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REVIEW ARTICLE (META-ANALYSIS)| Volume 102, ISSUE 12, P2464-2481.e33, December 2021

Physical Activity and the Health of Wheelchair Users: A Systematic Review in Multiple Sclerosis, Cerebral Palsy, and Spinal Cord Injury

Open AccessPublished:October 12, 2021DOI:https://doi.org/10.1016/j.apmr.2021.10.002

      Abstract

      Objective

      To understand the benefits and harms of physical activity in people who may require a wheelchair with a focus on people with multiple sclerosis (MS), cerebral palsy (CP), and spinal cord injury (SCI).

      Data Sources

      Searches were conducted in MEDLINE, Cumulative Index to Nursing and Allied Health, PsycINFO, Cochrane CENTRAL, and Embase (January 2008 through November 2020).

      Study Selection

      Randomized controlled trials, nonrandomized trials, and cohort studies of observed physical activity (at least 10 sessions on 10 days) in participants with MS, CP, and SCI.

      Data Extraction

      We conducted dual data abstraction, quality assessment, and strength of evidence. Measures of physical functioning are reported individually where sufficient data exist and grouped as “function” where data are scant.

      Data Synthesis

      No studies provided evidence for prevention of cardiovascular conditions, development of diabetes, or obesity. Among 168 included studies, 44% enrolled participants with MS (38% CP, 18% SCI). Studies in MS found walking ability may be improved with treadmill training and multimodal exercises; function may be improved with treadmill, balance exercises, and motion gaming; balance is likely improved with balance exercises and may be improved with aquatic exercises, robot-assisted gait training (RAGT), motion gaming, and multimodal exercises; activities of daily living (ADL), female sexual function, and spasticity may be improved with aquatic therapy; sleep may be improved with aerobic exercises and aerobic fitness with multimodal exercises. In CP, balance may be improved with hippotherapy and motion gaming; function may be improved with cycling, treadmill, and hippotherapy. In SCI, ADL may be improved with RAGT.

      Conclusions

      Depending on population and type of exercise, physical activity was associated with improvements in walking, function, balance, depression, sleep, ADL, spasticity, female sexual function, and aerobic capacity. Few harms of physical activity were reported in studies. Future studies are needed to address evidence gaps and to confirm findings.

      Keywords

      List of abbreviations:

      ADL (activities of daily living), AHRQ (Agency for Healthcare Research and Quality), CP (cerebral palsy), MS (multiple sclerosis), RCT (randomized controlled trial), RAGT (robot-assisted gait training), SCI (spinal cord injury), Vo2peak (peak oxygen consumption)
      The benefits of regular physical activity for the general population include reduced risk of heart disease, stroke, type 2 diabetes, dementia, depression, and various cancers (eg, breast, colon, lung cancer).

      Physical Activity Guidelines Advisory Committee. 2008 Physical Activity Guidelines for Americans. Available at: https://health.gov/paguidelines/2008/. Accessed February 27, 2020.

      Although routine physical activity combining aerobic exercise with strength and balance training is recommended for people with physical disabilities,

      2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Available at: https://health.gov/paguidelines/second-edition/report/pdf/PAG_Advisory_Committee_Report.pdf. Accessed February 27, 2020.

      less is known about the specific benefits and potential harms for this diverse population. In particular, the various populations using wheelchairs because of their physical disabilities is broad and poorly captured in the literature on physical activity; thus, we expanded our criteria for study inclusion beyond “wheelchair users.” This review includes 3 diverse conditions commonly associated with wheelchair use: multiple sclerosis (MS), cerebral palsy (CP), and spinal cord injury (SCI). One survey estimated that 45% of patients with MS have difficulties with mobility shortly after diagnosis and almost all have mobility issues after 10 years.
      • van Asch P
      Impact of mobility impairment in multiple sclerosis 2—patient perspectives.
      One study found 29% of children aged 3-18 years used a wheelchair indoors and 41% used a wheelchair outdoors.
      • Rodby-Bousquet E
      • Hägglund G
      Use of manual and powered wheelchair in children with cerebral palsy: a cross-sectional study.
      Depending on the level and extent of spinal cord injury, many persons with SCI require a wheelchair for all mobility.
      These 3 conditions not only represent different etiologies and pathophysiologies but different populations as well. Studies enrolling a population with MS are often in adult women, studies enrolling people with SCI are largely in adult men, and studies enrolling participants with CP are often in children and adolescents.
      The review was conducted to inform a National Institutes of Health Pathways to Prevention Workshop and guideline development on “Can Physical Activity Improve the Health of Wheelchair Users?” to evaluate evidence on the benefits and risks of physical activity for potential and current wheelchair users (https://prevention.nih.gov/research-priorities/research-needs-and-gaps/pathways-prevention/can-physical-activity-improve-health-wheelchair-users) and was nominated to the Agency for Healthcare Research and Quality (AHRQ), who funded this review (AHRQ contract no. HHSA290201500009I). AHRQ did not participate in the literature search, determination of study eligibility criteria, data analysis, or interpretation of findings.

      Methods

      This systematic review summarizes and synthesizes current research on the specific benefits and potential harms of physical activity for people with MS, CP, and SCI, regardless of current use of a wheelchair. This topic was nominated by the Director of the National Center for Medical Rehabilitation Research and supported by the National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, the National Institutes of Health Office of Disease Prevention, and the National Institutes of Health Medical Rehabilitation Coordinating Committee, along with other federal partners for a Pathways to Prevention workshop to assess the benefits and harms of physical activity on the physical and mental health of adults, children, and adolescents using a wheelchair or who may benefit from using a wheelchair in the future. Prior to conducting this review, the Evidence-based Practice Center refined the preliminary Key Questions and PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, Studies, Settings) with the AHRQ Task Order Officer and representatives from National Institutes of Health (tables 1 and 2). In considering studies related to physical activity among 3 representative populations, we prioritized certain outcomes. These include long-term health outcomes, function, activities of daily living, and quality of life, among others. We considered walking, balance, activities of daily living (ADL), and other outcomes individually when data permitted. When data were sparse, we grouped different outcomes under the umbrella term “function” to determine whether an intervention was beneficial or not overall. Individual study findings can be found in the supplemental tables S1-4 (available online only at http://www.archives-pmr.org/). We also specify the type of function involve in the summary of evidence table 3 (eg, mobility includes standing, stepping, walking, running, and jumping). Specific outcomes included in each function domain are found in supplemental table S5 (available online only at http://www.archives-pmr.org/). We evaluated outcomes of diverse physical activity interventions, inclusion/exclusion criteria, and research methodologies to identify future research needs. The protocol was published on the AHRQ website (https://effectivehealthcare.ahrq.gov/sites/default/files/pdf/wheelchair-users-amended-protocol.pdf). The protocol for this review was also submitted to the PROSPERO systematic review registry (CRD42019130060). Comprehensive methods including the search strategies, evidence tables, and study quality ratings are in the full report (in press to be available at https://effectivehealthcare.ahrq.gov/).
      Table 1PICOTS—inclusion and exclusion criteria
      PICOTSInclusionExclusion
      PopulationsPatients using a wheelchair or those who may benefit from using a wheelchair in the future because of MS, CP, or SCI. All ages included.• Other populations

      • Studies of mixed populations with <80% MS, CP, SCI
      InterventionsAny gross motor intervention with a defined period of directed physical activity that is expected to increase energy expenditure. Intervention must have a minimum of 10 sessions of activity on 10 d or more in a supervised or group setting. Include aerobic exercise, strength training, standing, balance, flexibility, and combination interventions.

      Included activities (not exhaustive, additional activities may qualify):

      Balance/flexibility

      • Stretching/flexibility

      • Yoga or Pilates

      • Martial arts (eg, tai chi)

      • Hippotherapy (equine-assisted therapy)

      Physical/aerobic exercise

      • Arm ergometry

      • Cycling (stationary, recumbent, arm)

      • Weight lifting/strength training

      • Functional electronic stimulation

      • Robot-assisted gait training

      • Swimming

      • Aquatic therapy

      • Group exercise

      • Team sports

      • Treadmill (including with body weight support)

      Strength/resistance training

      • Resistance bands

      • Weight lifting
      • Interventions with <10 sessions

      • Interventions over a period lasting <10 d

      • Unobserved physical activity

      • Family- or caregiver-observed physical activity

      • Patient-recalled physical activity

      • Postoperative physical activity

      • Intervention focused on improving reaching

      • Interventions without whole body effect (eg, targeting one joint)

      • Intervention reported in only one study
      ComparatorsComparisons with no physical activity or other types of physical activity or behavioral counseling.• All other active controls
      OutcomesCardiovascular

      • Cardiovascular mortality, myocardial infarction, stroke, all-cause mortality, resting heart rate, resting blood pressure, lipid profile

      Respiratory

      • Pulmonary function tests, V̇o2max/Vo2peak, spirometry

      Endocrine

      • Development of diabetes, Hb A1c, fasting blood glucose, development of metabolic syndrome, metabolic rate

      Gastrointestinal

      • Bowel function, bowel impaction

      Genitourinary

      • Bladder function, urinary tract infection

      Musculoskeletal

      • Fracture, bone mineral density, muscle strength, rotator cuff injury, shoulder pain, range of motion

      Reproductive

      • Sexual function
      • Outcomes not used to make clinical decisions (eg, estradiol)

      • Other outcomes (eg, head pitch and roll, kinematic variables, stepping kinematics, reaching, muscle thickness, muscle quality, blood flow restriction, premotoneuronal control)

      • Hospitalization or length of stay

      • Cognition

      • Pain other than shoulder pain
      Integumentary

      • Decubitus ulcers

      Body composition

      • Weight, BMI, development of obesity, waist circumference, % body fat

      Mental health

      • Depression, quality of life, anxiety, stress, sleep

      General function

      • Walking, falls, wheelchair use, function scales, disability, ADL, balance, physical fitness

      Neurologic

      • Autonomic dysreflexia, spasticity, thermodysregulation, carpal tunnel syndrome
      TimingAt least 10 d with at least 1 session of physical activity per day.• Acute SCI, undergoing stabilization

      • Immediate postoperative period
      SettingAny setting, including, clinic, home, or community setting (eg, gym or athletic class). Physical activity occurring in the home must still be observed by medical, research, or athletic staff.• Non-US applicable studies
      Study designs• Randomized controlled trials published since 2008

      • Controlled observational studies published since 2008

      • Systematic reviews published since 2014 to review for additional studies meeting inclusion criteria

      • Potentially include pre-post studies in the absence of clinical trials and controlled observational studies

      • Studies with the following sample sizes: MS (N≥30), CP (N≥20), SCI (N≥20).
      • All other study designs (eg, case series, case reports)

      • Studies published before 2008

      • Systematic reviews published before 2015
      Abbreviations: BMI, body mass index; Hb A1c, glycosylated hemoglobin; US, United States; V̇o2max, maximum oxygen consumption.
      Table 2Overview of included studies by intervention category and population
      Studies with multiple interventions appear more than once on the table. Studies with only intermediate outcome(s) appear in full report tables.
      CategoryInterventionMultiple Sclerosis

      n=74

      (85 Publications)
      Cerebral Palsy

      n=63

      (73 Publications)
      Spinal Cord Injury

      n=31

      (39 Publications)
      Total Studies

      N=168

      (197 Publications)
      Aerobic exerciseAerobics4 RCTs
      • Young HJ
      • Mehta TS
      • Herman C
      • et al.
      The effects of M2M and adapted yoga on physical and psychosocial outcomes in people wth multiple sclerosis.
      • Al-Sharman A
      • Khalil H
      • El-Salem K
      • et al.
      The effects of aerobic exercise on sleep quality measures and sleep-related biomarkers in individuals with multiple sclerosis: a pilot randomised controlled trial.
      • Aydin T
      • Akif Sariyildiz M
      • Guler M
      • et al.
      Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis.


