Table 2.
Functional exercise training studies in persons with multiple sclerosis
| Design | Sample Size | Age [yrs] | EDSS | MS type | Frequency | Intensity | Time | Type | Outcomes | Between-group | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Abbaspoor et al. 2020 | RCT | INT: 10 | 33.50 ± 6.37 | 3.06 ± 1.20 | RRMS |
3x/week 8 weeks |
RPE 10–16 55–70% HRmax |
5 exercises; 1–2 sets × 8–14 reps; 60–120 s rest 15–20 min |
WB resistance BW; elastic bands; TRX® suspension Rhythmic AT |
Serum markers (BDNF, IGF-1); walking speed (10MWT); walking endurance (2MWT); quadriceps strength (dynamometry); handgrip/finger strength (dynamometry) |
INT: IGF-1 ↑; 10MWT ↑; Handgrip strength (R) ↑; BDNF ↔; 2MWT ↔; Handgrip strength (L) ↔; Finger strength (R/L) ↔ |
| CON: 10 | 36.75 ± 6.80 | 3.00 ± 1.10 | Habitual lifestyle | ||||||||
| Akbar et al. 2020 | CT | INT1: 5 | 45.6 ± 12.8 | N/A |
RRMS SPMS PPMS |
3x/week 16 weeks |
N/A | 10 exercises; 1–3 sets × 10–15 reps |
WB resistance BW; elastic bands; weighted vests Stretching |
Fatigue (Modified Fatigue Impact Scale (total, physical, cognitive, psychosocial); physical activity (Godin Leisure-Time Exercise Questionnaire); grip strength (dynamometry); brain connectivity (resting-state functional MRI) | INT1 vs. INT2: Functional connectivity caudate and inferior parietal region (L), inferior frontal region (R/L), middle frontal region (L), insula (R) ↕; modified Fatigue Impact Scale (total, physical, cognitive, psychosocial) ↔; Godin Leisure-Time Exercise Questionnaire ↔; grip strength |
| INT2: 5 | 53.0 ± 10.7 | INT2: Stretching | |||||||||
| Ayán Pérez et al. 2007 | UCT | INT: 24 (36)1 | 44.4 ± 9.5 | 1.5 ± N/A | SPMS |
3x/week 6 weeks |
Self-chosen (2–3 reps less than subjective max) |
12 exercises; 1–2 sets x individual number of reps; ~ 2 min medicine ball throws; 60 min |
Core strength and WB mobility BW; Calisthenics; medicine balls |
Walking speed (9 m zig-zag run); mobility of arms and time–space orientation (clapping test, dynamic flexibility test); explosiveness of arms (overhead medicine ball throw); explosiveness of legs (vertical jump); trunk strength (abdominal test, back muscle test) leg lifts, Kraus-Weber test); Balance (flamingo balance test) | - |
| Bilek et al. 2022 | RCT | INT: 30 | 28.29 ± 6.57 | 1.71 ± 1.13 | RRMS |
3x/week 8 weeks |
N/A 70% V̇O2peak |
60–70 min; 10 exercises; 1–3 sets × 10–15 reps; rest N/A 30 min |
WB resistance Elastic bands; weighted vests AT (bicycle) |
Cardioresp. fitness (V̇O2 peak); serum markers (Contactin-1, Contaction-2); Cognition (PASAT-3) | INT vs. CON: V̇O2 peak ↑; Contactin-1 ↑; Contaction-2 ↑; PASAT-3 ↑ |
| CON: 30 | 31.36 ± 8.07 | 2.00 ± 1.14 | Habitual lifestyle | ||||||||
| Cakt et al. 2010 | RCT | INT1: 10 | 43.0 ± 10.2 | N/A |
RRMS SPMS |
2x/week 8 weeks |
N/A |
15–25 min LB plyometrics + balance; 2 exercises LB plyometrics 15 sets × 2 min high-resistance cycling, 2 min low-resistance/rest |
INT1: LB plyometrics INT 1: Balance exercise Walking, standing, balance board |
Mobility (TUG); dynamic balance (Dynamic Gait Index); static balance (Functional Reach); fear of falling (Falls Efficacy Scale); walking speed (10MWT); fatigue (Fatigue Severity Scale); depression (Beck Depression Inventory); HRQoL (Short Form-36); total maximum workload; exercise duration |
