ranged from 32.4 to 59.3 years. Mean EDSS scores ranged from 1.9 to 6.5. Mean MS duration ranged from 4.1 to 22.2 years, and the proportion of female participants ranged from 55% to 86%.

Individual study estimates of fatigue ranged from 28.4% to 88.2%. When pooled together, the global prevalence of MS-related fatigue was 59.1% (95% CI: 55.9–62.2%). In plain terms, roughly 6 in every 10 people with MS worldwide experience fatigue.

Heterogeneity was very high (I² = 97.3%, p < 0.01), meaning the individual studies varied far more than chance alone would explain. The sensitivity analysis showed that the estimates stayed largely unchanged when studies at high risk of selection or attrition bias were removed, indicating the findings were robust and reliable.

Who Is Most Affected? Key Patient Groups

Fatigue was not evenly distributed. Several groups stood out.

Sex. Fifteen studies compared men and women directly. Fatigue prevalence was 58% among 6,982 women compared with 56.5% among 2,598 men.

Age. Subgroup analysis split patients into three age bands, and prevalence climbed steadily with age:

• 30–40 years: 54.7%
• 40–50 years: 58.6%
• 50–60 years: 69.3%

Disability level. People with an EDSS score above 4 had a fatigue prevalence of 73.7%, considerably higher than those at or below 4. That is about 7 in 10 patients among those with greater disability.

Disease duration. Patients who had lived with MS for more than 10 years had a prevalence of 63.4%, compared with 55.6% among those with MS for 10 years or less.

MS phenotype. Fatigue tracked with disease form. SPMS had the highest prevalence at 74.4% across 10 studies, followed by PPMS at 64.3% across 8 studies, and RRMS at 54.7% across 15 studies.

Education. Across 4 studies, people with more than 12 years of education had a lower fatigue prevalence (47.9%) than those with 12 years or less (64.3%).

In total, 15 studies supplied data on sex distribution, 15 reported fatigue by MS phenotype, and 4 estimated prevalence by education level. Of the 34 studies that reported MS diagnostic criteria, two earlier studies used the Poser criteria, and all later ones used the continuously updated McDonald criteria (2001, 2005, 2010, and 2017).

How Fatigue Was Measured — and Why the Scale Matters

The included studies used four fatigue scales, and the choice of scale had a large effect on the numbers reported.

• Fatigue Severity Scale (FSS) — used by two-thirds of studies (n = 47).
• Modified Fatigue Impact Scale (MFIS) — used by about one-fifth (n = 16).
• Fatigue Scale for Motor and Cognitive Functions (FSMC) — used by 4 studies, with a cut-off of 43 (total score).
• EMIF-SEP — a validated French version of the Fatigue Impact Scale, used by 1 study with a cut-off of 55 (total score).

One additional study used both the FSS and MFIS, with cut-offs of 4 (mean score) and 38 (total score), respectively.

Even within the same scale, cut-off values differed. Of the 47 FSS studies, 28 defined fatigue at a cut-off of 4 (mean score), 17 used a cut-off of 5 (mean score), and 2 used cut-offs of 4.5 (mean score) and 28 (total score). Of the 16 MFIS studies, 14 used a total score of 38 as the cut-off, while 2 used 35.5 and 45.

These differences produced very different prevalence estimates. The FSMC gave the highest estimate at 70.4%. The MFIS with a cut-off of 38 gave the lowest at 51%. For the FSS, a cut-off of 4 yielded 65.6%, while a cut-off of 5 yielded 54.3%.

Fatigue Around the World and by Income Level

The 69 studies spanned 21 years (from 2002 onward) and 27 countries across four WHO regions. More than half (n = 36) were conducted in the European Region, and none came from the African Region or the Southeast Asia Region. Two studies were binational (USA and Sweden; Turkey and Israel), and three were multinational.

The countries contributing the most studies were the USA (n = 9), Argentina (n = 5), the UK (n = 4), Italy (n = 4), Australia (n = 4), Saudi Arabia (n = 3), the Netherlands (n = 3), China (n = 3), and Finland (n = 3).

The five countries with the highest fatigue prevalence were:

1. Austria — 80%
2. Norway — 79.5%
3. United Kingdom — 69.8%
4. Switzerland — 69.2%
5. Lithuania — 68.6%

By WHO region, the European Region had the highest pooled prevalence (61.2%), and the Western Pacific Region had the lowest (54.2%).

By income level, based on World Bank gross national income per capita, most studies came from high-income countries (n = 53, or 77%), followed by upper-middle-income countries. Fatigue prevalence was significantly higher in high-income countries (59.9%) than in upper-middle-income countries (53.4%).

In terms of where patients were recruited, nearly half of the studies were population-based (n = 34), 24 were conducted in MS outpatient clinics, and 4 took place in MS Medical Research Centres. Most studies used a cross-sectional design (n = 64, or 93%), 4 were case–control, and 1 was a cohort study.

What Drives the Differences Between Studies?

The researchers ran subgroup analyses to explain the extremely high heterogeneity. The results were striking.

