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Understanding lifestyle self-management regimens that improve the life quality of people living with multiple sclerosis: a systematic review and meta-analysis

Background Lifestyle self-management as an intervention for people living with multiple sclerosis (plwMS) is an emerging area of research. Previous reviews have highlighted a need to systematically identify effective self-management regimens that influence the health and well-being of plwMS using a common metric of success. Objectives To examine the effectiveness of lifestyle self-management strategies and interventions aimed at improving the quality of life (QOL), and/or disability of plwMS. The review also aimed to narratively explore common elements of self-management interventions that were effective at improving the outcomes of interest. Methods A systematic search was performed using five scientific databases. The review process followed the Cochrane Handbook for Systematic Reviews of Interventions and was registered with PROSPERO (Ref: CRD42021235982). Results A total of 57 studies including 5830 individuals diagnosed with MS, met the inclusion criteria. Self-management interventions included physical activity, fatigue, dietary, stress/coping, emotional, symptom and medical management, and lifestyle and wellbeing programs. Self-reported QOL improved in 35 of 47 studies. Dietary intervention had no statistically significant overall effect on reducing MS disability, (P = 0.18). Heterogeneity limited the ability to pool the effects from a large number of eligible studies of the same design. Conclusion Multicomponent self-management interventions, multimodal delivery methods, and cognitive behavioural theory principles were common elements of self-management interventions that improved the QOL of plwMS. However, these results should be interpreted with caution and care should be taken in its clinical application. This review has the potential to inform future management practices for plwMS and has revealed a significant gap in the literature, warranting high-quality, large-scale experimental, and observational studies that address lifestyle management. Supplementary Information The online version contains supplementary material available at 10.1186/s12955-022-02046-1.


Rationale
Living with multiple sclerosis (MS) is associated with unpredictable and debilitating neurological symptoms [1]. These symptoms include physical challenges (i.e. fatigue, pain, weakness, spasticity), cognitive deficits  20:153 (i.e. memory loss, slow processing, poor concentration), and/or emotional symptoms (i.e. anxiety, mood swings, irritability, depression) that fluctuate throughout the disease course, regardless of the MS phenotype [1,2]. While medical management, including the provision of disease-modifying therapies (DMT's), is important to maintain good health when living with MS, the impact of these symptoms is not restricted to routine healthcare visits. For most people living with MS (plwMS), these symptoms are experienced daily and create a multitude of challenges that can significantly impact quality of life (QOL) [2,3]. Therefore, it is the day-to-day management of the disease course and symptoms that can have a profound impact on the current and future health and wellbeing of plwMS. Self-management is a relatively new phenomenon within healthcare but has received increased attention as an effective management strategy for chronic health conditions; it is the ideology that acknowledges neurological conditions, such as MS, as a continuous experience [4]. Self-management focuses on equipping the individual with the skills and ability to manage their symptoms, monitor medication regimens and physical disability, engage in physical activity, maintain nutritional status, and adjust to the psychological demands of their condition [5,6]. There is considerable evidence that selfmanagement interventions are effective in improving the health and functional status, knowledge, adherence to treatment, and the physical, psychological, and social domains of QOL among people with chronic conditions [7][8][9]. The emergence of lifestyle self-management as an intervention for plwMS is a growing area of focus, and while currently limited, the effectiveness of self-management interventions holds promise [10].
A systematic review conducted by Kidd et al. examined the impact of self-management interventions on the psychological well-being of plwMS [11]. Despite the inclusion criteria, the limited number of published studies specific to MS care at the time (n = 10) and the heterogeneity between the included studies made it difficult to compare the effectiveness of different treatment strategies on self-reported outcome measures. Similarly, a second review exploring self-management support in people with neurological conditions generally, also concluded that the limited number of studies (n = 39) and the diversity in reported self-management outcome measures challenged the ability to comment on the overall effectiveness of the strategies [12]. More recently, Yamaguchi et al. examined the potential of self-management for people living with HTLV-1 associated myelopathy by reviewing the literature within an MS context. Again, the included studies reported inconsistent outcome measures (i.e. QOL, self-efficacy, cognitive changes) and only a limited range of medical, role (i.e. social life and independence) and emotional management strategies [13].
Previous reviews [11][12][13], therefore, highlight a need to systematically identify effective elements of self-management regimens that influence the health and well-being of plwMS using a common metric of success. QOL was chosen as an accepted outcome measure in clinical studies and has been identified as an important measure in MS research as it incorporates the personal and social context of a person's life [14]. Moreover, Mitchell et al. recommended that studies of interventions in MS populations use assessments of QOL rather than impairment or disability measures alone [15].

