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Table e-1 – Rehabilitation and Exercise Studies in MS Intervention targetInterventionOutcome Study DesignBalance Aerobic training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"cdjvangh4","properties":{"formattedCitation":"{\\rtf \\super 1\\nosupersub{}}","plainCitation":"1"},"citationItems":[{"id":960,"uris":[""],"uri":[""],"itemData":{"id":960,"type":"article-journal","title":"Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis","container-title":"Journal of the Neurological Sciences","page":"11-18","volume":"225","issue":"1-2","source":"PubMed","abstract":"In recent years it has become clear that multiple sclerosis (MS) patients benefit from physical exercise as performed in aerobic training but little is known about the effect on functional domains and physiological factors mediating these effects. We studied immunological, endocrine and neurotrophic factors as well as coordinative function and quality of life during an 8-week aerobic bicycle training in a waitlist control design. In the immune-endocrine study (1) 28 patients were included, the coordinative extension study (2) included 39 patients. Training was performed at 60% VO(2)max after determining individual exertion levels through step-by-step ergometry. Metabolic (lactate), endocrine (cortisol, adrendocortico-releasing hormone, epinephrine, norepinephrine), immune (IL-6, soluble IL-6 receptor), and neurotrophic (brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF)) parameters were compared from a prestudy and a poststudy endurance test at 60% VO(2)max for 30 min. In study (1), lowered lactate levels despite higher workload levels indicated a training effect. Disease-specific quality of life (as measured by the Hamburg Quality of Life Questionnaire for Multiple Sclerosis, HAQUAMS) significantly increased in the training group. No significant training effects were seen for endocrine and immune parameters or neurotrophins. In study (2), two out of three coordinative parameters of the lower extremities were significantly improved. In summary, low-level aerobic training in MS improves not only quality of life but also coordinative function and physical fitness.","DOI":"10.1016/j.jns.2004.06.009","ISSN":"0022-510X","note":"PMID: 15465080","journalAbbreviation":"J. Neurol. Sci.","language":"eng","author":[{"family":"Schulz","given":"Karl-Heinz"},{"family":"Gold","given":"Stefan M."},{"family":"Witte","given":"Jan"},{"family":"Bartsch","given":"Katharina"},{"family":"Lang","given":"Undine E."},{"family":"Hellweg","given":"Rainer"},{"family":"Reer","given":"Rüdiger"},{"family":"Braumann","given":"Klaus-Michael"},{"family":"Heesen","given":"Christoph"}],"issued":{"date-parts":[["2004",10,15]]},"PMID":"15465080"}}],"schema":""} 1 Improving symptoms and QoL Randomized, controlled studyBalanceBalance rehabilitation for motor and sensory strategies ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2l4csclbma","properties":{"formattedCitation":"{\\rtf \\super 2\\nosupersub{}}","plainCitation":"2"},"citationItems":[{"id":964,"uris":[""],"uri":[""],"itemData":{"id":964,"type":"article-journal","title":"Effects of balance exercises on people with multiple sclerosis: a pilot study","container-title":"Clinical Rehabilitation","page":"771-781","volume":"21","issue":"9","source":"PubMed","abstract":"OBJECTIVE: To evaluate the effects of balance retraining in a sample of people with multiple sclerosis.\nDESIGN: Randomized controlled trial.\nSETTING: Rehabilitation unit.\nSUBJECTS: A consecutive sample of 44 subjects was randomized into two experimental groups and one control group. The inclusion criteria were: ability to stand independently more than 30 seconds, ability to walk for 6 m.\nINTERVENTIONS: Group 1 received balance rehabilitation to improve motor and sensory strategies. Group 2 received balance rehabilitation to improve motor strategy. Group 3 received treatments not specifically aimed at improving balance.\nMAIN OUTCOME MEASURE: Berg Balance Scale, Dynamic Gait Index and fall frequency were used to assess balance impairments. Dizziness Handicap Inventory and Activities-specific Balance Confidence were used to assess handicap and the level of balance confidence.\nRESULTS: Frequency of falls post treatment was statistically different among groups (P=0.0001); The Berg Balance Scale showed an overall statistically significant difference (P=0.0008) among groups. Change pre-post scores were 6.7, 4.6 and 0.8 points for groups 1, 2 and 3. Dynamic Gait Index showed an overall near statistically significant difference among groups (P=0.14), with change pre-post scores of 3.85, 1.6 and 1.75 points for groups 1, 2 and 3; after the exclusion of drop-outs a statistically significant difference was observed (P=0.04). The self-administered tests (Activities-specific Balance Confidence and Dizziness Handicap Inventory) did not show clinically relevant improvements.\nCONCLUSIONS: Balance rehabilitation appeared to be a useful tool in reducing the fall rate and improving balance skills in subjects with multiple sclerosis. Exercises in different sensory contexts may have an impact in improving dynamic balance.","DOI":"10.1177/0269215507077602","ISSN":"0269-2155","note":"PMID: 17875557","shortTitle":"Effects of balance exercises on people with multiple sclerosis","journalAbbreviation":"Clin Rehabil","language":"eng","author":[{"family":"Cattaneo","given":"D."},{"family":"Jonsdottir","given":"J."},{"family":"Zocchi","given":"M."},{"family":"Regola","given":"A."}],"issued":{"date-parts":[["2007",9]]},"PMID":"17875557"}}],"schema":""} 2 Reduced fall rate and improved balanceRandomized, controlled trialBalanceBalance exercise program ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1ia2nnf3s9","properties":{"formattedCitation":"{\\rtf \\super 3\\nosupersub{}}","plainCitation":"3"},"citationItems":[{"id":814,"uris":[""],"uri":[""],"itemData":{"id":814,"type":"article-journal","title":"Balance exercise program reduced falls in people with multiple sclerosis: a single-group, pretest-posttest trial","container-title":"Archives of Physical Medicine and Rehabilitation","page":"2428-2434","volume":"95","issue":"12","source":"PubMed","abstract":"OBJECTIVE: To evaluate the effects of a balance exercise program on falls in people with mild to moderate multiple sclerosis (MS).\nDESIGN: Multicenter, single-blinded, single-group, pretest-posttest trial.\nSETTING: Seven rehabilitation units within 5 county councils.\nPARTICIPANTS: Community-dwelling adults with MS (N=32) able to walk 100m but unable to maintain 30-second tandem stance with arms alongside the body.\nINTERVENTION: Seven weeks of twice-weekly, physiotherapist-led 60-minute sessions of group-based balance exercise targeting core stability, dual tasking, and sensory strategies (CoDuSe).\nMAIN OUTCOME MEASURES: Primary outcomes: number of prospectively reported falls and proportion of participants classified as fallers during 7 preintervention weeks, intervention period, and 7 postintervention weeks. Secondary outcomes: balance performance on the Berg Balance Scale, Four Square Step Test, sit-to-stand test, timed Up and Go test (alone and with cognitive component), and Functional Gait Assessment Scale; perceived limitations in walking on the 12-item MS Walking Scale; and balance confidence on the Activities-specific Balance Confidence Scale rated 7 weeks before intervention, directly after intervention, and 7 weeks later.\nRESULTS: Number of falls (166 to 43; P≤.001) and proportion of fallers (17/32 to 10/32; P≤.039) decreased significantly between the preintervention and postintervention periods. Balance performance improved significantly. No significant differences were detected for perceived limitations in walking, balance confidence, the timed Up and Go test, or sit-to-stand test.\nCONCLUSIONS: The CoDuSe program reduced falls and proportion of fallers and improved balance performance in people with mild to moderate MS but did not significantly alter perceived limitations in walking and balance confidence.","DOI":"10.1016/j.apmr.2014.06.016","ISSN":"1532-821X","note":"PMID: 25004466","shortTitle":"Balance exercise program reduced falls in people with multiple sclerosis","journalAbbreviation":"Arch Phys Med Rehabil","language":"eng","author":[{"family":"Nilsag?rd","given":"Ylva Elisabet"},{"family":"von Koch","given":"Lena Kristina"},{"family":"Nilsson","given":"Malin"},{"family":"Forsberg","given":"Anette Susanne"}],"issued":{"date-parts":[["2014",12]]},"PMID":"25004466"}}],"schema":""} 3Reduced falls and improved balanceMulticenter, single-blinded, single-group, pretest-posttest trialBalance, cognition, fatigue, depression, walking, QoLExercise Training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2a3nr77sok","properties":{"formattedCitation":"{\\rtf \\super 4\\nosupersub{}}","plainCitation":"4"},"citationItems":[{"id":984,"uris":[""],"uri":[""],"itemData":{"id":984,"type":"article-journal","title":"Benefits of Exercise Training in Multiple Sclerosis","container-title":"Current Neurology and Neuroscience Reports","page":"62","volume":"15","issue":"9","source":"PubMed","abstract":"Exercise training represents a behavioral approach for safely managing many of the functional, symptomatic, and quality of life consequences of multiple sclerosis (MS). This topical review paper summarizes evidence from literature reviews and meta-analyses, supplemented by recent individual studies, indicating that exercise training can yield small but important improvements in walking, balance, cognition, fatigue, depression, and quality of life in MS. The paper highlights limitations of research on exercise training and its consequences and future research directions and provides an overview for promotion of exercise training in MS based on recent prescriptive guidelines. Collectively, the evidence for the benefits of exercise training in MS suggests that the time is ripe for the promotion of exercise by healthcare providers, particularly neurologists as a central part of the clinical care and management of MS patients.","DOI":"10.1007/s11910-015-0585-6","ISSN":"1534-6293","note":"PMID: 26223831","journalAbbreviation":"Curr Neurol Neurosci Rep","language":"eng","author":[{"family":"Motl","given":"Robert W."