      2 quasi-experimental studies
      • Sadeghi Bahmani D
      • Razazian N
      • Farnia V
      • et al.
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      • Kara B
      • Kucuk F
      • Poyraz EC
      • et al.
      Different types of exercise in multiple sclerosis: aerobic exercise or Pilates, a single-blind clinical study.
      • Keser I
      • Meric A
      • Kirdi N
      • et al.
      Comparing routine neurorehabilitation programme with callisthenic exercises in multiple sclerosis.
      2 RCTs
      • Teixeira-Machado L
      • Azevedo-Santos I
      • Desantana JM
      Dance improves functionality and psychosocial adjustment in cerebral palsy: a randomized controlled clinical trial.
      ,
      • Gibson N
      • Chappell A
      • Blackmore AM
      • et al.
      The effect of a running intervention on running ability and participation in children with cerebral palsy: a randomized controlled trial.
      No studiesn=8

      6 RCTs

      2 quasi-experimental studies
      Aerobic exerciseAquatics6 RCTs
      • Castro-Sanchez AM
      • Mataran-Penarrocha GA
      • Lara-Palomo I
      • et al.
      Hydrotherapy for the treatment of pain in people with multiple sclerosis: a randomized controlled trial.
      • Sadeghi Bahmani D
      • Motl RW
      • Razazian N
      • et al.
      Aquatic exercising may improve sexual function in females with multiple sclerosis - an exploratory study.
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized controlled trial to examine the impact of aquatic exercise training on functional capacity, balance, and perceptions of fatigue in female patients with multiple sclerosis.
      • Marandi SM
      • Nejad VS
      • Shanazari Z
      • et al.
      A comparison of 12 weeks of Pilates and aquatic training on the dynamic balance of women with mulitple sclerosis.
      • Marandi SM
      • Shahnazari Z
      • Minacian V
      • et al.
      A comparison between Pilates exercise and aquatic training effects on mascular strength in women with mulitple sclerosis.
      • Razazian N
      • Yavari Z
      • Farnia V
      • et al.
      Exercising impacts on fatigue, depression, and paresthesia in female patients with multiple sclerosis.
      • Kooshiar H
      • Moshtagh M
      • Sardar MA
      • et al.
      Fatigue and quality of life of women with multiple sclerosis: a randomized controlled clinical trial.
      1 RCT
      • Adar S
      • Dundar U
      • Demirdal ÜS
      • et al.
      The effect of aquatic exercise on spasticity, quality of life, and motor function in cerebral palsy.


      1 cohort study
      • Lai CJ
      • Liu WY
      • Yang TF
      • et al.
      Pediatric aquatic therapy on motor function and enjoyment in children diagnosed with cerebral palsy of various motor severities.
      2 RCTs
      • Gorman PH
      • Scott W
      • VanHiel L
      • et al.
      Comparison of peak oxygen consumption response to aquatic and robotic therapy in individuals with chronic motor incomplete spinal cord injury: a randomized controlled trial.
      ,
      • Jung J
      • Chung E
      • Kim K
      • et al.
      The effects of aquatic exercise on pulmonary function in patients with spinal cord injury.
      n=10

      9 RCTs

      1 cohort study
      Aerobic exerciseCycling7 RCTs
      • Negaresh R
      • Motl R
      • Mokhtarzade M
      • et al.
      Effect of short-term interval excercise training on fatigue, depression, and fitness in normal weight vs. overweight person with multiple sclerosis.
      • Hochsprung A
      • Granja Dominguez A
      • Magni E
      • et al.
      Effect of visual biofeedback cycling training on gait in patients with multiple sclerosis.
      • Baquet L
      • Hasselmann H
      • Patra S
      • et al.
      Short-term interval aerobic exercise training does not improve memory functioning in relapsing-remitting multiple sclerosis-a randomized controlled trial.
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      • Heine M
      • Verschuren O
      • Hoogervorst EL
      • et al.
      Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.
      • Hebert JR
      Effects of vestibular rehabilitation on MS-related fatigue: randomized control trial.
      • Collett J
      • Dawes H
      • Meaney A
      • et al.
      Exercise for multiple sclerosis: a single-blind randomized trial comparing three exercise intensities.


      1 quasi-experimental study
      • Niwald M
      • Redlicka J
      • Miller E
      The effects of aerobic training on the functional status, quality of life, the level of fatigue and disability in patients with multiple sclerosis-a preliminary report.
      2 RCTs
      • Bryant E
      • Pountney T
      • Williams H
      • et al.
      Can a six-week exercise intervention improve gross motor function for non-ambulant children with cerebral palsy? A pilot randomized controlled trial.
      • Demuth SK
      • Knutson LM
      • Fowler EG
      The PEDALS stationary cycling intervention and health-related quality of life in children with cerebral palsy: a randomized controlled trial.
      • Fowler EG
      • Knutson LM
      • Demuth SK
      • et al.
      Pediatric endurance and limb strengthening (PEDALS) for children with cerebral palsy using stationary cycling: a randomized controlled trial.


      1 quasi-experimental study
      • Nsenga AL
      • Shephard RJ
      • Ahmaidi S
      Aerobic training in children with cerebral palsy.
      1 RCT
      • Akkurt H
      • Karapolat HU
      • Kirazli Y
      • et al.
      The effects of upper extremity aerobic exercise in patients with spinal cord injury: a randomized controlled study.


      1 cohort study
      • Sadowsky CL
      • Hammond ER
      • Strohl AB
      • et al.
      Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord injury.


      1 quasi-experimental study
      • Lai CH
      • Chang WH
      • Chan WP
      • et al.
      Effects of functional electrical stimulation cycling exercise on bone mineral density loss in the early stages of spinal cord injury.
      n=14

      10 RCTs

      3 quasi-experimental studies

      1 cohort study
      Aerobic exerciseHand cyclingNo studiesNo studies2 RCTs
      • Akkurt H
      • Karapolat HU
      • Kirazli Y
      • et al.
      The effects of upper extremity aerobic exercise in patients with spinal cord injury: a randomized controlled study.
      ,
      • Lavado EL
      • Cardoso JR
      • Silva LG
      • et al.
      Effectiveness of aerobic physical training for treatment of chronic asymptomatic bacteriuria in subjects with spinal cord injury: a randomized controlled trial.


      1 cohort study
      • Valent L
      • Dallmeijer A
      • Houdijk H
      • et al.
      Effects of hand cycle training on wheelchair capacity during clinical rehabilitation in persons with a spinal cord injury.
      n=3 studies

      2 RCTs

      1 cohort study
      Aerobic exerciseRobot-assisted gait training5 RCTs
      • Russo M
      • Dattola V
      • De Cola MC
      • et al.
      The role of robotic gait training coupled with virtual reality in boosting the rehabilitative outcomes in patients with multiple sclerosis.
      • Straudi S
      • Fanciullacci C
      • Martinuzzi C
      • et al.
      The effects of robot-assisted gait training in progressive multiple sclerosis: a randomized controlled trial.
      • Straudi S
      • Manfredini F
      • Lamberti N
      • et al.
      Robot-assisted gait training is not superior to intensive overground walking in multiple sclerosis with severe disability (the RAGTIME study): a randomized controlled trial.
      • Pompa A
      • Morone G
      • Iosa M
      • et al.
      Does robot-assisted gait training improve ambulation in highly disabled multiple sclerosis people? A pilot randomized control trial.
      • Calabro RS
      • Russo M
      • Naro A
      • et al.
      Robotic gait training in multiple sclerosis rehabilitation: can virtual reality make the difference? Findings from a randomized controlled trial.
      5 RCTs
      • Wu M
      • Kim J
      • Arora P
      • et al.
      Effects of the integration of dynamic weight shifting training into treadmill training on walking function of children with cerebral palsy: a randomized controlled study.
      • Wu M
      • Kim J
      • Gaebler-Spira DJ
      • et al.
      Robotic resistance treadmill training improves locomotor function in children with cerebral palsy: a randomized controlled pilot study.
      • Wallard L
      • Dietrich G
      • Kerlirzin Y
      • et al.
      Robotic-assisted gait training improves walking abilities in diplegic children with cerebral palsy.
      • Wallard L
      • Dietrich G
      • Kerlirzin Y
      • et al.
      Effect of robotic-assisted gait rehabilitation on dynamic equilibrium control in the gait of children with cerebral palsy.
      • Aras B
      • Yasar E
      • Kesikburun S
      • et al.
      Comparison of the effectiveness of partial body weight-supported treadmill exercises, robotic-assisted treadmill exercises, and anti-gravity treadmill exercises in spastic cerebral palsy.
      • Klobucka S
      • Klobucky R
      • Kollar B
      Effect of robot-assisted gait training on motor functions in adolescent and young adult patients with bilateral spastic cerebral palsy: a randomized controlled trial.


      1 quasi-experimental study
      • Peri E
      • Turconi AC
      • Biffi E
      • et al.
      Effects of dose and duration of robot-assisted gait training on walking ability of children affected by cerebral palsy.


