Journal of

Clinical Medicine

Review
Electrical Stimulation Exercise for People with Spinal Cord
Injury: A Healthcare Provider Perspective
David R. Dolbow 1 , Ashraf S. Gorgey 2,3, * , Therese E. Johnston 4 and Ines Bersch 5

1 Department of Physical Therapy, College of Osteopathic Medicine, William Carey University,

Hattiesburg, MS 39401, USA
2 Spinal Cord Injury and Disorders Center, Hunter Holmes McGuire VA Medical Center,
Richmond, VA 23249, USA
3 College of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
4 Department of Physical Therapy, Arcadia University, Glenside, PA 19038, USA
5 International FES Centre® , Swiss Paraplegic Center, CH-6207 Nottwil, Switzerland
* Correspondence: [email protected]; Tel.: +1-804-675-5000 (ext. 3386); Fax: +1-804-675-5223

Abstract: Electrical stimulation exercise has become an important modality to help improve the
mobility and health of individuals with spinal cord injury (SCI). Electrical stimulation is used to
stimulate peripheral nerves in the extremities to assist with muscle strengthening or functional
activities such as cycling, rowing, and walking. Electrical stimulation of the peripheral nerves in
the upper extremities has become a valuable tool for predicting the risk of hand deformities and
rehabilitating functional grasping activities. The purpose of this paper is to provide healthcare
providers perspective regarding the many rehabilitation uses of electrical stimulation in diagnosing
and treating individuals with SCI. Electrical stimulation has been shown to improve functional
mobility and overall health, decrease spasticity, decrease the risk of cardiometabolic conditions
associated with inactivity, and assist in the diagnosis/prognosis of hand deformities in those with
tetraplegia. Studies involving non-invasive stimulation of the spinal nerves via external electrodes
aligned with the spinal cord and more invasive stimulation of electrodes implanted in the epidural
lining of the spinal cord have demonstrated improvements in the ability to stand and enhanced the
stepping pattern during ambulation. Evidence is also available to educate healthcare professionals in
using functional electrical stimulation to reduce muscle spasticity and to recognize limitations and
Citation: Dolbow, D.R.; Gorgey, A.S.;
barriers to exercise compliance in those with SCI. Further investigation is required to optimize the
Johnston, T.E.; Bersch, I. Electrical
Stimulation Exercise for People with dose-response relationship between electrical stimulation activities and the mobility and healthcare
Spinal Cord Injury: A Healthcare goals of those with SCI and their healthcare providers.
Provider Perspective. J. Clin. Med.
2023, 12, 3150. https://doi.org/ Keywords: peripheral nerve stimulation; functional electrical stimulation; neuromuscular electrical
10.3390/jcm12093150 stimulation; spinal cord injury

Academic Editor: Hiroyuki Katoh

Received: 6 March 2023

Revised: 5 April 2023 1. Introduction
Accepted: 15 April 2023
Spinal cord injury (SCI) disrupts efferent and afferent pathways, including the de-
Published: 27 April 2023
scending pathways from the motor cortex to the spinal motor neurons which activate
muscle activity [1]. Electrical stimulation can be used to bypass spinal disruption and
elicit muscle contractions for rehabilitation purposes [1]. Electrical stimulation exercise
Copyright: © 2023 by the authors.
has become an important modality for improving the health and mobility of individuals
Licensee MDPI, Basel, Switzerland. with SCI [2,3]. The two primary types of electrical stimulation producing exercise are
This article is an open access article (1) peripheral nerve stimulation (PNS), which is the electrical stimulation of the peripheral
distributed under the terms and nerves, usually in the extremities, and (2) spinal cord stimulation (SCS), which is the elec-
conditions of the Creative Commons trical stimulation of the spinal nerves at the spinal cord [4]. PNS is further classified into
Attribution (CC BY) license (https:// neuromuscular electrical stimulation (NMES) and functional electrical stimulation (FES).
creativecommons.org/licenses/by/ While some people use the two terms interchangeably, the two modalities are commonly
4.0/). separated into two categories. NMES is defined as electrically induced muscle contractions,