},{"family":"Sandroff","given":"Brian M."}],"issued":{"date-parts":[["2015",9]]},"PMID":"26223831"}}],"schema":""} 4Exercise can yield improvements in walking, balance, cognition, fatigue, depression, QoLLiterature review and meta-analysesFatigue and balanceVestibular rehabilitation ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"19e76grd9o","properties":{"formattedCitation":"{\\rtf \\super 5\\nosupersub{}}","plainCitation":"5"},"citationItems":[{"id":812,"uris":[""],"uri":[""],"itemData":{"id":812,"type":"article-journal","title":"Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial","container-title":"Physical Therapy","page":"1166-1183","volume":"91","issue":"8","source":"PubMed","abstract":"BACKGROUND: Fatigue and impaired upright postural control (balance) are the 2 most common findings in people with multiple sclerosis (MS), with treatment approaches varying greatly in effectiveness.\nOBJECTIVES: The aim of this study was to investigate the benefits of implementing a vestibular rehabilitation program for the purpose of decreasing fatigue and improving balance in patients with MS.\nDESIGN: The study was a 14-week, single-blinded, stratified blocked randomized controlled trial.\nSETTING: Measurements were conducted in an outpatient clinical setting, and interventions were performed in a human performance laboratory.\nPATIENTS: Thirty-eight patients with MS were randomly assigned to an experimental group, an exercise control group, or a wait-listed control group.\nINTERVENTION: The experimental group underwent vestibular rehabilitation, the exercise control group underwent bicycle endurance and stretching exercises, and the wait-listed control group received usual medical care.\nMEASUREMENTS: Primary measures were a measure of fatigue (Modified Fatigue Impact Scale), a measure of balance (posturography), and a measure of walking (Six-Minute Walk Test). Secondary measures were a measure of disability due to dizziness or disequilibrium (Dizziness Handicap Inventory) and a measure of depression (Beck Depression Inventory-II).\nRESULTS: Following intervention, the experimental group had greater improvements in fatigue, balance, and disability due to dizziness or disequilibrium compared with the exercise control group and the wait-listed control group. These results changed minimally at the 4-week follow-up. Limitations The study was limited by the small sample size. Further investigations are needed to determine the underlying mechanisms associated with the changes in the outcome measures due to the vestibular rehabilitation program.\nCONCLUSION: A 6-week vestibular rehabilitation program demonstrated both statistically significant and clinically relevant change in fatigue, impaired balance, and disability due to dizziness or disequilibrium in patients with MS.","DOI":"10.2522/ptj.20100399","ISSN":"1538-6724","note":"PMID: 21680771","shortTitle":"Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control","journalAbbreviation":"Phys Ther","language":"eng","author":[{"family":"Hebert","given":"Jeffrey R."},{"family":"Corboy","given":"John R."},{"family":"Manago","given":"Mark M."},{"family":"Schenkman","given":"Margaret"}],"issued":{"date-parts":[["2011",8]]},"PMID":"21680771"}}],"schema":""} 5Clinically relevant changes in fatigue and balanceRandomized, controlled trialFatigue and mobilityTreadmill training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2oaknq40bc","properties":{"formattedCitation":"{\\rtf \\super 6\\nosupersub{}}","plainCitation":"6"},"citationItems":[{"id":966,"uris":[""],"uri":[""],"itemData":{"id":966,"type":"article-journal","title":"Treadmill training for individuals with multiple sclerosis: a pilot randomised trial","container-title":"Journal of Neurology, Neurosurgery, and Psychiatry","page":"531-533","volume":"77","issue":"4","source":"PubMed","abstract":"This pilot study investigated whether 4 weeks of aerobic treadmill training in individuals with multiple sclerosis (MS) improved mobility and reduced fatigue. Individuals with MS were recruited to this prospective, randomised controlled trial. Individuals were assessed at baseline, week 7 and 12 with a 10 metre timed walk, a 2 minute walk, the Rivermead Mobility Index, and the Fatigue Severity Scale. After a pre-assessment familiarisation session and a baseline assessment, individuals were randomly allocated to an initial intervention or delayed intervention group. Treadmill training consisted of 4 weeks of supervised aerobic exercise delivered weeks 3-6 in the immediate group and 8-11 in the delayed group. Of the initial 19 recruits, 16 individuals completed the study. There was a significant difference in walking endurance between the delayed and immediate groups at baseline (p<0.05). On reassessment in week 7, decreases in 10 metre walk time were found in both groups, which was significant in the immediate group (p<0.05). The 2 minute walk distance significantly increased in both groups (p<0.05). In the training group, reassessed at week 12 after training ceased, there was a return towards baseline scores. No significant changes in fatigue scores were found. This study showed that in individuals with MS, aerobic treadmill training is feasible and well tolerated. Walking speed and endurance increased following training with no increase in reported fatigue. Detraining occurred in the period following training. A larger randomised clinical trial is warranted.","DOI":"10.1136/jnnp.2005.064410","ISSN":"0022-3050","note":"PMID: 16543538\nPMCID: PMC2077516","shortTitle":"Treadmill training for individuals with multiple sclerosis","journalAbbreviation":"J. Neurol. Neurosurg. Psychiatr.","language":"eng","author":[{"family":"van den Berg","given":"M."},{"family":"Dawes","given":"H."},{"family":"Wade","given":"D. T."},{"family":"Newman","given":"M."},{"family":"Burridge","given":"J."},{"family":"Izadi","given":"H."},{"family":"Sackley","given":"C. M."}],"issued":{"date-parts":[["2006",4]]},"PMID":"16543538","PMCID":"PMC2077516"}}],"schema":""} 6 Walking speed and endurance increased. No significant change in fatigue. Prospective, randomized, controlled trialFatigueFatigue management plus physical activity intervention ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"23dht9kfl5","properties":{"formattedCitation":"{\\rtf \\super 7\\nosupersub{}}","plainCitation":"7"},"citationItems":[{"id":1002,"uris":[""],"uri":[""],"itemData":{"id":1002,"type":"article-journal","title":"Randomized controlled trial of a teleconference fatigue management plus physical activity intervention in adults with multiple sclerosis: rationale and research protocol","container-title":"BMC neurology","page":"122","volume":"12","source":"PubMed","abstract":"BACKGROUND: Chronic fatigue and inactivity are prevalent problems among individuals with multiple sclerosis (MS) and may independently or interactively have detrimental effects on quality of life and ability to participate in life roles. However, no studies to date have systematically evaluated the benefits of an intervention for both managing fatigue and promoting physical activity in individuals with MS. This study involves a randomized controlled trial to examine the effectiveness of a telehealth intervention that supports individuals with MS in managing fatigue and increasing physical activity levels.\nMETHODS/DESIGN: A randomly-allocated, three-parallel group, time-series design with a social support program serving as the control group will be used to accomplish the purpose of the study. Our goal is to recruit 189 ambulatory individuals with MS who will be randomized into one of three telehealth interventions: (1) a contact-control social support intervention, (2) a physical activity-only intervention, and (3) a physical activity plus fatigue management intervention. All interventions will last 12?weeks and will be delivered entirely over the phone. Our hypothesis is that, in comparison to the contact-control condition, both the physical activity-only intervention and the physical activity plus fatigue management intervention will yield significant increases in physical activity levels as well as improve fatigue and health and function, with the physical activity plus fatigue management intervention yielding significantly larger improvements. To test this hypothesis, outcome measures will be administered at Weeks 1, 12, and 24. Primary outcomes will be the Fatigue Impact Scale, the Godin Leisure-Time Exercise Questionnaire (GLTEQ), and Actigraph accelerometers. Secondary outcomes will include the SF-12 Survey, Mental Health Inventory, Multiple Sclerosis Impact Scale, the Community Participation Indicator, and psychosocial constructs (e.g., self-efficacy).