      1 cohort study
      • Yazici M
      • Livanelioglu A
      • Gucuyener K
      • et al.
      Effects of robotic rehabilitation on walking and balance in pediatric patients with hemiparetic cerebral palsy.
      8 RCTs
      • Esclarin-Ruz A
      • Alcobendas-Maestro M
      • Casado-Lopez R
      • et al.
      A comparison of robotic walking therapy and conventional walking therapy in individuals with upper versus lower motor neuron lesions: a randomized controlled trial.
      • Yildirim MA
      • Ones K
      • Goksenoglu G
      Early term effects of robotic assisted gait training on ambulation and functional capacity in patients with spinal cord injury.
      • Field-Fote EC
      • Roach KE
      Influence of a locomotor training approach on walking speed and distance in people with chronic spinal cord injury: a randomized clinical trial.
      • Sandler EB
      • Roach KE
      • Field-Fote EC
      Dose-response outcomes associated with different forms of locomotor training in persons with chronic motor-incomplete spinal cord injury.
      • Kressler J
      • Nash MS
      • Burns PA
      • et al.
      Metabolic responses to 4 different body weight-supported locomotor training approaches in persons with incomplete spinal cord injury.
      • Kumru H
      • Benito-Penalva J
      • Valls-Sole J
      • et al.
      Placebo-controlled study of rTMS combined with Lokomat gait training for treatment in subjects with motor incomplete spinal cord injury.
      • Shin JC
      • Kim JY
      • Park HK
      • et al.
      Effect of robotic-assisted gait training in patients with incomplete spinal cord injury.
      • Huang Q
      • Yu L
      • Gu R
      • et al.
      Effects of robot training on bowel function in patients with spinal cord injury.
      • Duffell LD
      • Niu X
      • Brown G
      • et al.
      Variability in responsiveness to interventions in people with spinal cord injury: do some respond better than others?.
      • Midik M
      • Paker N
      • Bugdayci D
      • et al.
      Effects of robot-assisted gait training on lower extremity strength, functional independence, and walking function in men with incomplete traumatic spinal cord injury.


      n=20 studies

      18 RCTs

      1 quasi-experimental study

      1 cohort study
      Aerobic exerciseTreadmill4 RCTs
      • Gervasoni E
      • Cattaneo D
      • Jonsdottir J
      Effect of treadmill training on fatigue in multiple sclerosis: a pilot study.
      • Ahmadi A
      • Arastoo AA
      • Nikbakht M
      • et al.
      Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients.
      • Jonsdottir J
      • Gervasoni E
      • Bowman T
      • et al.
      Intensive multimodal training to improve gait resistance, mobility, balance and cognitive function in persons with multiple sclerosis: a pilot randomized controlled trial.
      • Samaei A
      • Bakhtiary AH
      • Hajihasani A
      • et al.
      Uphill and downhill walking in multiple sclerosis: a randomized controlled trial.
      10 RCTs
      • Bahrami F
      • Noorizadeh Dehkordi S
      • Dadgoo M
      The efficacy of treadmill training on walking and quality of life of adults with spastic cerebral palsy: a randomized controlled trial.
      • Chrysagis N
      • Skordilis EK
      • Stavrou N
      • et al.
      The effect of treadmill training on gross motor function and walking speed in ambulatory adolescents with cerebral palsy: a randomized controlled trial.
      • Willoughby KL
      • Dodd KJ
      • Shields N
      • et al.
      Efficacy of partial body weight-supported treadmill training compared with overground walking practice for children with cerebral palsy: a randomized controlled trial.
      • Swe NN
      • Sendhilnnathan S
      • van Den Berg M
      • et al.
      Over ground walking and body weight supported walking improve mobility equally in cerebral palsy: a randomised controlled trial.
      • Emara HA
      • El-Gohary TM
      • Al-Johany AA
      Effect of body-weight suspension training versus treadmill training on gross motor abilities of children with spastic diplegic cerebral palsy.
      • Grecco LA
      • Zanon N
      • Sampaio LM
      • et al.
      A comparison of treadmill training and overground walking in ambulant children with cerebral palsy: randomized controlled clinical trial.
      • Grecco LA
      • de Almeida Carvalho Duarte N
      • Mendonca ME
      • et al.
      Transcranial direct current stimulation during treadmill training in children with cerebral palsy: a randomized controlled double-blind clinical trial.
      • Johnston TE
      • Watson KE
      • Ross SA
      • et al.
      Effects of a supported speed treadmill training exercise program on impairment and function for children with cerebral palsy.
      • Kim OY
      • Shin YK
      • Yoon YK
      • et al.
      The effect of treadmill exercise on gait efficiency during overground walking in adults with cerebral palsy.
      • Duarte Nde A
      • Grecco LA
      • Galli M
      • et al.
      Effect of transcranial direct-current stimulation combined with treadmill training on balance and functional performance in children with cerebral palsy: a double-blind randomized controlled trial.


      2 quasi-experimental studies
      • Nsenga Leunkeu A
      • Shephard RJ
      • Ahmaidi S
      Six-minute walk test in children with cerebral palsy gross motor function classification system levels I and II: reproducibility, validity, and training effects.
      ,
      • Aviram R
      • Harries N
      • Namourah I
      • et al.
      Effects of a group circuit progressive resistance training program compared with a treadmill training program for adolescents with cerebral palsy.
      6 RCTs
      • Huang Q
      • Yu L
      • Gu R
      • et al.
      Effects of robot training on bowel function in patients with spinal cord injury.
      ,
      • van der Scheer JW
      • de Groot S
      • Tepper M
      • et al.
      Low-intensity wheelchair training in inactive people with long-term spinal cord injury: a randomized controlled trial on fitness, wheelchair skill performance and physical activity levels.
      • Yang JF
      • Musselman KE
      • Livingstone D
      • et al.
      Repetitive mass practice or focused precise practice for retraining walking after incomplete spinal cord injury? A pilot randomized clinical trial.
      • Alexeeva N
      • Sames C
      • Jacobs PL
      • et al.
      Comparison of training methods to improve walking in persons with chronic spinal cord injury: a randomized clinical trial.
      • Giangregorio L
      • Craven C
      • Richards K
      • et al.
      A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: effects on body composition.
      • Hitzig SL
      • Craven BC
      • Panjwani A
      • et al.
      Randomized trial of functional electrical stimulation therapy for walking in incomplete spinal cord injury: effects on quality of life and community participation.
      • Kapadia N
      • Masani K
      • Catharine Craven B
      • et al.
      A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: effects on walking competency.
      • Craven BC
      • Giangregorio LM
      • Alavinia SM
      • et al.
      Evaluating the efficacy of functional electrical stimulation therapy assisted walking after chronic motor incomplete spinal cord injury: effects on bone biomarkers and bone strength.
      • Musselman KE
      • Yang JF
      Spinal cord injury functional ambulation profile: a preliminary look at responsiveness.
      n=22

      20 RCTs

      2 quasi-experimental studies
      Postural controlBalance exercises12 RCTs
      • Sadeghi Bahmani D
      • Razazian N
      • Farnia V
      • et al.
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      ,
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      • Brichetto G
      • Piccardo E
      • Pedulla L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: a pilot randomized, controlled study.
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: a randomized, controlled trial.
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: a multi-centre, randomized, controlled pilot study.
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-based individualized comprehensive core stability intervention improves balance in persons with multiple sclerosis: a randomized controlled trial.
      • Forsberg A
      • von Koch L
      • Nilsagard Y
      Effects on balance and walking with the CoDuSe balance exercise program in people with multiple sclerosis: a multicenter randomized controlled trial.
      • Amiri B
      • Sahebozamani M
      • Sedighi B
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: a single-blinded randomized controlled trial.
      • Salci Y
      • Fil A
      • Armutlu K
      • et al.
      Effects of different exercise modalities on ataxia in multiple sclerosis patients: a randomized controlled study.
      • Arntzen EC
      • Straume B
      • Odeh F
      • et al.
      Group-based, individualized, comprehensive core stability and balance intervention provides immediate and long-term improvements in walking in individuals with multiple sclerosis: a randomized controlled trial.
      1 RCT
      • Curtis DJ
      • Woollacott M
      • Bencke J
      • et al.
      The functional effect of segmental trunk and head control training in moderate-to-severe cerebral palsy: a randomized controlled trial.


      2 quasi-experimental studies
      • Bleyenheuft Y
      • Ebner-Karestinos D
      • Surana B
      • et al.
      Intensive upper- and lower-extremity training for children with bilateral cerebral palsy: a quasi-randomized trial.
      ,
      • Lorentzen J
      • Greve LZ
      • Kliim-Due M
      • et al.
      Twenty weeks of home-based interactive training of children with cerebral palsy improves functional abilities.


      1 cohort study
      • Kim BJ
      • Kim SM
      • Kwon HY
      The effect of group exercise program on the self-efficacy and activities of daily living in adults with cerebral palsy.
      2 RCT
      • Hota D
      • Das S
      • Joseph NM
      Effect of dual task exercise to develop body balance, movement co-ordination and walking speed among post cervical injury clients.
      ,
      • Norouzi E
      • Vaezmousavi M
      Neurofeedback training and physical training differentially impacted on reaction time and balance skills among Iranian veterans with spinal cord injury.


      n=18

      15 RCTs

      2 quasi-experimental studies

      1 cohort study
      Postural controlHippotherapy2 RCTs
      • Vermohlen V
      • Schiller P
      • Schickendantz S
      • et al.
      Hippotherapy for patients with multiple sclerosis: a multicenter randomized controlled trial (MS-HIPPO).
      • Wollenweber V
      • Drache M
      • Schickendantz S
      • et al.
      Study of the effectiveness of hippotherapy on the symptoms of multiple sclerosis - outline of a randomised controlled multicentre study (MS-HIPPO).
      • Moraes AG
      • Neri SGR
      • Motl RW
      • et al.
      Effect of hippotherapy on walking performance and gait parameters in people with multiple sclerosis.
      8 RCTs
      • Kwon JY
      • Chang HJ
      • Yi SH
      • et al.
      Effect of hippotherapy on gross motor function in children with cerebral palsy: a randomized controlled trial.
      • Lee CW
      • Kim SG
      • Na SS
      The effects of hippotherapy and a horse riding simulator on the balance of children with cerebral palsy.
      • Deutz U
      • Heussen N
      • Weigt-Usinger K
      • et al.
      Impact of hippotherapy on gross motor function and quality of life in children with bilateral cerebral palsy: a randomized open-label crossover study.
      • Herrero P
      • Gomez-Trullen EM
      • Asensio A
      • et al.
      Study of the therapeutic effects of a hippotherapy simulator in children with cerebral palsy: a stratified single-blind randomized controlled trial.
      • Silva e Borges MB
      • Werneck MJ
      • da Silva Mde L
      • et al.
      Therapeutic effects of a horse riding simulator in children with cerebral palsy.
      • Mutoh T
      • Mutoh T
      • Tsubone H
      • et al.
      Impact of long-term hippotherapy on the walking ability of children with cerebral palsy and quality of life of their caregivers.
      • Matusiak-Wieczorek E
      • Dziankowska-Zaborszczyk E
      • Synder M
      • et al.
      The influence of hippotherapy on the body posture in a sitting position among children with cerebral palsy.
      • Lucena-Anton D
      • Rosety-Rodriguez I
      • Moral-Munoz JA
      Effects of a hippotherapy intervention on muscle spasticity in children with cerebral palsy: a randomized controlled trial.