Aims and objectives
Therefore, the present review aimed to examine the effectiveness of lifestyle self-management strategies and interventions aimed at improving QOL, as the primary outcome, and/or disability among plwMS [14,15]. The review also aimed to narratively explore common elements of self-management interventions that were effective at improving the outcomes of interest.

Registration and protocol
The present review was guided by the Cochrane Handbook for Systematic Reviews of Interventions [16] and reported according to the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) 2020 statement [17] and 27-item PRISMA checklist [17]. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) [18] (Ref: CRD42021235982) in February 2021, to reduce the potential for bias through a transparent review process [19].

Eligibility criteria
Studies were included in the review if they met the following criteria: Types of studies and publications Studies published in peer-reviewed journals, including both experimental and observational studies. Non-English studies were excluded. Studies including case studies, review articles, feasibility and pilot studies, protocols, grey literature, and publications including conference abstracts, editorials, and monographs were also excluded. No date restrictions were applied to the final search.
Types of participants Adults aged ≥ 18 years with a clinical diagnosis of MS using the McDonald criteria (2001, 2005, 2010, or 2017) [20] regardless of their time since diagnosis. Studies that included people diagnosed with a clinically isolated syndrome phenotype, pregnant or breastfeeding females, or paediatric MS were excluded.

Search strategy
The research question in the PICO format was: What is the effect of lifestyle self-management strategies and/ or interventions on QOL and/or disability in plwMS? A systematic search was conducted using five scientific databases: Cochrane Library, CINAHL via EBSCOhost platform, MEDLINE via Ovid platform, PubMed via ProQuest platform, and Scopus via Elsevier. Although PubMed is a subset of MEDLINE, both MEDLINE and PubMed databases were searched to ensure that the most recent studies were identified [27]. A preliminary search was performed in February 2021 to determine the feasibility of the search by identifying sentinel articles. The final search was conducted on 8 April 2021 (OW).
The search strategy included alternative phrases, spelling, and truncations, using both controlled vocabulary and free-text terms. For a detailed search strategy, please refer to Additional file 1: data 1. To increase the sensitivity, manual hand searching of the reference lists of extracted systematic reviews and meta-analyses was performed to obtain additional relevant studies.

Selection process
A three-phase screening process was implemented to ensure that the included studies met eligibility criteria. All studies were exported to Covidence (Covidence Systematic Review Software, 2019, Veritas) to manage the screening process, and duplicates were removed. Two reviewers (OW and ES) independently screened titles and abstracts of the search results. Where consensus was not reached, a third and more senior researcher (YP) was consulted. For studies and reviews that met the inclusion criteria, the full text was retrieved and screened by two researchers (OW and YP). Discrepancies were resolved by discussions between the two researchers.

Data extraction
One author (OW) extracted relevant information from the included studies based on the Cochrane Consumers and Communication Review Group's data extraction template [16]. Information extracted from each study included: study details (country, setting, date published), first author, study methodology (study design, recruitment, groups), participant characteristics (sex, age, MS phenotype, duration of disease, EDSS or PDDS score), study characteristics (intervention description, comparator/control description), description of primary and secondary outcomes (QOL or disability measurement tool used), results and a summary of the conclusions. Corresponding authors of studies with missing data were contacted via email to obtain additional information to be used in the synthesis of the results. No responses were obtained.
The effect measures of randomised control trials (RCT) included continuous outcome measures for both QOL and disability variables, which were summarised as the mean difference ( ± standard deviation) from pre to post intervention, unless otherwise stated. For observational Page 4  study designs, the relative risk was reported where available from the included studies.

