. 2021 Sep 30;16(9):e0257809. doi: 10.1371/journal.pone.0257809

Table 1. Summary of analyzed articles.

Article	Participant characteristics: sample size (N), disease severity (mean/range; EDSS/PDSS), age (mean years), MS type	Intervention	Assessments
Martini et al., 2018 [19]	N 40; EDSS:6; Age 56	Multicomponent walking aid program	TUG, 2MWT, T25W, FSST, MSWS-12, MSIS-29, ABC
Martini et al., 2018 [19]	MS type: NR	Multicomponent walking aid program	TUG, 2MWT, T25W, FSST, MSWS-12, MSIS-29, ABC
Russo et al., 2017 [20]	N 45; EDSS:3–5.5; Age 42	Robot gait training with virtual reality (Lokomat)	TUG, EDSS, TBS, HRSD
Russo et al., 2017 [20]	MS type: RR 45	Robot gait training with virtual reality (Lokomat)	TUG, EDSS, TBS, HRSD
Sandroff et al., 2017 [21]	N 83; PDDS:4; Age 49.8	Multimodal exercise training	GSTP, VO2, MS-IM, T25W, 6MWT, MSWS-12
Sandroff et al., 2017 [21]	MS type: NR	Multimodal exercise training	GSTP, VO2, MS-IM, T25W, 6MWT, MSWS-12
Calabro et al., 2017 [22]	N 40; EDSS: 4.1–5.5; Age 41	Robot assisted therapy with virtual reality	MAS, MS-LD, TUG, BBS, HRSD, COPE
Calabro et al., 2017 [22]	MS type: NR	Robot assisted therapy with virtual reality	MAS, MS-LD, TUG, BBS, HRSD, COPE
Conroy et al., 2017 [23]	N 24; PDDS:4.4; Age 50.4	Self-directed exercise at home	T25W, BBS, 6MWT, MSWS-12
Conroy et al., 2017 [23]	MS type: RR8, SP15, PP1	Self-directed exercise at home	T25W, BBS, 6MWT, MSWS-12
Pau et al.,	N 22; EDSS: 3.6; Age 47.4	Adapted physical activities	ROM, GSTP
2017 [24]	MS type: NR	Adapted physical activities	ROM, GSTP
Pompa et al., 2016 [25]	N 43; EDSS: 6–7.5; Age 47	Robot assisted gait training + conventional rehabilitation	VAS, FSS, EDSS, 2MWT, FAC
Pompa et al., 2016 [25]	MS type: SP40, PP3	Robot assisted gait training + conventional rehabilitation	VAS, FSS, EDSS, 2MWT, FAC
Davies et al.,	N 32; EDSS: 5.4; Age 53.3	High frequency physical therapy	GSTP, 6MWT
2016 [26]	MS type: RR22, SP10	High frequency physical therapy	GSTP, 6MWT
Kalron et al., 2016 [27]	N 45; EDSS:4.6; Age 44.3	Pilates/physical therapy for improving gait	FIS, TUG, 2MWT, FSST, BBS, 6MWT, MSWT-12
Kalron et al., 2016 [27]	MS type: RR45	Pilates/physical therapy for improving gait	FIS, TUG, 2MWT, FSST, BBS, 6MWT, MSWT-12
Straudi et al., 2016 [28]	N 52; EDSS:6.43; Age 52.3	Robot assisted gait training	FSS, TUG, BBS, 6MWT, 10m, QoLSF-36, PHQ-9
Straudi et al., 2016 [28]	MS type: SP36, PP16	Robot assisted gait training	FSS, TUG, BBS, 6MWT, 10m, QoLSF-36, PHQ-9
Straudi et al., 2014 [29]	N 24; EDSS:4.89; Age 52.6	Task oriented circuit training	FSS, TUG, 6MWT, DGI, MSWS-12, MSIS-29
Straudi et al., 2014 [29]	MS type RR6, SP8, PP10	Task oriented circuit training	FSS, TUG, 6MWT, DGI, MSWS-12, MSIS-29
Tyler et al., 2014 [30]	N 20; EDSS:5.25; Age:55.4	Non-invasive neuromodulation/physical therapy	DGI
Tyler et al., 2014 [30]	MS type: RR13, SP6, PP1	Non-invasive neuromodulation/physical therapy	DGI
Aydin et al., 2014 [31]	N 40; EDSS:3.6; Age 33	Home based calisthenic exercises	FSS, BBS, 10m, HADS, MusiQoL
Aydin et al., 2014 [31]	MS type: RR40	Home based calisthenic exercises	FSS, BBS, 10m, HADS, MusiQoL