      2 quasi-experimental studies
      • Kwon JY
      • Chang HJ
      • Lee JY
      • et al.
      Effects of hippotherapy on gait parameters in children with bilateral spastic cerebral palsy.
      ,
      • Matusiak-Wieczorek E
      • Malachowska-Sobieska M
      • Synder M
      Influence of hippotherapy on body balance in the sitting position among children with cerebral palsy.


      1 cohort study
      • Park ES
      • Rha DW
      • Shin JS
      • et al.
      Effects of hippotherapy on gross motor function and functional performance of children with cerebral palsy.
      No studiesn=13 studies

      10 RCTs

      2 quasi-experimental studies

      1 cohort study
      Postural controlTai chi1 RCT
      • Azimzadeh E
      • Hosseini MA
      • Nourozi K
      • et al.
      Effect of tai chi chuan on balance in women with multiple sclerosis.


      1 quasi-experimental study
      • Burschka JM
      • Keune PM
      • Oy UH
      • et al.
      Mindfulness-based interventions in multiple sclerosis: beneficial effects of tai chi on balance, coordination, fatigue and depression.
      No studies

      1 RCT
      • Qi Y
      • Zhang X
      • Zhao Y
      • et al.
      The effect of wheelchair tai chi on balance control and quality of life among survivors of spinal cord injuries: a randomized controlled trial.


      n=3 studies

      2 RCTs

      1 quasi-experimental study
      Postural controlMotion gaming6 RCTs
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: a single-blinded randomized controlled trial.
      ,
      • Kalron A
      • Fonkatz I
      • Frid L
      • et al.
      The effect of balance training on postural control in people with multiple sclerosis using the CAREN virtual reality system: a pilot randomized controlled trial.
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: a randomized controlled trial.
      • Nilsagard YE
      • Forsberg AS
      • von Koch L
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      • Khalil H
      • Al-Sharman A
      • El-Salem K
      • et al.
      The development and pilot evaluation of virtual reality balance scenarios in people with multiple sclerosis (MS): a feasibility study.


      7 RCTs
      • Hsieh HC
      Effects of a gaming platform on balance training for children with cerebral palsy.
      • Hsieh HC
      Preliminary study of the effect of training with a gaming balance board on balance control in children with cerebral palsy: a randomized controlled trial.
      • Tarakci D
      • Ersoz Huseyinsinoglu B
      • Tarakci E
      • et al.
      Effects of Nintendo Wii-Fit® video games on balance in children with mild cerebral palsy.
      • Pourazar M
      • Bagherzadeh F
      • Mirakhori F
      Virtual reality training improves dynamic balance in children with cerebral palsy.
      • Acar G
      • Altun GP
      • Yurdalan S
      • et al.
      Efficacy of neurodevelopmental treatment combined with the Nintendo Wii in patients with cerebral palsy.
      • Zoccolillo L
      • Morelli D
      • Cincotti F
      • et al.
      Video-game based therapy performed by children with cerebral palsy: a cross-over randomized controlled trial and a cross-sectional quantitative measure of physical activity.
      • El-Shamy SM
      Efficacy of Armeo robotic therapy versus conventional therapy on upper limb function in children with hemiplegic cerebral palsy.
      1 RCT
      • Tak S
      • Choi W
      • Lee S
      Game-based virtual reality training improves sitting balance after spinal cord injury: a single-blinded, randomized controlled trial.
      n=14 studies

      14 RCTs
      Postural controlWhole body vibration2 RCTs
      • Claerbout M
      • Gebara B
      • Ilsbroukx S
      • et al.
      Effects of 3 weeks' whole body vibration training on muscle strength and functional mobility in hospitalized persons with multiple sclerosis.
      ,
      • Abbasi M
      • Kordi Yoosefinejad A
      • Poursadeghfard M
      • et al.
      Whole body vibration improves core muscle strength and endurance in ambulant individuals with multiple sclerosis: a randomized clinical trial.
      2 RCTs
      • Lee BK
      • Chon SC
      Effect of whole body vibration training on mobility in children with cerebral palsy: a randomized controlled experimenter-blinded study.
      ,
      • Ahmadizadeh Z
      • Khalili MA
      • Ghalam MS
      • et al.
      Effect of whole body vibration with stretching exercise on active and passive range of motion in lower extremities in children with cerebral palsy: a randomized clinical trial.
      1 RCT
      • In T
      • Jung K
      • Lee MG
      • et al.
      Whole-body vibration improves ankle spasticity, balance, and walking ability in individuals with incomplete cervical spinal cord injury.


      5 RCTs
      • Ahmadi A
      • Arastoo AA
      • Nikbakht M
      • et al.
      Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients.
      ,
      • Garrett M
      • Hogan N
      • Larkin A
      • et al.
      Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial.
      • Garrett M
      • Hogan N
      • Larkin A
      • et al.
      Exercise in the community for people with multiple sclerosis–a follow-up of people with minimal gait impairment.
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The effect of community exercise interventions for people with MS who use bilateral support for gait.
      • Doulatabad SN
      • Nooreyan K
      • Doulatabad AN
      • et al.
      The effects of pranayama, hatha and raja yoga on physical pain and the quality of life of women with multiple sclerosis.
      • Najafidoulatabad S
      • Mohebbi Z
      • Nooryan K
      Yoga effects on physical activity and sexual satisfaction among the Iranian women with multiple sclerosis: a randomized controlled trial.
      • Hasanpour-Dehkordi A
      Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status in patients with multiple sclerosis: a randomized trial.
      • Hasanpour-Dehkordi A
      • Jivad N
      • Solati K
      Effects of yoga on physiological indices, anxiety and social functioning in multiple sclerosis patients: a randomized trial.
      • Hasanpour-Dehkordi A
      • Jivad N
      Comparison of regular aerobic and yoga on the quality of life in patients with multiple sclerosis.
      n=5 studies

      5 RCTs
      Postural controlYoga6 RCTs
      • Young HJ
      • Mehta TS
      • Herman C
      • et al.
      The effects of M2M and adapted yoga on physical and psychosocial outcomes in people wth multiple sclerosis.
      ,
      • Ahmadi A
      • Arastoo AA
      • Nikbakht M
      • et al.
      Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients.
      ,
      • Garrett M
      • Hogan N
      • Larkin A
      • et al.
      Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial.
      • Garrett M
      • Hogan N
      • Larkin A
      • et al.
      Exercise in the community for people with multiple sclerosis–a follow-up of people with minimal gait impairment.
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The effect of community exercise interventions for people with MS who use bilateral support for gait.
      • Doulatabad SN
      • Nooreyan K
      • Doulatabad AN
      • et al.
      The effects of pranayama, hatha and raja yoga on physical pain and the quality of life of women with multiple sclerosis.
      • Najafidoulatabad S
      • Mohebbi Z
      • Nooryan K
      Yoga effects on physical activity and sexual satisfaction among the Iranian women with multiple sclerosis: a randomized controlled trial.
      • Hasanpour-Dehkordi A
      Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status in patients with multiple sclerosis: a randomized trial.
      • Hasanpour-Dehkordi A
      • Jivad N
      • Solati K
      Effects of yoga on physiological indices, anxiety and social functioning in multiple sclerosis patients: a randomized trial.
      • Hasanpour-Dehkordi A
      • Jivad N
      Comparison of regular aerobic and yoga on the quality of life in patients with multiple sclerosis.
      No studies

      No studiesn=6 studies

      6 RCTs
      Strength exerciseMuscle strength exercises11 RCTs
      • Marandi SM
      • Nejad VS
      • Shanazari Z
      • et al.
      A comparison of 12 weeks of Pilates and aquatic training on the dynamic balance of women with mulitple sclerosis.
      ,
      • Marandi SM
      • Shahnazari Z
      • Minacian V
      • et al.
      A comparison between Pilates exercise and aquatic training effects on mascular strength in women with mulitple sclerosis.
      ,
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      The effects of mat Pilates and reformer Pilates in patients with multiple sclerosis: a randomized controlled study.
      • Duff WRD
      • Andrushko JW
      • Renshaw DW
      • et al.
      Impact of Pilates exercise in multiple sclerosis: a randomized controlled trial.
      • Fox EE
      • Hough AD
      • Creanor S
      • et al.
      Effects of Pilates-based core stability training in ambulant people with multiple sclerosis: multicenter, assessor-blinded, randomized controlled trial.
      • Dalgas U
      • Stenager E
      • Jakobsen J
      • et al.
      Resistance training improves muscle strength and functional capacity in multiple sclerosis.
      • Dalgas U
      • Stenager E
      • Jakobsen J
      • et al.
      Fatigue, mood and quality of life improve in MS patients after progressive resistance training.
      • Kjolhede T
      • Dalgas U
      • Gade AB
      • et al.
      Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis.
      • Dodd KJ
      • Taylor NF
      • Shields N
      • et al.
      Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial.
      • Freeman J
      • Fox E
      • Gear M
      • et al.
      Pilates based core stability training in ambulant individuals with multiple sclerosis: protocol for a multi-centre randomised controlled trial.
      • Ortiz-Rubio A
      • Cabrera-Martos I
      • Rodriguez-Torres J
      • et al.
      Effects of a home-based upper limb training program in patients with multiple sclerosis: a randomized controlled trial.


      1 quasi-experimental study
      • Kara B
      • Kucuk F
      • Poyraz EC
      • et al.
      Different types of exercise in multiple sclerosis: aerobic exercise or Pilates, a single-blind clinical study.
      7 RCTs
      • Scholtes VA
      • Dallmeijer AJ
      • Rameckers EA
      • et al.
      Lower limb strength training in children with cerebral palsy–a randomized controlled trial protocol for functional strength training based on progressive resistance exercise principles.
      • Scholtes VA
      • Becher JG
      • Comuth A
      • et al.
      Effectiveness of functional progressive resistance exercise strength training on muscle strength and mobility in children with cerebral palsy: a randomized controlled trial.
      • Scholtes VA
      • Becher JG
      • Janssen-Potten YJ
      • et al.
      Effectiveness of functional progressive resistance exercise training on walking ability in children with cerebral palsy: a randomized controlled trial.
      • Taylor NF
      • Dodd KJ
      • Baker RJ
      • et al.
      Progressive resistance training and mobility-related function in young people with cerebral palsy: a randomized controlled trial.
      • Bania TA
      • Dodd KJ
      • Baker RJ
      • et al.
      The effects of progressive resistance training on daily physical activity in young people with cerebral palsy: a randomised controlled trial.
      • Elnaggar RK
      • Elbanna MF
      • Mahmoud WS
      • et al.
      Plyometric exercises: subsequent changes of weight-bearing symmetry, muscle strength and walking performance in children with unilateral cerebral palsy.
      • Kara OK
      • Yardimci BN
      • Sahin S
      • et al.
      Combined effects of mirror therapy and exercises on the upper extremities in children with unilateral cerebral palsy: a randomized controlled trial.
      • Qi YC
      • Niu XL
      • Gao YR
      • et al.
      Therapeutic effect evaluation of neuromuscular electrical stimulation with or without strengthening exercise on spastic cerebral palsy.
      • Tedla JS
      Strength training effects on balance in spastic diplegia subjects: a randomized controlled trial.
      • Cho HJ
      • Lee BH
      Effect of functional progressive resistance exercise on lower extremity structure, muscle tone, dynamic balance and functional ability in children with spastic cerebral palsy.


