Multiple Sclerosis International

Research Article

The Effectiveness of Physiotherapy Interventions for Mobility in Severe Multiple Sclerosis: A Systematic Review and Meta-Analysis

Table 2

Main characteristics of studies included in the review (including both cohorts with only severe MS and mixed cohorts).


Study characteristics			Participant characteristics				Exercise training characteristics				Outcomes

Ref. (quality)	n	Exercise modality	Gender (% F)	EDSS	Disease duration(y) mean ± SD		Duration (weeks)	Frequency (x/week)	Time (min/session)	Intensity	Outcomes postintervention
Robot-Assisted Gait Training (RAGT) (17 studies)
Androwis, G. et al. [45]	6	RAGT	50%	Ambulation index ≥2	NR		4 weeks	2/week	45 min	Gradually ↓ BWS	↑ cognitive function, ↑ thalamocortical resting-state functional connectivity, ↓ TUG
Berriozabalgoitiaet al., [46]	18	RAGT+gait training Ex.	50%	4.5-7.0	12.94_8.11		3 months	2/week	40 min	Gradually ↑ time and ↓ BWS	↓ 10WMT, ↑ balance, ↓ fatigue, ↓ TUG
Druzbicki, M et al. [47]	14	RAGT	57%	5-6	NR		3 weeks	5/week	45-60 min	Gradually ↓ BWS	↔ balance, ↓ fatigue, ↓ T25-FW
Sconza, C.,et al. [48]	10	RAGT+general Ex. (cross-over design)	84.2%	3.5-7	NR	(36-74)	5 weeks	5/week	90 min	40% BWS treadmill speed of 1.5 km (↓ gradually)	↑ 6MWT, ↓ EDSS, ↓ T25FW, SLR, ↓ spasticity
Afzal et al. [36]	10	RAGT	80%	6.0-7.5			3 weeks	5/week	90 min	Gradually ↑ intensity	↔ 6MWT, ↑ T25FW-self-selected, ↔ T25FW-fast speed, ↓ NVO2 peak, ↔ TUG
Berchicci et al. [37]	5	RAGT	40%	5.0-7.0	NR		6 weeks	2x/5/week	45 min	NR	↑ T25FW, ↑ 2MWT, ↑ Tinetti test, ↑ BBS, ↓ fatigue , ↑ FSS, ↑ EBI, ↓ EDSS
Daniele Munaria et al. [42]	8	RAGT-VR	62.50%	3.0-6.0			6 weeks	2/week	40 min	Gradually ↓ BWS	,
Manfredini et al. [41]	23	RAGT	67%	6.0-7.0			6 weeks	2/week	40 min	Gradually ↑ (distance, speed), ↓ guidance force	↑ 6MWT, improve mitochondrial function biomarker, ↑ rmVO2
Straudi et al. [43]	36	RAGT	67%	6.0-7.0	12 (6-9)		4 weeks	3/week	120 min	Gradually ↑ (distance, speed), ↓ guidance force	↓ T25FW, ↑ 6MWT ↓ TUG, ↑ PHQ-9, ↓ FSS, ↑balance, ↑ QoL, ↑ mental health
McGibbon et al. [34]	35	Home lower exoskeleton (Keeogo) (cross-over design)	58.60%	4-6.5	NR		6 weeks	4 weeks at home (2 weeks with Keeogo, 2 weeks without Keeogo)	All the day	NR	, , ; post 2 weeks with Keeogo at home ⟶ ↑ unassisted 6MWT distance, ↑ unassisted stair climbing performance
Pompa et al. [31]	25	RAGT	47.60%	6.0–7.5			4 weeks	3/week	40	40-50% BWS (↓ gradually)	, , , , , ,
Straudi et al. [29]	30	RAGT	62.90%	6.0-7.0			6 weeks	2/week	60 min (30: walking)	100% guidance +50% BWS (↓ gradually)
Straudi et al. [24]	9	RAGT	50%	4.5–6.5			6 weeks	2/week	60 min (30 min/walking)	Gradually (↑ distance, speed), (↓ guidance force)	Improvements in spatiotemporal parameters (, , , ),
Claude Vaney et al. [23]	26	RAGT	NR	3.0-6.5	NR	58.23 (9.42)	3 weeks	3/week	(30 min/walking)	50% BWS (↓gradually), ↑speed to normal gait speed	↑ QoL, ↑ 3-minute walking speed, , , , , , ,
Schwartz et al. [22]	15	RAGT	57%	5.5–7			4 weeks	2-3/week	45 min (30 min/walking)	40% BWS (↓ gradually)
Beer et al. [14]	19	RAGT	63.20%	6.0–7.5			3 weeks	5/week	30 min	40–80% BWS, gradually ↑ (distance, speed), ↓ BWS	, , ,
Lo et al. [15]	13	RAGT+BWST (cross-over design)	48% F	3.0 -7.0	NR		6 weeks (3 weeks/phase)	2/week	40 min	30%-40% BWS (↓ gradually), ↑ speed	, , , ,
Body weight-supported treadmill training (BWSTT) (5 studies)
Devasahayam et al. [39]	10	BWSTT+ cooling room (16°C)	90%	6.0-7.0 (sensitive to heat)			10 weeks	3/week	40 min	Gradually increased to vigorous intensity (40–65% HRR)	, , , , , , , , ,
Willingham et al. [35]	6	BWSTT+ antigravity treadmill training	50%	6.0-6.5	NR		8 weeks	2/week	20 min	35%-70% BWS, speed of 8.0	,