\nDISCUSSION: The proposed study is novel, in that it represents a multi-disciplinary effort to merge two promising lines of research on MS: fatigue management and physical activity promotion. Collectively, the proposed study will be the largest randomized controlled trial to examine the effects of a lifestyle physical activity intervention in people with MS.\nTRIAL REGISTRATION: NCT01572714.","DOI":"10.1186/1471-2377-12-122","ISSN":"1471-2377","note":"PMID: 23072517\nPMCID: PMC3495833","shortTitle":"Randomized controlled trial of a teleconference fatigue management plus physical activity intervention in adults with multiple sclerosis","journalAbbreviation":"BMC Neurol","language":"eng","author":[{"family":"Plow","given":"Matthew"},{"family":"Finlayson","given":"Marcia"},{"family":"Motl","given":"Robert W."},{"family":"Bethoux","given":"Francois"}],"issued":{"date-parts":[["2012"]]},"PMID":"23072517","PMCID":"PMC3495833"}}],"schema":""} 7 Novel, multidisciplinary effort to combine fatigue management and physical activity promotionRandomized, controlled trialFatigueEndurance exercise ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1idvg90g49","properties":{"formattedCitation":"{\\rtf \\super 8\\nosupersub{}}","plainCitation":"8"},"citationItems":[{"id":939,"uris":[""],"uri":[""],"itemData":{"id":939,"type":"article-journal","title":"Endurance exercise improves walking distance in MS patients with fatigue","container-title":"Acta Neurologica Scandinavica","page":"251-257","volume":"120","issue":"4","source":"PubMed","abstract":"OBJECTIVES: Effects of endurance training in multiple sclerosis (MS) patients complaining of motor fatigue.\nMATERIALS AND METHODS: Thirty MS patients complaining of fatigue with low to moderate disabilities randomly allocated to the intervention (thrice weekly 45-min intervals of endurance exercise) or control treatment (three 45-min episodes of stretching, balance training and coordination), both as 'add-on' therapy for 3 weeks during inpatient rehabilitation.\nRESULTS: Maximal walking distance before intervention averaged 1043 +/- 568 and 1163 +/- 750 m in the two groups. The intervention group increased its maximal walking distance by 650 +/- 474 m. The control group extended its walking distance by 96 +/- 70 m.\nCONCLUSIONS: The present data confirm a strong effect of endurance exercise on maximal walking distance. Remarkably, there were no parallel improvements on the Modified Fatigue Impact Scale, the Beck Depression Inventory and the Hamburg Quality of Life Questionnaire for MS.","DOI":"10.1111/j.1600-0404.2008.01152.x","ISSN":"1600-0404","note":"PMID: 19178385","journalAbbreviation":"Acta Neurol. Scand.","language":"eng","author":[{"family":"Dettmers","given":"C."},{"family":"Sulzmann","given":"M."},{"family":"Ruchay-Pl?ssl","given":"A."},{"family":"Gütler","given":"R."},{"family":"Vieten","given":"M."}],"issued":{"date-parts":[["2009",10]]},"PMID":"19178385"}}],"schema":""} 8Maximal walking distance improved. Randomized, controlled trialFatigue Aerobic training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1p64qav7v6","properties":{"formattedCitation":"{\\rtf \\super 9\\nosupersub{}}","plainCitation":"9"},"citationItems":[{"id":958,"uris":[""],"uri":[""],"itemData":{"id":958,"type":"article-journal","title":"Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study","container-title":"Physical Therapy","page":"545-555","volume":"87","issue":"5","source":"PubMed","abstract":"BACKGROUND AND PURPOSE: Physical deconditioning is involved in the impaired exercise tolerance of patients with multiple sclerosis (MS), but data on the effects of aerobic training (AT) in this population are scanty. The purpose of this study was to compare the effects of an 8-week AT program on exercise capacity-in terms of walking capacity and maximum exercise tolerance, as well as its effects on fatigue and health-related quality of life-as compared with neurological rehabilitation (NR) in subjects with MS.\nSUBJECTS AND METHODS: Nineteen subjects (14 female, 5 male; mean age [X+/-SD]=41+/-8 years) with mild to moderate disability secondary to MS participated in a randomized crossover controlled study. Eleven subjects (8 female, 3 male; mean age [X+/-SD]=44+/-6 years) completed the study.\nRESULTS: After AT, but not NR, the subjects' walking distances and speeds during a self-paced walk were significantly improved, as were their maximum work rate, peak oxygen uptake, and oxygen pulse during cardiopulmonary exercise tests. The increases in peak oxygen uptake and maximum work rate, but not in walking capacity, were significantly higher after AT, as compared with after NR. Additionally, the subjects who were most disabled tended to benefit more from AT. There were no differences between AT and NR in effects on fatigue, and the results showed that AT may have partially affected health-related quality of life.\nDISCUSSION AND CONCLUSION: The results suggest that AT is more effective than NR in improving maximum exercise tolerance and walking capacity in people with mild to moderate disability secondary to MS.","DOI":"10.2522/ptj.20060085","ISSN":"0031-9023","note":"PMID: 17405806","shortTitle":"Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis","journalAbbreviation":"Phys Ther","language":"eng","author":[{"family":"Rampello","given":"Anais"},{"family":"Franceschini","given":"Marco"},{"family":"Piepoli","given":"Massimo"},{"family":"Antenucci","given":"Roberto"},{"family":"Lenti","given":"Gabriella"},{"family":"Olivieri","given":"Dario"},{"family":"Chetta","given":"Alfredo"}],"issued":{"date-parts":[["2007",5]]},"PMID":"17405806"}}],"schema":""} 9Maximum exercise tolerance and walking capacity improved. Randomized, crossover controlled studyIntervention targetInterventionOutcome Study DesignFatigue, moodAerobic training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"tqibbmelb","properties":{"formattedCitation":"{\\rtf \\super 10\\nosupersub{}}","plainCitation":"10"},"citationItems":[{"id":941,"uris":[""],"uri":[""],"itemData":{"id":941,"type":"article-journal","title":"Impact of aerobic training on fitness and quality of life in multiple sclerosis","container-title":"Annals of Neurology","page":"432-441","volume":"39","issue":"4","source":"PubMed","abstract":"Fifty-four multiple sclerosis (MS) patients were randomly assigned to exercise (EX) or nonexercise (NEX) groups. Before and after 15 weeks of aerobic training, aspects of fitness including maximal aerobic capacity (VO2max), isometric strength, body composition, and blood lipids were measured. Daily activities, mood, fatigue, and disease status were measured by the Profile of Mood States (POMS), Sickness Impact Profile (SIP), Fatigue Severity Scale (FSS), and neurological examination. Training consisted of 3 x 40-minute sessions per week of combined arm and leg ergometry. Expanded Disability Status Scale (EDSS) scores were unchanged, except for improved bowel and bladder function in the EX group. Compared with baseline, the EX group demonstrated significant increases in VO2max, upper and lower extremity strength, and significant decreases in skinfolds, triglyceride, and very-low-density lipoprotein (VLDL). For the EX group, POMS depression and anger scores were significantly reduced at weeks 5 and 10, and fatigue was reduced at week 10. The EX group improved significantly on all components of the physical dimension of the SIP and showed significant improvements for social interaction, emotional behavior, home management, total SIP score, and recreation and past times. No changes were observed for EX or NEX groups on the FSS. Exercise training resulted in improved fitness and had a positive impact on factors related to quality of life.","DOI":"10.1002/ana.410390405","ISSN":"0364-5134","note":"PMID: 8619521","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Petajan","given":"J. H."},{"family":"Gappmaier","given":"E."},{"family":"White","given":"A. T."},{"family":"Spencer","given":"M. K."},{"family":"Mino","given":"L."},{"family":"Hicks","given":"R. W."