• Sample size: studies with more than 1,000 participants reported 67% prevalence versus 59.9% for smaller studies.
• Survey year: prevalence fell every decade — 64.4% in 2000–2009, 59.6% in 2010–2019, and 51% in 2020–2023.
• Proportion of women: 49.9% in studies with fewer than 60% women, 58.5% in those with 60–80% women, and 64.6% in those with 80% or more women.
• Patient source: 61.4% in population-based studies, 58.9% in outpatient studies, 50.2% in MS Medical Research Centres, and 54.9% in mixed populations.

Of the 10 study and sample characteristics examined, all except WHO region and patient source had a statistically significant impact on reported fatigue prevalence. That means these factors are likely genuine sources of variation between studies rather than random noise.

The decline over time is notable. Prevalence dropped by more than 13 percentage points between the earliest and most recent survey periods. This may reflect better MS diagnosis and treatment, greater use of non-drug fatigue management, or changing measurement practices.

Meta-Regression: Pinpointing the Sources of Variation

Even within subgroups, studies still disagreed widely. So the team ran a meta-regression, a statistical technique that tests which factors explain differences between studies.

Four factors were significantly linked to heterogeneity, and together they explained 86.4% of the variance between studies:

• Fatigue scale: 46.4% of the variance — by far the largest single source.
• EDSS score (disability level): 18.4%.
• Age: 14.6%.
• MS duration: 7.1%.

In other words, which questionnaire a study chose mattered more than anything else in determining whether it reported a high or low fatigue rate. EDSS and MS duration had 25 and 43 available data points, respectively, for these analyses. For the remaining variables, 56 data points were excluded because of missing data. Missing mean age values were filled in using medians, a previously validated approach. The team did not assess publication bias, because standard methods such as funnel plots are not suited to prevalence studies.

Study Quality and Risk of Bias

Overall, study quality was reasonable, but there were notable weaknesses.

Among the four case–control studies and the one cohort study, Newcastle–Ottawa Scale scores ranged from 4 to 6 stars, indicating a moderate risk of bias. Among the 64 cross-sectional studies, the mean AHRQ score was 7.6 (range 5–10), pointing to a low overall risk of bias. Of these, 59% were rated "moderate quality," and 28 studies (41%) were rated "high quality."

The main problems that raised risk of bias were:

• Insufficient detail about quality-control methods for outcome measures.
• Use of non-blinded evaluators (assessors who knew which group patients belonged to).
• Unclear handling of missing data in the statistical analyses.

What This Means for Patients

The headline message is simple: fatigue is the norm, not the exception, in MS. About 6 in 10 people with MS worldwide live with it, and the true figure may be higher in certain groups.

Several practical implications follow from the data.

First, fatigue deserves routine attention at every stage of MS care — not just when a patient brings it up. The study's authors emphasize that healthcare professionals should screen for and manage fatigue as early as possible rather than waiting for it to become disabling.

Second, certain patients should be watched especially closely. The data point to higher prevalence among:

• People with greater disability (EDSS above 4: 73.7%)
• Those with secondary progressive MS (74.4%)
• People aged 50–60 years (69.3%)
• Those who have had MS for more than 10 years (63.4%)
• People with 12 years of education or less (64.3%)

Third, patients should know that the fatigue they feel is a recognized, measurable feature of MS — not a personal failing or something they must simply endure. The awareness that fatigue cannot be fixed by rest or sleep is important, both for patients and for the people supporting them.

Fourth, the steady decline in prevalence since 2000 (from 64.4% to 51%) is encouraging. It suggests that improvements in MS diagnosis, treatment, and non-drug fatigue management may be making a real difference over time.

Limitations: What the Study Could Not Prove

This is an analysis of published studies, not a new study of individual patients, so it carries inherent limits.

Heterogeneity was extremely high (I² = 97.3%), and even after subgroup and meta-regression analyses, substantial variation remained within groups. The authors identified the fatigue scale as the largest driver, but other unmeasured factors could also play a role.

Coverage was uneven. More than half the studies came from the European Region, and there were no studies at all from the African Region or the Southeast Asia Region. Two of the four WHO regions were not represented. That means the global estimate leans heavily on data from Europe, the Americas, and other well-studied regions. The global estimate may not reflect the experience of patients in under-represented parts of the world.

Measurement varied widely. Studies used different scales, different cut-off values, and even different definitions of what counts as "clinically significant fatigue." For example, the FSS cut-off of 4 versus 5 changed the reported prevalence by more than 11 percentage points (65.6% vs 54.3%). Because of this, comparisons across studies and countries should be read with caution.

Meta-regression analyses were also limited by missing data. EDSS and MS duration had only 25 and 43 data points available, and 56 data points were excluded because of missing values. Some mean ages had to be estimated. These gaps reduce the precision of the findings about which factors matter most.

Finally, the researchers did not assess publication bias, because standard methods are not considered suitable for prevalence studies. This means it is possible that studies showing different results were less likely to be published, although the sensitivity analysis suggested the overall findings were stable.

