Effective Rehabilitation Interventions for Multiple Sclerosis (PDF)

Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Available online at ScienceDirect www.sciencedirect....

Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Available online at ScienceDirect www.sciencedirect.com Review Effective rehabilitation interventions and participation among people with multiple sclerosis: An overview of reviews Anne-Mette Hedeager Momsen a,*, Lisbeth Ørtenblad a, Thomas Maribo a,b a DEFACTUM - Social & Health Services and Labour Market, Corporate Quality, Central Denmark Region, Aarhus, Denmark b Department of Public Health, Aarhus University, Aarhus, Denmark A R T I C L E I N F O A B S T R A C T Article history: Multiple sclerosis (MS) is the most common cause of non-traumatic disability in people aged 10–65 Received 14 September 2020 years. Evidence exists for the effectiveness of multidisciplinary rehabilitation and exercise. However, the Accepted 20 March 2021 effectiveness of other rehabilitation approaches in MS needs further evaluation. The purposes were to systematically synthesise and evaluate knowledge on effectiveness of rehabilitation interventions and Keywords: determinants for participation among persons with MS (pwMS) to inform clinical guidelines on Multiple sclerosis rehabilitation. Joanna Briggs Institute methodology was used. PubMed, Embase, CINAHL, PsycINFO and Rehabilitation Web of Science were searched for reviews, systematic reviews, meta-analyses, and meta-syntheses Functioning Activity published 2009–2019. All types of rehabilitation interventions provided to pwMS at any time and in all Participation settings were eligible. Two reviewers independently screened and extracted data. The most recently Quality of life published reviews on mixed and specific modalities were included. The findings were reported in a narrative summary and a mixed-method analysis. Among 108 eligible reviews, 6 qualitative or mixed- method reviews and 66 quantitative were included (total pwMS > 90,000). This overview provides solid evidence for effectiveness of a spectrum of modalities. Among the modalities, there was strong evidence for the effectiveness of multidisciplinary, cognitive and exercise approaches, physiotherapy, and occupational therapy including full body training on functioning and participation outcomes. Employment significantly influenced quality of life; thus, vocational rehabilitation should be initiated early. The healthcare professionals should identify personal factors including relations and coping, and the rehabilitation process should involve partners or close family. The mixed-method analysis revealed insufficient consensus between the perspectives of pwMS on their rehabilitation and reported effects indicating that further research should target the experiences of pwMS. Further, results showed that rehabilitation should be patient-centred, focus on the complexity of needs, and be organised and performed by an experienced multidisciplinary team. Evidence-based rehabilitation should be initiated early after pwMS are diagnosed and follow international guidelines. Database registration: PROSPERO ID: CRD42020152422. C 2021 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction commonly MS begins with acute or subacute onset of neurologic symptoms, which vary in expression and severity over the course. Multiple Sclerosis (MS) is a leading cause of non-traumatic Advanced disease-modifying therapies may decrease and progres- neurologic disability with a 10% increase in the age-standardized sion and alleviate symptoms. Recent guidelines focus on disease- prevalence since 1990, significantly higher among women , with modifying pharmacological treatment , primarily aimed at important variability among persons with MS (pwMS) in terms of reducing relapse rates. Due to the complexity of MS, implications for the person’s life. MS is classified into: benign, multidisciplinary rehabilitation is an essential part of treatment, relapsing-remitting (the most common variant), progressive- and comprehensive rehabilitation interventions are needed to relapsing, primary progressive and secondary progressive. Most improve functioning, activity and participation in pwMS. The aims of rehabilitation are to achieve the highest possible independence and the best quality of life (QoL). The International Classification of * Corresponding author. DEFACTUM, P.P. Oerums Gade 11, 1B, 8000 Aarhus C, Functioning, Disability and Health (ICF) endorsed by the WHO is a Denmark. E-mail address: [email protected] (A.-M. Hedeager). worldwide accepted model providing a universal language for the https://doi.org/10.1016/j.rehab.2021.101529 1877-0657/ C 2021 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 description of functioning and disability [5,6]. The ICF offers a disagreements were solved by consensus. The full text of reviews conceptual framework where the health condition (here MS) might was screened that at least one of two reviewers deemed potentially affect functioning at the mutually interacting domains of body eligible; disagreement was resolved by third reviewer. The functions/structures (BF), activities and participation (D)., Reha- selection process was recorded in a flow diagram. Data were bilitation of pwMS should target and be tailored to disease phase extracted by one reviewer, and accuracy was checked by a second and these ICF domains in closely interaction with contextual reviewer. An initial form was piloted to ascertain extraction within factors, including environmental (E) and personal factors (P) the reviewers. Quality assessment rating and level of evidence. Rehabilitation interventions within the physiological domain were extracted as reported. (neuroplasticity and neuromodulation) and the neurorehabilita- tion domain (e.g. physiotherapy) have been shown to be beneficial 2.4. Analysis in improving functioning and QoL despite progression of MS. Several systematic reviews report on evidence of rehabilitation If there was more than one eligible review on the same in general [9,10] as well as on specific modalities, e.g. exercise , modality, data from the latest published review were extracted. cognitive intervention and fatigue management. Howev- Effectiveness was reported according to acknowledged hierarchy er, implementation of evidence-based rehabilitation varies in of evidence level: execution. Being considered as an important health strategy for the 21st century rehabilitation has to be documented. Thus,  overviews; an overview on rehabilitation for pwMS that includes qualitative as  Cochrane reviews (CRs); well as quantitative systematic reviews was decided upon. The  meta-analysis; objectives were to systematically synthesise and evaluate evidence  systematic reviews. on effectiveness of and determinants for participation in rehabili- tation for pwMS to inform clinical guidelines on rehabilitation. The modalities were presented with priority given to complex- ity, e.g. telerehabilitation followed by less complex modalities (e.g. yoga). The evidence levels are presented on outcomes at the ICF 2. Material and methods domains regarding functioning: BF and D. Furthermore, a mixed-method synthesis was conducted, Joanna