}],"issued":{"date-parts":[["1996",4]]},"PMID":"8619521"}}],"schema":""} 10 Improved upper- and lower-extremity strength, reduced depression and anger scores, improved fitness and QoL. Randomized, controlled studyFatigue, function and participationMultidisciplinary rehabilitation and fatigue management courses ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"13s0oudfk2","properties":{"formattedCitation":"{\\rtf \\super 11\\nosupersub{}}","plainCitation":"11"},"citationItems":[{"id":956,"uris":[""],"uri":[""],"itemData":{"id":956,"type":"article-journal","title":"Strong evidence exists that multidisciplinary rehabilitation and fatigue management courses improve function and participation in people with multiple sclerosis","container-title":"Australian Occupational Therapy Journal","page":"288-289","volume":"61","issue":"4","source":"CrossRef","DOI":"10.1111/1440-1630.12154","ISSN":"00450766","language":"en","author":[{"family":"George","given":"Stacey"},{"family":"White","given":"Jennifer"}],"issued":{"date-parts":[["2014",8]]},"accessed":{"date-parts":[["2016",3,5]]}}}],"schema":""} 11Rehabilitation improves function and participation Systematic review Fatigue Review of 38 studies of variety of exercise and behavioral change interventions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2iooi5h824","properties":{"formattedCitation":"{\\rtf \\super 12\\nosupersub{}}","plainCitation":"12"},"citationItems":[{"id":945,"uris":[""],"uri":[""],"itemData":{"id":945,"type":"article-journal","title":"A scoping review of rehabilitation interventions that reduce fatigue among adults with multiple sclerosis","container-title":"Disability and Rehabilitation","page":"729-738","volume":"37","issue":"9","source":"PubMed","abstract":"OBJECTIVE: To identify and summarize available research literature about rehabilitation interventions for multiple sclerosis (MS) fatigue management.\nMETHODS: Database searches (PubMed, EMBASE, CINAHL and PsychINFO) were conducted in October 2011 and last updated in July 2013. To be included, studies must have been published in a peer-reviewed scientific journal, written in English and included an intervention to manage MS fatigue. Effect size (ES) were calculated for the quantitative studies to estimate intervention effects, and major themes were summarized for the qualitative studies.\nRESULTS: Thirty-eight studies were included in this review. A variety of exercise and behavior change interventions were prescribed to adults with MS. The two most common interventions were progressive resistive training and fatigue management programs. Three exercise intervention studies and nine behavior change intervention studies with quantitative data presented significant ES. Four studies with qualitative data supported the positive impact of certain exercise and behavior change interventions.\nCONCLUSIONS: This review identified a variety of exercise and behavior change interventions for MS fatigue management. While the findings may provide helpful information to inform practice, future researchers need to develop and evaluate knowledge translation strategies to facilitate the application of this evidence to daily practice to advance MS rehabilitation care.\nIMPLICATIONS FOR REHABILITATION: Both exercise and behavior change interventions demonstrate some degree of effectiveness for managing MS fatigue. Effect sizes for exercise and behavior change interventions are similar, although the populations examined are different. Overall, evidence for exercise focuses on people who are less disabled, while evidence for behavior change interventions includes a broader population. Future researchers need to develop and evaluate knowledge translation strategies that facilitate application of evidence in daily practice in order to advance MS rehabilitation.","DOI":"10.3109/09638288.2014.944996","ISSN":"1464-5165","note":"PMID: 25066069","journalAbbreviation":"Disabil Rehabil","language":"eng","author":[{"family":"Asano","given":"Miho"},{"family":"Berg","given":"Elizabeth"},{"family":"Johnson","given":"Katherine"},{"family":"Turpin","given":"Merrill"},{"family":"Finlayson","given":"Marcia L."}],"issued":{"date-parts":[["2015"]]},"PMID":"25066069"}}],"schema":""} 12 Exercise and behavior change interventions are effective in managing MS fatigueLiterature review Fatigue, impairment, disability and QoLResistance-, endurance-, and combined training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"22hjrm4s0v","properties":{"formattedCitation":"{\\rtf \\super 13\\nosupersub{}}","plainCitation":"13"},"citationItems":[{"id":943,"uris":[""],"uri":[""],"itemData":{"id":943,"type":"article-journal","title":"Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training","container-title":"Multiple Sclerosis (Houndmills, Basingstoke, England)","page":"35-53","volume":"14","issue":"1","source":"PubMed","abstract":"This review summarizes the existing knowledge regarding the effects of physical exercise in patients suffering from multiple sclerosis (MS). Furthermore, recommendations are given regarding exercise prescription for MS patients and for future study directions. Previously, MS patients were advised not to participate in physical exercise. During recent years, it has been increasingly acknowledged that exercise benefits MS patients. The requirement for exercise in MS patients is emphasized by their physiological profile, which probably reflects both the effects of the disease per se and the reversible effects of an inactive lifestyle. To date the effects of exercise have only been studied in moderately impaired MS patients with an EDSS score of less than 7. Evidence exists for recommending participation in endurance training at low to moderate intensity, as the existing literature demonstrates that MS patients can both tolerate and benefit from this training modality. Also, resistance training of moderate intensity seems to be well tolerated and to have beneficial effects on MS patients, but the methodological quality of the existing evidence is in general low and the number of studies is limited. Only two studies have evaluated the effects of combined resistance- and endurance training, making solid conclusions regarding this training modality impossible.","DOI":"10.1177/1352458507079445","ISSN":"1352-4585","note":"PMID: 17881393","shortTitle":"Multiple sclerosis and physical exercise","journalAbbreviation":"Mult. Scler.","language":"eng","author":[{"family":"Dalgas","given":"U."},{"family":"Stenager","given":"E."},{"family":"Ingemann-Hansen","given":"T."}],"issued":{"date-parts":[["2008",1]]},"PMID":"17881393"}}],"schema":""} 13 Beneficial effects and improved QoLLiterature reviewImpairment, disability and QoLVaried exercise protocols ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1qumcl4vam","properties":{"formattedCitation":"{\\rtf \\super 14\\nosupersub{}}","plainCitation":"14"},"citationItems":[{"id":970,"uris":[""],"uri":[""],"itemData":{"id":970,"type":"article-journal","title":"Exercise in the management of persons with multiple sclerosis","container-title":"Therapeutic Advances in Neurological Disorders","page":"123-130","volume":"8","issue":"3","source":"CrossRef","DOI":"10.1177/1756285615576663","ISSN":"1756-2856, 1756-2864","language":"en","author":[{"family":"Giesser","given":"B. S."}],"issued":{"date-parts":[["2015",5,1]]},"accessed":{"date-parts":[["2016",3,7]]}}}],"schema":""} 14 Helpful in managing symptoms, preventing complications and comorbidities, and may have neuroprotective effects. Literature reviewImpairment, disability and QoLInpatient physical rehabilitation ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1vcaunb2ir","properties":{"formattedCitation":"{\\rtf \\super 15\\nosupersub{}}","plainCitation":"15"},"citationItems":[{"id":968,"uris":[""],"uri":[""],"itemData":{"id":968,"type":"article-journal","title":"Physical rehabilitation has a positive effect on disability in multiple sclerosis patients","container-title":"Neurology","page":"57-62","volume":"52","issue":"1","source":"PubMed","abstract":"BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established.\nOBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial.\nMETHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician.\nRESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001).\nCONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.","ISSN":"0028-3878","note":"PMID: 9921849","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Solari","given":"A."},{"family":"Filippini","given":"G."},{"family":"Gasco","given":"P."},{"family":"Colla","given":"L."},{"family":"Salmaggi","given":"A."},{"family":"La Mantia","given":"L."},{"family":"Farinotti","given":"M."},{"family":"Eoli","given":"M."},{"family":"Mendozzi","given":"L."}],"issued":{"date-parts":[["1999",1,1]]},"PMID":"9921849"}}],"schema":""} 15 Improved functional independence, disability and QoLRandomized, single-blind, controlled trialDisability and QoLRobot-assisted and conventional body-weight-supported treadmill training (BWSTT) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"14sam9oc97","properties":{"formattedCitation":"{\\rtf \\super 16\\nosupersub{}}","plainCitation":"16"},"citationItems":[{"id":962,"uris":[""],"uri":[""],"itemData":{"id":962,"type":"article-journal","title":"Effect of robot-assisted versus conventional body-weight-supported treadmill training on quality of life for people with multiple sclerosis","container-title":"Journal of Rehabilitation Research and Development","page":"483-492","volume":"48","issue":"4","source":"PubMed","abstract":"This study describes the effect of body-weight-supported treadmill training (BWSTT) on quality of life (QoL) for multiple sclerosis (MS) patients. Thirteen individuals with MS and gait impairment randomly received two blocks of six biweekly training sessions: (1) robot-assisted BWSTT then BWSTT alone (R-T) or (2) BWSTT alone then robot-assisted BWSTT (T-R). No statistically significant differences were found between robot-assisted BWSTT and unassisted BWSTT for improving QoL outcome measures. The change in Physical Component Summary scores from baseline to the end of the 12 training sessions improved significantly more in the R-T than the T-R group. Within-participant longitudinal changes in QoL for all participants from both groups combined showed significant improvements in 5 of the 13 QoL measures. The results of this pilot study suggest that both types of BWSTT may improve QoL for people with gait dysfunction secondary to MS.","ISSN":"1938-1352","note":"PMID: 21674396","journalAbbreviation":"J Rehabil Res Dev","language":"eng","author":[{"family":"Wier","given":"Lauren M."