J. Clin. Med. 2023, 12, 3150. https://doi.org/10.3390/jcm12093150 https://www.mdpi.com/journal/jcm

J. Clin. Med. 2023, 12, 3150 2 of 14

which includes resistance training [5]. FES is defined as electrically induced functional
activities, including FES cycling, FES rowing, FES walking, and FES-assisted grasping
activities [6–9]. Similarly, SCS is further divided into transcutaneous spinal stimulation
and epidural electrical stimulation [3,9,10]. Transcutaneous spinal stimulation provides
electrical input via surface electrodes aligned along the external surface of the spine, while
epidural stimulation is derived from electrodes surgically implanted in the epidural spaces
of the spinal cord [10–12]. Three primary electrical stimulation parameters are adjusted to
optimize the activity of interest: pulse duration (time duration for a single pulse), frequency
(pulses produced per second), and amplitude (strength of the current) that is often referred
to as stimulation intensity [13].
The potential benefits of electrical stimulation in individuals with SCI may include
changes in body composition, such as increasing muscle mass and bone mass while decreas-
ing fat mass; improving cardiovascular and metabolism efficiency; decreasing spasticity;
and improving functional mobility [2,8,14–16]. In addition, electrical stimulation can be
used as a diagnostic tool for determining lower motor neuron damage caused by cervical
SCI which may affect the risk of developing grasping anomalies [16]. Most recently, electri-
cal stimulation has been employed to guide clinicians and researchers in the estimation
of the quantities of muscle and bone. During NMES, Gorgey and colleagues used the
amplitude of the current (<100 mA) and the number of leg extension repetitions (>70) as
cut-offs to provide both diagnostic and prognostic assessments of the muscle cross-sectional
area and knee bone mineral densities in persons with SCI [17].
Electrical stimulation activities have been shown to be safe with proper supervi-
sion and instruction by healthcare professionals. Telehealth monitoring has also been
successfully used for the application of home-based NMES. Participants were educated
to use surface NMES to induce resistance training exercises of the knee extensors and
were monitored over an eight-week period via telehealth [18]. However, some impor-
tant contraindications and precautions should be recognized, including very low bone
density; a history of bone fractures; uncontrolled autonomic dysreflexia; uncontrolled
hyper/hypotension; open pressure wounds; thrombosis; pregnancy; cancer; pacemaker
and defibrillator, depending on the on distance from the implant; and orthopedic problems
that preclude the selected activity [19]. The purpose of this paper is to provide a healthcare
provider’s perspective regarding the many rehabilitation uses of electrical stimulation in
diagnosing and treating individuals with SCI.

2. Body Composition Assessment

Along with optimizing functional mobility, healthcare providers use FES activities
to decrease the risk of secondary conditions after SCI, including cardiometabolic diseases
which is two to three times greater than in the able-bodied population [20]. Two recent
systematic literature reviews concluded that NMES and FES activities provided positive
results on muscle mass after eight to sixteen weeks of training [21,22]. Atkins and Bickel [21]
reported increases in muscle volume that range from 20–72% with an average increase of
26% among NMES and FES studies. Similarly, Bekhet et al. [22] reported skeletal muscle
increases in cross-section areas (CSA) from 5.7% to 75% via NMES and FES, with NMES
resistance training typically providing greater increases in muscle than FES cycling.
Johnston et al. [6] demonstrated that there is a significant correlation between accu-
mulated torque and muscle volume. In a comparison between low cadence/high torque
and high cadence/low torque FES cycling groups, 17 adults with chronic C4-T6 motor
complete SCI all increased in muscle volume, but the low cadence/high torque group had
a 9% greater increase (Figure 1). Participants cycled three times per week for six months.
In a study of ten adults with chronic SCI, Dolbow et al. [23] found a 5.7% increase in lean
leg mass and a 2.4% decrease in body fat percentage when combining resistance-guided
high-intensity interval FES cycling three times per week for eight weeks with once weekly
nutritional counseling.
 sistance training twice a week for twelve weeks on an individual with chronic cervical
SCI. The results revealed a 72% increase in CSA of the whole thigh and a 53% decrease in
intramuscular fat. This initial report was later confirmed in a randomized clinical trial
that demonstrated the efficacy of utilizing NMES-RT with and without androgen re-
J. Clin. Med. 2023, 12, 3150
placement therapy to evoke muscle hypertrophy and provide other favorable outcomes 3 of 14
similar to an increase in basal metabolic rate and enhancing carbohydrate profile in per-
sons with SCI [24,26].

