FES is the clinical application of electric current to a decentralized muscle. Neuromuscular electrical stimulation involves placing electrodes on a motor point and sending an electric current to produce muscle contraction.¹⁾ The technique can generate functional movements in individuals with paralysis caused by damage to the central nervous system. It entails the use of a low-energy electrical pulse and generates muscle contractions in a sequence to promote tasks such as walking or grasping.²⁰⁾ Specifically, FES electrically stimulates the dorsiflexor muscles (i.e., the tibialis anterior [TA]) of the foot, which facilitates ankle dorsiflexion during the swing phase of gait and allows for a more natural gait pattern.¹⁴⁾

FES has several advantages for gait training in patients with stroke. It can be used to enhance muscle strength and physical performance by increasing the range of motion and decreasing muscle weakness and spasticity.^1,2,14) FES can also be used to relearn recruitment and timing of muscle activation in the paretic lower limb, which further helps in producing a normal gait. Individuals who experience stroke may have foot drop or weakness in the muscles lifting the foot during walking, which can further lead to falls or secondary health problems.^21,22) If muscle contraction is appropriately timed and coordinated, gait performance can be facilitated in individuals with paralyzed lower extremities, such as patients who experience stroke.²³⁾ Thus, FES activation of muscles in the paralyzed limb is important to improve gait performance.

Electrical stimulation can be classified into invasive and non-invasive stimulation electrodes. Invasive stimulation electrodes are further separated into implanted and percutaneous electrodes, which differ in their placement duration and depth. Implanted electrodes are more suitable for longer-term use than percutaneous electrodes and are placed near the target nerve. Percutaneous electrodes are more suitable for short-term use than implanted electrodes and typically penetrate the skin by partially stimulating the targeted motor neurons.²⁴⁾ The typical current amplitude for both implanted and percutaneous electrodes is 25 mA. Invasive stimulation electrodes commonly require surgery; therefore, their placement and electrical intensity cannot be changed. In contrast, non-invasive stimulation electrodes self-adhere to the body surface. Unlike the fixed current amplitude of invasive stimulation electrodes, the typical current amplitude for non-invasive stimulation varies from 2 mA to 120 mA. Their placement on the skin also facilitates early intervention, which results in better recovery. Moreover, the electric intensity can be modified without surgery.²⁵⁾ However, targeting deep muscles is not feasible because stimulation of these muscles often requires greater intensity, which may result in stimulating untargeted muscles.

No studies have directly compared invasive and non-invasive electrical stimulation in post-stroke patients. However, previous studies have demonstrated the effectiveness of both methods in patients with spinal cord injury (SCI). Demchak et al.²⁶⁾ reported a greater cross-sectional area of the vastus lateralis muscle in the leg undergoing non-invasive electrical stimulation than that of the non-stimulated leg. Gad et al.²⁷⁾ also reported a higher increase in handgrip strength in the presence of non-invasive stimulation. The invasive approach also showed a restoring effect on walking and independent standing in individuals with SCI.^28,29) Thus, both invasive and non-invasive electrical stimulation can help increase muscle cross-sectional area and muscle strength in patients with SCI. Furthermore, selecting an appropriate electrical stimulation method according to the patient’s condition is recommended.

Although the clinical effects of FES on gait patterns have been reported,^2,17) the mechanism is not yet clearly understood. “Central” and “peripheral” mechanisms have been proposed to describe the therapeutic effects of FES. The peripheral mechanism of FES involves improving the muscle strength, flexibility, range of motion, and muscle spasticity of the paralyzed limb. While these improvements in muscle fitness may appear to have lasting effects, none of the peripheral mechanisms can explain these lasting effects.^30,31) Instead, the central mechanism has attracted increasing attention to account for these effects. The central mechanism of FES is as follows (Fig. 1). First, FES can stimulate both afferent sensory and motor nerve fibers. A previous preclinical showed that a change in afferent sensory signals was sufficient to reorganize the motor cortex.³²⁾ Prolonged peripheral stimulation can induce excitability of the human motor cortex and reorganize the motor networks of the corresponding muscles.^33,34) The results of studies suggest that FES-triggered afferent feedback may facilitate persistent brain plasticity. Second, electrical stimulation can antidromically activate motor nerve fibers, which are then polarized when the antidromic impulses of the fibers reach the anterior horn cell. The combination of FES-induced antidromic impulse and voluntary movement promotes pre- and postsynaptic coupling and synaptic remodeling, which are necessary for changes in neural plasticity.³⁰⁾ Thus, these two hypotheses have been proposed as plausible mechanisms by which FES corrects and improves gait patterns.