Briggs Institute (JBI) methodology was followed allowing integration of quantitative estimates of effects with [16,17]. An a priori protocol was registered in the PROSPERO. perceptions of pwMS. Themes from the qualitative reviews were combined with estimates from the quantitative reviews 2.1. Searching covering the same topics to analyse whether the compilation showed a match: interventions addressed the theme and were An initial search was conducted in the Cochrane Library, JBI effective; a mismatch: the addressed theme was associated Database of Systematic Reviews, PubMed, Epistomonikos and with ineffective interventions; or a gap: interventions did not PROSPERO. PubMed, Embase, CINAHL, PsycINFO and Web of address the theme. The synthesis could explain why the Science were searched for reviews, systematic reviews, meta- interventions may be effective/ineffective and thus clarify analyses and meta-syntheses published in English from 2009 to recommendations [19,20]. The quantitative reviews were 2019. The PubMed search strategy was refined with assistance restricted to CRs, taking the high level of evidence as an inclusion from a research librarian. Predefined search filters or specific criterion. keywords were applied in the databases without predefined filters (Appendix 1. Search history). 3. Results 2.2. Inclusion criteria The search resulted in 977 reviews (Fig. 1), and screening left Peer-reviewed, quantitative, qualitative or mixed-methods 143 articles for full text assessment for eligibility. Most common systematic reviews reporting effects of interventions and/or were reviews on exercise therapy and cognitive interventions determinants for participation in rehabilitation and everyday life , including cognitive behavioural therapy (CBT). Six qualitative were eligible. Syntheses of existing evidence using internationally or mixed-method reviews met the inclusion criteria [22–27], and accepted methodologies were included. Excluded were reviews 66 quantitative reviews were included: three overviews on mixed involving coexisting neurological diseases or incorporating theo- interventions [9,10,28] and nine CRs [11,29–36]. For excluded retical studies or opinion as a source of evidence. reviews with reasons, see Appendix 2. PwMS > 18 years were included regardless of MS type, phase, The number of participants ranged from N = 36 to N = 22,864 duration and disability. All rehabilitation approaches were eligible. , in total around 90,005 pwMS; seven reviews did not report Intervention was defined as any initiative to rehabilitate pwMS of number [9,10,27,38–41]. Only two reviews were authored by non- any type, duration, intensity or time after diagnosis and in all Western world researchers [21,42]. settings. Eligible were any organisation and type of professional in Characteristics of the reviews are described in detail in healthcare and vocational services. Appendixes 3 and 4. Synthesis of the evidence of effectiveness The primary outcome was evidence of effectiveness reported for mixed rehabilitation followed by specific modalities are with clinical or patient-reported outcomes, e.g. BF, symptoms, presented in Table 1. functioning, D including QoL. In qualitative reviews, outcomes Synthesis and evidence on determinants (facilitators, barriers were determinants for participation in rehabilitation and everyday and motivational factors) for participation in rehabilitation and life. everyday life are presented in Table 2. The qualitative reviews concerned impact on participation regarding exercise and physical 2.3. Data extraction activity [22,25,43], cognitive rehabilitation [24,26] and vocational rehabilitation. The search results were merged into the platform, Covidence C. Five qualitative reviews and three CRs [11,30,31] were eligible Two reviewers independently screened titles and abstracts; for mixed-method synthesis (Table 3). 2 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Fig. 1. Flow diagram. 3.1. Quality assessment physiotherapy (including robot-assisted gait training, virtual reality training, electrical stimulation, respiratory training), The most frequently used methods were the Cochrane whole-body vibration, aquatic therapy, hippo therapy, Pilates, Collaboration Risk of Bias Tool, Critical Appraisal Skills Programme Tai Chi, yoga, dietary and educational programs, and vocational and Physiotherapy Evidence Database scale (Table 3). Eight rehabilitation. quantitative reviews and two qualitative reviews [22,27] reported no tools. Most reviews applied the PRISMA checklist , meta- 3.4. Mixed rehabilitation interventions analysis of observational studies (MOOSE) , strengthening the reporting of observational studies in epidemiology (STROBE) Two overviews found moderate-quality evidence for multidis- or Cochrane guidelines. Twenty-four reviews reported no ciplinary rehabilitation regarding body, activity and participation guidelines (Appendixes 3 and 4). outcomes [9,28]. The evidence was strong for fatigue. Exercise, physiotherapy, psychotherapy and educational rehabilitation 3.2. Evidence on effectiveness and qualitative findings showed significant effect on fatigue, whereas the evidence for medications was weak. Younger, less severely disabled pwMS Outcomes measured, duration, follow-up time and estimates experienced benefit, whereas the effect was unknown in older regarding effectiveness varied greatly; meta-analyses were not pwMS with severe disability and progressive MS. Rehabilita- performed. Synthesis of results, level of evidence and recommen- tion should include a spectrum from exercise to education and dations are presented in Tables 1 and 2 and in the following medication. sections. Multidisciplinary rehabilitation, including physiotherapy and exercise modalities (respiratory training) were effective regarding 3.3. Interventions expiratory lung volume , balance, and gait. Outpatient exercise followed by home-based training may be efficient for improved Two overviews and three CRs reported on mixed modalities, e.g. functioning, although long-term (> 12 weeks) effects were exercise, fatigue management and dietary intervention ; two unknown. Two CRs found low-level evidence for effectiveness overviews reported on exercise and occupational therapy of exercise, electrical stimulation, whole-body vibration and. The majority of reviews reported on specific modalities: psychotherapy on pain and spasticity [32,33]. telerehabilitation, cognitive interventions, fatigue management, For CBT and education programs, the evidence was moderate exercise therapy, physical activity, occupational therapy, regarding depression. An overview including CBT, mindfulness, 3 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Table 1 Summary of findings of quantitative systematic reviews. Author; year; country; Outcomes; Intervention/modality Evidence level type of review ICF domains: BF = body functions, D = activity and participation Mixed rehabilitation interventions Amatya; 2019; Australia; Cochrane D: ADL, function, QoL Physical activity, exercise Strong evidence overview Other modalities Limited evidence Khan; 2017; Australia; Overview BF: Fatigue Exercise-based educational, Cognitive Strong evidence D: Different outcomes behavioural