Muslce volume (cm3) 2000

1600

1200

800

400

0
Low Cadence High Cadence
Baseline 6 months

Figure 1. Muscle volume changes between low versus high cadence FES-LEC. Changes in muscle
Figure 1. Muscle volume changes between low versus high cadence FES-LEC. Changes in muscle
volume after six months of low cadence/high torque cycling (LOW) or high cadence/low torque
volume after six months of low cadence/high torque cycling (LOW) or high cadence/low torque
cycling (HIGH). Between groups p = 0.318; within groups LOW p = 0.014 and HIGH p = 0.049.
cycling (HIGH). Between groups p = 0.318; within groups LOW p = 0.014 and HIGH p = 0.049.
Ye et al. [27] completed a systematic review of the literature on FES rowing exercis-
A nutritional counseling-only group displayed no changes in body composition.
es on individuals with SCI and reported mixed results in body composition. For exam-
Similarly, Gorgey et al. [24] compared NMES resistance training plus nutritional counseling
ple, Kim et al. [28] found a 14% decrease in body fat percentage and a 5.8% increase in
twice a week for twelve weeks to a control group that received nutritional counseling only.
muscle mass after six weeks of training, while Jeon et al. [29] and Wilbanks et al. [30]
The results showed skeletal muscle CSA increases of 28% for the whole thigh, 35% for the
found no change in body fat after FES rowing training after twelve and six weeks respec-
knee extensors, and 16% for the knee flexors for those that received NMES and nutritional
tively. A recent
counseling. randomized
Additionally, clinical
there was trial
a 25%demonstrated that, compared
increase in insulin-like growthto factor
passive move-
1 (IGF-1)
ment training, NMES-RT induced 30% muscle hypertrophy accompanied
which is associated with muscle hypertrophy. Interestingly, there was a concomitant by a 14% in-
crease in oxygen uptake. The authors also reported improvement in
25% reduction in visceral adipose tissue (VAT) CSA in the L5-S3 region. Gorgey andindices of cardio-
vascular
Shepard performance
[25] publishedasa measured by ventilation/carbon
unilateral leg dioxide
case report using NMES production
resistance (VE/VCO
training twice2a)
[31].
weekInterestingly, the same
for twelve weeks on anstudy notedwith
individual an increase in wholeSCI.
chronic cervical body
Thefat utilization
results as aa
revealed
primary source of energy expenditure during FES lower extremities cycling at
72% increase in CSA of the whole thigh and a 53% decrease in intramuscular fat. This initial low in-
tensity. The study may conceivably shed light on the significance of evoking
report was later confirmed in a randomized clinical trial that demonstrated the efficacy muscle hy-
pertrophy
of utilizingprior to enhancing
NMES-RT with andthewithout
cardio-metabolic
androgen profile with FES
replacement lowertoextremities
therapy evoke musclecy-
cling [32].
hypertrophy and provide other favorable outcomes similar to an increase in basal metabolic
rate and enhancing carbohydrate profile in persons with SCI [24,26].
Ye et al. [27] completed a systematic review of the literature on FES rowing exercises
on individuals with SCI and reported mixed results in body composition. For example,
Kim et al. [28] found a 14% decrease in body fat percentage and a 5.8% increase in muscle
mass after six weeks of training, while Jeon et al. [29] and Wilbanks et al. [30] found no
change in body fat after FES rowing training after twelve and six weeks respectively. A
recent randomized clinical trial demonstrated that, compared to passive movement training,
NMES-RT induced 30% muscle hypertrophy accompanied by a 14% increase in oxygen
uptake. The authors also reported improvement in indices of cardiovascular performance
as measured by ventilation/carbon dioxide production (VE/VCO2 ) [31]. Interestingly,
the same study noted an increase in whole body fat utilization as a primary source of
energy expenditure during FES lower extremities cycling at low intensity. The study
may conceivably shed light on the significance of evoking muscle hypertrophy prior to
enhancing the cardio-metabolic profile with FES lower extremities cycling [32].
Due to the slower metabolic processes in bone compared to muscle and fat, it is
widely accepted that interventions require several months or more to produce significant
changes in bone mass [33]. Positive results on bone mineral density have been sparse and
relatively inconsistent when examining the most fracture-prone sites (distal and proximal
J. Clin. Med. 2023, 12, 3150 4 of 14

femur and tibia) in those with SCI [34,35]. The Clinical Practice Guidelines provided by
Craven et al. [36] suggested FES cycling, FES rowing, or NMES resistance exercise as
possible options for preventing the decline of bone mineral density in the hip and knee
regions for individuals with SCI. They further recommend a pulse duration of ≥200 µs,
20–33 Hz for frequency, and an amplitude/intensity of up to 140 mA that should create
strong visible muscle contractions. For exercise duration, they recommend three to five
days per week for thirty or more minutes per session for at least a year to see changes
in bone.