INT2 vs. INT 1 vs. CON: TUG ↑; Dynamic Gait Index ↑; Functional Reach ↑; Falls Efficacy Scale ↑; Fatigue Severity Scale ↑; Beck Depression Inventory ↑; total maximum workload ↑; exercise duration ↑; 10MWT ↔; SF-36 ↔ INT2 vs. CON: 10MWT ↑ |
| INT2: 14 | 36.4 ± 10.5 | 40% total maximum workload |
INT 2: Additional High-resistance cycling Bicycle ergometer |
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| CON: 9 | 35.5 ± 10.9 | Habitual lifestyle | |||||||||
| Coote et al. 2015 | RCT | INT1: 10 | 51.8 ± 12.1 | N/A |
RRMS SPMS PPMS BMS |
2x/week 6 weeks; 3x/week 6 weeks |
Adj. until muscular failure | 6 exercises; 1–3 sets × 12 reps, 2–3 min rest |
INT1: LB resistance BW, wooden box, free weights (hand, ankle, backpack) |
Knee extension strength (dynamometry); hip extension strength (dynamometry); lower extremity strength (maximum rep Sit To Stand Test); lower-limb spasticity (VAS); mobility (TUG); self-reported walking impairment (MS Walking Scale–12); balance (Berg Balance Scale); impact of MS (MS Impact Scale-29); fatigue (Modified Fatigue Impact Scale) | INT1 vs. INT2: Modified Fatigue Impact Scale (total) ↓; hip/knee extension strength ↔; Sit To Stand ↔; spasticity VAS ↔; TUG ↔; MS Walking Scale-12 ↔; MS Impact Scale (physiological/psychological score) ↔; Berg Balance Scale ↔ |
| INT2: 15 | 51.8 ± 12.6 | INT2: LB resistance combined with neuromuscular electric stimulation s.a | |||||||||
| Correale et al. 2021 | RCT | INT: 14 | 45.4 ± 7.2 | 2.25 ± 0.8 | RRMS |
2x/week 12 weeks |
Self-chosen |
45–60 min; 3 sets × 8–12 reps; 60–90 s rest 25 min; 50–70% HRR |
WB resistance Calisthenics; dumbbells; elastic bands AT (bicycle/treadmill) |
Strength quadriceps (MVIC, 1-RM leg extension); strength chest (1-RM chest press); strength back (1-RM seated row); fatigue (MFIS); depressive symptoms (BDI-II); HRQoL (MSQOL-54) |
INT vs. CON: MFIS ↑; MSQOL-54 (mental composite) ↑; MVIC ↔; 1-RM leg extension ↔; 1-RM chest press ↔; 1-RM seated row ↔; depressive symptoms ↔; MSQOL-54 (physical composite) ↔ |
| CON: 13 | 48.3 ± 6.1 | Habitual lifestyle | |||||||||
| De Bolt and McCubbin 2004 | RCT | INT: 19 | 51.63 ± 6.71 | 3.97 ± 1.79 |
RRMS PMS BMS |
3x/week 8 weeks |
≥ 0.5% BW | 25–30 min, 2–3 sets × 8–12 reps; self-chosen rests |
LB resistance BW, weighted vests, ankle weights, step |
Balance (anteroposterior sway, mediolateral sway, sway velocity); leg extensor power (maximal leg extension power); mobility (TUG) | INT vs. CON: absolute/relative leg extensor power ↑; anteroposterior/mediolateral sway ↔; sway velocity ↔; TUG ↔ |
| CON: 18 | 47.78 ± 10.47 | 3.50 ± 1.50 | Habitual lifestyle | ||||||||
| Frevel and Mäurer 2015 | RCT | INT1: 9 | 44.3 ± 8.1 | 3.8 ± 1.5 | RRMS 6 (67) SPMS 3 (33) |
2x/week 12 weeks |
RPE 11–14 | 45 min; 5–8 exercises; 2–3 sets × 8–15 reps, |
INT1: LB resistance BW, elastic bands, gym ball, mat INT1: Balance Standing, unstable surface |
Balance (Berg Balance Scale; Dynamic Gait Index); knee extensor/flexor strength (MVIC); trunk extensor/flexor strength (MVIC); mobility (TUG); walking speed (2MWT 1 min/total); HRQoL (Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, total, all subscales); fatigue (Fatigue Severity Scale; Modified Fatigue Impact Scale) | INT vs. INT2: MFIS cognitive subscale ↑; HAQUAMS upper limb ↑; Berg Balance Scale ↔; Dynamic Gait Index ↔; knee extensor/flexor MVIC ↔; trunk extensor/flexor MVIC ↔ |
| INT2: 9 | 46.9 ± 7.6 | 3.8 ± 1.1 | 20–30 min | INT2: Hippotherapy | |||||||
| Garrett et al. 2013 | RCT | INT1: 63# | 51.7 ± 10 | N/A |