Data synthesis
The authors (OW, YP) identified what self-management regimen was being explored in each study and categorised it into one of five dimensions based on MS Australia's Modifiable Lifestyle Factors Guidance document [21]. This included: (1) physical activity, (2) diet, (3) fatigue management, (4) coping, depression, stress, and emotional management, and (5) symptom and medical management. Some interventions had multiple components (i.e. diet, exercise, and energy conservation); therefore, these interventions were categorised into a sixth dimension of (6) lifestyle and wellbeing programs. Individual studies were qualitatively synthesised under each self-management dimension to identify the findings related to participant outcomes. The outcomes are reported quantitatively in the final data summary table.
The primary outcome measure was QOL (including their respective domains), and the secondary outcomes were measures of disability such as EDSS, relapse rate, and number and volume of T1 and/or T2 weighted brain lesions. Statistical significance was set at P < 0.05. A meta-analysis was performed when there were two or more studies under the same self-management dimension that used the same disability measure or QOL domain with compatible summary measures (i.e. mean change (SD)), using Review Manager (RevMan) (Mac OS X, Version 5.4, The Cochrane Collaboration, 2020). Summary estimates were reported for studies of randomised controlled trials only, as the heterogeneity of comparing different study designs may increase the complexity of the analyses and impact the interrelation of quantitative outcomes [16,28].
An inverse variance with random effects model was used because of the heterogeneity among participants in terms of MS disability and population characteristics [29]. The RevMan Calculator was used to calculate the standard deviation from the 95% confidence intervals and reported changes in means [30]. The I 2 statistic was used to quantify the proportion of total variation attributable to between-study heterogeneity. Heterogeneity was categorised according to the Cochrane guidelines: (1) I 2 = 0-40%: low heterogeneity; (2) I 2 = 30-60%: moderate heterogeneity; (3) I 2 = 50-90%, substantial heterogeneity; and (4) I 2 = 75-100%: considerable heterogeneity [16].

Risk of bias assessment
The risk of bias (RoB) of each study was appraised according to the study design. Version 2 of the Cochrane RoB tool, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions [16], was used to assess RoB in each RCT. The studies were appraised according to the RoB arising from (1) the randomisation process, (2) deviations from the intended interventions (effect of assignment to intervention), (3) missing outcome data, (4) measurements of the outcome, and (5) selection of the reported result. A proposed RoB judgment for each domain was generated using an algorithm [31] and each study was assessed as having low risk, some concerns, or high RoB.
The RoB in non-randomised studies of interventions was assessed using the ROBINS-I tool [32]. This tool focuses on seven domains of bias including: bias due to confounding, selection of participants into the study, classification of interventions, deviations from intended interventions, missing data, outcome measurements and selection of the reported results. Risk levels of low, moderate, serious, critical, or insufficient information were assigned to each of these domains.
The RoB in case-control and cohort studies was assessed according to the Newcastle Ottawa Quality Assessment Scale (NOS) [33]. This scale was adapted from the NOS for cohort studies to provide RoB assessment of cross-sectional studies [34]. A star system was used to appraise each study under the following domains: (1) the selection of study groups, (2) the comparability of the study groups, and (3) ability to identify the exposure or outcome of interest. Each study was awarded one star for each criterion under the selection and exposure/ outcome categories, and a maximum of two stars for the comparability category. Therefore, cohort/case-control studies with 7-8, 5-6, 4 and 0-3 stars were identified as very good, good, satisfactory, or unsatisfactory, respectively. Cross-sectional studies with 5, 4, 3 or 0-2 stars were identified as very good, good, satisfactory, and unsatisfactory, respectively [35].

Certainty assessment
The certainty of the body of evidence of the quantitative synthesis was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria [36]. The certainty of the body of evidence considered within-study risk of bias, precision and consistency of effect estimates, directness of evidence and risk of publication bias. An overall GRADE was determined as one of four levels of evidence: high, moderate, low and very low, by the two researchers (OW, YP). Randomised controlled trials begin with a high level of evidence. Factors that may increase or decrease the quality level of a body of evidence have been described elsewhere [36].

Study selection
A total of 1664 references were identified from the database search, and an additional 14 references were obtained from manual searches. After removing the duplicates (n = 762), 902 references were retained. The full texts of 310 references were screened, and 43 studies met the inclusion criteria. Therefore, 57 studies were included in this systematic review . the full selection process is presented in Fig. 1.

Participant characteristics
The 57 included studies included a total of 5830 individuals diagnosed with MS, with a median of 82 individuals per study (IQR,110 Intervention had no effect on EDSS.
Among those studies reporting a significant improvement in outcome measures, group-based interventions were a common occurrence, and exercise sessions ranged from to 60-90 minutes in duration.
General exercise interventions ranged from six weeks to 14 months, with typical programs involving team sports, walking, and group activities. Of these, none of the general exercise programs saw a significant change in MS disability, with only one study reporting a significant improvement in QOL for up to 14-months after a combined exercise program.
Of the five studies assessing aerobic exercise [38,46,51,55,56], four reported significant improvements in QOL subscales [38,51,55,56] including mental, physical, pain, energy, social, sexual function, fatigue, and overall QOL. Two studies reported a significant decrease in the disability measures [46,55]. One of these studies was restricted to participants with only the RRMS phenotype and included only those prescribed fingolimod as a DMT. Among those studies exploring yoga as an intervention, two reported significant improvements in emotional, energy, and vitality QOL domains at the six month time point.