3. Cardiovascular and Metabolism

In a systematic review of the literature, van der Scheer et al. [37] found that 16 out of
21 selected studies using electrical stimulation exercise for individuals with SCI showed
improvements in cardiovascular and metabolic outcomes. The most common outcomes
measured were power output and peak oxygen volume (VO2peak). These studies provide
consistent evidence that FES cycling can improve aerobic fitness and has the potential
to reduce the risk of cardiovascular and metabolic conditions after SCI. On the contrary,
Hamzaid and Davis [38] concluded that the lack of consistency in the various studies
resulted in insufficient evidence to determine if health and fitness benefits could be derived
from FES exercise in individuals with SCI. They suggested that the VO2peak utilized
may be more limited due to the reduced active muscle mass and peripheral blood flow
than due to central cardiac reserve. Figoni and Dolbow [39] studied the possible benefits
of aerobic exercise on those with tetraplegia and concluded that, while further study
is needed, the current evidence suggests that the greatest cardiovascular and metabolic
benefits derived from FES cycling are likely to result from thirty or more minutes of
moderate-intensity exercise, three or more times per week for at least eight to twelve weeks.
Studies investigating training programs using FES cycling and FES rowing for individuals
with SCI have reported improved VO2peak, lowered blood glucose levels, and enhanced
skeletal muscle glucose uptake [27,29,40]. Akins and Bickel [21] summarized the effects
of FES activities on metabolic health by suggesting that FES interventions can help to
normalize glucose uptake and metabolism after SCI. FES activities also have been shown to
improve energy expenditure, increase cardiac output, reverse myocardial atrophy, increase
cardiac protective high-density lipoprotein cholesterol, and assist in the reduction of body
fat percentage [40–43].

4. Muscle Spasticity
Muscle spasticity is a common condition secondary to SCI and can potentially increase
the level of disability [44]. Spasticity typically results from upper motor neuron injury in
those with injuries above T12/L1 [44]. The SCI reduces or eliminates control of reflexes
from the supraspinal level of the central nervous system resulting in spasticity that is
characterized by increased muscle tone, hyperreflexia, clonus sign, and muscle spasms [44].
NMES is thought to improve spasticity by eliciting disynaptic reciprocal inhibition of the
opposing muscle group Alashram et al. [44] completed a systematic review investigating
the changes in lower extremities’ spasticity after FES cycling. The investigation included ten
independent studies totaling 161 individuals with SCI. Alashram and associates concluded
that more randomized control trials are needed; however, current evidence indicates that
FES cycling can reduce lower extremities’ spasticity for individuals at all levels of SCI. It
is interesting to note that ankle dorsiflexor and plantarflexor spasticity have been shown
to be reduced during FES cycling even though electrical stimulation is provided to the
quadriceps, hamstrings, and gluteal muscles [44].
Fang et al. [45] completed a twelve-study systematic review of the qualitative data
involving spasticity after SCI and an eight-study meta-analysis on quantitative data re-
garding spasticity after SCI. The eight studies used in the meta-analysis included a total
of 99 participants with SCI. Fang and associates concluded that FES cycling can decrease
spasticity for individuals with SCI. Other important evidence highlighted by Fang and
J. Clin. Med. 2023, 12, 3150 5 of 14

colleagues concerning the use of FES cycling to decrease spasticity include that (1) the
correlation between the number of FES cycling sessions and the level of decrease in spas-
ticity is not linear; and (2) generally, about twenty FES cycle training sessions need to
be completed to obtain the efficacy to decrease spasticity. More specifically, six studies
reported by Fang and colleagues used multiple FES cycling sessions as the intervention and
found that the post-intervention Modified Ashworth Scores (MAS) for the lower extremities
were significantly decreased from the pre-intervention scores. Two other studies reported
by the same authors found decreased MAS after a single bout of FES cycling.

5. Exercise Adherence
A national health survey by the Centers for Disease Control and Prevention in 2020 [46]
determined that only 24.2% of adults aged 18 and over met the physical activity guidelines
for Americans for both aerobic and muscle-strengthening activities (150 min per week
of moderate-intensity aerobic exercise and muscle strengthening exercises to the major
muscle groups twice per week) [46]. Individuals with SCI perform only 35–40% as much
exercise as the largely sedentary able-bodied population, demonstrating the extreme lack
of physical activity in the SCI population [47,48]. Recently, Tui et al. [49] completed a
qualitative study concerning the motivations and barriers that limit adherence to exercise
programs for individuals with SCI. The common self-reported reasons for poor adherence
to exercise guidelines for those with SCI were time constraints (54%), lack of motivation
(31%), decreased accessibility (24%), and SCI-specific barriers (23%). The 144 participants
in the study reported the possible following solutions: scheduling exercise sessions for time
constraints (47.9%); introducing fun during the exercise sessions to increase motivation
(21.8%); providing equipment to allow home exercise (30.3%); and locating accessible facili-
ties to resolve accessibility barriers (27.3%). In agreement that access to exercise facilities is
a problem, Dolbow and Figoni [50] investigated the accommodation of wheelchair users by
community fitness centers and found accommodation lacking, especially regarding access
to exercise equipment.
Dolbow et al. [48] investigated exercise adherence in a home-based FES cycling pro-
gram for 17 chronic SCI adults for two consecutive eight-week exercise periods. Partici-
pation during the first eight weeks was incentivized with the knowledge that the rented
FES cycle would be purchased for the participants if they maintained good exercise ad-
herence with the requested 30 to 40 min FES cycling sessions three times per week for the
eight weeks. The second eight weeks of FES cycling provided no incentive for participa-
tion. During the first eight weeks, the adherence rate to the exercise program was 71.7%
while, during the second eight weeks, exercise adherence was 63.7%, a nominal but not
statistically significant decrease. The main factors involved with higher adherence rates
were age (under 50 years of age had a higher adherence rate); self-reported prior history
of regular exercise; and having a history of recurrent pain but finding the FES cycling
activity to be pain-free. The last factor fostered the development of the Pain-Free Affinity
Model which states that “when living with frequent or recurrent pain, there is an increased
affinity toward activities that are perceived as pain-free” [48]. The level of injury, time since
injury, and history of depression did not significantly affect exercise adherence in the study.
Another follow-up study determined the feasibility of a video conferencing approach as a
telehealth communication to deliver a home-based NMES-RT program for eight weeks. The
authors intentionally performed unilateral training on one leg while the other leg served
as the control. The training paradigm was successful in enhancing muscle hypertrophy in
the trained leg but not in the control limb [18]. The telehealth paradigms were important
because, even with a short period of de-training or dose de-escalation, persons with SCI
experience a gradual loss in muscle size and a decline in cardio-metabolic gains after a
routine training program [51]. Today, the telehealth home-based training paradigm via
video conferencing has been extended to implement 12 months of training for persons with
lower motor neuron injury [52].
J. Clin. Med. 2023, 12, 3150 6 of 14

