Table 1.

Summary of selected contributions.

Author/Year	Study	N, EG/CG	Intervention	Outcome Measures	Results
Russo et al. [23]	Single-blind randomized trial	N = 45 EG: 30 CG: 15	EG: 6 weeks Lokomat (3 times/week, 60 min) + 12 weeks traditional training (3 times/week, 60 min) CG: 18 weeks traditional training. Measurements: beginning (T1), final (six weeks later; T2), one month later (T3)	Expanded Disability Severity Scale (EDSS); Functional Independence Measure (FIM); Hamilton Rating Scale for Depression (HRSD); TUG, Tinetti	EG improved on all scales, while CG only on TUG. GC improved at all values of T1 and T2, while EG only improved TUG at those times. At T2 and T3 there were no major differences between the two groups.
Calabró RS et al. [24]	Single-blind randomized clinical trial	N = 40 EG: 20 CG: 20	EG: Lokomat-Nanos (RAGT − VR) CG: Lokomat-Pro (RAGT + VR) 5 times/week, 8 weeks. Measurements: beginning to end of treatment	TUG, Berg, Coping Orientation to Problem Experience (COPE), FIM, Modified Ashworth scale, Hamilton Rating Scale for Depression (HRSD)	There are no differences between values obtained in Berg and TUG. In the rest of the scales, they show significant improvements (p < 0.05) in the use of RAGT and VR. The combined use of Lokomat treatment with virtual reality exercises improves symptoms in MS patients.
Sconza C et al. [25]	Randomized controlled crossover trial	N = 17 EG: 8 CG: 9	EG: Lokomat + physiotherapy CG: physiotherapy 5 times/week 5 weeks	25-foot walking test (T25FW), 6-minute walking test (6MWT), Tinetti; Ashworth, Modified Motricity Index for Lower Limbs, FIM, Quality-Of-Life Index, gait parameters	Both groups showed improved results, but EG improved especially in the 25FW and 6MWT trials.
Niedermeier M et al. [26]	Crossover study	N = 14 EG: 7 CG: 7	EG: Lokomat CG: Bobath principles, comprised mobilization, strengthening, and sensomotoric stimulating techniques. One Lokomat session and one conventional physiotherapy session, administered randomly to each group. Measurement at the beginning and end of each session	Personal perception questionnaire, Short version of the German Mood Survey Scale (MSS) Functional Ambulation Category (FAC)	RAGT showed significantly increased euphoria and calm after the treatment session. Affective responses between physical therapy and RAGT differed significantly in favor of RAGT in affective states.
Russo M et al. [27]	Rater-blinded, active controlled, parallel-group pilot study	N = 40 EG: 20 CG: 20	EG: Sativex + Lokomat CG: other antispasmodic + Lokomat 45 min, 3 times/week. Duration: 20 sessions. Measurement: beginning–final–30 days later	EDSS, Functional Independence Measure (FIM), MAS, NRS, 10MWT, 6-minute walking test (6MWT), Hamilton Rating Scale for Depression (HRSD), and MSQOL54. Cortical plasticity was evaluated by means of TMS methodology. Blood pressure and mean heart rate were assessed	Patients treated with Sativex and Lokomat improved gait and balance motor values, compared to patients treated with another type of antispasmodic.
Pompa A et al. [28]	Pilot, single-blind randomized controlled trial	N = 43 EG: 21 CG: 22	EG: robot-assisted gait training (RAGT), CG: conventional walking training (CWT) In the morning, 3 times/week, 4 weeks, 40 min/session. Measurement: pre- and post-intervention	2-min walking test (2MWT) Functional Ambulatory Category (FAC), Rivermead Mobility Index (RMI), Modified Barthel Index (mBI), fatigue severity scale (FSS), visual analogue scale (VAS)	Experimental group presented better results on the scales than the control group, which means that assisted gait training leads to improvement in gait.