      1 quasi-experimental study
      • Kirk H
      • Geertsen SS
      • Lorentzen J
      • et al.
      Explosive resistance training increases rate of force development in ankle dorsiflexors and gait function in adults with cerebral palsy.
      1 RCT
      • Chen X
      • Wei K
      • Miao F
      • et al.
      Improvement of pulmonary function and life quality on high paraplegia patients through pulmonary rehabilitation.
      ,
      • Mogharnasi M
      • TaheriChadorneshin H
      • Papoli-Baravati SA
      • et al.
      Effects of upper-body resistance exercise training on serum nesfatin-1 level, insulin resistance, and body composition in obese paraplegic men.


      n=21 studies

      19 RCTs

      2 quasi-experimental study
      Multimodal exercisePRE or strength exercise plus aerobic or balance12 RCTs
      • Sangelaji B
      • Nabavi SM
      • Estebsari F
      • et al.
      Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study.
      • Sangelaji B
      • Kordi M
      • Banihashemi F
      • et al.
      A combined exercise model for improving muscle strength, balance, walking distance, and motor agility in multiple sclerosis patients: a randomized clinical trial.
      • Ebrahimi A
      • Eftekhari E
      • Etemadifar M
      Effects of whole body vibration on hormonal & functional indices in patients with multiple sclerosis.
      • Tarakci E
      • Yeldan I
      • Huseyinsinoglu BE
      • et al.
      Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial.
      • Sandroff BM
      • Bollaert RE
      • Pilutti LA
      • et al.
      Multimodal exercise training in multiple sclerosis: a randomized controlled trial in persons with substantial mobility disability.
      • Cakit BD
      • Nacir B
      • Genc H
      • et al.
      Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study.
      • Faramarzi M
      • Banitalebi E
      • Raisi Z
      • et al.
      Effect of combined exercise training on pentraxins and pro-inflammatory cytokines in people with multiple sclerosis as a function of disability status.
      • Banitalebi E
      • Ghahfarrokhi MM
      • Negaresh R
      • et al.
      Exercise improves neurotrophins in multiple sclerosis independent of disability status.
      • Wens I
      • Dalgas U
      • Vandenabeele F
      • et al.
      High intensity excercise in multiple sclerosis: effects on muscle contractile characteristics and excercise capacity, a randomised controlled trial.
      • Kerling A
      • Keweloh K
      • Tegtbur U
      • et al.
      Effects of a short physical excercise intervention on patients with multiple sclerosis (MS).
      • Wens I
      • Hansen D
      • Verboven K
      • et al.
      Impact of 24 weeks of resistance and endurance excercise on glucose tolerance in persons with multiple sclerosis.
      • Williams KL
      • Low Choy NL
      • Brauer SG
      Center-based group and home-based individual exercise programs have similar impacts on gait and balance in people with multiple sclerosis: a randomized trial.
      • Ozkul C
      • Guclu-Gunduz A
      • Eldemir K
      • et al.
      Combined exercise training improves cognitive functions in multiple sclerosis patients with cognitive impairment: a single-blinded randomized controlled trial.


      1 quasi-experimental study
      • Roppolo M
      • Mulasso A
      • Gollin M
      • et al.
      The role of fatigue in the associations between exercise and psychological health in multiple sclerosis: direct and indirect effects.
      5 RCTs
      • Slaman J
      • Roebroeck M
      • Dallmijer A
      • et al.
      Can a lifestyle intervention programme improve physical behaviour among adolescents and young adults with spastic cerebral palsy? A randomized controlled trial.
      • Slaman J
      • Roebroeck M
      • van der Slot W
      • et al.
      Can a lifestyle intervention improve physical fitness in adolescents and young adults with spastic cerebral palsy? A randomized controlled trial.
      • Slaman J
      • Roebroeck ME
      • van Meeteren J
      • et al.
      Learn 2 Move 16-24: effectiveness of an intervention to stimulate physical activity and improve physical fitness of adolescents and young adults with spastic cerebral palsy; a randomized controlled trial.
      • Slaman J
      • van den Berg-Emons HJ
      • van Meeteren J
      • et al.
      A lifestyle intervention improves fatigue, mental health and social support among adolescents and young adults with cerebral palsy: focus on mediating effects.
      • Van Wely L
      • Balemans AC
      • Becher JG
      • et al.
      Physical activity stimulation program for children with cerebral palsy did not improve physical activity: a randomised trial.
      • Van Wely L
      • Balemans AC
      • Becher JG
      • et al.
      The effectiveness of a physical activity stimulation programme for children with cerebral palsy on social participation, self-perception and quality of life: a randomized controlled trial.
      • Van Wely L
      • Becher JG
      • Reinders-Messelink HA
      • et al.
      Learn 2 Move 7-12 years: a randomized controlled trial on the effects of a physical activity stimulation program in children with cerebral palsy.
      • Kaya Kara O
      • Livanelioglu A
      • Yardimci BN
      • et al.
      The effects of functional progressive strength and power training in children with unilateral cerebral palsy.
      • Fosdahl MA
      • Jahnsen R
      • Kvalheim K
      • et al.
      Effect of a combined stretching and strength training program on gait function in children with cerebral palsy, GMFCS level I & II: a randomized controlled trial.
      • Makhov AS
      • Medvedev IN
      The ability to reduce the severity of motor disorders in children with cerebral palsy.


      3 RCTs
      • Jones ML
      • Evans N
      • Tefertiller C
      • et al.
      Activity-based therapy for recovery of walking in chronic spinal cord injury: results from a secondary analysis to determine responsiveness to therapy.
      • Jones ML
      • Evans N
      • Tefertiller C
      • et al.
      Activity-based therapy for recovery of walking in individuals with chronic spinal cord injury: results from a randomized clinical trial.
      • Galea MP
      • Dunlop SA
      • Geraghty T
      • et al.
      SCIPA Full-On: a randomized controlled trial comparing intensive whole-body exercise and upper body exercise after spinal cord injury.
      • Galea MP
      • Dunlop SA
      • Davis GM
      • et al.
      Intensive exercise program after spinal cord injury ("Full-On"): study protocol for a randomized controlled trial.
      • Liu H
      • Li J
      • Du L
      • et al.
      Short-term effects of core stability training on the balance and ambulation function of individuals with chronic spinal cord injury: a pilot randomized controlled trial.
      • Totosy de Zepetnek JO
      • Pelletier CA
      • Hicks AL
      • et al.
      Following the physical activity guidelines for adults with spinal cord injury for 16 weeks does not improve vascular health: a randomized controlled trial.


      1 cohort study
      • Harness ET
      • Yozbatiran N
      • Cramer SC
      Effects of intense exercise in chronic spinal cord injury.
      n=21 studies

      19 RCTs

      1 cohort study

      1 quasi-experimental study
      Abbreviations: PRE, progressive resistance exercise.
      low asterisk Studies with multiple interventions appear more than once on the table. Studies with only intermediate outcome(s) appear in full report tables.
      Table 3Summary of evidence
      CategoryInterventionNo. of Studies; Study Design; Participants (n)Key PointsStrength of Evidence
      KQ 1. Prevention of cardiovascular conditions, diabetes, and obesity
      No studiesNANANANA
      KQ 2. Benefits and harms of physical activity vs usual care, attention control, waitlist control, no intervention
      Aerobic exerciseAerobicsMS: 2 RCTs (77)

      MS/CP: 2 RCTs (81)
      Improved sleep scores

      Improved function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.
      Low

      Low
      AquaticsMS: 2 RCTs (62)

      MS: 1 RCT (73)

      MS: 1 RCT (60)

      MS: 1 RCT (73)
      Improved balance

      Improved ADL

      Improved female sexual function

      Improved spasticity
      Low

      Low

      Low

      Low
      CyclingMS: 6 RCTs (277)

      CP: 2 RCTs (85)
      No clear benefit on function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).


      Improved function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).
      Low

      Low
      Robot-assisted gait trainingMS: 2 RCTs (97)

      MS: 2 RCTs (97)

      SCI: 2 RCTs (176)

      SCI: 3 RCTs (170)
      No clear benefit on function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.


      Improved balance

      Improved ADL

      No clear benefit on function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).
      Low

      Low

      Low

      Low
      TreadmillMS: 2 RCTs (50)

      CP: 2 RCTs (53)
      Improved walking

      Improved function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).
      Low

      Low
      Postural control interventionsBalance exercisesMS: 7 RCTs (369)

      MS: 10 RCTs (553)

      MS: 2 RCTs (128)
      Improved function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).


      Improved balance

      Improved fall risk
      Low

      Moderate

      Low
      HippotherapyCP: 5 RCTs, 2 QENRS (333)

      CP: 1 RCT, 2 QENRS (150)
      Improved function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).


      Improved balance
      Low

      Low
      Tai chiMS, CP, SCIAny included outcomeInsufficient
      Motion gamingMS: 4 RCTs (177)

      MS: 3 RCTs (94)
      Improved function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.


      Improved balance
      Low

      Low
      Whole body vibrationMS, CP, SCIAny included outcomeInsufficient
      YogaMS: 4 RCTs (215)No clear benefit on function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.
      Low
      Strength interventionsMuscle strength exercisesMS: 8 RCTs (332)

      MS: 5 RCTs (178)

      MS: 3 RCTs (100)

      MS: 6 RCTs (319)

      MS: 1 RCT (71)

      CP: 3 RCTs (140)

      CP: 3 RCTs (134)
      Improved walking

      No clear benefit on function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.


      No clear benefit on quality of life

      No clear benefit on balance

      No clear benefit on spasticity

      No clear benefit on walking

      No clear benefit on function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).
      Low

      Low

      Low

      Low

      Low

      Low

      Low
      Multimodal interventionsPRE or strength exercise plus aerobic or balanceMS: 4 RCTs (176)

      MS: 4 RCTs (224)

      MS: 2 RCTs (123)

      CP: 3 RCTs (135)

      CP: 2 RCTs (107)
      Improved walking

      Improved balance

      Improved cardiovascular fitness

      No clear benefit on function (motor)
      Motor outcomes measure gross motor or upper extremity function (Gross Motor Function Measure-66, Gross Motor Function Measure-88, Quality of Upper Extremity Skills Test).