6. Physical Function
Sadowsky et al. [53] hypothesized that restoring normal activity levels should optimize
neural regeneration after SCI. This hypothesis was supported by their retrospective cohort
cross-sectional evaluation comparing twenty-five people with chronic SCI who underwent
an activity-based restorative exercise program including FES cycling to twenty individuals
with SCI that received regular standard of care therapy, including a range of motion
exercises and stretching of the paralyzed limbs. The participants were matched by age,
gender, injury level, the severity of the injury, and duration of the injury. After 29 months,
those in the FES cohort demonstrated an 80% increase in neurological function, including
motor and sensory advancements as shown on the American Spinal Injury Association
Impairment scale. This was a more statistically significant increase than the 40% increase
shown by the group receiving the regular standard of care.
The systematic review and meta-analysis performed by Fang et al. [45] included two
studies that measured functional walking gains induced by FES cycling in individuals
with SCI via the Six Minute Walk Test (6MWT) and the Timed Get Up and Go Test (TUG).
The evidence displayed significantly improved scores in the 6MWT and TUG after FES
cycling [54,55]. In those two studies, Kuhn et al. [54] investigated the effects of FES cycling
for 20-min sessions twice a week for four weeks. In addition, Mazzoleni and colleagues [55]
combined 20 sessions of FES cycling followed by 20 training sessions of exoskeleton
overground walking.
Transcutaneous spinal cord electrical stimulation can be considered a form of FES
walking although the activity is unique due to the noninvasive stimulation of the nerves
along the lumbosacral region of the spine. This relatively recent innovation in electrical
stimulation therapy allows neuromodulation of the spinal circuitry promoting an effective
stepping motion that may potentially fine-tune locomotion for those with SCI [56]. Dif-
ferent leg muscles can be stressed by altering the placement of electrodes along the spine,
depending on the needs of the individual. For example, low transcutaneous spinal-cord
stimulation intensities at the T10–T11 segment produced a higher magnitude response in
the vastus lateralis and rectus femoris with a lesser magnitude in the medial gastrocnemius,
soleus, and medial hamstrings muscles. The same intensity stimulation at the T12-L1
segment created the reverse relationship of these muscle groups [56].
Sutor et al. [10] combined the use of transcutaneous spinal cord electrical stimulation
with the use of a robotic exoskeleton system. Exoskeleton walking uses an external appli-
cation to provide passive/assistive locomotion involving the legs. However, when it was
combined with the transcutaneous spinal cord electrical stimulation over the lumbosacral
area of the spine, participants were able to produce significantly more steps and display
greater quadricep muscle electromyographic activity than those using the exoskeleton
alone. Transcutaneous spinal cord stimulation is considered noninvasive with the external
placement of the cathode over the posterior of the spine and the anodes placed bilaterally
over the iliac crests [10]. The applications of transcutaneous spinal stimulation (TSS) have
extended to include enhancement of upper extremity functions in persons with SCI, spastic-
ity control, and bladder functions. Gad et al. [9] noted that just four weeks of TSS resulted
in improvement in unilateral and bilateral hand dexterity. Many daily life activities have
been significantly improved following TSS applications on the cervical neural circuitries.
Research showed that TSS applications may be associated with cortical inhibition as well
as an increased level of excitability of spared dormant spinal axonal tracts at the level
of injury. A recent scoping review has included a summary of the research studies and
protocols that implemented different TSS techniques to enhance upper and lower extremity
motor functions in persons with SCI [57]. The scoping review highlighted that there is
inconclusive evidence concerning the exact neurophysiological mechanism by which TSS
augments motor functions after SCI. This mechanism may include cortical inhibition, direct
stimulation of the dorsal nerve roots, or activation of the spared spinal cord circuitry. It is
also unclear whether the amplitude of the current should be set at the motor threshold level,
sub-motor, or supra-motor threshold levels. The authors also attempted to summarize
J. Clin. Med. 2023, 12, 3150 7 of 14