RRMS SPMS PPMS BMS |
1x/week 10 weeks 2x/week 10 weeks |
Until muscular failure 65% HRmax, RPE 11–14 |
60 min; 3 sets × 12 reps 30 min 30 min |
INT1: WB resistance BW, free weights INT1: AT Mode of choice (walking/cycling/swimming/running) |
HRQoL (Multiple Sclerosis Impact Scale-29 (physical/psychological)); fatigue (Modified Fatigue Impact Scale (total/physical/cognitive)); walking endurance (6MWT) |
INT1 vs. CON: Multiple Sclerosis Impact Scale-29 (physical/psychological) ↑; Modified Fatigue Impact Scale (total/physical) ↑; Modified Fatigue Impact Scale (cognitive) ↔; 6MWT ↑ INT2 vs. CON: Multiple Sclerosis Impact Scale-29 (physical/psychological) ↑; Modified Fatigue Impact Scale (total/physical) ↑; Modified Fatigue Impact Scale (cognitive) ↔; 6MWT ↑ INT3 vs. CON: Multiple Sclerosis Impact Scale-29 (psychological) ↑; Modified Fatigue Impact Scale (total/physical) ↑; Multiple Sclerosis Impact Scale-29 (physical) ↔; Modified Fatigue Impact Scale (cognitive) ↔; 6MWT ↔ |
| INT2: 67# | 50.3 ± 10 |
1x/week 10 weeks |
Not predefined | Not predefined | INT2: Resistance training/AT/combined training Not predefined | ||||||
| INT3: 63# | 49.6 ± 10 |
1x/week 10 |
Not predefined | Not predefined | INT3: Yoga Not predefined | ||||||
| CON: 49# | 48.8 ± 11 | Habitual lifestyle | |||||||||
| Hosseini et al. 2018 | RCT | INT1: 9 | 32.9 ± 8.1 | N/A | N/A |
3x/week 8 weeks |
≥ 1% bodyweight | 5 exercises; 3 sets × 10 reps, 30–60 s rest (betw. exercises) |
INT1: LB resistance Free weights (fastened to the body) |
Leg extensor strength (1-RM); leg strength (leg press); walking speed (10MWT); balance (postural sway balance index, two legs open/closed eyes, one leg open eyes) | INT1 vs. INT2 vs. CON: Leg extensor 1-RM ↕ (INT1 ↑) |
| INT2: 9 | 31.3 ± 7.1 | 60–70 min; 1 set × 30–60 s, 30–60 s rest |
INT2: Hatha Yoga Standing, sitting, lying |
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| CON: 8 | 33.0 ± 9.7 | Habitual lifestyle | |||||||||
| Learmonth et al. 2012 | RCT | INT: 20 | 51.4 ± 8.06 | 6.14 ± 0.36 | N/A |
2x/week 12 weeks |
Self-chosen |
30–40 min; 8–12 exercises; N/A sets × 1 min; ≥ 60 s rest |
WB resistance BW, dumbbells, chair AT Walking/stepping/bike/Foot pedals Balance Sitting/standing/walking |
Walking speed (T25FW); body mass index; walking endurance (6MWT); balance (Berg Balance Scale); mobility (TUG); quadriceps strength (maximum isometric force leg extension, weaker leg); activity level (PhoneFITT); balance confidence (Activities Balance Confidence); fatigue (Fatigue Severity Scale); anxiety and depressive symptoms (HADS); HRQoL (LMSQOL); goal attainment (Goal Attainment Scale) | T25FW ↔; PhoneFITT ↕; Activities Balance Confidence ↑ (0–12 wks); body mass index ↔; 6MWT ↔; Berg Balance Scale ↔; TUG ↔; maximum isometric force leg extension ↔; fatigue severity scale ↔; HADS ↔; LMSQOL ↔ |
| CON: 12 | 51.8 ± 8.0 | 5.82 ± 0.51 | Habitual lifestyle | ||||||||
| Mardaniyan Ghahfarrokhi et al. 2022 | RCT | INT1: 15 | 39.87 ± 9.09 | 4.13 ± 0.97 | RRMS |
3x/week 8 weeks |
CR-10: 2–6 |
120–190 min, 14 exercises, 1–2 sets × 10–12 reps |
INT1: WB resistance Elastic bands |
Static balance (wide/narrow, single-leg (R/L, open/closed eyes), semi-tandem, tandem open/closed eyes); dynamic balance (tandem walk test); mobility (TUG); walking endurance (6MWT); walking speed (10MWT, T25FWT); walking ability (6 Spot Step Test (dominant/non-dominant); lower extremity strength (5 Times Sit to Stand); hand grip strength (dynamometry) | INT1 vs. INT2: Tandem walk ↓; Six Spot Step Test (non-dominant) ↓; 6MWT ↓; all other outcomes ↔ |