Ruiz et al., 2013 [32]	N 7; EDSS: 5; Age 47	Robot assisted, body weight support training	GSTP, T25W, FRT, 6MWT
Ruiz et al., 2013 [32]	MS type: RR5, PP2	Robot assisted, body weight support training	GSTP, T25W, FRT, 6MWT
Schwartz et al., 2012 [33]	N 32; EDSS: 6; Age 48.6	Robot assisted gait training	TUG, EDSS, BBS, 6MWT, 10m, Rand-36
Schwartz et al., 2012 [33]	MS type: NR	Robot assisted gait training	TUG, EDSS, BBS, 6MWT, 10m, Rand-36
Vaney et al., 2012 [34]	N 49; EDSS:5.8; Age 56.2	Robot assisted step training (Lokomat)	MAS, VAS, BBS, 3MWT, 10m, Ac, WE
Vaney et al., 2012 [34]	MS type: NR	Robot assisted step training (Lokomat)	MAS, VAS, BBS, 3MWT, 10m, Ac, WE
Dodd et al.,	N 71; EDSS:0–6.5; Age49	Progressive resistance training	MSSS-88, MS-MD, FIS,2MWT, WHOQoL-Bref
2011 [35]	MS type: RR71	Progressive resistance training	MSSS-88, MS-MD, FIS,2MWT, WHOQoL-Bref
Conklyn et al., 2010 [36]	N 10; EDSS NR Age: 48.5	Home based walking program (rhythmic auditory)	MAS, VAS, MRC, Kinematics, PDDS, T25W, AI
Conklyn et al., 2010 [36]	MS type: RR7, SP2, PP1	Home based walking program (rhythmic auditory)	MAS, VAS, MRC, Kinematics, PDDS, T25W, AI
Cakit et al., 2010 [37]	N 45; EDSS:0–6; Age 38.1	Cycling progressive resistance training programs	FSS, TUG, FRT, 10m, DGI, FES, QoLSF-36, BDI
	MS type: NR	Cycling progressive resistance training programs	FSS, TUG, FRT, 10m, DGI, FES, QoLSF-36, BDI
Robinson et al., 2015 [38]	N 56; EDSS:0–6; Age 52.9	Exergaming	GSTP, MSW-12, WHODAS2.0
Robinson et al., 2015 [38]	MS type: NR	Exergaming	GSTP, MSW-12, WHODAS2.0
Garret et al., 2013 [39]	N 121; GNDRS:0,1–2; Age50.05	Circuit exercises, aerobic exercise, yoga	FIS, GNDS,6MWT, MSIS-29
Garret et al., 2013 [39]	MS type: RR65, SP20, PP13, Bening 5 Unknown 18	Circuit exercises, aerobic exercise, yoga	FIS, GNDS,6MWT, MSIS-29
Gandolfi et al., 2014 [40]	N 22; EDSS:4.1; Age 50.4	Robot assisted gait training	GSTP, FSS, BBS, SOT, SA, MSQoL-54, ABC
Gandolfi et al., 2014 [40]	MS type: NR	Robot assisted gait training	GSTP, FSS, BBS, SOT, SA, MSQoL-54, ABC
Peruzzi et al., 2017 [41]	N 25; EDSS:3.8; Age 42.8	Virtual reality and treadmill	ROM, Kinematics, TUG, EDSS, FSST, BBS,6MWT
	MS type: NR	Virtual reality and treadmill	ROM, Kinematics, TUG, EDSS, FSST, BBS,6MWT
Shahraki et al., 2017 [42]	N 18; EDSS:3–6.0; Age 39.2	Gait training/ rhythmic auditory stimulation	GSTP
Shahraki et al., 2017 [42]	MS type: NR	Gait training/ rhythmic auditory stimulation	GSTP
Braendvik et al., 2016 [43]	N 29; EDSS:3.2; Age 47.9	Treadmill training	GSTP, Ac
Braendvik et al., 2016 [43]	MS type RR19 SP2 PP5	Treadmill training	GSTP, Ac
Straudi et al., 2019 [44]	N 72; EDSS:6.5; Age 55.5	Robot assisted gait training	FSS, TUG, T25W, MSWS-12, QoLSF-36, MSIS-29, PHQ-9
Straudi et al., 2019 [44]	MS type SP38 PP34	Robot assisted gait training	FSS, TUG, T25W, MSWS-12, QoLSF-36, MSIS-29, PHQ-9
Heine et al., 2019 [45]	N 10; EDSS:3; Age 48.8	Sequential exercise intervention	GSTP, CPET, MFIS, FMSC, MSWS-12
Heine et al., 2019 [45]	MS type RR2 SP3 PP5	Sequential exercise intervention	GSTP, CPET, MFIS, FMSC, MSWS-12