Jonsdottir et al. [32]	26	BWSTT if needed+dual task training	44.70%	3.5–7			4 weeks	5/week	30 min	–16 RPE
Pilutti et al. [20]	6	BWSTT	66%	5.5–8.0			12 weeks	3/week	30 min	Gradually ↑ speed, ↓ BWS	↓ T25-FW, ↓ fatigue, ↑ QoL, ↓ EDSS
Giesser et al. [13]	4	BWSTT	75%	7.0-8.0			20 weeks	2/week	60 min	100% BWS (↓ gradually), ↑ speed to normal gait speed	↓ 10WMT, ↑ 6MWT, ↑ balance, ↑ QoL, ↓ spasticity, ↑ muscle strength (not all patients were able to complete the 10WMT, 6MWT)
Total-body recumbent stepper training (TBRST) (1 study)
Pilutti et al. [28]	5	TBRST	40%	6.0-8.0		58.8 (3.0)	12 weeks	3/week	30 min	Gradually ↑ according to participant ability	↓ fatigue, ↑ QoL, ↔ T25FW
Home-based exercise (2 studies)
de Bolt et al. [12]	19	Home based resistance Ex.	78.95%	1.0 – 6.5.			8 weeks	3/week	50 min	Resistance by 0.5% of body weight, ↑ (.05%–1.5%) every 2 weeks	↓ TUG, ↑ leg extensor power, ↑balance,
Miller et al. [19]	15	Home Ex. of task-specific programme	73.30%	6.5–8			8 weeks	2/week	60 min	NR	↑ MSIS-29, ↓ 10WMT, ↑ muscle strength, ↓ timed sit-stand, ↓ EDSS, ↓ FIM
Electrical stimulation (2 studies)
JE Esnouf et al. [17]	32	FES (ODFS)	61.50%	4.0-6.5	12.5	53	18 weeks	Daily mobility	All the day	NR	↓ effort for walking, ↓ tripping, ↑ confidence while walking, ↑ walking distance
CL Barrett et al. [16]	25	FES (ODFS)	75%	4.0-6.5			18 weeks	Daily mobility	All the day	Gradually to be worn all the day	↑ walking speed, ↑ walking distance, ↔ physiological cost index
Blood flow-restriction (2 study)
Chotiyarnwong, C et al. [38]	39	Remote ischaemic preconditioning (RIPC)	44.7%	1.0-7.0			1 session	Blood pressure cuff inflated to (30 mm Hg) above resting systolic pressure	Inflation for 5 min followed by deflation for 5 min/3	NR	, ,
Lamberti et al. [40]	12	Blood flow restricted slow walking (BFR-W)	46%				6 weeks	2/week	60 min	↑ speed by 3 steps/min, BFR stable	, , , , , ,
Conventional exercise training (3 studies)
Resistance training
S Briken et al. [25]	12	Arm Ergometry	50%	4.0-6.0			8-10 weeks	2-3/week	15-45 min	Gradually increase
	12	Rowing	36.60%	4.0-6.0			8-10 weeks	2-3/week	15-45 min		↔ 6MWT
	12	Bicycle ergometry	54.50%	4.0-6.0			8-10 weeks	2-3/week	15-45 min
Hayes et al. [18]	11	Lower limb resistance ex	55.50%	3.5-6.5		48.0 (11.9)	12 weeks	3/week	45-60 min	Gradually increase	↑ lower limb strength, ↔ TUG, ↔ 10WMT, ↔ 6MWT, ↑ balance, ↔ fatigue
Aerobic exercise
Jackson et al. [21]	15	Kick boxing	81.80%	1.0-6.0			5 weeks	3/week		Gradually increased ≤75% HRR or ≤5 RPE
Exergaming (1 study)
Robinson et al. [27]	20	(Exergaming) Nintendo Wii Fit	70%	6.00	NR		4 weeks	2/week	40-60 min	↑ difficulty	↓ postural sway, ↑ balance, ↑ step length, ↑ stride length, ↓ MSWS-12
Robinson et al. [27]	18	Balance training	63%	6.00	NR		4 weeks	2/week	40-60 min	↑ difficulty	↓ postural sway, ↑ balance, ↑ step length, ↑ stride length, ↓ MSWS-12
Assistive device selection, training and education program (ADSTEP) (1 study)
Martini et al. [33]	20	ADSTEP	14%	(history of fall)	NR		6 weeks	1/week	40 min	Aid selection, fitting, task-oriented gait training	, , , , , , , ,
Community exercise (2 study)
KL Williams et al. [44]	26	Community group exercise	65.4%	0-5 disease step rating scale	12.4(10.2)	52.7(11.9)	8 weeks	2/week	60 min	↑intensity	↑ 6MWT, ↑ 10WMT, ↑ balance
Hogan et al. [26]	66	Group physiotherapy	62.50%	3–4 on the mobility section of (GNDS)	18(9)	57 (10)	10 weeks	1/week	60 min	Increase the set of (12 repetitions)	, , , component, ↓MFIS
	45	1:1 physio-therapy	57%		13(8)	52 (11)	10 weeks	1/week	60 min	Increase the set of 12 repetitions	, , , , ,
	16	Yoga	61.50%		15(8)	58 (8)	10 weeks	1/week	60 min	NR	, , , , ,
Ankle robotic training (1 study)
Lee Y et al. [30]	7	Ankle robotic training for impaired leg	83.30%				6 weeks	3/week	45 min	NR	, , , ,