the impact of different anatomical placements of the cathodal electrodes, single versus
multiple sites, and different waveforms. Finally, the influence of carrier frequency on the
neuromodulation capacity of TSS was raised with some studies favoring the application
of the carrier frequency (5–10 kHz) and other studies not supporting its applications. The
rationale of using carrier frequencies is based on using interferential current that may
facilitate deep penetration to stimulate the neural circuitries and reduce painful feelings or
sensations underneath the stimulating electrodes.
Today, our experience in applications of TSS is rudimentary and based on a lim-
ited number of randomized clinical trials and published case reports. Others have uti-
lized TSS in conjunction with exoskeleton training and noted enhancement in motor
performance, [58,59] reduction in spasticity, and an improvement in autonomic profile in
persons with SCI. Currently, there is limited evidence that non-invasive TSS may be a
feasible rehabilitation strategy that can facilitate motor control to restore locomotion in
persons with SCI [60,61].
Spinal cord epidural stimulation (SCES) is an experimental approach that can be either
surgically implanted using a paddle or percutaneous leads to enhance motor function, auto-
nomic regulation, and bladder function, and to reduce spasticity. Most of these case reports
and case series showed beneficial effects on restoring motor function as demonstrated by
enhancing overground ambulation with a walking aid [62–67]. The use of percutaneous
leads for SCES has been recommended for a century in the reduction of spasticity and
restoration of motor control around specific joints. Whether the less invasive percutaneous
SCES has the potential to restore motor function similar to the paddle implantation is yet
to be determined.
It is still difficult to indicate whether participants were able to restore total functional
ambulation on a daily basis or become less dependent on their wheelchairs based on the
published reports. Today, the exact mechanisms of how SCES may influence motor control
to enhance functional recovery have yet to be explored [68]. Shah and Lavrov [68] inves-
tigated optimal stimulation configurations for neuromodulation of the stepping pattern
in spinally transected rats. They found that the stepping patterns were better during a
stimulation frequency of 30–40 Hz at the second lumbar and first sacral segments compared
to lower frequencies of 5–20 Hz. Stimulation frequency of greater than 50 Hz produced
poorer stepping patterns. Improved stepping patterns were found after six training sessions
as early as three weeks post-injury. Harkema et al. [68] demonstrated that using SCES
below the level of injury (lumbosacral region) was helpful in improving the standing and
stepping ability of a 23-year-old male three to four years after a motor vehicle accident
causing C7T1 paraplegia.
Gill et al. [12] used task-specific training with implanted SCES to produce bilateral
stepping on a treadmill, independent from trainer assistance or body-weight support
in an individual with complete T6 paraplegia. Walking speed increased from 0.05 to
0.20 m per second. The restoration of ambulation required over 100 SCES sessions for
43 weeks. In addition to the treadmill training, the individual also underwent independent
stepping overground ambulation with a front-wheeled walker and trainer assistance with
balance at the hips. Gorgey et al. [69] also found improved stepping with the combination
of SCES with exoskeletal-assisted walking in a case report involving a participant with
complete C7 SCI. After 24 sessions of exoskeletal-assisted walking with SCES, volitional
stepping was achieved with a reduction of the swing phase assistance from the exoskeletal
system from 100–35%. Temporal and rhythmic improvements were also captured with
electromyography (EMG) of muscle patterns in the lower extremities.
While both transcutaneous spinal and epidural electrical stimulation provide potential
rehabilitation benefits including increased muscle activity and the facilitation of standing
and overground ambulation [3], rodent participants have shown greater improvements
than human participants with SCES of the spine. One possible reason for this difference in
results is that, in humans, there may be more interference between electrical stimulation
and proprioceptive information.
J. Clin. Med. 2023, 12, 3150 8 of 14

Formento et al. [70] hypothesized that this interference prevents the modulation of the
reciprocal inhibitory system used during walking and decreases leg position awareness.
However, there is evidence that proprioceptive information can be preserved through
alteration in the spaciotemporal stimulation protocols [70]. Angeli et al. [66] successfully
demonstrated the benefits of customizing SCES on two individuals with chronic post-
traumatic SCI. The electrical stimulation was combined with stepping on a treadmill,
over-ground standing, and over-ground walking. The electrical stimulation configurations
were modified every two to four weeks to enhance the standing and stepping based on
observation and electromyographic activity. After 278 sessions of epidural stimulation and
physical training, both participants achieved over-ground walking, independent standing,
and trunk stability.