The benefits of FES on gait performance of patients with chronic stroke are summarized in Table 1. In their single-subject study, Daly et al.³⁵⁾ reported that gait training with functional neuromuscular stimulation improved the gait patterns in older adults with chronic stroke. Specifically, the use of a combined treatment resulted in significant improvements in volitional knee flexion function compared to conventional treatment alone. Israel et al.³⁶⁾ reported a case series of stroke patients, in which two participants showed improved functional ambulation and decreased ankle plantarflexion, demonstrating that overground gait training with FES can improve foot clearance during gait. In addition, a pilot study reported that patients who had experienced a stroke produced greater propulsive force via the combination of treadmill and overground walking at a maximal speed with FES, which was accompanied by improvements in functional balance and walking ability.³⁷⁾ As balance ability is an important goal of stroke rehabilitation, a recent study reported that the combination of balance training with FES was is acceptable and effective in improving static and dynamic balance.³⁸⁾ In a long-term follow-up randomized controlled trial over 12 months, FES showed similar effects to ankle-foot orthosis in all primary outcomes related to gait quality and function, suggesting that FES may be an appropriate alternative to orthosis for individuals with chronic stroke.³⁹⁾

FES treatment of the dorsiflexors is effective in correcting foot drop to balance gait patterns after stroke but not in correcting asymmetric weight-shifting during gait.³⁶⁾ One reason for the asymmetric gait pattern is the lack of activation of the hip abductors, which work as pelvic stabilizers.⁴⁰⁾ A previous study reported that FES-triggered gait training of the gluteus medius (GM) and TA improved gait velocity, dynamic balance, and gait symmetry during walking, among patients aged <60 years.⁴¹⁾ In that study, FES applied to the GM stabilized the pelvic muscles in the stance phase, while FES applied to the TA strengthened the ankle dorsiflexors in the swing phase, which improved functional gait performance in individuals with chronic hemiparetic stroke. These findings were consistent with those reported by Kim et al.,⁴²⁾ who demonstrated that FES applied to the GM in the stance phase and TA in the swing phase of gait improved gait performance in patients who had experienced a stroke. Specifically, the combined effect of GM activation with TA generates a more normal gait pattern than that generated by TA activation alone.⁴²⁾ Consequently, FES treatment of the hip abductors and dorsiflexors has the potential to improve gait symmetry and gait speed during walking. The recovery of stroke-induced gait disorders through FES treatment in middle-aged patients aged <60 years may have a positive effect on sarcopenia prevention in those aged >60 years.

As in chronic stroke, FES also affects physical performance in patients with subacute stroke, as summarized in Table 2.⁴³⁾ Several studies have reported that FES can increase dorsiflexor strength in the swing phase of gait to prevent foot drop after stroke, which can further improve gait performance.²¹⁾ Tong et al.⁴⁴⁾ reported that the therapeutic combined effect of FES and gait training was superior to gait training alone in individuals after acute stroke. They reported significant improvements in Barthel Index, Berg Balance Scale, Functional Ambulation Categories scale, 5-m timed walking test, and Motricity Index in the combination group compared to those in the training alone group after 4 weeks of treatment. Moreover, these improvements persisted even after 6 months. In one pilot study, the “gait training with FES” group had a larger effect size of gait speed than the “gait training only” group, indicating a superior treatment effect; however, no significant differences were observed.⁴⁵⁾ Another pilot study showed that active cycling training with FES may be effective in improving gait velocity in the subacute recovery period after stroke, although no group effect was found.⁴⁶⁾ The results of these pilot studies may have been more robust if the sample sizes were larger. A study comparing the effect of active interventions involving leg cycling with and without FES performed three times weekly for 20 minutes each session for 4 weeks showed improved walking and balance abilities in the FES group.⁴⁷⁾ Thus, the application of FES in the subacute phase of stroke may have a positive effect on physical performance. Several studies have demonstrated that FES helps patients with subacute and chronic stroke recover from low physical performance.

However, few studies have demonstrated the effectiveness of FES in increasing muscle mass and strength in patients after stroke, especially in older adults. Several studies showed that FES significantly improved muscle strength in middle-aged patients with subacute and chronic stroke.^48-50) Dorsiflexor muscle strength significantly increased by 56.6% in the “combination of FES and conventional rehabilitation” group and by 27.7% in the “conventional rehabilitation alone” group.⁴⁹⁾ These findings can be explained by the fact that FES reduces muscle spasticity through motor recovery, which further improves muscle strength. In addition, 18 patients with subacute and chronic stroke who participated in a 12-week conventional rehabilitation program combined with FES showed significantly improved dorsiflexor strength, measured by surface EMG signal.⁴⁸⁾ The combined effects of FES and rehabilitation also increased the maximal voluntary contractions of the dorsiflexors in middle-aged patients with stroke.⁵⁰⁾ The previous studies showing that FES increased muscle strength in middle-aged patients with stroke suggest the positive effects of FES on muscle mass, which is positively correlated with muscle strength. Muscle mass and strength may also be correlated in stroke survivors.⁵¹⁾ Most studies were conducted among participants with a median age of 50 years, an age range that also encompasses older adults.^48-50) Therefore, the same results may be observed in older adults, although studies with larger samples of older adults are required. Moreover, FES significantly restored muscle mass in denervated muscles of patients after SCI, although the patient age was relatively low.⁵²⁾ As stroke and SCI share common features, FES may also restore muscle mass in post-stroke patients.

In addition, FES may improve muscle mass by altering muscle-specific transcriptional mechanisms.⁵³⁾ During muscle contraction, muscle fibers produce and release myokines, which have local and systemic effects on the body.⁵⁴⁾ FES in older adults changes this myokine secretion, especially that of insulin-like growth factor-1 (IGF-1).⁵⁵⁾ A previous study showed that neuromuscular electrical stimulation induced increased expression of IGF-1 and its downstream pathways, a well-known major anabolic signal for skeletal muscle development, and decreased expression of MuRF-1 and Atrogin-1, which are muscle atrophy-related ubiquitin ligase genes.⁵⁶⁾ Considering these changes at the molecular level, FES may also be effective in counteracting muscle atrophy in older adults.