Recommendations for Patients and Clinicians

The authors draw four main recommendations from their findings.

1. Screen early and routinely. Healthcare professionals should assess fatigue in people with MS as soon as possible and repeat this over time, rather than waiting for patients to report it.
2. Focus on high-prevalence groups. Extra attention is warranted for patients who are older, have greater disability (EDSS above 4), or have lived with MS for more than 10 years. Extra attention is also warranted for patients who have progressive forms of MS or have lower education levels. These groups carry the heaviest fatigue burden.
3. Agree on the best screening tool. The huge variation caused by different fatigue scales shows that the field needs consensus on which questionnaires and cut-offs to use. Until then, comparing fatigue rates across studies, clinics, and countries will remain difficult.
4. Treat fatigue as a core MS problem. Because fatigue drives lost quality of life, unemployment, and disability claims, it should be managed as a priority in MS care, not as an afterthought.

For patients, the takeaway is practical. If you have MS and experience persistent fatigue that rest does not relieve, this is a recognized symptom of your disease, and it is worth raising with your care team. Ask about screening, and ask about non-drug options such as physical activity, dietary changes, and cognitive behavioral therapy. Also ask whether any of your other symptoms or medications could be contributing to secondary fatigue.

Frequently Asked Questions

How common is fatigue in multiple sclerosis?

In a review of 69 studies covering 44,468 people with MS in 27 countries, the pooled global prevalence of fatigue was 59.1%. That means roughly 6 in every 10 people with MS worldwide experience fatigue. Individual study estimates ranged widely, from 28.4% to 88.2%, largely because different fatigue questionnaires and cut-off values were used.

Which groups of people with MS are more likely to have fatigue?

Fatigue was more common in women, older patients, those with greater disability, those who had lived with MS longer, and those with less education. For example, prevalence was 73.7% in people with an EDSS score above 4, 74.4% in secondary progressive MS, 69.3% in those aged 50–60, and 63.4% in those with MS for more than 10 years.

Does the choice of fatigue questionnaire affect how common fatigue appears?

Yes. In the analysis, the fatigue scale used explained 46.4% of the variation between studies — the largest single source. The FSMC gave the highest estimate at 70.4%, while the MFIS with a cut-off of 38 gave the lowest at 51%. Even within the FSS, a cut-off of 4 yielded 65.6% versus 54.3% for a cut-off of 5.

Is MS-related fatigue different from ordinary tiredness?

Yes. MS-related fatigue is defined as a significant lack of physical and/or mental energy that interferes with normal and desired activities. Crucially, it is disabling and does not improve with rest or sleep. It can appear at any stage of the disease and is one of the most common and most burdensome MS symptoms.

What can help with MS-related fatigue?

No medication convincingly treats MS-related fatigue. Non-drug approaches — physical activity, dietary changes, and cognitive behavioral therapy — can help. The review authors recommend screening for fatigue early and routinely, and paying extra attention to high-prevalence groups. The review authors also recommend agreeing on a standard screening tool, and treating fatigue as a core MS problem rather than an afterthought.

What are the limitations of this global review of fatigue in MS?

It analysed published studies, not individual patients. Heterogeneity was extremely high, and coverage was uneven: more than half the studies came from the European Region, with none from the African or Southeast Asia Regions. Measurement varied widely, and meta-regression was limited by missing data. Publication bias was not assessed because standard methods are not suited to prevalence studies.

I have MS and my fatigue is getting worse — when should I get a second opinion about how it's being managed?

Fatigue affects about 59% of people with MS worldwide, and it is more common in those with greater disability, longer disease duration, progressive forms, and lower education levels. No medication convincingly treats MS-related fatigue, and non-drug approaches such as physical activity, dietary changes, and cognitive behavioral therapy can help. A second opinion is reasonable when fatigue is not being routinely screened. A second opinion is also reasonable when secondary causes such as sleep problems, mood disorders, or treatment side effects have not been reviewed. A second opinion is also reasonable when your management plan has not been reassessed over time. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Global prevalence of fatigue in patients with multiple sclerosis: a systematic review and meta-analysis.

Authors: Xiaodong Yi, Yue Zhang, Qiufeng Du, Jing Kang, Shuang Song, Tao Li, and Yunlan Jiang

Author affiliations: College of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, China; and Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China

Journal: Frontiers in Neurology, Volume 15, Article 1457788

Publication details: Received 03 July 2024; Accepted 20 September 2024; Published 02 October 2024

DOI: 10.3389/fneur.2024.1457788

Study registration: PROSPERO international prospective register of systematic reviews, CRD42024499139

Note: This patient-friendly article is based on peer-reviewed research. It is an open-access publication distributed under the terms of the Creative Commons Attribution License (CC BY). All figures, statistics, and conclusions presented here are drawn directly from the original systematic review and meta-analysis. Patients should discuss any questions about their own MS fatigue with their healthcare team, as this article is for information only and is not a substitute for personalized medical advice.