Coping, depression, stress and emotional management interventions
Of the ten studies that explored coping, depression, stress, and emotional self-management strategies [58][59][60][61][62][63][64][65][66][67], seven studies were RCT's, all of which reported a significant improvement in QOL post intervention, relative to the controls [59-63, 66, 67]. Controls were not exposed to the interventions and continued with routine standardised MS care. Six were delivered face to face [59, 61-63, 66, 67] and one was delivered via telephone [60]. One of these studies was conducted among adults with a RRMS phenotype only, all others did not restrict the MS phenotype in their inclusion criteria. Physical (n = 6) and mental health (n = 5)-related QOL were the most common domains reported. A key finding was that significant improvements in QOL domains among the seven interventional studies were reported almost immediately and lasted for up to six months. Few studies have included data on the long-term effects of these interventions (i.e. 12 months and beyond).
Common theories, models, and practical strategies were used in the seven studies that reported a significant improvement in QOL domains. The most popular theory was cognitive behavioural theory (n = 3), followed by supportive/positive expressive psychotherapy (n = 3), and mindfulness practice (n = 2). Two studies explored the effect of the Social Cognitive Can Do Program (SCDP) among people with a RRMS phenotype [64,65]. Each study collectively reported a significant immediate improvement in mental and physical health-related QOL at six months; however, only physical QOL maintained statistical significance at 12-months post intervention.

Dietary interventions
The impact of dietary patterns and nutritional supplementation on QOL and disability measures in plwMS was assessed in eight studies. [68][69][70][71][72][73][74][75] Of the three studies that assessed the impact of fish oil supplementation [73][74][75], only one reported an immediate improvement in the physical composite score of QOL post intervention relative to a control group [74]. The intervention group received a combination of six fish oil capsules per day (198 mg EPA, 132 mg DHA), 400 units of vitamin E, 1 multivitamin, and 500 mg calcium while following a very low fat diet (i.e. < 15% total energy from fat). The control group was fed a low-cholesterol diet (i.e. < 30% total energy from fat), 400 units of vitamin E, 1 multivitamin, 500 mg calcium, and an olive oil supplement as a placebo.
No clinical benefit of fish oil supplementation was found in relation to disability measured using the EDSS or the number of new T1 enhanced and hypo-intensive brain lesions [73,75].
One study evaluated the effect of probiotic intake and reported a significant improvement in EDSS and general health QOL, favouring the intervention [72].
Only one study assessing the impact of vitamin D supplementation found a significant improvement in mental and health-related subscales [69]. The intervention consisted of patients on interferon-beta as their main DMT, supplementing 50,000 IU vitamin D3 every five days for three months. Controls consumed a placebo. Vitamin D supplementation at 20,000 IU was found to have no significant impact on disability measures via the EDSS or relapse rate [68,71] however, one study of the same supplemental dose did observe a significant decrease in the number of T1 weighted lesions [68]. Control participants were given a placebo and continued with usual care.

Lifestyle and wellbeing
Of the eight studies that assessed lifestyle and/or wellbeing programs, all were delivered face-to-face, and all reported a significant improvement in QOL, favouring lifestyle self-management courses or exposures [76][77][78][79][80][81][82][83]. The most common QOL domains that saw a significant improvement across the eight studies included mental health (n = 7) [76,[78][79][80][81][82][83] and physical health (n = 6) [76,[78][79][80][81][82] related QOL. All studies included an intervention or exposure to at least two or more self-management dimensions, and the most common combinations included a dietary (n = 6), exercise (n = 6), and a psychological (emotional, fatigue, stress, coping, support) component (n = 6). In two studies, a group-based selfmanagement workshop, delivered by trained healthcare professionals, reported both a short-term (immediate) and long-term (three years) improvement in QOL [80,82]. A key finding, however, was the sustained improvement in a majority of QOL subscales, including physical health, mental health, pain, and social and overall QOL, for up to five years post intervention [78,79]. Only one study [83] used a combination of delivery methods including a face-to-face lifestyle program, followed by three months of accountability telephone calls. Improvements in QOL domains, including pain and mental health, were sustained for the duration of the 8-month intervention period.