},{"family":"Hatcher","given":"Mary S."},{"family":"Triche","given":"Elizabeth W."},{"family":"Lo","given":"Albert C."}],"issued":{"date-parts":[["2011"]]},"PMID":"21674396"}}],"schema":""} 16Both types of BWSTT may improve QoL and decrease overall disability. Randomized, controlled trialCognitive dysfunctionCognitive rehabilitation intervention ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1j1r71i0so","properties":{"formattedCitation":"{\\rtf \\super 17\\nosupersub{}}","plainCitation":"17"},"citationItems":[{"id":1004,"uris":[""],"uri":[""],"itemData":{"id":1004,"type":"article-journal","title":"A randomized controlled trial of a cognitive rehabilitation intervention for persons with multiple sclerosis","container-title":"Clinical Rehabilitation","page":"882-893","volume":"26","issue":"10","source":"PubMed","abstract":"OBJECTIVE: To explore the feasibility and effects of a computer-assisted cognitive rehabilitation intervention - Memory, Attention, and Problem Solving Skills for Persons with Multiple Sclerosis (MAPSS-MS) - for persons with multiple sclerosis on cognitive performance, memory strategy use, self-efficacy for control of symptoms and neuropsychological competence in activities of daily living (ADL).\nDESIGN: A randomized controlled single-blinded trial with treatment and wait list control groups.\nSETTING: Southwestern United States.\nSUBJECTS: Convenience sample of 61 persons (34 treatment, 27 wait list control) with multiple sclerosis (mean age 47.9 years, SD 8.8).\nINTERVENTION: The eight-week MAPSS-MS intervention program included two components: (a) eight weekly group sessions focused on building efficacy for use of cognitive compensatory strategies and (b) a computer-assisted cognitive rehabilitation program with home-based training.\nOUTCOME MEASURES: A neuropsychological battery of performance tests comprising the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and self-report instruments (use of memory strategies, self-efficacy for control of multiple sclerosis and neuropsychological competence in ADL) were completed at baseline, two months (after classes), and at five months.\nRESULTS: Both groups improved significantly (P < 0.05) over time on most measures in the MACFIMS battery as well as the measures of strategy use and neuropsychological competence in ADL. There was a significant group-by-time interaction for scores on the measures of verbal memory and the use of compensatory strategies.\nCONCLUSIONS: The MAPSS-MS intervention was feasible and well-accepted by participants. Given the large relative increase in use of compensatory strategies by the intervention group, it holds promise for enhancing cognitive function in persons with multiple sclerosis.","DOI":"10.1177/0269215511434997","ISSN":"1477-0873","note":"PMID: 22301679","journalAbbreviation":"Clin Rehabil","language":"eng","author":[{"family":"Stuifbergen","given":"Alexa K."},{"family":"Becker","given":"Heather"},{"family":"Perez","given":"Frank"},{"family":"Morison","given":"Janet"},{"family":"Kullberg","given":"Vicki"},{"family":"Todd","given":"Ana"}],"issued":{"date-parts":[["2012",10]]},"PMID":"22301679"}}],"schema":""} 17 Promising for improving cognitive functionRandomized, controlled trialIntervention targetInterventionOutcome Study DesignCognitive dysfunctionTreadmill walking, cycle ergometer, guided yoga ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1p18vp6ato","properties":{"formattedCitation":"{\\rtf \\super 18\\nosupersub{}}","plainCitation":"18"},"citationItems":[{"id":986,"uris":[""],"uri":[""],"itemData":{"id":986,"type":"article-journal","title":"Acute effects of walking, cycling, and yoga exercise on cognition in persons with relapsing-remitting multiple sclerosis without impaired cognitive processing speed","container-title":"Journal of Clinical and Experimental Neuropsychology","page":"209-219","volume":"37","issue":"2","source":"PubMed","abstract":"INTRODUCTION: Cognitive impairment is a highly prevalent, disabling, and poorly managed consequence of multiple sclerosis (MS). Exercise training represents a promising approach for managing cognitive impairment in this population. However, there is limited evidence supporting an optimal exercise stimulus for improving cognition in MS. The current study compared the acute effects of moderate-intensity treadmill walking, moderate-intensity cycle ergometry, and guided yoga with those of quiet rest on executive control in 24 persons with relapsing-remitting MS without impaired cognitive processing speed using a within-subjects, repeated measures design.\nMETHOD: Participants completed four experimental conditions that consisted of 20 minutes of moderate-intensity treadmill walking exercise, moderate-intensity cycle ergometer exercise, guided yoga, and quiet rest in a randomized, counterbalanced order. Participants underwent a modified-flanker task as a measure of executive control immediately prior to and following each condition.\nRESULTS: Repeated measures analyses of variance (ANOVAs) indicated general pre-to-post improvements in reaction time, but not accuracy, on the modified-flanker task for all three exercise modalities compared with quiet rest. However, there were additional, selective pre-to-post reductions in the cost of interfering stimuli on reaction time on the modified-flanker task for treadmill walking, F(1, 23) = 4.67, p = .04, η(p)2 = .17, but not cycle ergometry, F(1, 23) = 0.12, p = .73, η(p)2 < .01, or guided yoga, F(1, 23) = 0.73, p = .40, η(p)2 = .03, compared with quiet rest.\nCONCLUSIONS: The present results support treadmill walking as the modality of exercise that might exert the largest beneficial effects on executive control in persons with relapsing-remitting MS without impaired cognitive processing speed. This represents an exciting starting point for delineating the appropriate exercise stimulus (i.e., modality and intensity) for inclusion in a subsequent longitudinal exercise training intervention for improving cognitive performance in this population.","DOI":"10.1080/13803395.2014.1001723","ISSN":"1744-411X","note":"PMID: 25658772","journalAbbreviation":"J Clin Exp Neuropsychol","language":"eng","author":[{"family":"Sandroff","given":"Brian M."},{"family":"Hillman","given":"Charles H."},{"family":"Benedict","given":"Ralph H. B."},{"family":"Motl","given":"Robert W."}],"issued":{"date-parts":[["2015"]]},"PMID":"25658772"}}],"schema":""} 18 Treadmill walking has a beneficial effect on executive functionRandomized, controlled trialCognitive dysfunctionCognitive retraining treatment strategies ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1onlaqu1n3","properties":{"formattedCitation":"{\\rtf \\super 19\\nosupersub{}}","plainCitation":"19"},"citationItems":[{"id":947,"uris":[""],"uri":[""],"itemData":{"id":947,"type":"article-journal","title":"Cognition, cognitive dysfunction, and cognitive rehabilitation in multiple sclerosis","container-title":"Physical Medicine and Rehabilitation Clinics of North America","page":"663-672","volume":"24","issue":"4","source":"PubMed","abstract":"This article focuses on approaches and techniques for effective cognitive rehabilitation with people who have multiple sclerosis (MS). The patterns of preserved versus disrupted neuropsychological functions are reviewed. The relevant brain anatomy and physiology that underlie the common neurocognitive and neurobehavioral changes are described. The essential role is highlighted of comprehensive neuropsychological, speech language pathology, and clinical evaluations in the design and refinements of cognitive retraining treatment. The functional impact of cognitive problems expected with MS is emphasized, accompanied by examples of cognitive retraining approaches used to manage them and improve day-to-day performance.","DOI":"10.1016/j.pmr.2013.06.009","ISSN":"1558-1381","note":"PMID: 24314684","journalAbbreviation":"Phys Med Rehabil Clin N Am","language":"eng","author":[{"family":"Pepping","given":"Mary"},{"family":"Brunings","given":"Julie"},{"family":"Goldberg","given":"Myron"}],"issued":{"date-parts":[["2013",11]]},"PMID":"24314684"}}],"schema":""} 19Improves day-to-day performance Review articleCognitive dysfunctionExercise intervention programs. Includes review of 12 controlled clinical trials ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"79gd6m8um","properties":{"formattedCitation":"{\\rtf \\super 20\\nosupersub{}}","plainCitation":"20"},"citationItems":[{"id":949,"uris":[""],"uri":[""],"itemData":{"id":949,"type":"article-journal","title":"Efficacy of exercise intervention programs on cognition in people suffering from multiple sclerosis, stroke and Parkinson's disease: A?systematic review and meta-analysis of?current evidence","container-title":"NeuroRehabilitation","page":"273-289","volume":"37","issue":"2","source":"PubMed","abstract":"BACKGROUND: Cognitive impairment is a well-established sequela of people suffering from neurological pathologies.