therapy Strong evidence D: Different outcomes Physiotherapy Moderate evidence BF: Depression Multidisciplinary rehabilitation Moderate evidence Improved patient knowledge Cognitive behavioural therapy Moderate evidence BF: Fatigue, spasticity Information-provision interventions Limited evidence Psychological. Symptom management programs Haselkorn; 2015; USA; Overview BF: Balance, gait. D: Disability Outpatient physiotherapy Moderate evidence (ambulatory BF: Upper extremity dexterity Outpatient physiotherapy pwMS). BF: Balance, function, respiration. D: Exercise No evidence Disability Moderate evidence BF: Balance Balance training Low evidence BF: Respiration. D: Gait Breathing-enhanced upper extremity Low evidence BF: Function gait exercises Unclear evidence Multidisciplinary rehabilitation Amatya; 2018; Australia; Cochrane BF: Pain, fatigue, psychological symptoms, Mixed rehabilitation intervention Low evidence review spasm (TENS, Tai Chi, tDCS, tRNS, telephone- delivered self-management program, EEG biofeedback) Sosnoff; 2015; USA; Systematic review BF: Falling, balance Different interventions exercise-based, Low evidence device-based and pharmaceutical agent–based interventions Amatya; 2013; Australia; Cochrane BF: Spasticity Physical activity used in combined with Low evidence review BF: Spasticity magnetic stimulation with/without No evidence for use exercise TENS, sports climbing and vibration therapy Telerehabilitation (eHealth) Khan; 2015; Australia; Cochrane BF: Backspace fatigue. D: functional Multifaceted, often psychotherapeutic Low-evidence review activities, quality of life approaches Dennett; 2018; UK; Systematic review D: Increased physical activity Web-based exercise programs and Strong evidence (ambulant pwMS) promotion of physical activity No evidence (not ambulant pwMS) Rintala; 2018; Belgium; Systematic D: Increased physical activity Technology-based distance physical Strong evidence review rehabilitation interventions Proctor; 2018; UK; Systematic review BF: Depression, fatigue, MS symptoms, D: Telephone psychotherapy Varying evidence physical activity, QoL Amatya; 2015; Australia; Systematic BF: MS symptom e.g. fatigue. D: Functional Telecommunications technology to Low evidence review activities, QoL provide therapy at a distance Cognitive and psychological interventions das Nair; 2016; UK; Cochrane review BF: Memory. D: ADL, QoL Memory rehabilitation Moderate evidence Rosti-Otajarvi; 2014; Cochrane review BF: Memory, attention Cognitive training combined with other Low evidence neuropsychological rehabilitation. Lampit; 2019; Australia; Systematic BF: Cognition, attention, memory Computerized cognitive training Moderate evidence review Dardiotis; 2018; Greece; Systematic BF: Cognition, memory Computer-based cognitive training Moderate evidence review Phyo; 2018; Australia; Systematic BF: Fatigue Cognitive behavioural therapy, Moderate evidence review relaxation, mindfulness. Chalah; 2018; France; Systematic BF: Fatigue Cognitive behavioural therapy Low evidence review Goverover; 2018; USA; Systematic BF: Attention, memory, cognition. D: Cognitive behavioural therapy Moderate evidence review Learning Taylor; 2019; Australia; Systematic BF: Stress, depression, anxiety Stress management interventions Moderate evidence review incorporating elements of mindfulness and/or psycho-education. Group-based interventions produced some of the most promising results Sesel; 2018; Australia; Systematic BF: Depressive symptoms, anxiety, fatigue. Psychological interventions Low evidence review D: QoL Kidd; 2017; UK; Systematic review BF: Depressive symptoms, anxiety. D: QoL Self-management interventions. Moderate evidence Mind-body interventions Simpson; 2014; UK; Systematic review BF: Mental health. D: QOL Mindfulness based interventions Low evidence Senders; 2012; USA; Systematic review BF: Depression, anxiety, fatigue, bladder Mindfulness, yoga, biofeedback, Low evidence incontinence, balance, pain. D: QoL relaxation 4 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Table 1 (Continued ) Author; year; country; Outcomes; Intervention/modality Evidence level type of review ICF domains: BF = body functions, D = activity and participation Fatigue management Khan; 2014; Australia; Overview BF: Fatigue Endurance and resistance-training, Varying evidence BF: Fatigue, symptoms, function. D: QoL Aquatic exercise Low evidence BF: Fatigue Mindfulness Low evidence BF: Fatigue. D: QoL Energy conservation Moderate evidence Cognitive behavioural therapy Asano; 2014; Canada; Systematic BF: Fatigue Exercise Moderate evidence review Exercise therapy Safari; 2017 UK; Overview BF: Fatigue Exercise. No clear insight regarding the Low evidence effectiveness of specific types or modes of exercise Heine; 2015; Netherlands; Cochrane BF: Fatigue Endurance training, mixed training, and Moderate evidence review ‘other’ training Demaneuf; 2019; Australia; Systematic BF: Pain Exercise interventions Moderate evidence review Ewanschuk; 2018; Canada; Scoping BF: Obesity, hyperlipidemia, arterial Exercise training Moderate evidence review function, hypertension, and diabetes Manca; Italy; 2019; Systematic review BF: Muscle strength, walking speed, Resistance training Moderate evidence walking distance. Campbell; 2018; UK; Systematic review D: Fitness High intensity interval training Strong evidence (pwMS and low levels of disability) No evidence (pwMS and higher level of disability) Jorgensen; 2017; Denmark; Systematic BF: Muscle function Progressive resistance training Strong evidence review Venasse; 2018; Canada; Systematic BF: Cardiorespiratory fitness Aerobic exercise- Low evidence (persons with review BF: Psychological distress, depression, Mindfulness training progressive MS) anxiety, pain Moderate evidence (persons with D: QoL Dietary modification progressive MS) Inadequate evidence Kuspinar; 2012; Canada; Systematic D: QoL Psychological interventions to improve High quality evidence review D: QoL mood Moderate evidence D: QoL Exercise Moderate evidence Cognitive training Physical activity Coulter; 2018; UK; Systematic review D: Physical activity. Exercise prescription, behaviour Moderate evidence (pwMS mild- change interventions, combined moderate disability) exercise, and behaviour change techniques, education Sangelaji; 2016; New Zealand; Behaviour change interventions can Moderate evidence Systematic review increase physical activity participation Charron; 2018; Canada; Systematic BF: Muscle strength, muscle endurance. D: Resistance exercise Moderate evidence review physical activity. Combined resistance-and endurance Moderate evidence BF: Mobility, balance, coordination D: exercise Moderate evidence Physical activity. Endurance training D: Physical activity, Walking Casey; 2018; Ireland; Systematic D: Physical activity Behavioural interventions Low evidence review Occupational therapy Angela; 2019; Italy; Overview BF: Fatigue Fatigue management programs Moderate evidence BF: Fatigue Occupational therapy strategies Low evidence including telerehabilitation Yu; 2014; USA; Systematic review BF: Depression, self-efficacy Cognitive behavioural therapy-based Moderate evidence BF: Endurance, muscle strength, walking intervention Strong evidence Exercise