Fatigue management
Of the seven studies that assessed the impact of fatigue management programs on QOL [84][85][86][87][88][89][90], four reported a significant improvement in QOL, favouring the fatigue management course. Five were delivered face-to-face [85-87, 89, 90] and two were delivered remotely [84,88] via teleconference sessions. Of the interventions delivered remotely, both were conducted over a 6-month period however only one reported a significant improvement in physical, vitality and social QOL, favouring the intervention [91][92][93]. The remaining study comprised of a simpler intervention including only three teleconference sessions and four individually tailored counselling phone calls [88].
Of the interventions delivered face-to-face, three reported a significant improvement in domains of QOL [84][85][86]. These three studies ranged from six weeks to three years, however they displayed similar participant characteristics, including mean age of participants around 48 years and disease duration of ~ 9.5 years. The most common QOL domains that saw a significant improvement after fatigue and energy conservation courses included vitality, social, mental health, and physical health-related QOL [84][85][86]90]. One study that reported no significant improvement after a fatigue intervention accompanied by usual care suggested a longer term follow-up of two years or more may be required to observe a consistent and significant change in QOL [89].

Symptom and medical management
The impact of symptom and medical management on QOL was assessed in three studies [92,94]. Participants followed either a symptom self-care program [91,92] or program combining medication management and education [93]. Of these three, one study reported a significant improvement in general health-related QOL after a 12 month intervention period, relative to a control group [91]. This study was delivered via an electronic messaging system between plwMS and their clinicians, to enhance symptom control and management. Controls continued their usual MS care. Of the remaining two observational studies, only one revealed a significant improvement in physical, psychological, social, and environmental QOL after a self-care management course [92]. The remaining study found no significant improvement in QOL after a DMT self-management program; however, they reported a 33.6% significant decrease in relapse rate [93].

Meta-analysis of studies
Only one self-management dimension met the inclusion criteria for a meta-analysis to calculate pooled estimates of the effect of self-management interventions on homogenous disability outcome measures. An additional two meta-analyses were eligible based purely on a homogenous self-management dimension, QOL domain and summary measure. However, the heterogeneity that was created by comparing different study designs would impact the interrelation of results and a decision to exclude these meta-analyses was made by the authors.

i. Diet
Five studies, including 286 participants, examined the effect of dietary interventions on disability, using the EDSS [68,[70][71][72]75]. Aivo et al. [68] Kouchaki et al. [72] and Zandi-Esfahan et al. [75] reported a reduction in EDSS scores following dietary intervention, while Bitarafan et al. [70] and Kampan et al. [71] did not observe a change in EDSS between the intervention and control arms. None of the results were statistically significant.
As demonstrated in Fig. 2, dietary intervention had no statistically significant overall effect on reducing disability as measured by EDSS scores (MD = − 0.13, 95% CI = − 0.31-0.06, Heterogeneity: Tau 2 = 0.02, Chi 2 = 8.55, df = 4 (P = 0.07); I 2 = 53%, test for overall effect Z = 1.35 (P = 0.18). An I 2 value of 53% indicated substantial heterogeneity between studies therefore caution is warranted in interpreting these summary estimates. The certainty of the body of evidence by GRADE for dietary interventions was very low, based on downgrading for inconsistency, indirectness, and imprecision. Results of individual GRADE domains are outlined in Additional file 1: data 3.
The RoB in nonrandomised studies of interventions ranged from low to serious. Overall, one study had a low RoB [77], five had a moderate [42,57,58,77,85] and one had a serious RoB due to intervention classification [49]. All (100%) of studies had a low RoB due to confounding and selective reporting of results. However, 57% (n = 4) [49,57,58,82] studies had a moderate RoB due to measurement of the outcome, and 42% (n = 3) [58,82,85] studies had a moderate RoB in the selection of participants.
Based on the NOS, four of the 13-cohort/case control studies were of good quality [41,78,87,93], three were of satisfactory quality [39,64,65], and the remaining six were unsatisfactory [37,52,79,80,83,92]. Most studies with unsatisfactory scores did not follow appropriate recruitment methods, assessment of outcomes, and/or adequate follow-up of cohorts. The two cross-sectional studies were of satisfactory quality [47,48]. None of the studies were appraised as having very good quality, mainly because the selected participants were not representative of the exposed cohort and a poor description of outcome assessments. This was possibly due to the nature of the study design and the inability to blind the participants.