| INT2: 15 | 37.50 ± 8.58 | 4.57 ± 1.30 |
CR-10: 2–6 |
90–120 min, 2 sets × 8 reps, 2 min rest |
INT2: Neurofunctional exercise Balance (standing, walking), walking, WB resistance, pelvic control, core stability, BW, cones, Swiss ball |
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| Moghadasi et al. 2020 | CT | INT: 19 | 37.62 ± 4.58 | 2.18 ± 0.85 | RRMS: |
3x/week 8 weeks |
N/A | 30 min; 8 exercises; 3 sets × 5–10 reps |
WB Resistance TRX® suspension |
Mobility (TUG); walking speed (10MWT); walking endurance (2MWT); lower extremity strength (5 Times Sit to Stand); joint position sense (knee proprioception absolute error); quadriceps/knee extensor strength (MVIC); knee flexor strength (MVIC) | INT vs. CON: TUG ↑; 10MWT ↑; 2MWT ↑; 5 Times Sit to Stand ↑; knee proprioception absolute error non-dominant leg (60°) ↑;MVIC knee extensors dominant/non-dominant (20° and 70°) ↑; MVIC knee flexors dominant/non-dominant (20°) ↑; MVIC knee flexors dominant (70°) ↑; knee proprioception absolute error dominant leg (60°) ↔; proprioception absolute error dominant and non-dominant leg (30°) ↔; MVIC knee flexors non-dominant (70°) ↔ |
| CON: 15 | 34.72 ± 5.01 | 2.59 ± 1.01 | Habitual lifestyle | ||||||||
| Motl et al. 2012 | UCT | INT: 13 | 51.5 ± 11.3 | 5.58 ± 0.79 |
RRMS SPMS PPMS |
3x/week 8 weeks |
RPE 13 RPE 13 RPE 13 |
15–60 min; 5–20 min; 5 exercises; sets/reps N/A 5–20 min 5–20 min |
LB resistance Elastic bands AT Ergometry (bicycle, rowing, elliptical)/treadmill Balance Standing, walking |
Walking speed (T25FW); self-reported walking impairment (MS Walking Scale-12); mobility (TUG); gait efficiency (Functional Gait Profile score, spatial and temporal gait measures) | – |
| Najafi et al., 2019 | RCT | INT: 30 | 38.39 ± 4.59 | 2.51 ± 1.22 | RRMS |
3x/week 8 weeks |
N/A | 45–60 min; 5 exercises; 3–4 sets × 10–15 s, 10–15 s rest |
Core training BW Balance Standing, walking (open/closed eyes) |
Postural control (Center of Pressure sway area and path length, opened/closed eyes); balance (Berg Balance Scale); walking speed (T25FW); mobility (TUG) | Center of Pressure sway area (opened/closed eyes) ↑; Center of Pressure path length (opened/closed eyes) ↑; Berg Balance Scale ↑; T25FW ↑; TUG ↑ |
| CON: 30 | 36.36 ± 3.54 | 2.44 ± 0.77 | N/A | ||||||||
| Sabapathy et al. 2011 | RCT |
INT1: 11 (14)1 |
55 ± 7 | N/A |
RRMS SPMS PPMS |
2x/week 8 weeks |
CR10 3–5 |
8 exercises, 2–3 sets × 6–10 reps, ≥ 30–60 s rest 15–20 min |
INT1: WB resistance and balance Elastic band, dumbbell (1–4 kg), parallel bar, Swiss ball, ankle weights (1–5 kg), foam mat, foam beam, wobble board INT1: Stretching |
Grip strength (dynamometry); static balance (functional reach), dynamic balance (4 Step Square); mobility (TUG); walking endurance (6MWT); HRQoL (Multiple Sclerosis Impact Scale (physical/psychological); Short Form-36 (Physical and Mental Component Summary); fatigue (Modified Fatigue Impact Scale (physical/cognitive/psychosocial)); depressive symptoms (Becks Depression Inventory) | INT1 vs. INT 2: all outcomes ↔ |
|
INT2: 5 (6)1 |
8 stations × 5 min, 2 min rest every 10 min 15–20 min |
INT2: AT Arm crank, cycling, cross-trainer, step-ups, recumbent cycling, treadmill INT2: Stretching |
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| Sosnoff et al. 2014 | RCT | INT: 13 | 60.1 ± 6.3 | 5.5 (2.5) |