\nOBJECTIVE: To examine the effects of exercise intervention programs on cognitive performance in participants suffering from stroke, multiple sclerosis and Parkinson's disease.\nMETHODS: Four online databases (CINAHL, Cochrane Library, MEDLINE, PEDro) were comprehensively searched from their inception through December 2014. The search query was phrased as follows: In people suffering from MS, stroke or Parkinson's disease, do exercise intervention programs improve cognitive performance?\nRESULTS: Twelve controlled clinical trials met our inclusion criteria. Studies were classified according to three clinical subgroups: Parkinson's disease (n?=?3), stroke (n?=?1) and multiple sclerosis (n?=?8). Eight studies employed an aerobic intervention program; one used an active exercise program based on virtual reality systems, three reports examined the effect of yoga and one compared the intervention program with sport climbing. Significant improvements in cognition were found in nine out of the twelve studies. Nevertheless, the total effect size was non-significant (0.18 (95% CI, - 4.1, 3.8)) for changes in executive functions.\nCONCLUSION: Due to lack of commonality between measures of cognition, training sequences and intervention period, it remains unclear as to whether exercise training can be effective in improving the cognitive functions of neurological patients.","DOI":"10.3233/NRE-151260","ISSN":"1878-6448","note":"PMID: 26484519","shortTitle":"Efficacy of exercise intervention programs on cognition in people suffering from multiple sclerosis, stroke and Parkinson's disease","journalAbbreviation":"NeuroRehabilitation","language":"eng","author":[{"family":"Kalron","given":"Alon"},{"family":"Zeilig","given":"Gabi"}],"issued":{"date-parts":[["2015"]]},"PMID":"26484519"}}],"schema":""} 20Significant improvements in cognition were found in 9 of 12 studies. Systematic review and meta-analysisDepressionCognitive behavioral therapy (CBT) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"thgsp4kag","properties":{"formattedCitation":"{\\rtf \\super 21\\nosupersub{}}","plainCitation":"21"},"citationItems":[{"id":951,"uris":[""],"uri":[""],"itemData":{"id":951,"type":"article-journal","title":"A single-group pilot feasibility study of cognitive behavioural therapy in people with multiple sclerosis with depressive symptoms","container-title":"Disability and Rehabilitation","page":"1-9","source":"PubMed","abstract":"Purpose The aims were to evaluate (a) the feasibility of face-to-face cognitive behavioural therapy (CBT) in people with MS (PwMS) with depressive symptoms; (b) the feasibility of methods and measurements used; and (c) the outcome of the intervention before the conducting of an equivalence study of comparative methods of face-to-face CBT. Design A single-group pilot feasibility study. Patients PwMS (n?=?15) with sub-threshold to moderate depressive symptoms, recruited at the Karolinska University Hospital, Stockholm, Sweden. Methods The intervention consisted of 15-20 sessions of face-to-face CBT. Feasibility outcomes included recruitment rate, recruitment procedure and adverse events. Primary clinical outcome was the Beck Depression Inventory-II (BDI-II). Follow-ups were conducted after 3 weeks and 3 months. An estimated sample size calculation was conducted. Results The face-to-face CBT intervention, methods and measurements used were feasible. The outcome on BDI-II indicated that face-to-face CBT is an effective method for alleviating sub-threshold to moderate depressive symptoms in PwMS. Conclusion Face-to-face CBT is feasible for use in PwMS aiming at decrease depressive symptoms. For an equivalence study, a screening process for depressive symptoms and two comparative intervention arms including traditional face-to-face CBT and low-intensity face-to-face CBT is recommended. Primary outcomes should include the BDI-II and also assessment of anxiety symptoms. Implications for Rehabilitation Depression is common among people with MS (PwMS), however, depressed PwMS do not always receive adequate treatment for depression which may lead to increased disability and worse health-related quality of life (HRQL). Cognitive behavioural therapy (CBT) is a psychological treatment method that might be beneficial for PwMS with depressive symptoms, but the evidence is still weak and further research is needed. The results from our pilot feasibility study demonstrate that for an effectiveness study of face-to-face CBT for PwMS with sub-threshold to moderate depressive symptoms the following points should be acknowledged. The design of an effectiveness study should be a randomized controlled trial including two treatment arms: traditional face-to-face CBT and a low-intensity face-to-face CBT. To increase the inclusion rate a screening process for depressive symptoms is recommended. Primary outcomes besides the Beck Depression Inventory-II should include the Hospital Anxiety and Depression Scale in order to capture anxiety symptoms and the Multiple Sclerosis Impact Scale-29 to capture HRQL.","DOI":"10.3109/09638288.2015.1130179","ISSN":"1464-5165","note":"PMID: 26750510","journalAbbreviation":"Disabil Rehabil","language":"ENG","author":[{"family":"Chruzander","given":"Charlotte"},{"family":"Gottberg","given":"Kristina"},{"family":"Ytterberg","given":"Charlotte"},{"family":"Backenroth","given":"Gunnel"},{"family":"Fredrikson","given":"Sten"},{"family":"Widén Holmqvist","given":"Lotta"},{"family":"Johansson","given":"Sverker"}],"issued":{"date-parts":[["2016",1,10]]},"PMID":"26750510"}}],"schema":""} 21 Face-to-face CBT is feasible for use in decreasing depressive symptomsSingle-group pilot feasibility studyMoodTreadmill walking ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1nnrd9rsin","properties":{"formattedCitation":"{\\rtf \\super 22\\nosupersub{}}","plainCitation":"22"},"citationItems":[{"id":990,"uris":[""],"uri":[""],"itemData":{"id":990,"type":"article-journal","title":"Intensity of treadmill walking exercise on acute mood symptoms in persons with multiple sclerosis","container-title":"Anxiety, Stress, and Coping","page":"1-11","source":"PubMed","abstract":"BACKGROUND/OBJECTIVES: An acute bout of moderate-intensity treadmill walking exercise has previously been associated with improvements in overall mood disturbance and vigor, without worsening fatigue, among persons with multiple sclerosis (MS).This study examined the effects of light-, moderate-, and high-intensity bouts of treadmill walking exercise on immediate and delayed mood states in MS.\nDESIGN: This was a within-subjects, randomized, and counter-balanced study.\nMETHODS: 23 women and 1 man with MS undertook 20-minute bouts of light-, moderate-, and high-intensity treadmill walking, and seated quiet rest. Participants completed the profile of mood states (POMS) questionnaire before, immediately after, and 45 minutes after each condition. Total mood disturbance (TMD) and six subscales of the POMS were analyzed using 2-way, repeated-measures analysis of variance (ANOVA).\nRESULTS: There was a significant condition-by-time interaction on TMD scores ([Formula: see text]) and vigor scores ([Formula: see text]). The moderate-intensity treadmill walking yielded the largest improvements in TMD and vigor immediately post-condition (p?<?.05). These improvements were no longer significant at 45 minutes post-condition (p?>?.05).\nCONCLUSION: TMD and vigor improved immediately after moderate-intensity walking, but the changes dissipated over time. Fatigue did not worsen after any of the walking conditions. These results indicate that an acute bout of moderate-intensity walking may help with mood management in persons with MS, without worsening fatigue.","DOI":"10.1080/10615806.2016.1146710","ISSN":"1477-2205","note":"PMID: 26828264","journalAbbreviation":"Anxiety Stress Coping","language":"ENG","author":[{"family":"Ensari","given":"Ipek"},{"family":"Sandroff","given":"Brian M."},{"family":"Motl","given":"Robert W."}],"issued":{"date-parts":[["2016",2,25]]},"PMID":"26828264"}}],"schema":""} 22Moderate-intensity walking may help with mood managementRandomized, and counter-balanced study. MoodWalking exercise, yoga ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"90ero1dhv","properties":{"formattedCitation":"{\\rtf \\super 23\\nosupersub{}}","plainCitation":"23"},"citationItems":[{"id":983,"uris":[""],"uri":[""],"itemData":{"id":983,"type":"article-journal","title":"Effects of Single Bouts of Walking Exercise and Yoga on Acute Mood Symptoms in People with Multiple Sclerosis","container-title":"International Journal of MS Care","page":"1-8","volume":"18","issue":"1","source":"CrossRef","DOI":"10.7224/1537-2073.2014-104","ISSN":"1537-2073","language":"en","author":[{"family":"Ensari","given":"Ipek"},{"family":"Sandroff","given":"Brian M."},{"family":"Motl","given":"Robert W."