Discussion
To the best of our knowledge, this is the first review to systematically explore the effectiveness of lifestyle self-management strategies and/or intervention(s) that influence the health and well-being of plwMS, using a common metric of success. For each of the six selfmanagement dimensions (physical activity and exercise; coping, depression, stress, and emotional management; diet, lifestyle, and well-being; fatigue management; and symptom management), varying impacts on participants' self-reported QOL and objective measures of disability were reported. Qualitative syntheses of results initially appear promising and are reflected in previous work that has explored lifestyle self-management in MS cohorts [11][12][13]. However, the meta-analysis did not identify any statistically significant effects, which may be a result of the heterogeneity between the included studies and/or due to the small number of studies being meta-analysed [94]. Further to this, the review found that the evidence base for high-quality randomised controlled trials (n = 9) designed to improve QOL and reduce objective measures of disability was limited. Therefore, the overall ability to answer the research question: What are the elements of lifestyle self-management strategies and/or interventions that improve the QOL of plwMS patients, was challenged.
The first key finding was that the eight studies that incorporated multicomponent self-management interventions (i.e. lifestyle and well-being programs) [76][77][78][79][80][81][82][83] all reported a significant improvement in self-reported QOL. A reasonable explanation for this finding can be provided through their respective self-management programs that assist participants in gaining skills to control physical symptoms, identify coping strategies to deal with emotional challenges, conserve energy to deal with fatigue, and provide education regarding appropriate dietary choices. As lifestyle is multidimensional, these results were somewhat expected, as the interventions were able to address multiple aspects of care to improve overall QOL. This is consistent with the findings of other studies that have explored multicomponent interventions to improve QOL in chronic disease [95]. Furthermore, these studies used a range of teaching modalities, which have been found to reinforce knowledge comprehension and ensure individual learning styles are addressed [96]. This may have further contributed to the positive improvements in QOL, as self-reported by the participants. Future research should explore the best combinations of self-management dimensions with the greatest effect on improving QOL.
A second key finding was the positive effect of coping, depression, stress, mental health, and/or emotional management strategies in improving the QOL of plwMS [58][59][60][61][62][63][64][65][66][67]. This result has been described in the literature for other chronic diseases [97][98][99]. It is well established that people with chronic illness find it difficult to cope with the physical and/or emotional challenges of their condition [100]. Furthermore, these challenges have been previously reported to significantly affect QOL due to the impact on one's ability to work, participate in leisure activities, and engage in social functions. Therefore, it was anticipated that a program equipped with plwMS with the confidence to self-manage the emotions of their diagnosis and develop coping strategies to deal with stress would reduce the burden of their condition and improve QOL. This finding is consistent with a previous systematic review exploring the effectiveness of selfmanagement to improve depression, anxiety and QOL among plwMS [11]. As reported by Kidd et al. effective interventions included principles of the cognitive behavioural theory, in 30% of the studies. One meta-analysis reported that incorporating cognitive behavioural theory in interventions for plwMS is effective in improving QOL domains [11,101]. The present review has validated this finding.
Fatigue is one of the most common symptoms and burdens approximately 75% of plwMS [102]. It is well established that fatigue is independently associated with impaired QOL in MS, suggesting that recognising and treating fatigue can potentially improve overall life quality [102,103]. Therefore, interventions encapsulating selfmanagement of fatigue would significantly improve QOL. However, this assumption was only reflected in four out of the seven studies exploring fatigue self-management with interventions ranging from six weeks to three years. One possible reason for these inconsistencies is that behavioural change takes time and, therefore, longer term follow up of two years or more may be required to observe a consistent and significance change in QOL. This was observed in a similar review of fatigue self-management in patients with chronic health conditions such as chronic fatigue syndrome, rheumatoid arthritis, and cancer, suggesting longer follow up times are needed [104].
The pooled estimate of the effect of dietary interventions among the five studies indicated no significant reduction in disability measures reported through the EDSS. According to Higgins et al. [105] the I 2 value indicated substantial heterogeneity; therefore, the results should be interpreted with caution. This may be attributed to the substantial variation in the study design, intervention, and methodology among the six included studies. Due to the scarcity of evidence confirming particular food(s) or dietary patterns that are effective in reducing the symptom burden of MS, it was anticipated that no significant effect would be found in this review. These results are consistent with a 2020 Cochrane review, which indicated that there is an insufficient level of evidence to determine whether dietary supplementation and certain dietary patterns have an impact on MS-related outcomes [106]. However, a promising effect of diet on improving QOL domains was observed in these studies. Despite this, high-quality, foodfocused clinical trials exploring dietary interventions as a self-management strategy are still warranted.
The reported effect of physical activity on outcome measures was largely inconsistent across 21 studies. In total, 50% (n = 9/18) of studies reported a significant improvement in QOL, and only 38% (n = 3/8) of studies