Callessen et al., 2019 [46]	N 142; EDSS:2–6.5; Age 52	Resistance, Balance, Motor Control training	T25FW, SSST, mBest test, 6MWT, FIS, MS-IM, MSWS-12, CTSIB, ABC
Callessen et al., 2019 [46]	MS type RR99 SP25 PP18	Resistance, Balance, Motor Control training
Hochsprung et al., 2020 [47]	N 61; EDSS:2.5–6.5; Age NR	Cycling training with visual feedback	GSTP
Hochsprung et al., 2020 [47]	MS type RR27 SP20 PP14	Cycling training with visual feedback	GSTP
Manca et al., 2020 [48]	N 28; EDSS:2.0–5.5; Age 46	High-intensity resistance training	GSTP, ROM, MS-IM
	MS type RR28	High-intensity resistance training	GSTP, ROM, MS-IM
Mahler et al., 2018 [49]	N 34; EDSS:3.0; Age 50	Robot assisted gait training/	6MWT, 10MWT, Calorimetry, WLT
Mahler et al., 2018 [49]	MS type RR 34	Overground walking training	6MWT, 10MWT, Calorimetry, WLT
Mansour 2013 [50]	N 24; EDSS 2.9; Age 40,42	Partial body weight supported treadmill training	TUG, GSTP, Kinematics
Mansour 2013 [50]	MS type RR 24	Partial body weight supported treadmill training	TUG, GSTP, Kinematics
Manca et al., 2017 [51]	N 30; EDSS:3.4; Age 45.1	Strength training	2MWT, 6MWT, 10MWT, TUG, MS-IM
Manca et al., 2017 [51]	MS type RR30	Strength training	2MWT, 6MWT, 10MWT, TUG, MS-IM
Felippe et al., 2019 [52]	N 28; EDSS3.0; Age 50	Treadmill training	TUG, MMSE, FAB
Felippe et al., 2019 [52]	MS type RR 28	Treadmill training	TUG, MMSE, FAB
McGibbon et al., 2018 [53]	N 29; EDSS:5.2; Age NR	Robot assisted gait training	6MWT, TUG, TST, Ac
McGibbon et al., 2018 [53]	MS type NR	Robot assisted gait training	6MWT, TUG, TST, Ac
Munari et al.,2020 [54]	N 17; EDSS:5.2; Age 54.35	Robot assisted gait training, Virtual reality	PASAT, 2MWT, MSQoL-54, 10MWT, GSTP
Munari et al.,2020 [54]	MS type RR 4 SP 14	Robot assisted gait training, Virtual reality	PASAT, 2MWT, MSQoL-54, 10MWT, GSTP
Flachenecker et al, 2020 [55]	N 84; EDSS:4.1; Age 47	Internet-based exercise program	WEI-MuS, MSIS-29, 2MWT, 10MWT, TBS
Flachenecker et al, 2020 [55]	MS type RR 39 SP45	Internet-based exercise program	WEI-MuS, MSIS-29, 2MWT, 10MWT, TBS
Elwishly et al.,2020 [56]	N 29; EDSS: 4–6; Age 33.1	Dual task training	2MWT, 10mWT, MMSE, EDSS
Elwishly et al.,2020 [56]	MS type RR 29	Dual task training	2MWT, 10mWT, MMSE, EDSS
Esnouf et al., 2010 [57]	N 53; EDSS:5.6; Age 55	FES	COMP, FD
Esnouf et al., 2010 [57]	MS type RR 53	FES	COMP, FD
Feys et al., 2019 [58]	N 35; EDSS:NR; Age 40.5	Start to run program	VO2, STST, 6MWT, MSFCS, FSMCF, MSIS-29, DTI
Feys et al., 2019 [58]	MS type NR	Start to run program	VO2, STST, 6MWT, MSFCS, FSMCF, MSIS-29, DTI
Gutierrez et al., 2020 [59]	N 31; EDSS: 3.7; Age 43.5	Strength and dual task combined training program	MS-SS, STS, SA, GSTP
Gutierrez et al., 2020 [59]	MS type NR	Strength and dual task combined training program	MS-SS, STS, SA, GSTP
Tollar et al., 2020 [60]	N 68; EDSS:5–6; Age	Exercise therapy	MSIS-29, QoLEQ-5D, TBS, BBS, 6MWT, SA
Tollar et al., 2020 [60]	MS type	Exercise therapy	MSIS-29, QoLEQ-5D, TBS, BBS, 6MWT, SA