}],"issued":{"date-parts":[["2016",1]]},"accessed":{"date-parts":[["2016",3,7]]}}}],"schema":""} 23Walking and yoga show improvement in mood symptomsRandomized, controlled trialMuscular and cardiorespiratory fitness Exercise training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"27os82aled","properties":{"formattedCitation":"{\\rtf \\super 24\\nosupersub{}}","plainCitation":"24"},"citationItems":[{"id":977,"uris":[""],"uri":[""],"itemData":{"id":977,"type":"article-journal","title":"The effect of exercise training on fitness in multiple sclerosis: A meta-analysis","container-title":"Archives of Physical Medicine and Rehabilitation","source":"PubMed","abstract":"OBJECTIVES: To provide a quantitative synthesis of randomized controlled trials (RCT) examining the effect of exercise training on muscular and cardiorespiratory fitness in persons with MS.\nDATA SOURCES: Three electronic databases, Pubmed, Google Scholar and Web of Science were searched for all relevant articles published up until October 2014.\nSTUDY SELECTION: Keywords included \"exercise\" OR \"aerobic\" OR \"strength\" OR \"resistance training\" OR \"cardiorespiratory\" AND \"multiple sclerosis\". Trials examining the effect of exercise training on muscular and/or cardiorespiratory fitness parameters were included.\nDATA EXTRACTION: The initial search yielded 1501 articles of which 62 were reviewed in detail and 20 RCTs met the inclusion criteria and provided enough data to compute effect sizes (ESs; Cohen d). The meta-analyses was conducted using Comprehensive Meta-Analysis software and a random-effects model was used to compute the overall or mean ES per fitness parameter.\nDATA SYNTHESIS: The mean ES was 0.27 (SE=0.05, 95% CI=0.17-0.38, z=5.05, p< .001) for muscular fitness outcomes and 0.47 (SE=0.09, 95% CI=0.30-0.65, z=5.40, p< .001) for cardiorespiratory fitness outcomes. The weighted mean ES was not heterogeneous for muscular (Q=11.09, df=13, p=.60, I(2)=0.00) or cardiorespiratory (Q=7.83, df=9, p=0.55, I(2)=0.00) fitness outcomes.\nCONCLUSIONS: The cumulative evidence supports that exercise training is associated with changes in muscular (small in magnitude) and cardiorespiratory (moderate in magnitude) fitness outcomes in persons with MS. Such an indication of magnitude is important for clinical research and practice by providing an evidence-based estimate of the actual benefit that exercise training confers on physiological fitness.","DOI":"10.1016/j.apmr.2016.01.023","ISSN":"1532-821X","note":"PMID: 26896750","shortTitle":"The effect of exercise training on fitness in multiple sclerosis","journalAbbreviation":"Arch Phys Med Rehabil","language":"ENG","author":[{"family":"Platta","given":"M. E."},{"family":"Ensari","given":"I."},{"family":"Motl","given":"R. W."},{"family":"Pilutti","given":"L. A."}],"issued":{"date-parts":[["2016",2,16]]},"PMID":"26896750"}}],"schema":""} 24 Exercise training is associated with improvements in muscular and cardiorespiratory fitness changesMeta-analysis of randomized controlled trialsBenefits and safety of exercise Prescription of exercise ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2n4eipaqfg","properties":{"formattedCitation":"{\\rtf \\super 25\\nosupersub{}}","plainCitation":"25"},"citationItems":[{"id":992,"uris":[""],"uri":[""],"itemData":{"id":992,"type":"article-journal","title":"Benefits, safety, and prescription of exercise in persons with multiple sclerosis","container-title":"Expert Review of Neurotherapeutics","page":"1429-1436","volume":"14","issue":"12","source":"PubMed","abstract":"Exercise represents a behavioral approach for the restoration of function and management of symptoms among persons with multiple sclerosis (MS). The current paper provides a review on the topic of exercise in MS and is separated into four sections. The first section defines exercise and related constructs. The second section summarizes evidence for the benefits of exercise in MS based on literature reviews and meta-analyses. The third section focuses on the safety of exercise in MS based on the reporting of relapses and other adverse events, and the last section describes guidelines for exercise. The paper concludes with a discussion of major limitations with the existing body of research and highlights some of the pressing areas for future research on exercise in MS.","DOI":"10.1586/14737175.2014.983904","ISSN":"1744-8360","note":"PMID: 25413175","journalAbbreviation":"Expert Rev Neurother","language":"eng","author":[{"family":"Motl","given":"Robert W."}],"issued":{"date-parts":[["2014",12]]},"PMID":"25413175"}}],"schema":""} 25Summary of benefits and safetyLiterature reviews and meta-analysesSafety of exerciseExercise training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"7ml2k9hs2","properties":{"formattedCitation":"{\\rtf \\super 26\\nosupersub{}}","plainCitation":"26"},"citationItems":[{"id":808,"uris":[""],"uri":[""],"itemData":{"id":808,"type":"article-journal","title":"The safety of exercise training in multiple sclerosis: a systematic review","container-title":"Journal of the Neurological Sciences","page":"3-7","volume":"343","issue":"1-2","source":"PubMed","abstract":"There are many reviews documenting the benefits of exercise training among persons with multiple sclerosis (MS). To date, we are unaware of a review that summarizes the risks of relapse and other adverse events (AEs) associated with exercise training, yet this is critical for informing decisions and recommendations regarding the safety of this behavior. We conducted a systematic review of relapse and other AEs reported in randomized controlled trials (RCTs) of exercise training in MS. We searched electronic databases for RCTs of exercise training in MS. We calculated the rate of relapse and AEs, and the relative risk of relapse and AEs for exercise training versus control. Twenty-six studies were reviewed that included 1295 participants. We determined that the rate of relapse was 6.3% and 4.6% for control and exercise, respectively. The rate of AEs was 1.2% and 2.0% for control and exercise, respectively. The relative risk of relapse for exercise training was 0.73, whereas the relative risk of AE for exercise training was 1.67. Exercise training was not associated with an increased risk of relapse, and risk of AEs was not higher than in healthy populations. This evidence should alleviate uncertainty regarding the safety of exercise training in MS.","DOI":"10.1016/j.jns.2014.05.016","ISSN":"1878-5883","note":"PMID: 24880538","shortTitle":"The safety of exercise training in multiple sclerosis","journalAbbreviation":"J. Neurol. Sci.","language":"eng","author":[{"family":"Pilutti","given":"Lara A."},{"family":"Platta","given":"Matthew E."},{"family":"Motl","given":"Robert W."},{"family":"Latimer-Cheung","given":"Amy E."}],"issued":{"date-parts":[["2014",8,15]]},"PMID":"24880538"}}],"schema":""} 26Exercise training was not associated with increased risk of relapse or increased risk of adverse eventsSystematic review of relapse and other adverse events in randomized controlled trialsIntervention targetInterventionOutcome Study DesignOutcome measuresOutcome measures used by physical therapist in studies of patients with MS ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"363jibbk6","properties":{"formattedCitation":"{\\rtf \\super 27\\nosupersub{}}","plainCitation":"27"},"citationItems":[{"id":1006,"uris":[""],"uri":[""],"itemData":{"id":1006,"type":"article-journal","title":"Outcome measures for individuals with multiple sclerosis: recommendations from the American Physical Therapy Association Neurology Section task force","container-title":"Physical Therapy","page":"593-608","volume":"94","issue":"5","source":"PubMed","DOI":"10.2522/ptj.20130149","ISSN":"1538-6724","note":"PMID: 24363338","shortTitle":"Outcome measures for individuals with multiple sclerosis","journalAbbreviation":"Phys Ther","language":"eng","author":[{"family":"Potter","given":"Kirsten"},{"family":"Cohen","given":"Evan T."},{"family":"Allen","given":"Diane D."},{"family":"Bennett","given":"Susan E."},{"family":"Brandfass","given":"Kathi G."},{"family":"Widener","given":"Gail L."},{"family":"Yorke","given":"Amy M."}],"issued":{"date-parts":[["2014",5]]},"PMID":"24363338"}}],"schema":""} 27The Multiple Sclerosis Task Force of the APTA offers a summary of standardized measures used in MS. Systematic literature reviewFall riskHome-based exercise program, education program, and combined exercise-and-education program ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1njva3g363","properties":{"formattedCitation":"{\\rtf \\super 28\\nosupersub{}}","plainCitation":"28"},"citationItems":[{"id":973,"uris":[""],"uri":[""],"itemData":{"id":973,"type":"article-journal","title":"Fall risk and incidence reduction in high risk individuals with multiple sclerosis: a pilot randomized control trial","container-title":"Clinical Rehabilitation","page":"952-960","volume":"29","issue":"10","source":"PubMed","abstract":"OBJECTIVE: To determine the feasibility of three fall prevention programs delivered over 12 weeks among individuals with multiple sclerosis: (A) a home-based exercise program targeting physiological risk factors; (B) an educational program targeting behavioral risk factors; and (C) a combined exercise-and-education program targeting both factors.