      No clear benefit on quality of life
      Low

      Low

      Low

      Low

      Low
      All ExerciseMS: 10 RCTs (448)

      MS: 25 RCTs (1436)

      MS: 17 RCTs (906)

      MS: 15 RCTs (743)

      CP: 11 RCTs (500)

      CP: 2 QENRS (54)

      SCI: 3 RCTs (171)

      SCI: 4 RCTs (129)

      SCI: 2 RCTs/1 Cohort study (88)
      Improved depression scores

      Improved walking

      Improved balance

      No clear benefit on function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.


      Improved function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).


      Improved cardiovascular fitness

      No clear benefit on depression scores

      Improved function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).


      Improved cardiovascular fitness
      Moderate

      High

      Moderate

      Moderate

      Low

      Low

      Low

      Low

      Low
      Benefits and harms of physical activity vs another physical activity
      Aerobic exerciseRobot-assisted gait training vs overground walking

      Treadmill training vs overground walking
      MS: 1 RCT (72)

      MS: 1 RCT (72)

      MS: 1 RCT (72)

      CP: 5 RCTs (130)

      CP: 4 RCTs (109)
      No clear benefit on function (mobility)
      Mobility outcomes involve standing, stepping, walking, running, jumping.


      No clear benefit on quality of life

      No clear benefit on balance

      No clear benefit on walking

      No clear benefit on function (multifactorial)
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).
      Low

      Low

      Low

      Low

      Low
      KQ 3. Patient factors affect the benefits and harms of physical activity
      MS: 1 RCT (69)

      MS: 1 RCT (89)

      CP: 1 RCT (39)

      SCI: 2 RCTs (58)

      Greatest strength improvement in women who were least strong at baseline

      Improvements in walking, function, and Vo2 peak with multimodal exercise compared with a waitlist control, but these differences were not statistically significant after adjustment for baseline disability

      6-7 year olds had improved sitting scores with hippotherapy compared with no hippotherapy, whereas children aged 8-12 years had similar scores, but there was no difference in the effect of the intervention based on disability level at baseline

      Better baseline function and more recent injury were associated with greater improvements in walking
      NA

      NA

      NA

      NA
      KQ 4. Methodological weaknesses or gaps
      No studiesNANANANA
      NOTE. Specific instruments/measures that comprised function outcomes can be found in supplemental table S5.
      Abbreviations: KQ, key question; NA, not applicable; PRE, PRE, progressive resistance exercise; QENRS, quasi-experimental nonrandomized studies.
      low asterisk Mobility outcomes involve standing, stepping, walking, running, jumping.
      Multifactorial outcomes include outcomes from multiple domains or scales that assess multiple domains (activities of daily living, balance, participation, motor skills, mobility).
      Motor outcomes measure gross motor or upper extremity function (Gross Motor Function Measure-66, Gross Motor Function Measure-88, Quality of Upper Extremity Skills Test).
      The key questions for this report include the following:
      • 1.
        What is the evidence base on physical activity interventions to prevent obesity, diabetes, and cardiovascular conditions, including evidence on harms of the interventions in people with MS, CP, or spinal cord injury?
      • 2.
        What are the benefits and harms of physical activity interventions for people with MS, CP, or spinal cord injury?
      • 3.
        What are the patient factors that may affect the benefits and harms of physical activity in patients with MS, CP, or spinal cord injury?
      • 4.
        What are methodological weaknesses or gaps that exist in the evidence to determine benefits and harms of physical activity in patients with MS, CP, or spinal cord injury?
      For the search strategy a research librarian searched MEDLINE, Cumulative Index to Nursing and Allied Health, PsycINFO, Cochrane CENTRAL, Embase, Rehabilitation and Sports Medicine Source, and ClinicalTrials.gov. We limited the search to studies published since 2008, when the first United States Department of Health and Human Services physical activity guidelines were published,

      Physical Activity Guidelines Advisory Committee. 2008 Physical Activity Guidelines for Americans. Available at: https://health.gov/paguidelines/2008/. Accessed February 27, 2020.

      and systematic reviews since 2014. An updated literature search was conducted in November 2020. The full search strategies are in appendix 1 of the full report (in press to be available at https://effectivehealthcare.ahrq.gov/).
      We reviewed reference lists of systematic reviews for includable literature, Technical Expert Panel members were asked to provide suggestions about unpublished literature, and authors of studies were contacted for information (no additional information was provided).
      • Young HJ
      • Mehta TS
      • Herman C
      • et al.
      The effects of M2M and adapted yoga on physical and psychosocial outcomes in people wth multiple sclerosis.
      ,
      • Negaresh R
      • Motl R
      • Mokhtarzade M
      • et al.
      Effect of short-term interval excercise training on fatigue, depression, and fitness in normal weight vs. overweight person with multiple sclerosis.
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Hsieh HC
      Preliminary study of the effect of training with a gaming balance board on balance control in children with cerebral palsy: a randomized controlled trial.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      Methods were consistent with those outlined in the AHRQ Evidence-based Practice Center Program Methods Guidance (https://effectivehealthcare.ahrq.gov/topics/cer-methods-guide/overview) and are detailed in the full report (in press to be available at https://effectivehealthcare.ahrq.gov/).
      The criteria for selection of studies to be included in the review were preestablished and used to determine eligibility for inclusion and exclusion of abstracts according to the Evidence-based Practice Center Methods Guide (see table 1).

      Agency for Healthcare Research and Quality. Methods guide for effectiveness and comparative effectiveness reviews. Available at: https://effectivehealthcare.ahrq.gov/topics/cer-methods-guide/overview. Accessed September 12, 2019.

      We included studies from countries with a very high or high score on the Human Development Index because results from these studies are more likely similar to studies conducted in the United States. Using these predefined eligibly criteria, 2 independent investigators reviewed abstract and full-text articles. Systematic reviews were used to identify additional studies.
      Interventions with a defined period of observed physical activity (movement using more energy than rest) with a minimum of 10 sessions of activity on 10 days or more in a supervised or group setting were included (fig 1). Observed sessions were required to ensure the physical activity intervention took place. Unobserved sessions were allowed as long as 10 sessions were observed. We required studies to have analyzed a minimum of 30 participants in MS and 20 participants in CP and SCI (differences in required sample sizes was because of fewer participants in CP and SCI studies and a desire not to exclude a bulk of the evidence).
      Fig 1
      Fig 1Analytic framework diagram. The analytic framework for physical activity and the health of wheelchair users with multiple sclerosis, cerebral palsy, and spinal cord injury concepts are illustrated based on key questions and clinical outcomes as well intermediate outcomes and are described in detail in the full report. Evidence base descriptions are of studies that evaluate prevention of obesity, diabetes, cardiovascular conditions, and harms. Abbreviations: BMI, body mass index; Hb A1c, glycosylated hemoglobin; KQ, key question; V̇o2max, maximum oxygen consumption.
      *Outcomes are specified in the Methods section
      Studies that evaluate prevention of obesity, diabetes, cardiovascular conditions, and harms.
      The findings are summarized in evidence tables indicating study characteristics and outcome results and study quality ratings and are included in summary tables of the key findings (see tables 2 and 3, detailed in the full report). Findings are organized by the intervention categories: aerobic exercise (eg, aquatics, cycling, robot-assisted gait training [RAGT]), postural control (eg, balance exercises, hippotherapy, motion gaming, yoga), and strength exercises and multimodal exercise with strength as a major component. Results for each of these categories are reported by etiology of disability (ie, MS, CP, SCI). Study quality was independently assessed by 2 investigators and rated as good, fair, or poor using predefined criteria; disagreements were resolved by consensus.
      We conducted quantitative synthesis involving pooling of study findings in meta-analyses when studies were homogeneous enough to provide meaningful combined estimates to summarize data from multiple studies and to obtain more precise and accurate estimates of effects.
      Meta-analyses were conducted using STATA 14.0/14.2a and RevMan v5.3.b
      Because of the large number of potential outcomes, quantitative synthesis focused on outcomes previously prioritized for strength of evidence rating (table 4) with the addition of the Berg Balance Scale, which was not a prioritized outcome but was the outcome with the most evidence.
      Table 4Effects of physical activity interventions compared with usual care
      Intervention

      Category

      Intervention
      Multiple Sclerosis

      Studies

      Strength of Evidence

      (Direction of Finding)
      Cerebral Palsy

      Studies

      Strength of Evidence

      (Direction of Finding)
      Spinal Cord Injury

      Studies

      Strength of Evidence

      (Direction of Finding)
      Aerobic exercise

      dance (1 RCT in MS and 1 RCT in CP)
      Strength of evidence based on combining the 2 populations, multiple sclerosis and cerebral palsy.
      Low

      (function improvement)
      Low

      (function improvement)
      Insufficient
      Aerobic exercise

      Aerobics
      Low

      (sleep improvement)
      InsufficientInsufficient
      Aerobic exercise

      Aquatics
      Low

      (balance, ADL improvement, female sexual function)
      InsufficientInsufficient
      Aerobic exercise

      Cycling
      Low

      (no clear benefit on walking)
      Low

      (function improvement)
      Insufficient
      Aerobic exercise

      Robot-assisted gait training
      Low

      (balance improvement)

      Low

      (no clear benefit in function)
      InsufficientLow

      (ADL improvement)

      Low

      (no clear benefit on function)
      Aerobic exercise

      Treadmill
      Low

      (walking, function, balance improvement)
      Low

      (function improvement)
      Insufficient
      Postural control

      Balance exercises
      Moderate

      (balance improvement)
      InsufficientInsufficient
      Postural control

      Balance exercises
      Low

      (fall risk improvement)
      InsufficientInsufficient
      Postural control

      Balance exercises
      Low

      (function improvement)
      InsufficientInsufficient
      Postural control HippotherapyInsufficientLow

      (balance and function improvement)
      Insufficient
      Postural control

      Tai chi
      InsufficientInsufficientInsufficient
      Postural control

      Motion gaming
      Low

      (function, balance improvement)
      Low

      (balance improvement)
      Insufficient
      Postural control

      Whole body vibration
      InsufficientInsufficientInsufficient
      Postural control

      Yoga
      Low

      (no clear benefit on function)
      InsufficientInsufficient
      Strength interventions Muscle strength exerciseLow

      (no clear benefit on walking, function, balance, quality of life, spasticity)
      Low

      (no clear benefit on walking and function)
      Insufficient
      Multimodal exercise

      Progressive resistance or strength exercise plus aerobic and/or balance exercise
      Low

      (walking, balance, V̇o2 improvement)
      Low

      (no clear benefit on function, quality of life)
      Insufficient
      All types of exerciseHigh

      (walking improvement)
      Low

      (function)
      Low

      (function)
      Moderate

      (balance, depression improvement, no clear benefit on function)
      Low

      (V̇o2 improvement)
      Low

      (V̇o2 improvement, increased episodes of autonomic dysreflexia,
      Whole body exercise versus exercise limited to upper body.
      no clear benefit on depression)
      Abbreviation: V̇o2, peak/max (studies reported either peak or max which are slightly different).
      low asterisk Strength of evidence based on combining the 2 populations, multiple sclerosis and cerebral palsy.
      Whole body exercise versus exercise limited to upper body.