interventions Physiotherapy Etoom; 2018; Jordan; Systematic BF: Spasticity, muscle tone Exercise, especially robot gait training Strong evidence (nonambulatory review and outpatient exercise programs pwMS Campbell; 2016; UK; Systematic review Different outcomes Physiotherapy, e.g. exercise therapy, Moderate evidence (progressive multidisciplinary rehabilitation, MS) functional electrical stimulation, botulinum toxin injections and manual stretches, inspiratory muscle training, therapeutic standing, acupuncture, and treadmill training Paltamaa; 2012; Finland; Systematic D: Changing and maintaining body position Physiotherapy based on an Moderate evidence (ambulatory review individualized problem-solving pwMS) approach, and resistance and aerobic exercises on improving balance 5 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Table 1 (Continued ) Author; year; country; Outcomes; Intervention/modality Evidence level type of review ICF domains: BF = body functions, D = activity and participation Block; 2015; USA; Systematic review BF: Incontinence Physiotherapy, e.g. pelvic floor muscle Moderate evidence D: QoL training, neuromuscular electrical stimulation, pelvic floor muscle advice Robot-assisted gait training Sattelmayer; 2019; Schwitzerland; D: Walking Robot-assisted gait training No evidence for robot-assisted gait Systematic review training Xie; 2017; China; Systematic review D: Walking distance Robot-assisted gait training Low evidence, no clinically significance Swinnen; 2012; Belgium; Systematic D: Gait speed, Gait endurance Treadmill training with body weight Low evidence review support or robot assistance Virtual reality training Casuso-Holgado; 2018 Spain; BF: Balance Virtual reality balance training Low evidence Systematic review D: Walking Virtual reality balance training Inconclusive results Massetti; 2016; Brazil; Systematic BF: Balance. D: Gait, arm movement Virtual reality-based balance training Low evidence review Maggio; 2019; Italy; Systematic review BF: Balance, cognitive function. D: Gait Virtual reality training Moderate evidence Electrical stimulation Miller; 2018; UK; Systematic review D: Walking speed Functional electrical stimulation used Strong evidence for foot drop Sawant; 2015; Canada; Systematic BF: Pain Transcutaneous electrical Strong evidence review nervestimulation Respiratory training Rietberg; Netherlands; 2017; Cochrane BF: Respiration Resistive inspiratory muscle training Low evidence (mild to moderate review MS) Levy; 2018; France; Systematic review BF: Respiration Respiratory muscle training Low evidence Whole-body vibration, aquatic therapy, Pilates, Tai Chi, yoga, hippo-therapy Kantele; 2015; Finland; Systematic D: Walking endurance Whole body vibration training Low evidence (pwMS with low review disability) No evidence (pwMS severely disabled) Corvillo; 2017; Spain; Systematic BF: Balance, mobility, strength, fatigue, Aquatic Tai Chi Varying evidence review BF: Muscle strength, cardiorespiratory Aerobic aquatic ex High evidence fitness depression, fatigue Aquatic cycling Low evidence BF: anti-inflammatory impact, muscle Aquatic ex/cycling. No differences Low evidence strength between Pilates and aquatic training BF: Blood circulation, body temperature. D: QoL, gait Bronson; 2010; New Zealand; BF: Balance Hippo therapy Limited data Systematic review D: QoL Sánchez-Lastra; 2019; Spain; BF: Fatigue, cardiorespiratory fitness Pilates No evidence for Pilates Systematic review D: Mobility, QoL Taylor; 2017; USA; Systematic review BF: Balance, flexibility, fatigue, depression. Tai Chi Low evidence D: Gait, QoL Nutritional and dietary supplements Pommerich; 2018; Denmark; BF: Fatigue Different diet interventions Low evidence Systematic review Information provision, Education Kopke; 2014; Germany; D: Decision making, QoL Information provision Limited data Cochrane review Wendebourg; 2017; Germany; BF: Fatigue Patient education programs Moderate evidence Systematic review D: Depression No evidence Vocational rehabilitation Khan; 2009; Australia; Cochrane D: Competitive employment, workability Vocational rehabilitation programs Inconclusive evidence review D: Supported employment/disability No evidence pensions Sweetland; 2012; UK; Systematic Multiple outcomes Vocational rehabilitation approaches Evidence gives clear indicators as to review what the barriers to working with MS are, and what is required for vocational rehabilitation service Dorstyn; 2019; Australia; Systematic BF: Mood. D: QoL Employment Strong evidence review ADL: activities of daily living; NS: no significant; MS: multiple sclerosis; pwMS: people with MS; QoL: quality of life; TENS: Transcutaneous Electrical Nerve Stimulation; tDCS: transcranial direct stimulation; tRNS: transcranial random noise stimulation; EEG: electroencephalogram. 6 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Table 2 Summary of findings of qualitative and mixed-method systematic reviews. Author; year; country; type of Synthesis of results Evidence of effectiveness; recommendations review Cognitive and psychological interventions Jones; 2017; UK; Mixed D: 28 studies were classified as good quality and methods Five key patterns of relating oneself to others were identified: 10 studies as medium quality 1) Overprotective-Controlled Reciprocal Role Positive experiences and potentials to improve mental 2) Intrusive-Intruded Reciprocal Role health by interventions using cognitive therapy that 3) Ignoring-Neglecting Reciprocal Role involve families and support couples and families to 4) Rejecting-Rejected Reciprocal Role reduce unhelpful patterns and improve coping in order 5) Accepting-Supportive Reciprocal Role. to move towards relating in an accepting-supporting A diagrammatic formulation is proposed that interconnects these way patterns with well-being and suggests potential exits to improve mental health, for example, assisting families to minimize overprotection Klein; 2019; UK; Qualitative BF; D: Quality assessment was performed but the quality was meta-synthesis, Thematic Six analytical themes that encompassed the findings of included studies not reported synthesis were identified: The patients reported that participating in cognitive 1) Importance of group environment rehabilitation improved cognitive functioning and 2) Increased reflection and awareness overall they experienced positive impact on their QoL 3) Improved knowledge and understanding 4) Improved strategy use 5) Positive impact on quality of life 6) Suggested improvements. Cognitive rehabilitation facilitated the participants’ reflection and awareness of their cognitive deficits, and was associated with increased knowledge and understanding of their illness. Increased strategy use was associated with improvements in cognitive functioning and greater confidence and perseverance. Participants reported emotional and social improvements, and felt more optimistic. Exercise/physical activity Christensen; 2016; Denmark; BF: Quality assessment was performed but overall Qualitative meta-synthesis Factors identified as influencing intention to exercise and the execution classification not reported of exercise were: social support, professional support and outcome Health professionals can influence the intention and the expectations. The study identified a strong relationship between these execution of exercise when there exists a personal and themes and the intention and/or the execution of exercise supportive pt.