\nDESIGN: Randomized controlled trial.\nSETTING: Home-based training with assessments at research laboratory.\nPARTICIPANTS: A total of 103 individuals inquired about the investigation. After screening, 37 individuals with multiple sclerosis who had fallen in the last year and ranged in age from 45-75 years volunteered for the investigation. A total of 34 participants completed postassessment following the 12-week intervention.\nINTERVENTION: Participants were randomly assigned into one of four conditions: (1) wait-list control (n = 9); (2) home-based exercise (n = 11); (3) education (n = 9); or (4) a combined exercise and education (n = 8) group.\nMEASURES: Before and after the 12-week interventions, participants underwent a fall risk assessment as determined by the physiological profile assessment and provided information on their fall prevention behaviors as indexed by the Falls Prevention Strategy Survey. Participants completed falls diaries during the three-months postintervention.\nRESULTS: A total of 34 participants completed postintervention testing. Procedures and processes were found to be feasible. Overall, fall risk scores were lower in the exercise groups (1.15 SD 1.31) compared with the non-exercise groups (2.04 SD 1.04) following the intervention (p < 0.01). There was no group difference in fall prevention behaviors (p > 0.05).\nCONCLUSIONS: Further examination of home-based exercise/education programs for reducing falls in individuals with multiple sclerosis is warranted. A total of 108 participants would be needed in a larger randomized controlled trial. #NCT01956227.","DOI":"10.1177/0269215514564899","ISSN":"1477-0873","note":"PMID: 25540170","shortTitle":"Fall risk and incidence reduction in high risk individuals with multiple sclerosis","journalAbbreviation":"Clin Rehabil","language":"eng","author":[{"family":"Sosnoff","given":"Jacob J."},{"family":"Moon","given":"Yaejin"},{"family":"Wajda","given":"Douglas A."},{"family":"Finlayson","given":"Marcia L."},{"family":"McAuley","given":"Edward"},{"family":"Peterson","given":"Elizabeth W."},{"family":"Morrison","given":"Steve"},{"family":"Motl","given":"Robert W."}],"issued":{"date-parts":[["2015",10]]},"PMID":"25540170"}}],"schema":""} 28 Fall risk scores were lower in the exercise group. Randomized, controlled trialFall risk and mobility impairmentsRehabilitation and fall prevention ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2q8a1bo6hf","properties":{"formattedCitation":"{\\rtf \\super 29\\nosupersub{}}","plainCitation":"29"},"citationItems":[{"id":971,"uris":[""],"uri":[""],"itemData":{"id":971,"type":"article-journal","title":"Reducing falls and improving mobility in multiple sclerosis","container-title":"Expert Review of Neurotherapeutics","page":"655-666","volume":"15","issue":"6","source":"PubMed","abstract":"Falls are common in persons with multiple sclerosis (MS), and are related to physical injury and reduce the quality of life. Mobility impairments are a significant risk factor for falls in persons with MS. Although there is evidence that mobility in persons with MS can be improved with rehabilitation, much less is known about fall prevention. This review focuses on fall prevention in persons with MS. Ten fall prevention interventions consisting of 524 participants with a wide range of disability were systematically identified. Nine of the 10 investigations report a reduction in falls and/or proportion of fallers following treatment. The vast majority observed an improvement in balance that co-occurred with the reduction in falls. Methodological limitations preclude any firm conclusions. Numerous gaps in the understanding of fall prevention in persons with MS are discussed. Well-designed randomized control trials targeting mobility and falls are warranted.","DOI":"10.1586/14737175.2015.1046377","ISSN":"1744-8360","note":"PMID: 25973774","journalAbbreviation":"Expert Rev Neurother","language":"eng","author":[{"family":"Sosnoff","given":"Jacob J."},{"family":"Sung","given":"JongHun"}],"issued":{"date-parts":[["2015",6]]},"PMID":"25973774"}}],"schema":""} 29 9 of 10 investigations report reduction in falls after rehab intervention. Improved balance also noted. Literature reviewWalking abilityExercise training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"25ob2v0qbn","properties":{"formattedCitation":"{\\rtf \\super 30\\nosupersub{}}","plainCitation":"30"},"citationItems":[{"id":979,"uris":[""],"uri":[""],"itemData":{"id":979,"type":"article-journal","title":"Exercise as a Therapy for Improvement of Walking Ability in Adults With Multiple Sclerosis: A Meta-Analysis","container-title":"Archives of Physical Medicine and Rehabilitation","page":"1339-1348.e7","volume":"96","issue":"7","source":"CrossRef","DOI":"10.1016/j.apmr.2015.02.011","ISSN":"00039993","shortTitle":"Exercise as a Therapy for Improvement of Walking Ability in Adults With Multiple Sclerosis","language":"en","author":[{"family":"Pearson","given":"Melissa"},{"family":"Dieberg","given":"Gudrun"},{"family":"Smart","given":"Neil"}],"issued":{"date-parts":[["2015",7]]},"accessed":{"date-parts":[["2016",3,7]]}}}],"schema":""} 30Exercise improves walking speed and enduranceMeta-analysis of randomized, controlled trialsWalking mobilityExercise training ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1imiqgrsmc","properties":{"formattedCitation":"{\\rtf \\super 31\\nosupersub{}}","plainCitation":"31"},"citationItems":[{"id":980,"uris":[""],"uri":[""],"itemData":{"id":980,"type":"article-journal","title":"Effect of Exercise Training on Walking Mobility in Multiple Sclerosis: A Meta-Analysis","container-title":"Neurorehabilitation and Neural Repair","page":"108-116","volume":"23","issue":"2","source":"CrossRef","DOI":"10.1177/1545968308320641","ISSN":"1545-9683","shortTitle":"Effect of Exercise Training on Walking Mobility in Multiple Sclerosis","language":"en","author":[{"family":"Snook","given":"E. M."},{"family":"Motl","given":"R. W."}],"issued":{"date-parts":[["2008",11,7]]},"accessed":{"date-parts":[["2016",3,7]]}}}],"schema":""} 31Exercise training is associated with improvement in walking mobilityMeta-analysisUpper extremities 8-week, home-based program ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2mfddcht","properties":{"formattedCitation":"{\\rtf \\super 32\\nosupersub{}}","plainCitation":"32"},"citationItems":[{"id":1078,"uris":[""],"uri":[""],"itemData":{"id":1078,"type":"article-journal","title":"Effects of a Home-Based Upper Limb Training Program in Patients With Multiple Sclerosis: A Randomized Controlled Trial","container-title":"Archives of Physical Medicine and Rehabilitation","source":"PubMed","abstract":"OBJECTIVE: To evaluate the effects of a home-based upper limb training program on arm function in patients with multiple sclerosis (MS). Additionally, the effects of this program on manual dexterity, handgrip strength, and finger prehension force were analyzed.\nDESIGN: Randomized, single-blind controlled trial.\nSETTING: Home based.\nPARTICIPANTS: Patients with a clinical diagnosis of MS acknowledging impaired manual ability (N=37) were randomized into 2 groups.\nINTERVENTIONS: Patients in the experimental group were included in a supervised home-based upper limb training program for 8 weeks twice a week. Patients in the control group received information in the form of a leaflet with a schedule of upper limb exercise training.\nMAIN OUTCOME MEASURES: The primary outcome measure was arm function (motor functioning assessed using the finger tapping test and a functional measure, the Action Research Arm Test). The secondary outcome measures were manual dexterity assessed with the Purdue Pegboard Test and handgrip strength and finger prehension force evaluated with a handgrip and a pinch dynamometer, respectively.\nRESULTS: After 8 weeks, a significant between-group improvement (P<.05) was found on the Action Research Arm Test bilaterally and the finger tapping test in the most affected upper limb. The secondary outcomes also improved in the most affected limb in the experimental group.\nCONCLUSIONS: An 8-week home-based intervention program focused on upper limbs twice a week improved arm function and physiologic variables with a primary focus on the more affected extremity in patients with MS compared with the control group.","DOI":"10.1016/j.apmr.2016.05.018","ISSN":"1532-821X","note":"PMID: 27343343","shortTitle":"Effects of a Home-Based Upper Limb Training Program in Patients With Multiple Sclerosis","journalAbbreviation":"Arch Phys Med Rehabil","language":"ENG","author":[{"family":"Ortiz-Rubio","given":"Araceli"},{"family":"Cabrera-Martos","given":"Irene"},{"family":"Rodríguez-Torres","given":"Janet"},{"family":"Fajardo-Contreras","given":"Waldo"},{"family":"Díaz-Pelegrina","given":"Ana"},{"family":"Valenza","given":"Marie Carmen"}],"issued":{"date-parts":[["2016",6,22]]},"PMID":"27343343"}}],"schema":""} 32Intervention program improved arm function and physiologic variablesRandomized, controlled trialAPTA= American Physical Therapy AssociationQoL= Quality of LifeReferences ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1. 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