Vedkamp et al., 2019 [61]	N 40; EDSS: 3.5; Age 40	Dual task training	T25WT, TUG, DGI, 2MWT, MSWS-12, FES, MSIS-29
Vedkamp et al., 2019 [61]	MS type	Dual task training	T25WT, TUG, DGI, 2MWT, MSWS-12, FES, MSIS-29
Kahraman et al, 2020[62]	N 35; EDSS: 1.5; Age 35.2	Motor imagery	DGI, T25WT, 2MWT, MSWS-12, TUG, ABC, MFIS, HADS, SA, SDMT, SRT
Kahraman et al, 2020[62]	MS type NR	Motor imagery
Renfrew et al., 2018 [63]	N 78; EDSS: 5.0; Age 39	Electrical stimulation	5MWT, VO2, 25FWT
Renfrew et al., 2018 [63]	MS type RR35 SP18 PP13 NR 12	Electrical stimulation	5MWT, VO2, 25FWT
Duff et al., 2018 [64]	N 30; EDSS:NR, PDDS: 2.2; Age 45.5	Pilates	6MWT, TUG, MSQoL-54, FBS, SRT, Ac, MVC
Duff et al., 2018 [64]	MS type RR 25, SP 2, PP 3	Pilates	6MWT, TUG, MSQoL-54, FBS, SRT, Ac, MVC

Abbreviations: N Number of participants; EDSS Expanded disability status scale; PDDS Patient determined disease steps; NR Not reported; TUG Timed up and go test; 2MWT 2 minute walking test; T25W Timed 25 foot walk; FSST Four square step test; MSWS-12 Multiple sclerosis walking scale-12; MSIS-29 Multiple sclerosis impact Scale_29; ABC Activities-specific balance confidence scale; TBS Tinetti balance scale; HRSD Hamilton rating scale for depression; GSTP Gait spatiotemporal parameters; VO2 oxygen peak uptake; MS-IM Muscle strength isokinetik measures; 6MWT 6-minute walking test; MAS Modified Ashworth scale; MS-MD Muscle strength mechanical device; COPE Coping orientation to problem experienced; MS Type Multiple sclerosis type; RR Remittent recurrent; SP Secondary progressive; PP Primary progressive; ROM Range of movement; VAS visual Analogical Scale; FAC Functional ambulatory scale; FIS Fatigue impact scale; FSS Fatigue severity scale; BBS Berg balance scale; 10m 10-meter walking test; QoL SF-36 Quality of life Short form 36; PHQ-9 Patient health questionnaire; DGI Dynamic gait index; HADS Anxiety and depression scale; MusiQoL Multiple Sclerosis International Quality of Life scale; FRT functional reach test; Rand-36 Random 36 health survey; 3MWT 3-minute walking tests; Ac Accelerometer; WE Wurzburger inventory; MSSS-88 Multiple sclerosis spasticity scale– 88; WHOQoL-bref WHO quality of life bref; AI Ambulatory index; MSIS-29Bref Multiple sclerosis impact scale_29; MRC Medical research council; BDI Beck depression inventory; WHODAS2.0 World health organization disability assessment schedule; GNDS Guy’s neurological disability scale; SOT Sensory organization test; SA Stabilometric assessment; CPET Maximal cardiopulmonary exercise test; FMSC Fatigue scale for motor and cognitive function; SSST Six spot step test; WLT Working load support; MMSE Mini mental state examination; FAB Frontal assessment battery; TST Timed stair test; PASAT Paced auditory serial attention test; Wei-MuS Wurzburger fatigue inventory; COPM Canadian occupational performance measure; FD Falls diary; STS Sit to stand test; MSFCS Multiple sclerosis functional composite; MS-SS Muscle strength static strength; QoL EG-D Quality of life questionnaire; SRT Sit and reach test; 5MWT 5 minute walking test; FBS Fullerton balance scale.