–prof. relationship Health professionals influence the part of the process where PwMS Outcome expectations impact motivation and play an enter the exercise setting, as well as the PwMS’s intention to exercise important role regarding intention to exercise and execution of exercise. Learmonth; 2016; USA; BF: 3 studies were reported of low quality and 16 studies Qualitative review Common barriers and facilitators to participation in PA and beneficial moderate/high quality consequences and adverse effect in participation were identified. Both barriers and facilitators were related to environmental and personal PA behaviour is subject to a number of modifiable factors. Beneficial consequences of PA were mainly improved physical determinants. Healthcare professionals working to functions and increased social participation while adverse promote PA should choose to endorse the positive consequences mainly were increased fatigue benefits of participation. Future PA interventions may be improved by incorporating behavioural management strategies Ploughman; 2017; UK; Mixed BF: The barriers categorized into 5 domains from greatest to least Quality assessment was not reported. methods frequently predictive: Physical therapists, other health team members, and 1) MS-related impairment and disability volunteers are more likely to be successful in breaking 2) Attitude and outlook the barriers to physical activity in MS by working 3) Fatigue together. Barriers can be addressed concurrently by 4) Knowledge/perceived benefits of exercise employing tailored and combined approaches using 5) Logistical factors: finances, support, accessibility education, motivational interviewing, exercise practice Approaches to break down barriers as behavioural modification, peer and problem-solving support, use of technology, adapted community exercise improves PA participation It requires the physical therapists to extend their role beyond the patient–provider relationship to become coach, educator, and community liaison Vocational rehabilitation Sweetland; 2012; UK; Mixed D: Quality assessment was performed methods Factors leading to unemployment were identified using ICF headings: Further, research is needed to identify the efficacy of Disease related factors (course, impairment, activity limitations). Work different models of VR, and their cost-effectiveness. place factors (lack of information, poor support, inflexible employment Particularly research for identifying and measuring the structures) effectiveness of interventions that support work Factors facilitating employment: Personal factors (education level, age, retention psychical adjustment to diagnosis, self-reported readiness and belief about ability to work) Early interventions; personal services; liaison with employers to ensure work-place accommodation; support (e.g. from VR specialists) ICF: International Classification of Functioning; Disability and Health; MS: multiple sclerosis; PA: physical activity; prof: professional; pt: patient; pwMS: people with MS; VR: vocational rehabilitation 7 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Table 3 Mixed-methods analysis. Qualitative reviews Quantitative reviews (Cochrane reviews) Themes (in the qualitative studies) Extent to which addressed in the Mismatch, match, gaps Recommendation (research, intervention interventions) Cognitive rehabilitation Group environment: being grouped with 6 studies addressed learning: 4 report Gaps Group environment may be an people in the same situation and sharing/ no significant differences and 2 report important factor in supporting and learning from each other is an important improvements for the treatment group. understanding positive effects of aspect of the experienced benefits (among The importance of the group cognitive rehabilitation other things learning) environment is not mentioned or unclear CR allowed reflecting about cognitive deficits as Studies addressed this issue by focusing Mismatch Measuring possibilities for reflection as part of MS and cognitive problems in various on effect on subjective memory tests. part of cognitive rehabilitation may situations Insufficient or no evidence to support support positive effects this CR improved knowledge and understanding of Interventions address memory function Mismatch Out-come measures may be too specific mechanisms behind memory, attention and/ but there is unclear evidence of effect: Gaps or narrow to encompass pwMS’s or executive functions studies reporting positive outcome are experiences judged risk of bias and well-designed studies report no or negative effect Some studies show effect on subcategories as memory span and working memory Cognitive training combined with other neuropsychological methods showed effect on attention and verbal and visual memory Better knowledge and use of strategies to 1 review addressed use of memory Match A broader focus than memory to assess handle cognitive deficits; strengthened strategies, reporting positive effect. No Gaps the effectiveness. Transferability to ability to transfer the use of strategies to new interventions addressed other new situations should be included situations strategies or transferability of strategies Improved QoL, cognitive functioning (memory), Positive effect on Qol scores, but not Match (partly) Low-level evidence for positive effect confidence, emotional and social maintained on long-term follow-up Mismatch on cognitive rehabilitation. improvements, better perseverance Heterogeneous outcome No effect on QoL, everyday cognitive measurements and interventions– functioning, mood, fatigue, personality, single studies might prove differently anxiety. However, some positive results were found if results were individually evaluated Cognitive therapy showed how key patterns of No interventions addressed cognitive Gaps Focus on balanced roles and relations reciprocal roles determine relations between therapy in relation to roles, relations are important in providing cognitive one self and others and were interconnected and well-being/mental health rehabilitation with well-being: Strategies to find a healthy balance may improve mental health Exercise therapy Exercise maintained and improved physical Interventions address fatigue; a Match (fatigue) It is relevant to address other factors functioning; improve MS symptoms; better significant effect is found in favour of Gap than fatigue in future studies on sleep; reducing fatigue and support feeling of exercise therapy. The overall quality of (rest of the mentioned benefits/effects of exercise therapy healthy tiredness; improve general well- studies was moderate and the content themes) being and quality of life [22,25] of exercise therapy was heterogeneous Some experience that exercise may worsen MS symptoms Barriers and incentives: No interventions addressed barriers or Gap It is important to include behavioural Support from family, friends, peers and co- incentives and personal components in future workers increase exercise participation