7. Diagnosis and Treatment of Hand Function in Tetraplegia

Regaining unrestricted use of the hand in gross and fine motor skills is one of the main
health priorities after cervical SCI [71,72], with many regarding it as more important than
walking [73,74]. The development of a tenodesis grip is the gold standard for people with
tetraplegia in regaining hand function [75]. The tenodesis grip is based on a deliberate
shortening of the long finger flexors causing flexion in the metacarpophalangeal and
interphalangeal joints during active or passive dorsiflexion of the wrist. Thus, despite
the absence of selective finger function, grasping and releasing objects can be achieved by
opening the hand through volar flexion, taking an object in the open hand, and passively
closing the hand through dorsiflexion in the wrist. Often, positioning, taping, and splinting
in the first twelve weeks after injury are unreliable for the development of a tenodesis
grip. Consequently, clawed hands, open hands, or insufficient fist closure may result
(Figure 2). Neurophysiological factors such as damage to the lower motor neuron of key
actuators for grasping can be the underlying mechanism [76,77]. To detect the underlying
mechanism, electrical stimulation can be used as a diagnostic assessment. Stimulation
of the defined motor points by means of motor point mapping [78] can be used with a
pulse width of 300 µs, a frequency of 35 Hz, and a stimulation intensity of 20–60 mA to
determine the integrity of the lower motor neuron (Figure 3). Thus, a standardized motor
point mapping can reveal that a greater percentage of muscles on the dorsal aspect of the
forearm show damage to either the lower or upper motor neuron. This finding may contrast
with the flexors on the ventral aspect of the forearm, which may show significantly more
partial damage to the lower motor neuron [8] and a less clear distribution between upper
and lower motor neuron damage. Looking at the patterns of damage to the individual
muscles of the forearm and hands in people with tetraplegia may be useful in predicting
the development of different hand deformities. Testing within the first six to eight weeks
after the onset of a SCI, motor point mapping can serve as a predictor for the development
of voluntary muscle activity 24 weeks after injury [79].
The implication for treatment is that functional and structural training with electrical
stimulation can be started in a targeted and timely manner. So-called open hands usually
present with lower motor neuron damage of the flexor digitorum profundus (FDP) and the
extensor digitorum communis (EDC). In terms of muscle physiology, this type of damage
presents a risk of denervation atrophy combined with the development of contractures in
all finger joints. Timely stimulation of the denervated muscles with long pulse widths to
maintain mobility and contractility of the muscles is recommended [80,81]. If the lower
motor neurons are intact, synergistic balancing should be considered, and functional, task-
oriented training, combined with EMG-triggered FES, should be started in a reasonable
time. In the case of an intact lower motor neuron on the EDC resulting in increased reflex
activity in this spinal segment due to upper motor neuron syndrome, and if the lower
motor neuron of the FDP is damaged, a claw hand will likely develop. Often, taping
the fingers in 90◦ flexion in the metacarpophalangeal joints stimulates muscle spindles,
aggravating the condition and leading to claw hand [82,83]. Stimulation of the denervated
FDP is recommended to maintain contractility and, secondarily, to avoid joint contractures,
J. Clin. Med. 2023, 12, 3150 9 of 14

especially in the metacarpophalangeals. Denervation occurring on the EDC while the same
lower motor neuron on the FDP as the antagonist is intact promotes the development of
a tenodesis grip. FES of the wrist extensors with time-delayed stimulation of the finger
J. Clin. Med. 2023, 12, x FORflexors, triggered optimally via EMG, supports functional task-oriented training
PEER REVIEW 9 of 14 for learning
to grasp with the tenodesis grip (Figure 4).
J. Clin. Med. 2023, 12, x FOR PEER REVIEW 9 of 14

Figure 2. Hand shapes that hinder efficient grasping. Original source of the photo: International
2. Hand
FigureFES Centre®shapes
Nottwil,that hinder
Swiss efficient
Paraplegic Centregrasping. Original source of the photo: International FES
Nottwil, Switzerland.
Figure 2. Hand shapes that hinder efficient grasping. Original source of the photo: International
Centre® Nottwil, Swiss Paraplegic Centre Nottwil, Switzerland.
FES Centre® Nottwil, Swiss Paraplegic Centre Nottwil, Switzerland.

