Shaping neuroplasticity by using powered exoskeletons in patients with stroke: a randomized clinical trial

Rocco Salvatore Calabrò, Antonino Naro, Margherita Russo, Placido Bramanti, Luigi Carioti, Tina Balletta, Antonio Buda, Alfredo Manuli, Serena Filoni, Alessia Bramanti, Rocco Salvatore Calabrò, Antonino Naro, Margherita Russo, Placido Bramanti, Luigi Carioti, Tina Balletta, Antonio Buda, Alfredo Manuli, Serena Filoni, Alessia Bramanti

Abstract

Background: The use of neurorobotic devices may improve gait recovery by entraining specific brain plasticity mechanisms, which may be a key issue for successful rehabilitation using such approach. We assessed whether the wearable exoskeleton, Ekso™, could get higher gait performance than conventional overground gait training (OGT) in patients with hemiparesis due to stroke in a chronic phase, and foster the recovery of specific brain plasticity mechanisms.

Methods: We enrolled forty patients in a prospective, pre-post, randomized clinical study. Twenty patients underwent Ekso™ gait training (EGT) (45-min/session, five times/week), in addition to overground gait therapy, whilst 20 patients practiced an OGT of the same duration. All individuals were evaluated about gait performance (10 m walking test), gait cycle, muscle activation pattern (by recording surface electromyography from lower limb muscles), frontoparietal effective connectivity (FPEC) by using EEG, cortico-spinal excitability (CSE), and sensory-motor integration (SMI) from both primary motor areas by using Transcranial Magnetic Stimulation paradigm before and after the gait training.

Results: A significant effect size was found in the EGT-induced improvement in the 10 m walking test (d = 0.9, p < 0.001), CSE in the affected side (d = 0.7, p = 0.001), SMI in the affected side (d = 0.5, p = 0.03), overall gait quality (d = 0.8, p = 0.001), hip and knee muscle activation (d = 0.8, p = 0.001), and FPEC (d = 0.8, p = 0.001). The strengthening of FPEC (r = 0.601, p < 0.001), the increase of SMI in the affected side (r = 0.554, p < 0.001), and the decrease of SMI in the unaffected side (r = - 0.540, p < 0.001) were the most important factors correlated with the clinical improvement.

Conclusions: Ekso™ gait training seems promising in gait rehabilitation for post-stroke patients, besides OGT. Our study proposes a putative neurophysiological basis supporting Ekso™ after-effects. This knowledge may be useful to plan highly patient-tailored gait rehabilitation protocols.

Trial registration: ClinicalTrials.gov , NCT03162263 .

Keywords: Effective connectivity; Ekso™; Plasticity; Stroke recovery; Wearable exoskeleton.

Conflict of interest statement

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Our Local Ethic Committee approved the study. All the patients gave their written informed consent to study participation.

Consent for publication

All the patients gave their written informed consent for publication of any individual person’s data in any form.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Experimental study flow diagram
Fig. 2
Fig. 2
Ekso™ device
Fig. 3
Fig. 3
Primary outcome measures (10MWT 10 m walk test, RMI Rivermead Mobility Index, TUG timed up and go test) assessed at TPRE and TPOST in the two groups (EGT and OGT). Minimally Clinically Important Difference (MCID) and Minimal Detectable Change (MDC) are reported as well. * refer to post-hoc p-values of within-group analysis (significant whether p < 0.016), whereas # refer to p-values of between-group analysis for TPOST-TPRE difference (p < 0.05). Vertical error bars refer to SD
Fig. 4
Fig. 4
Mean gait parameters of the affected and unaffected lower limbs at baseline (TPRE) and after gait training (TPOST) in Ekso™ (EGT) and overground gait training (OGT). Normative values are reported as well (black horizontal lines). * refer to p-values of within-group analysis (significant whether p < 0.008), whereas # refer to p-values of between-group analysis for TPOST-TPRE difference (p < 0.05). Vertical error bars refer to SD
Fig. 5
Fig. 5
Mean muscle activity of the paretic (aff) and non-paretic (unaff) muscles (TA tibialis anterior; S soleus; RF rectus femoris; BF biceps femoris) during gait at baseline (TPRE) and after gait training (TPOST) in EGT and OGT. Normative values are reported as well (black horizontal lines). Vertical error bars refer to SD
Fig. 6
Fig. 6
rTMS outcome measures assessed at TPRE and TPOST in the two groups (EGT and OGT). Left and right columns illustrate the rTMS findings (MEP -motor evoked potential- and SMI -sensory-motor integration- in the affected -aff- and unaffected -unaff- hemispheres) before and after gait training, respectively. * refer to post-hoc p-values of within-group analysis (significant whether p < 0.008), whereas # refer to p-values of between-group analysis for TPOST-TPRE difference (p < 0.05). Vertical error bars refer to SD
Fig. 7
Fig. 7
Shows that the difference in sensory-motor integration (SMI) between the two groups at baseline was not correlated with rTMS-induced SMI aftereffects
Fig. 8
Fig. 8
Illustrates the connectivity paths at baseline and following gait training (EGT and OGT). Red color indicates a path-coefficient increase (significant whether p < 0.0001), while blue color a decrease at TPOST as compared to TPRE. Line thickness indicates whether the TPOST-TPRE changes were detectable only following EGT –thick-, greater following EGT than OGT –medium- or equally significant in both groups –thin. Legend: l left hemisphere; O occipital areas; CP centroparietal areas; PF prefrontal areas; r right hemisphere; SMA supplementary motor area
Fig. 9
Fig. 9
Scatterplot and univariate regression line of electrophysiological outcomes on composite outcome measure (primary) in patients undergoing EGT and OGT

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