and studies on benefits/effects of exercise persistence with exercise and exercise increase therapy participation in social activities [22,23,25] Self-monitoring tools and activity diaries support exercise activities Social activities may be barriers to participating in exercise: family crisis monopolize time and energy, lack of understanding from family and friends, stressful events Personal factors may be barriers: health condition, especially fatigue , cognitive and behavioural factors, lack of knowledge Knowledge and information: Poor advice from No interventions addressed the Gaps It is important to be aware of proper health professionals is a barrier. importance of knowledge and information when reducing barriers to Conflicting beliefs about the benefits of exercise information participate in exercise therapy due to information received is a barrier Participating in exercise may lead to frustration No interventions addressed this theme Gap It is important to be aware of this issue due to lost control compared to previous in supporting maintenance in exercise capabilities [22,25] participation 8 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 Table 3 (Continued ) Qualitative reviews Quantitative reviews (Cochrane reviews) Themes (in the qualitative studies) Extent to which addressed in the Mismatch, match, gaps Recommendation (research, intervention interventions) Logistic factors (finance; transport and parking; No interventions addressed the Gaps Logistic factors are important for childcare) and environmental factors importance of logistic factors possibilities in participating in exercise (accessibility; no disabled facilities; therapy inappropriate temperature) are barriers for participation Logistic factors should be addressed individually [22,23,25] Staff attitude are important for participation: No interventions addressed the Gap It is important to be aware of proper Positive professional support consisting of importance of staff attitude staff attitude in supporting personal relation, individual approach and participation in exercise therapy. professional supervision encourage safety and participation [22,23] Feeling safe (qualified instructors, safe Exercise therapy was shown to be safe Match Assurance of a high degree of safeness is environments, flexibility to choose preferred estimated by relapse and fall: no important for participation mode) increase participation associated with relapse of MS or fall was found. The overall quality of studies was moderate and the content of exercise therapy was heterogeneous MS: multiple sclerosis; pwMS: people with multiple sclerosis. Mismatch: factors are associated with ineffective interventions; Match: intervention match recommendations from qualitative studies; Gaps: no association with effective or ineffective intervention. training, aqua therapy, Tai Chi, electrical stimulation, and found for the effect of self-management programmes, e.g. CBT, medications concluded that CBT is clinically relevant and cost motivational interviewing or telephone advising, on depression effective. The evidence on exercise was strong regarding and anxiety. endurance and strength, whereas moderate regarding fatigue and PwMS’ perspectives showed that group-based CBT had effect on QoL. Prevention of fall interventions primarily exercise-based, mental health and QoL. PwMS experienced that CBT facilitated showed reduction on pwMS falling; however, studies were of low reflections, increased understanding of deficits and use of methodological quality. strategies to improve cognitive functioning, thus provided greater confidence. Five central patterns associated with mental well- 3.5. Telerehabilitation and CBT being were identified that determined the relation between pwMS and their families. To minimise overprotection, it was important Mixed interventions and technologies showed low quality that relatives were involved, relating to pwMS in an accepting, evidence regarding symptoms and functioning. Two meta- supporting way. analyses found a positive effect on physical activity level among pwMS retaining gait function [51,52]. 3.6. Exercise and physical activity Telephone-based psychotherapy showed moderate effect on fatigue, depression, physical activity level, QoL, and medication Regarding fatigue three overviews on mixed interventions compliance. However, telerehabilitation may best be provided in showed strong evidence for the effectiveness of exercise modalities connection with conventional physiotherapy , and both pwMS’ [9,10,28], whereas an overview showed moderate effect. Ex- and relatives’ perspectives on its use should be included. ercise was safe and effective regarding fatigue. Furthermore, Computer-based CBT programs or training with internal/ an effect was found on pain; however, more high quality studies external memory aids showed effect on memory functions and are needed. QoL, the latter only at short-term follow-up. There was Meta-analyses confirmed that resistance exercise was effective evidence regarding memory span, delayed and immediate verbal regarding strength, walking distance and pace ; progressive memory, but not on emotional functions. Furthermore, there resistance exercise increased muscle function. Exercise and was evidence regarding specific cognitive domains (memory, yoga showed effect regarding physical function and fitness. A selective reminding test, attention), but not for executive speed minimum of 12 weeks was needed, and high intensity exercise domain [55,56]. The effect disappeared without training, and was may be most effective to reduce risk factors [67,68]. For persons uncertain among persons with progressive MS. Computer- with progressive MS, exercise and wellness therapies showed an based approaches were more efficient than traditional CBT, less effect on pain, anxiety, depression, stress, fitness, and QoL work intensive, involved less face-to-face training and thus cost. Complimentary interventions had higher effect on QoL, and less. CBT combined with exercise or pharmacological intervention also Stress-management, especially group-based mindfulness, was showed effect. effective in relieving stress, depression, and anxiety. Mind- Supervised combined resistance training and aerobic exercise fullnes-based Stress Reduction (MBSR) was effective on anxiety, were effective regarding mobility, strength, balance and coordina- fatigue, and QoL at up to 6 months’ follow-up [58,59]. CBT, MBSR tion, and effects were maintained after 10 weeks. Lifestyle and relaxation therapy were effective regarding fatigue and mental interventions including exercise showed an effect on physical health [39,60]. CBT should not be the only rehabilitation approach activity level among persons with mild to moderate MS ; and may be combined with non-invasive brain stimulation to findings were confirmed regarding physical activity interventions achieve a long-term effect on fatigue. Some evidence was [72,73]. However, the level of evidence was low. 9 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 PwMS experienced that exercise both reduced and induced supervised standing compared to no training on fatigue, fatigue [22,25]; to solve this paradox energy conserving techniques postural