Therapeutic effectiveness of a single exercise session combined with WalkAide functional electrical stimulation in post-stroke patients: a crossover design study

Abstract

A growing body of evidence has suggested that the imbalance of epigenetic markers and oxidative stress appears to be involved in the pathophysiology and progression of stroke. Thus, strategies that modulate these biomarkers might be considered targets for neuroprotection and novel therapeutic opportunities for these patients. Physical exercise has been reported to induce changes in these epigenetic markers and improve clinical outcomes in different populations. However, little is reported on this in post-stroke patients. The purpose of this study was to investigate the effect of a single exercise session with WalkAide functional electrical stimulation (FES) on cognitive performance, clinical functional parameters, oxidative stress and epigenetic modulation in post-stroke individuals. In this crossover design study, 12 post-stroke individuals aged 54-72 years of either sexes were included and subjected to a single session of exercise (45 minutes) without WalkAide functional electrical stimulation (EXE alone group), followed by another single session of exercise (45 minutes) with WalkAide functional electrical stimulation (EXE + FES group). The clinical functional outcome measures, cognitive performance and blood collections for biomarker measurements were assessed pre- and post-intervention. After intervention, higher Berg Balance Scale scores were obtained in the EXE + FES group than in the EXE alone group. There was no significant difference in the Timed Up and Go test results post-intervention between EXE alone and EXE + FES groups. After intervention, a better cognitive performance was found in both groups compared with before the intervention. After intervention, the Timed Up and Go test scores were higher in the EXE + FES group than in the EXE alone group. In addition, the intervention induced lower levels of lipid peroxidation. After intervention, carbonyl level was lower, superoxide dismutase activity and superoxide dismutase/catalase activity ratio were higher in the EXE + FES group, compared with the EXE group alone. In each group, both histone deacetylase (HDAC2) and histone acetyltransferase activities were increased after intervention compared with before the intervention. These findings suggest that a single exercise session with WalkAide FES is more effective on balance ability and cognitive performance compared with conventional exercise alone in post-stroke patients. This is likely to be related to the regulation of oxidative stress markers. The present study was approved by the Research Ethics Committee of the Methodist University Center-IPA (approval No. 2.423.376) on December 7, 2017 and registered in the Brazilian Registry of Clinical Trials-ReBEC (RBR-9phj2q) on February 11, 2019.

Keywords: WalkAide; cognition; epigenetic; exercise; functional electrical stimulation; functional mobility; oxidative stress; stroke.

Figure 1

Study design. BBS: The Berg Balance Scale; EXE: exercise; FES: functional electrical stimulation; MoCA: the Montreal Cognitive Assessment; TUG: Timed Up and Go test.

Figure 2

The impact of a single exercise session with FES (Exercise + FES group) or without FES (Exercise group) on clinical functional parameters in post-stroke patients. Generalized estimating equationswere conducted to identify the factors associated, with Sidak post hoc test, considering P < 0.05 statistically different. These factors, time and FES used, effects isolated and interaction were evaluated. (A) Berg scale. Time effect: P = 0.005; FES effect: P = 0.662; Time × FES effect: P = 0.942. *P < 0.05. (B) Time Up and Go test. Time effect: P = 0.586; FES effect: P = 0.577; Time × FES effect: P = 0.431. Data were expressed as the mean ± standard deviation. FES: Functional electrical stimulation.

Figure 3

The impact of a single exercise session with FES (Exercise + FES group) or without FES (Exercise alone group) on cognitive performance in post-stroke patients. Generalized estimating equationswere conducted to identify the factors associated, with Sidak post hoc test, considering P < 0.05 statistically different. These factors, time and FES used, effects isolated and interactionwere evaluated. Time effect: P = 0.000; FES effect: P = 0.033; Time × FES effect: P = 0.118; *P < 0.05. #P < 0.05, vs. Exercise alone group, the same moment with or without FES. Data were expressed as the mean ± standard deviation. FES: Functional electrical stimulation; MoCA: the Montreal Cognitive Assessment.

Figure 4

The impact of a single exercise session with FES (Exercise + FES group) or without FES (Exercise alone group) on (A) lipid peroxidation (TBARS), (B) protein oxidation (carbonyl levels) and (C) non-enzimatic content (sulfhydril levels) in post-stroke patients. Generalized estimating equations were conducted to identify the factors associated, with Sidak post hoc test, considering P < 0.05 statistically different. These factors, time and FES used, effects isolated and interactionwere evaluated. (A) TBARS levels. Time effect: P = 0.012; FES effect: P = 0.001; Time × FES effect: P = 0.643; *P < 0.05; #P < 0.05 for intergroup comparison, differences between with or without FES. (B) Carbonyl levels. Time effect: P = 0.984; FES effect: P = 0.983; Time × FES effect: P = 0.000. (C) Sulfhydril levels. Time effect: P = 0.212; FES effect: P = 0.261; Time × FES effect: P = 0.504. Data were expressed as the mean ± standard deviation. FES: Functional electrical stimulation; TNB: 2-nitro-5-thiobenzoate.

Figure 5

The impact of a single exercise session with FES (Exercise + FES group) or without FES (Exercise alone group) on SOD activity (A), CAT activity (B) and SOD/CAT activity ratio (C) in post-stroke patients. Generalized estimating equations were conducted to identify the factors associated, with Sidak pos hoc test, considering P < 0.05 statistically different. These factors, time and FES used, effects isolated and interactionwere evaluated. (A) SOD activity. Time effect: P = 0.051; FES effect: P = 0.976 Time × FES effect: P = 0.012. *P < 0.05. (B) CAT activity. Time effect: P = 0.331; FES effect: P = 0.573 Time × FES effect: P = 0.072. (C) SOD/CAT activity ratio. Time effect: P = 0.775; FES effect: P = 0.008; Time × FES effect: P = 0.324. *P < 0.05 for intergroup comparison of FES effect. Data were expressed as the mean ± standard deviation. CAT: Catalase; FES: functional electrical stimulation; SOD: superoxide dismutase.

Figure 6

The impact of a single exercise session with FES (Exercise + FES group) or without FES (Exercise alone group) on epigenetic modulation in post-stroke patients. Generalized estimating equations were conducted to identify the factors associated, with Sidak post hoc test, considering P < 0.05 statistically different. These factors, time and FES use, effects isolated and interaction were evaluated. (A) HDAC2 levels. Time effect: P = 0.007; FES effect: P = 0.510; Time × FES effect: P = 0.374. (B) HAT activity. Time effect: P = 0.032; FES effect: P = 0.688; Time × FES effect: P = 0.497. Data were expressed as the mean ± standard deviation. FES: Functional electrical stimulation; HAT: histone acetyltransferase; HDAC2: histone deacetylase.