Ziliotto N et al. [29]	Parallel-assignment, single-blinded, randomized controlled trial	N = 61 EG: 33 CG: 28	12 sessions; duration: two hours each for six weeks. EG: RAGT on a Lokomat treadmill with a duration of about 40 min CG: assisted walking on the ground. Sessions of approximately 40 min, inserted between 10 min warm-up and cool-down periods	Gait speed, assessed by the T25FWT, the 6-min walking test (6MWT), the Berg Balance Scale (BBS), and the MS impact scale-29 (MSIS-29)	The protein concentration and blood concentration values after motor treatment varied from one group to another, and an increase in protein concentration was found in EG, leading to an improvement in motor skills.
Androwis GJ et al. [30]	Pilot single-blind, randomized controlled trial	N = 10 EG: 6 CG: 4	Compared the effects of 4 weeks of REAER with 4 weeks of conventional gait training (CGT). Duration: 4 weeks, 2 times/week. Measurement: beginning–final	Functional mobility (timed up-and-go- TUG-), walking endurance (six-minute walking test- 6MWT-), cognitive processing speed (CPS; Symbol Digit Modalities Test- SDMT-), and brain connectivity (thalamocortical resting-state functional connectivity (RSFC)	REAER improved the items evaluated, due to the adaptive and integrative plasticity of the central nervous system.
Puyuelo-Quintana G et al. [31]	Cross-sectional study	N = 5 (four stroke patients and one with MS)	5 sessions of 50 min. Pre- and post-measurement, combining measurements without a device, with a device, and with different gait modes that the MAK exoskeleton allows	10-m walking test (10MWT), the Gait Assessment and Intervention Tool (G.A.I.T.) and Tinetti Performance Oriented Mobility Assessment (gait subscale) Modified QUEST 2.0 Questionnaire	The MAK exoskeleton appears to offer positive preliminary results in terms of safety, feasibility, acceptability, and use by patients.
Łyp M et al. [32]	Pilot study	N = 20 (10 males and 10 females)	A six-week-long training period with the use of robot-assisted treadmill training of increasing intensity of the Lokomat type	Difference in motion dependent torque of lower extremity joint muscles after training compared with baseline before training	The robot-assisted body-weight-supported treadmill training may be a potential adjunct measure in the rehabilitation paradigm of “gait reeducation” in peripheral neuropathies.
Straudi S et al. [33]	Parallel-group, randomized controlled trial	N = 98	EG: RAGT intervention on a robotic-driven gait orthosis (Lokomat) CG: individual conventional physiotherapy focusing on over-ground walking training performed with the habitual walking device Measurements: beginning (6 sessions) to final (12 sessions) to three months later. 3 sessions/week, two hour duration	T25FW; QoL; 6-min walking test (6MWT); Berg Balance Scale; timed up-and-go test; fatigue severity scale; Modified Ashworth Scale; Patient Health Questionnaire; Short Form Health Survey; Multiple Sclerosis Impact Scale; Multiple Sclerosis Walking Scale	The RAGT training is expected to improve mobility compared to the active control intervention in progressive MS. Unique to this study is the analysis of various potential markers of plasticity in relation with clinical outcomes, identifying the effectiveness of intensive rehabilitative interventions through the changes of clinical and circulating biomarkers of MS plasticity.
Straudi S et al. [34]	Randomized controlled trial	N = 72 EG: 36 CG: 36	EG: robot-assisted gait training (RAGT) CG: conventional therapy (CT) 12 sessions, for 4 weeks. Measurements: beginning (6 sessions) to final (12 sessions) to three months later	T25FW test, the 6-min walking test (6MWT), the Berg Balance Scale (BBS), the timed up-and-go (TUG) test, the fatigue severity scale (FSS), the Patient Health Questionnaire (PHQ), the Short Form Health Survey 36 (SF-36), the MS impact scale-29 (MSIS-29), and the MS walking scale-12 (MSWS-12)	RAGT was not superior to CT in improving gait speed in patients with progressive MS and severe gait disabilities where a positive, even transitory, effect of rehabilitation was observed.