control, fear of falling, gait, psychological effect of and medicinal treatment were suggested. PwMS reported MS, and flow experience. A review also found an effect on several advantages of exercising: improved strength, balance, postural control, balance, gait and arm movements, although physical functioning, and self-care strategies, all of which evidence was limited. Thus, evidence regarding virtual improved their sleeping, feeling of ‘healthy’ tiredness, depression, reality for balance and gait outcomes was of low quality and participation in social activities. However, pwMS experienced. However, the advantages were motivational, and without that they became more aware of reduced functionality due to MS the need for postural control and stabilising, the virtual reality. training was effective for pwMS using a wheelchair or with Barriers for participation in exercise were insufficient disability multiple disabilities. facilities, problems with the temperature, poor health, cognitive challenges, poor advice and lack of support from healthcare 3.11. Electrical stimulation professionals (HCPs). PwMS described the following determinants for participation in Transcutaneous electrical nerve stimulation (TENS) was report- exercise: professional supervision which increased a sense of edly a safe and effective alternative in the management of central safeness, HCPs’ influence, e.g. a personal, supporting and individual pain. Furthermore, an effect was found on gait (walking approach. Furthermore, individual expectations regarding partici- distance and speed) after functional electrical stimulation among pation, and HCPs can strengthen pwMS’ expectations by using self- pwMS with walking impairment. monitoring tools reporting activity. Individually adjusted exercise, family and peer support motivated participation 3.12. Respiratory training [25,43]. PwMS experienced group-based training and family support as conducive for participation; however, they may also Training showed an effect on maximal inspiratory and constitute barriers, e.g. if family problems took up the pwMS’ time expiratory pressure, mainly in pwMS with better functioning and energy.. However, studies and guidelines for respiratory care are needed [36,84]. 3.7. Occupational therapy 3.13. Whole-body vibration, aquatic therapy, Pilates, Tai Chi, yoga, An overview found evidence for the effect of fatigue manage- hippo therapy ment approaches on functioning. Occupational therapy showed low level evidence , whereas on-line or face-to-face inter- There was indication of an effect on endurance after whole- ventions showed a moderate effect on fatigue, and multidisci- body vibration training. Aerobic training in water improved plinary rehabilitation showed an effect on self-efficacy fatigue, depression, endurance, muscle strength, cardiorespiratory. Among modalities (activity of daily life training, comput- fitness, and QoL. Bike training in water improved neurotropic er-based cognitive training, memory and physical training), only factor with an anti-inflammatory impact, and fitness related to physical training showed an effect on endurance, strength and QoL. No difference was found between aerobic training and Pilates gait. Occupational therapy should include full body training. Pilates showed no effect on fatigue, mobility, fitness, and QoL and be combined with goal setting, patient education and home compared to other physical activities. However, Pilates may be exercises. useful for pwMS with a moderate level of functioning. Tai Chi was safe and had positive effects on fatigue, depression, 3.8. Physiotherapy balance, gait, mobility, and QoL. Hatha or Iyengar yoga showed no effect on fatigue and no difference compared to exercise Physiotherapy modalities (gait exercise, ambulatory or robot-. Hippo therapy showed only weak evidence of effectiveness on assisted training) showed an effect on spasticity; however, balance and QoL. heterogeneity and poor descriptions made conclusions difficult. Balance training, strengthening exercise, aerobic, whole-body 3.14. Nutritional and dietary supplements vibration and neuro-therapy showed an effect on balance among persons with mild to moderate MS, but a meta-analysis showed no There was an effect on fatigue after plant-based modified Paleo significant , among persons with progressive MS level of diet, whereas low-fat diet increased fatigue. Diet supple- evidence was low due to small sample sizes and lack of common mented with folate and magnesium reduced fatigue, supporting outcomes with a valid clinical relevance. the theory of biotic mediation of inflammation. Pelvic floor exercise, electric stimulation and biofeedback showed an effect on incontinence and QoL; increased QoL may 3.15. Information provision and education be due to less incontinence, fatigue, or depression. CBT-inspired education showed an effect on fatigue compared 3.9. Robot-assisted gait training to other approaches; individual face-to-face interventions were most efficient. Information programmes were an ethic One review found no effect on walking distance or functioning necessity to increase pwMS’ knowledge on MS, but which method , whereas compared to usual training, there was an effect on to use could not be concluded. endurance. Robot-assisted treadmill training improved walking distance and endurance, although there was no long- 3.16. Vocational rehabilitation term effect. Employment had significant influence on mood and QoL; 3.10. Virtual reality training employed pwMS experienced less work-related and MS-related difficulties than unemployed pwMS and coped better with stress A meta-analysis showed an effect of ‘Nintendo’ home-based. Regarding return to work evidence was insufficient; balance training, supervised treadmill and physiotherapist- vocational rehabilitation should be initiated early and include 10 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 practical solutions for work adjustments and education of diagnosis of MS and moderate disease activity. Exercise and managers. There was strong evidence for risk factors for face-to-face cognitive-inspired educational programmes were unemployment among pwMS in all the ICF domains. Thus, more effective in ameliorating fatigue than commonly prescribed vocational rehabilitation should identify barriers and minimise the medications. effect of MS symptoms, thereby maintain pwMS at work for a Cognitive rehabilitation was safe; MBSR programmes reduced longer time. The complexity of needs and focus on personal stress, depression and anxiety. Cognitive impairments were a factors should be taken into account by HCPs. critical factor for functioning, especially regarding pwMS’s working status. Computer-based interventions (e.g. telere- 3.17. Mixed-methods synthesis habilitation) could be a supplement because they are more effective and convenient and require less face-to-face training Evidence of effectiveness supporting or contradicting the than other interventions, and thus reduce the costs of healthcare perspectives of pwMS was assessed by juxtaposing qualitative [41,56]. factors that influenced participating and benefits of cognitive Occupational therapy should be combined with goal setting, rehabilitation and exercise