RRMS SPMS PPMS |
3x/week 12 weeks |
N/A |
45–60 min; 3 sets × 8–12 reps |
LB and core resistance Elastic bands, BW Balance Standing, walking |
Fall risk (Physiological Profile Assessment total, subcomponents); balance (Berg Balance Scale); balance confidence (Activities-Specific Balance Confidence scale); walking speed (T25FW); walking endurance (6MWT); mobility (TUG); self-reported walking impairment (MS Walking Scale-12); self-reported fall frequency |
INC vs. CON: Physiological Profile Assessment total ↑; postural sway subcomponent ↑; T25FW ↑; Activities- Specific Balance Confidence scale ↑; other subcomponents (Melbourne Edge detection test, proprioception, strength, reaction time) ↔; 6MWT ↔; TUG ↔; MS Walking Scale-12 ↔; Berg Balance Scale ↔ |
| CON: 14 | 60.1 ± 6.0 |
5.5 (3.5) [Mdn (IQR)] |
Habitual lifestyle | ||||||||
| Zaenker et al. 2018 | UCT |
INT: 26 (30)1 |
44.6 ± 7.9 | 2.46 ± 1.52 |
RRMS SPMS PPMS |
2x/week 1–4 week 3x/week 5–12 week |
N/A Intervals at 90–110% maximal tolerated power, rest at anaerobic threshold moderate |
4 exercises, 4–5 sets × 10–15 reps s.a 17 min 35–45 min |
LB resistance BW, resistance band, ankle weight Additional LB resistance (5–12 weeks, every 2nd week) AT HIIT: 5 intervals, 3 min rest Additional AT (5–12 weeks, every 2nd week) Self-chosen |
Cardiorespiratory fitness (VO2 peak, lactate at the end of the maximum aerobic test, HRpeak), physical capacity (maximal tolerated power), quadriceps strength (isokinetic peak torque), hamstring strength (isokinetic peak torque); HRQoL (MSQOL-54 total, subscales) | – |
Intervention duration without warm-up/cool-down periods; #whole group prior drop-out; bold = in multicomponent interventions considered as “functional training”
↔ = no change, ↑ = significant improvement/between-group effect in favor of INT(1); ↓ = significant worsening/between-group in favor of INT2/CON; ↕ = unspecified significant difference, 1Data presented for n completing the program, initial sample size in brackets
AT aerobic training, BDNF brain-derived neurotrophic factor, BDI-II Beck depression inventory-II, BMS benign MS, CPET cardiopulmonary exercise test, CON control group, CT controlled trial, EDSS expanded disability status scale, f female, HRR heart rate reserve, HADS hospital anxiety and depression scale, HAQUAMS Hamburg quality of life questionnaire in multiple sclerosis, HRmax/HRpeak maximum/peak heart rate, HRQoL health-related quality of life, IGF-1 insulin like growth factor, INT intervention group, L left, LB lower body, m male, LMSQOL Leeds multiple sclerosis quality of life scale, MFIS modified fatigue impact scale, MRI magnetic resonance imaging, MSQOL-54 multiple sclerosis quality of life instrument-54 item, MVIC maximal voluntary isometric contraction, PASAT-3 paced auditory serial addition test with 3 s stimulus, PMS progressive MS, PPMS primary progressive MS, PSFS patient-specific functional scale, R right, RCT randomized controlled trial, RPE rate of perceived exertion, RRMS relapsing–remitting MS, RT resistance training, SF-36 Short Form-36, SPMS secondary progressive MS, TUG timed up and go, TSD time since diagnosis, T25FW timed 25-foot walk, UCT uncontrolled trial, VAS visual analog scale, V̇O2 max/V̇O2 peak maximum/peak oxygen consumption, WB whole body, 1-RM 1-repition maximum, 2MWT 2-min walk test, 6MWT 6-min walk test, 10MWT 10-m walk test