2MWT: 2 minutes walking test; 5TST: 5-time sit to stand; 6MWT: 6 min walk test; 10WMT: Ten-Meter Walking Test; ADSTEP: Assistive Device Selection Training and Education Program; BBS: Berg Balance Scale; BFR-W: Blood flow-restricted slow walking; BWS: body weight support; BWST: body weight supported training; DGI: dynamic gait index; DST: double support time; EBI: Extended Barthel Index; EDSS: Expanded Disability Status Scale; FAC: Functional Ambulation Category; FSS: Fatigue Severity score; FES: functional electrical stimulation; FSST: Four Square Step Test; FIM: Functional Independence Measure; GNDS: The Guy’s Neurological Disability Scale; MAS: Modified Ashworth Scale; mBI: modified Barthel Index; mFIS: modified Fatigue Impact Scale; Mini-BESTest: mini Balance Evaluation System Test: MSIS-29: multiple sclerosis impact scale; MSWS: Multiple Sclerosis Walking Scale questionnaire; ODFS: Odstock dropped foot stimulator; PHQ: patient health questionnaire; QoL: quality of life; RAGT: Robot-Assisted Gait Training; RAGT-VR: Robot-Assisted Gait Training combined with Virtual Reality; rmVO2: resting muscle oxygen consumption; RMI: Rivermead Mobility Index; ROM: range of motion; RPE: rating of perceived exertion; SLR: step length ratio; TBRST: Total-Body Recumbent Stepper Training; T25FW: timed 25-foot walk test; TST: timed stair test; TUG: Timed Up and Go; VAS: Visual Analogue Scale.; VO2peak: peak oxygen consumption; NR: not reported. Disease duration in years presented in , otherwise Mean (range). Abbreviations are presented in an alphabetical order. Statistically significant at or .