therapy with CRs on the same home assignments, education and discussion forums; e.g. pwMS modalities. A concurrence between themes and findings of the could be recommended to develop strategies for recall of task steps different methods was not found. Thus, regarding cognitive. rehabilitation, the following themes were not addressed or showed PwMS experienced that nutrition, stress, temperature and no effect in intervention studies: the importance of group physical activity affected the severity of symptoms; therefore, environments for the experienced benefits, improving under- rehabilitation should include lifestyle intervention and meet standing of cognitive deficits, ability to transfer strategies handling individual needs. Patient education including diet showed cognitive deficits to new situations, balancing new roles and an effect on fatigue, which may support the inflammation theory relations. Furthermore, several aspects of QoL were addressed in. Furthermore, individual CBT-inspired programmes were CRs but no effect was found. A match was identified regarding use effective compared to other approaches, including use of of memory strategies and on some aspects of QoL (Table 3). medications. Educational programmes increased the pwMS’ Regarding exercise therapy, two matches were identified: disease-related knowledge; there were no negative effects of reducing fatigue was concordant and CRs found exercise safe, informing persons about MS. which was an important issue for pwMS. Several gaps were found because no CRs addressed the following themes: pwMS experienc- 4.2. Strength and weaknesses ing improvements of numerous symptoms; mention of several barriers and incentives to participate, including logistic factors; Rehabilitation may reach out for primary, secondary and attitude of and relation to staff (Table 3). tertiary symptoms. This overview targeted all the ICF domains, from symptomatic management of functioning to psychosocial support and vocational rehabilitation including environmental 4. Discussion factors. Both qualitative and quantitative data were included. Due to a high number of reviews, choices were made to make This overview summarised the best, up-to-date qualitative and the synthesis manageable. Thus, only the most recently published quantitative evidence on rehabilitation for pwMS. Six qualitative reviews on all modalities were presented. The advantage of this reviews and 66 quantitative, five of which were overviews or CRs of selection was the avoidance of excessive numbers and overlap of mixed interventions, were included. Thus, the findings presented the included primary studies. broad evidence on rehabilitation approaches regarding effective- The mixed-method synthesis allowed integrating quantitative ness, determinants for participation, and perspectives on rehabili- effect estimates with qualitative perspectives from pwMS. Only tation among pwMS. CRs were included and other reviews may have revealed more findings and gaps. However, CRs results were based on high-level 4.1. Evidence and recommendations for rehabilitation evidence. It was a limitation that findings were few regarding inter- There is high quality evidence for the effectiveness of ventions for specific MS types or stages. Furthermore, only a few multidisciplinary rehabilitation [9,28,35], physiotherapy [74,76], reviews reported on long-term effectiveness. The level of quality and exercise regarding improved physical functioning [10,11,28], and the evidence for the effect of the interventions were presented and for CBT/MBSR regarding cognitive functioning. Multidisciplin- as reported, but they were not homogeneous, making comparisons ary inpatient rehabilitation significantly improved QoL for pwMS between rehabilitation modalities difficult.. Vocational multidisciplinary rehabilitation should be initiated The reviews were primarily authored by researchers in Western early and consider risk factors for work participation, e.g. fatigue countries, limiting generalisation. However, MS is most prevalent and work accommodation. in North American and European countries. Specific modalities were effective for some pwMS, e.g. cognitive therapy, physiotherapy including exercise, respiratory training, robot-assisted training, electrical stimulation, virtual-reality train- 4.3. Recommendation for rehabilitation professionals ing, Pilates and Tai Chi. Virtual-reality training represented advantageous, alternative methods of exercise and thus provided As MS is chronic and progressive, pwMS’ level of functioning effective training for pwMS using wheelchairs or with multiple varies over time and rehabilitation goals differ. Still, the main goals disabilities. for pwMS are the highest levels of functioning, independence and Furthermore, exercise modalities were safe and advantageous QoL. as primary, secondary and tertiary prevention; exercise should be Effectiveness regarding specific outcomes depended on the individually prescribed and tailored as ‘medication’, because individual pwMS’ level of functioning and participation. A patient- symptoms are usually unaffected by medical treatment. The centred rehabilitation approach and individual goal setting are exercise-postponement theory suggests that long-term moderate- thus needed, and HCPs should identify personal factors including to-high intensity exercise may postpone the onset of clinical those with an impact on coping with MS. Comprehensive 11 A.-M.H. Momsen, L. Ørtenblad and T. Maribo Annals of Physical and Rehabilitation Medicine 65 (2022) 101529 information and advice from HCPs and a personal relationship Acknowledgements and individual approach are important [22,23]. For pwMS at working age rehabilitation may be undertaken by professionals in Helene Sognstrup, research librarian, Aarhus University Library, healthcare and vocational rehabilitation. Home-based reha- assisted the searching process. bilitation after outpatient exercise may improve functioning in all types of MS. However, when participating in physical activity, pwMS may experience awareness of reduced functionality due to MS , and self-monitoring tools may support participation Appendix A. Supplementary data. Cognitive impairments often affect participation; thus, cognitive approaches are needed to empower pwMS , and Supplementary data associated with this article can be found, in HCP could employ telephone psychotherapy to support pwMS the online version, at https://doi.org/10.1016/j.rehab.2021.. Group environment is an important aspect of the benefits 101529.. The findings revealed that involving partners or close family members was of importance, as they experienced the consequen- References ces of MS and may have a voice. However, the type of relation Adelman G, Rane SG, Villa KF. The cost burden of multiple sclerosis in the (from controlling to accepting) with the pwMS’ network was United States: a systematic review of the literature. J Med Econ 2013;16:639– important for their mental health. 47. Logistic factors, like child-care and access to rehabilitation Kobelt G, Thompson A, Berg J, Gannedahl M, Eriksson J. New insights into the burden and costs of multiple sclerosis in Europe. 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