      Results

      The literature search and selection resulted in 19,247 potentially relevant articles. After dual review of abstracts and full text, we included 168 studies (N=7511), of which 146 were randomized controlled trials (RCTs), 15 were quasi-experimental studies, and 7 were cohort studies. Figure 2 indicates the literature flow, and included studies with primary outcomes are listed in table 2 and supplemental figure 1 (available online only at http://www.archives-pmr.org/).
      Fig 2
      Fig 2Literature flow diagram. The diagram indicates the number of abstracts and full-text articles reviewed for inclusion and subsequently included or excluded and the final studies included for each population. *Interventions with <10 sessions/<10 d, or only family/caregiver observed. Case reports and case series are not included because of methodological limitations. Studies before January 2008 and systematic reviews from 2014 or older are outside of the search dates. §Studies with sample sizes <30 for multiple sclerosis and cerebral palsy and <20 for spinal cord injury. Systematic reviews not used because they did not meet all inclusion criteria but checked for includable studies.
      Seventy-four studies enrolled participants with MS (44%), 63 studies enrolled participants with CP (38%), and 31 studies enrolled participants with SCI (18%). The average number of participants per study was 45 (range, 20-242), with only 3 studies having a sample size of 100 or more. In MS, the mean number of physical activity sessions was 25 over a mean of 9 weeks, with a mean of 28 sessions over 10 weeks in CP and 68 sessions over 17 weeks in SCI. Studies compared one physical activity intervention with another physical activity intervention, usual care and/or standard physical therapy, attention control, waitlist control, or no intervention. Some studies had more than 1 comparator arm. Age and sex of study participants varied by population enrolled (ie, MS, CP, SCI). Reporting of baseline disability also varied by population. Fifty-five MS studies reported baseline scores on the Expanded Disability Status Scale (average study mean 3.6±1.77, representing moderate disability); most studies in CP (63%) reported scores on the Gross Motor Function Classification System, with disability levels I to III most frequently studied (average Gross Motor Function Classification System study mean 2.40±0.87, representing mild to moderate disability). Reporting of baseline impairment status in SCI studies varied, with studies reporting specific spinal injury levels, proportion with paraplegia vs tetraplegia, proportion with complete vs incomplete injury, and proportion with each American Spinal Injury Association Impairment Scale score. Studies were conducted most often in Iran (26 studies), Turkey (19 studies), and the United States (15 studies). Most studies were conducted in an outpatient setting (51%) or an inpatient hospital or rehabilitation center (14%); the study location was not specified in 20% of studies. Eight percent (n=13) of the studies were considered good quality, two-thirds of the studies were rated fair quality (n=113), and one-fourth were poor quality (n=42). Studies were downgraded because of unclear randomization methods, lack of blinding of outcome assessors, and high attrition.

      Key question 1. Prevention of cardiovascular conditions, diabetes, and obesity

      No studies on the effects of physical activity in participants with MS, CP, or SCI assessed the prevention of cardiovascular conditions (eg, myocardial infarction, stroke, development of hypertension) or the development of diabetes or obesity.

      Key question 2. Benefits and harms of physical activity

      Aerobic exercise interventions

      Aerobic interventions included aerobic exercises, aquatics, cycling, RAGT, and treadmill training. Individual study findings can be found in the supplemental tables S1-4 (available online only at http://www.archives-pmr.org/).
      In studies that enrolled participants with MS, compared with usual care or attention control, we found evidence that aerobic exercise may improve sleep.
      • Al-Sharman A
      • Khalil H
      • El-Salem K
      • et al.
      The effects of aerobic exercise on sleep quality measures and sleep-related biomarkers in individuals with multiple sclerosis: a pilot randomised controlled trial.
      ,
      • Sadeghi Bahmani D
      • Razazian N
      • Farnia V
      • et al.
      Compared to an active control condition, in persons with multiple sclerosis two different types of exercise training improved sleep and depression, but not fatigue, paresthesia, and intolerance of uncertainty.
      Aquatic exercises may improve ADL,
      • Castro-Sanchez AM
      • Mataran-Penarrocha GA
      • Lara-Palomo I
      • et al.
      Hydrotherapy for the treatment of pain in people with multiple sclerosis: a randomized controlled trial.
      female sexual function,
      • Sadeghi Bahmani D
      • Motl RW
      • Razazian N
      • et al.
      Aquatic exercising may improve sexual function in females with multiple sclerosis - an exploratory study.
      balance,
      • Kargarfard M
      • Shariat A
      • Ingle L
      • et al.
      Randomized controlled trial to examine the impact of aquatic exercise training on functional capacity, balance, and perceptions of fatigue in female patients with multiple sclerosis.
      ,
      • Marandi SM
      • Nejad VS
      • Shanazari Z
      • et al.
      A comparison of 12 weeks of Pilates and aquatic training on the dynamic balance of women with mulitple sclerosis.
      and spasticity.
      • Castro-Sanchez AM
      • Mataran-Penarrocha GA
      • Lara-Palomo I
      • et al.
      Hydrotherapy for the treatment of pain in people with multiple sclerosis: a randomized controlled trial.
      RAGT may improve balance
      • Russo M
      • Dattola V
      • De Cola MC
      • et al.
      The role of robotic gait training coupled with virtual reality in boosting the rehabilitative outcomes in patients with multiple sclerosis.
      ,
      • Straudi S
      • Fanciullacci C
      • Martinuzzi C
      • et al.
      The effects of robot-assisted gait training in progressive multiple sclerosis: a randomized controlled trial.
      compared with usual care but with no clear benefit in function (mobility).
      • Russo M
      • Dattola V
      • De Cola MC
      • et al.
      The role of robotic gait training coupled with virtual reality in boosting the rehabilitative outcomes in patients with multiple sclerosis.
      ,
      • Straudi S
      • Fanciullacci C
      • Martinuzzi C
      • et al.
      The effects of robot-assisted gait training in progressive multiple sclerosis: a randomized controlled trial.
      There was also no clear benefit on function (mobility), balance, or quality of life when RAGT was compared with overground walking.
      • Straudi S
      • Manfredini F
      • Lamberti N
      • et al.
      Robot-assisted gait training is not superior to intensive overground walking in multiple sclerosis with severe disability (the RAGTIME study): a randomized controlled trial.
      Two studies in MS found evidence that walking may improve with treadmill training compared with usual care or waitlist control.
      • Gervasoni E
      • Cattaneo D
      • Jonsdottir J
      Effect of treadmill training on fatigue in multiple sclerosis: a pilot study.
      ,
      • Ahmadi A
      • Arastoo AA
      • Nikbakht M
      • et al.
      Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients.
      Six studies found no clear benefit of cycling on walking in participants with MS compared with usual care, attention control, or waitlist control.
      • Negaresh R
      • Motl R
      • Mokhtarzade M
      • et al.
      Effect of short-term interval excercise training on fatigue, depression, and fitness in normal weight vs. overweight person with multiple sclerosis.
      • Hochsprung A
      • Granja Dominguez A
      • Magni E
      • et al.
      Effect of visual biofeedback cycling training on gait in patients with multiple sclerosis.
      • Baquet L
      • Hasselmann H
      • Patra S
      • et al.
      Short-term interval aerobic exercise training does not improve memory functioning in relapsing-remitting multiple sclerosis-a randomized controlled trial.
      • Hebert JR
      • Corboy JR
      • Manago MM
      • et al.
      Effects of vestibular rehabilitation on multiple sclerosis-related fatigue and upright postural control: a randomized controlled trial.
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      • Heine M
      • Verschuren O
      • Hoogervorst EL
      • et al.
      Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.
      One study in MS
      • Young HJ
      • Mehta TS
      • Herman C
      • et al.
      The effects of M2M and adapted yoga on physical and psychosocial outcomes in people wth multiple sclerosis.
      and 1 in CP
      • Teixeira-Machado L
      • Azevedo-Santos I
      • Desantana JM
      Dance improves functionality and psychosocial adjustment in cerebral palsy: a randomized controlled clinical trial.
      together provided evidence that dance may improve function (mobility) compared with usual care.
      In study participants with CP, function (multifactorial) may be improved with stationary cycling compared with a no intervention control.
      • Bryant E
      • Pountney T
      • Williams H
      • et al.
      Can a six-week exercise intervention improve gross motor function for non-ambulant children with cerebral palsy? A pilot randomized controlled trial.
      • Demuth SK
      • Knutson LM
      • Fowler EG
      The PEDALS stationary cycling intervention and health-related quality of life in children with cerebral palsy: a randomized controlled trial.
      • Fowler EG
      • Knutson LM
      • Demuth SK
      • et al.
      Pediatric endurance and limb strengthening (PEDALS) for children with cerebral palsy using stationary cycling: a randomized controlled trial.
      Function (multifactorial) may also be improved with treadmill training compared with usual care,
      • Bahrami F
      • Noorizadeh Dehkordi S
      • Dadgoo M
      The efficacy of treadmill training on walking and quality of life of adults with spastic cerebral palsy: a randomized controlled trial.
      ,
      • Chrysagis N
      • Skordilis EK
      • Stavrou N
      • et al.
      The effect of treadmill training on gross motor function and walking speed in ambulatory adolescents with cerebral palsy: a randomized controlled trial.
      but evidence was inconsistent and demonstrated no clear benefit of treadmill training on walking or function (multifactorial) compared with overground walking.
      • Willoughby KL
      • Dodd KJ
      • Shields N
      • et al.
      Efficacy of partial body weight-supported treadmill training compared with overground walking practice for children with cerebral palsy: a randomized controlled trial.
      • Swe NN
      • Sendhilnnathan S
      • van Den Berg M
      • et al.
      Over ground walking and body weight supported walking improve mobility equally in cerebral palsy: a randomised controlled trial.
      • Emara HA
      • El-Gohary TM
      • Al-Johany AA
      Effect of body-weight suspension training versus treadmill training on gross motor abilities of children with spastic diplegic cerebral palsy.
      • Grecco LA
      • Zanon N
      • Sampaio LM
      • et al.
      A comparison of treadmill training and overground walking in ambulant children with cerebral palsy: randomized controlled clinical trial.
      In study participants with SCI, ADL may be improved with RAGT compared with usual care or walking overground without robot-assistance
      • Esclarin-Ruz A
      • Alcobendas-Maestro M
      • Casado-Lopez R
      • et al.
      A comparison of robotic walking therapy and conventional walking therapy in individuals with upper versus lower motor neuron lesions: a randomized controlled trial.
      ,
      • Yildirim MA
      • Ones K
      • Goksenoglu G
      Early term effects of robotic assisted gait training on ambulation and functional capacity in patients with spinal cord injury.
      (see supplemental table S1 [available online only at http://www.archives-pmr.org/]. Benefits and harms of physical activity—aerobic exercise intervention studies).