McGibbon CA et al. [35]	An open-label, randomized, crossover trial	N = 29	Unassisted (rehab effect) performance was observed after using the device at home for 2 weeks, compared to 2 weeks at home without the device, and participants improved their ability to use the device over the trial period (training effect)	6-minute walking test (6MWT); TUG test; timed stair test (TST)	Keeogo appears to deliver an exercise-mediated benefit to individuals with MS that improved their unassisted gait endurance and stair climbing ability.
Berrozabalgoitia R et al. [36]	Randomized controlled trial	N = 36	CG: rehabilitation program consisting of weekly 1-hour individualized sessions. EG: also participated in this program in addition to a twice-weekly individualized and progressive OR gait training intervention for 3 months, aiming to reach a maximum of 40 min by the end of the 3-month period	10-meter walking test (10MWT); the Short Physical Performance Battery, the timed up-and-go (TUG) test, and the Modified Fatigue Impact Scale	The evaluated intervention could preserve gait speed and significantly improve functional mobility without increasing perceived fatigue in participants. Thus, OR exoskeletons could be considered a tool to deliver intensive practice of good-quality gait training in individuals with MS and moderate to severe gait impairments.
Drużbicki M et al. [37]	Single-group longitudinal preliminary study	N = 14	15 exoskeleton-assisted gait training sessions, reflected by the muscle strength of the lower limbs and by walking speed. Assessments were performed 4 times, that is, prior to the start of the program (T0), at the end of the physiotherapy without an exoskeleton (T1), at the end of the exoskeleton-assisted training (T2), and at 6-week follow-up (T3)	Dynamometric knee extensor and flexor strength (Biodex Pro4), postural balance, and center of pressure displacements (Zebris FMD-S), walking speed measured with the timed 25-foot walking test and fatigue (fatigue severity scale)	Individuals with MS and severe gait impairment participating in exoskeleton-assisted gait training achieved significant improvement in lower-limb muscle strength and increase in walking speed, yet the effect was not long-lasting.
Maggio MG et al. [38]	Randomized controlled trial	N = 60 EG: 30 CG: 30	The effect of semi-immersive virtual reality training (sVRT) on neuropsychological and motor recovery individuals suffering (EG) was evaluated. CG: conventional cognitive training. Measurement: beginning–final	Cognitive and motor outcomes were investigated through clinical and neuropsychological scales	A significant improvement in cognitive parameters and motor scores was observed only for EG.
Munari D et al. [39]	Randomized controlled trial	N = 17	EG: robot-assisted gait training with virtual reality CG: robot-assisted gait training without virtual reality Measurements: beginning–final (one month later)	Paced Auditory Serial Addition Test, Phonemic Fluency Test, Novel Task, Digit Symbol, Multiple Sclerosis Quality of Life-54, 2-min walking test, 10-meter walking test, Berg Balance Scale, gait analysis, and stabilometric assessment	Both forms of training led to positive influence on executive functions. However, larger positive effects on gait ability were noted after robot-assisted gait training engendered by virtual reality with multiple sclerosis.

PT: physical therapy; RAGT: robotic-assisted gait training; EG: experimental group; CG: control group; EDSS: Expanded Disability Severity Scale; FIM: Functional Independence Measure; HRSD: Hamilton Rating Scale for Depression; TUG: timed up-and-go; VR: virtual reality; RAGT: robot-assisted gait training; COPE: Coping Orientation to Problem Experience; MS: multiple sclerosis; T25FW: 25-foot walk test; 6MWT: 6-Minute Walking Test; MSS: Mood Survey Scale; FAC: Functional Ambulation Category; MSQOL54: Multiple Sclerosis Quality of Life-54; CWT: conventional walking training; 2MWT: 2-minute Walking Test; mBI: Modified Barthel Index; FSS: fatigue severity scale; VAS: visual analogue scale; BBS: Berg Balance Scale; MSIS-29: Multiple Sclerosis Impact Scale-29; CGT: Conventional Gait Training; CPS: cognitive processing speed; SDMT: Symbol Digit Modalities Test; RSFC: Resting State Functional Connectivity; 10MWT: 10-m walking test; GAIT: Gait Assessment and Intervention Tool; MSWS-12: Multiple Sclerosis Walking Scale-12; SVRT: semi-immersive virtual reality training.