      Postural control interventions

      Postural control or balance interventions included balance exercises, hippotherapy, tai chi, motion gaming, whole body vibration, and yoga. Hippotherapy involved riding a horse or horse simulator. Motion gaming used body movement rather than a mouse or game controller to play a game using a computer or television screen (eg, Xbox, Wii).
      In participants with MS, studies found that balance exercises likely improve balance
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Afrasiabifar A
      • Karami F
      • Najafi Doulatabad S
      Comparing the effect of Cawthorne-Cooksey and Frenkel exercises on balance in patients with multiple sclerosis: a randomized controlled trial.
      • Brichetto G
      • Piccardo E
      • Pedulla L
      • et al.
      Tailored balance exercises on people with multiple sclerosis: a pilot randomized, controlled study.
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: a randomized, controlled trial.
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: a multi-centre, randomized, controlled pilot study.
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-based individualized comprehensive core stability intervention improves balance in persons with multiple sclerosis: a randomized controlled trial.
      • Forsberg A
      • von Koch L
      • Nilsagard Y
      Effects on balance and walking with the CoDuSe balance exercise program in people with multiple sclerosis: a multicenter randomized controlled trial.
      • Amiri B
      • Sahebozamani M
      • Sedighi B
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: a single-blinded randomized controlled trial.
      including decreased risk for falls,
      • Gandolfi M
      • Munari D
      • Geroin C
      • et al.
      Sensory integration balance training in patients with multiple sclerosis: a randomized, controlled trial.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: a multi-centre, randomized, controlled pilot study.
      and may improve function (multifactorial)
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Carling A
      • Forsberg A
      • Gunnarsson M
      • et al.
      CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: a multi-centre, randomized, controlled pilot study.
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      • Arntzen EC
      • Straume BK
      • Odeh F
      • et al.
      Group-based individualized comprehensive core stability intervention improves balance in persons with multiple sclerosis: a randomized controlled trial.
      • Forsberg A
      • von Koch L
      • Nilsagard Y
      Effects on balance and walking with the CoDuSe balance exercise program in people with multiple sclerosis: a multicenter randomized controlled trial.
      • Amiri B
      • Sahebozamani M
      • Sedighi B
      The effects of 10-week core stability training on balance in women with multiple sclerosis according to Expanded Disability Status Scale: a single-blinded randomized controlled trial.
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: a single-blinded randomized controlled trial.
      compared with usual care, waitlist control, attention control, or no intervention. Balance
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: a single-blinded randomized controlled trial.
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: a randomized controlled trial.
      and function (mobility)
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Ozkul C
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      Effect of immersive virtual reality on balance, mobility, and fatigue in patients with multiple sclerosis: a single-blinded randomized controlled trial.
      ,
      • Yazgan YZ
      • Tarakci E
      • Tarakci D
      • et al.
      Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Nilsagard YE
      • Forsberg AS
      • von Koch L
      Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.
      may also be improved with motion gaming vs usual care or waitlist control. There was no clear benefit on function (mobility) with yoga vs usual care or waitlist control.
      • Young HJ
      • Mehta TS
      • Herman C
      • et al.
      The effects of M2M and adapted yoga on physical and psychosocial outcomes in people wth multiple sclerosis.
      ,
      • Ahmadi A
      • Arastoo AA
      • Nikbakht M
      • et al.
      Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients.
      ,
      • Garrett M
      • Hogan N
      • Larkin A
      • et al.
      Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial.
      • Garrett M
      • Hogan N
      • Larkin A
      • et al.
      Exercise in the community for people with multiple sclerosis–a follow-up of people with minimal gait impairment.
      • Hogan N
      • Kehoe M
      • Larkin A
      • et al.
      The effect of community exercise interventions for people with MS who use bilateral support for gait.
      In CP studies, balance
      • Lee CW
      • Kim SG
      • Na SS
      The effects of hippotherapy and a horse riding simulator on the balance of children with cerebral palsy.
      ,
      • Kwon JY
      • Chang HJ
      • Lee JY
      • et al.
      Effects of hippotherapy on gait parameters in children with bilateral spastic cerebral palsy.
      and function (multifactorial)
      • Kwon JY
      • Chang HJ
      • Yi SH
      • et al.
      Effect of hippotherapy on gross motor function in children with cerebral palsy: a randomized controlled trial.
      ,
      • Deutz U
      • Heussen N
      • Weigt-Usinger K
      • et al.
      Impact of hippotherapy on gross motor function and quality of life in children with bilateral cerebral palsy: a randomized open-label crossover study.
      • Herrero P
      • Gomez-Trullen EM
      • Asensio A
      • et al.
      Study of the therapeutic effects of a hippotherapy simulator in children with cerebral palsy: a stratified single-blind randomized controlled trial.
      • Silva e Borges MB
      • Werneck MJ
      • da Silva Mde L
      • et al.
      Therapeutic effects of a horse riding simulator in children with cerebral palsy.
      • Mutoh T
      • Mutoh T
      • Tsubone H
      • et al.
      Impact of long-term hippotherapy on the walking ability of children with cerebral palsy and quality of life of their caregivers.
      ,
      • Kwon JY
      • Chang HJ
      • Lee JY
      • et al.
      Effects of hippotherapy on gait parameters in children with bilateral spastic cerebral palsy.
      ,
      • Park ES
      • Rha DW
      • Shin JS
      • et al.
      Effects of hippotherapy on gross motor function and functional performance of children with cerebral palsy.
      may be improved with hippotherapy compared with usual care or waitlist control. Motion gaming may also improve balance in participants with CP compared with usual care or motion gaming using a mouse.
      • Hsieh HC
      Effects of a gaming platform on balance training for children with cerebral palsy.
      • Hsieh HC
      Preliminary study of the effect of training with a gaming balance board on balance control in children with cerebral palsy: a randomized controlled trial.
      • Tarakci D
      • Ersoz Huseyinsinoglu B
      • Tarakci E
      • et al.
      Effects of Nintendo Wii-Fit® video games on balance in children with mild cerebral palsy.
      • Pourazar M
      • Bagherzadeh F
      • Mirakhori F
      Virtual reality training improves dynamic balance in children with cerebral palsy.
      There was insufficient evidence to draw conclusions regarding the effect of postural control interventions in participants with SCI (see supplemental table S2 [available online only at http://www.archives-pmr.org/]). Benefits and harms of physical activity—postural control intervention studies)

      Strength interventions

      Strength interventions included progressive resistance exercises and body weight resistance exercises (eg, abdominal crunches, Pilates).
      In MS studies, there was limited evidence for no clear benefit on balance,
      • Kara B
      • Kucuk F
      • Poyraz EC
      • et al.
      Different types of exercise in multiple sclerosis: aerobic exercise or Pilates, a single-blind clinical study.
      ,
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      The effects of mat Pilates and reformer Pilates in patients with multiple sclerosis: a randomized controlled study.
      • Duff WRD
      • Andrushko JW
      • Renshaw DW
      • et al.
      Impact of Pilates exercise in multiple sclerosis: a randomized controlled trial.
      • Fox EE
      • Hough AD
      • Creanor S
      • et al.
      Effects of Pilates-based core stability training in ambulant people with multiple sclerosis: multicenter, assessor-blinded, randomized controlled trial.
      function (mobility),
      • Marandi SM
      • Nejad VS
      • Shanazari Z
      • et al.
      A comparison of 12 weeks of Pilates and aquatic training on the dynamic balance of women with mulitple sclerosis.
      ,
      • Marandi SM
      • Shahnazari Z
      • Minacian V
      • et al.
      A comparison between Pilates exercise and aquatic training effects on mascular strength in women with mulitple sclerosis.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      The effects of mat Pilates and reformer Pilates in patients with multiple sclerosis: a randomized controlled study.
      • Duff WRD
      • Andrushko JW
      • Renshaw DW
      • et al.
      Impact of Pilates exercise in multiple sclerosis: a randomized controlled trial.
      walking,
      • Tollar J
      • Nagy F
      • Toth BE
      • et al.
      Exercise effects on multiple sclerosis quality of life and clinical-motor symptoms.
      ,
      • Callesen J
      • Cattaneo D
      • Brincks J
      • et al.
      How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.
      ,
      • Kalron A
      • Rosenblum U
      • Frid L
      • et al.
      Pilates exercise training vs. physical therapy for improving walking and balance in people with multiple sclerosis: a randomized controlled trial.
      ,
      • Duff WRD
      • Andrushko JW
      • Renshaw DW
      • et al.
      Impact of Pilates exercise in multiple sclerosis: a randomized controlled trial.
      • Fox EE
      • Hough AD
      • Creanor S
      • et al.
      Effects of Pilates-based core stability training in ambulant people with multiple sclerosis: multicenter, assessor-blinded, randomized controlled trial.
      • Dalgas U
      • Stenager E
      • Jakobsen J
      • et al.
      Resistance training improves muscle strength and functional capacity in multiple sclerosis.
      • Dalgas U
      • Stenager E
      • Jakobsen J
      • et al.
      Fatigue, mood and quality of life improve in MS patients after progressive resistance training.
      • Kjolhede T
      • Dalgas U
      • Gade AB
      • et al.
      Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis.
      • Dodd KJ
      • Taylor NF
      • Shields N
      • et al.
      Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial.
      quality of life,
      • Bulguroglu I
      • Guclu-Gunduz A
      • Yazici G
      • et al.
      The effects of mat Pilates and reformer Pilates in patients with multiple sclerosis: a randomized controlled study.
      ,
      • Duff WRD
      • Andrushko JW
      • Renshaw DW
      • et al.
      Impact of Pilates exercise in multiple sclerosis: a randomized controlled trial.
      ,
      • Dalgas U
      • Stenager E
      • Jakobsen J
      • et al.
      Fatigue, mood and quality of life improve in MS patients after progressive resistance training.
      and spasticity
      • Dodd KJ
      • Taylor NF
      • Shields N
      • et al.
      Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial.
      with strength exercises compared with usual care, attention control, or waitlist control.
      In studies that enrolled participants with CP, there was no clear benefit of strength exercises on walking
      • Scholtes VA
      • Dallmeijer AJ
      • Rameckers EA
      • et al.
      Lower limb strength training in children with cerebral palsy–a randomized controlled trial protocol for functional strength training based on progressive resistance exercise principles.
      • Scholtes VA
      • Becher JG
      • Comuth A
      • et al.
      Effectiveness of functional progressive resistance exercise strength training on muscle strength and mobility in children with cerebral palsy: a randomized controlled trial.
      • Scholtes VA
      • Becher JG