Figure 3. Motor point mapping of the extensor digitorum communis by applying stimulation with a
pen electrode on the defined motor point. Original source of the photo: International FES Centre®
Nottwil, Swiss Paraplegic Centre Nottwil, Switzerland.
 time-delayed stimulation of the finger flexors, triggered optimally via EMG, supports
functional task-oriented training for learning to grasp with the tenodesis grip (Figure 4).
Electrical stimulation can be considered a diagnostic tool (motor point mapping) to
detect eventual damage to the lower motor neuron. Identifying the type of damage at an
early stage after the onset of SCI (six to eight weeks) serves as a predictor for the devel-
J. Clin. Med. 2023, 12, 3150 opment of hand deformities 24 weeks after injury [79]. Prospectively, individualized
10 of 14
treatment, as well as a targeted choice of appropriate stimulation parameters for the tet-
raplegic hand, can be applied in time.

Figure 4. Example of an EMG-triggered stimulation of the hand and finger extensors. Original source
of the photo: International FES Centre® Nottwil, Swiss Paraplegic Centre Nottwil, Switzerland.

Electrical stimulation can be considered a diagnostic tool (motor point mapping) to

detect eventual damage to the lower motor neuron. Identifying the type of damage at
an early stage after the onset of SCI (six to eight weeks) serves as a predictor for the
development of hand deformities 24 weeks after injury [79]. Prospectively, individualized
treatment, as well as a targeted choice of appropriate stimulation parameters for the
tetraplegic hand, can be applied in time.

8. Summary and Conclusions

As healthcare professionals, we have discussed evidence to help substantiate the
importance of the use of electrical stimulation activities for individuals with SCI. These
activities can play an important role during rehabilitation and as long-term activities to
prevent secondary inactivity-associated conditions, such as cardiovascular and metabolic
diseases. Additionally, electrical stimulation activities can help determine individual
treatment strategies regarding hand function in individuals with cervical SCI. Further study
is required to continue to fine-tune the dose-response relationships with rehabilitation and
physical conditioning goals, and to discover new modalities to aid in the enhancement of
the quality of life of people with SCI.

Funding: United States Department of Veterans Affairs: 1 I01 RX002649-01A.

Conflicts of Interest: The authors declare no conflict of interest.

References
1. Karamian, B.A.; Siegel, N.; Nourie, B.; Serruya, M.D.; Heary, R.F.; Harrop, J.S.; Vaccaro, A.R. The role of electrical stimulation for
rehabilitation and regeneration after spinal cord injury. J. Orthop. Traumatol. 2022, 23, 2. [CrossRef]
2. Gater, D.R.; Dolbow, D.; Tsui, B.; Gorgey, A.S. Functional Electrical Stimulation Therapies after Spinal Cord Injury. NeuroRehabili-
tation 2011, 28, 231–248. [CrossRef]
3. Dolbow, D.R.; Gorgey, A.S.; Sutor, T.W.; Bochkezanian, V.; Musselman, K. Invasive and Non-Invasive Approaches of Electrical
Stimulation to Improve Physical Functioning after Spinal Cord Injury. J. Clin. Med. 2021, 10, 5356. [CrossRef] [PubMed]
J. Clin. Med. 2023, 12, 3150 11 of 14

4. Duffell, L.D.; Donaldson, N.N. A Comparison of FES and SCS for Neuroplastic Recovery after SCI: Historical Perspectives and
Future Directions. Front. Neurol. 2020, 11, 607. [CrossRef] [PubMed]
5. Gorgey, A.S.; Khalil, R.E.; Lester, R.M.; Dudley, G.A.; Gater, D.R. Paradigms of Lower Extremity Electrical Stimulation Training
after Spinal Cord Injury. J. Vis. Exp. 2018, 1, 57000. [CrossRef]
6. Johnston, T.E.; Marino, R.J.; Oleson, C.V.; Schmidt-Read, M.; Leiby, B.E.; Sendecki, J.; Singh, H.; Modlesky, C.M. Musculoskeletal
Effects of 2 Functional Electrical Stimulation Cycling Paradigms Conducted at Different Cadences for People with Spinal Cord
Injury: A Pilot Study. Arch Phys. Med. Rehabil. 2016, 97, 1413–1422. [CrossRef] [PubMed]
7. Hettinga, D.M.; Andrews, B.J. Oxygen consumption during functional electrical stimulation-assisted exercise in persons with
spinal cord injury: Implications for fitness and health. Sports Med. 2008, 38, 825–838. [CrossRef] [PubMed]
8. Bersch, I.; Koch-Borner, S.; Fridén, J. Motor Point Topography of Fundamental Grip Actuators in Tetraplegia: Implications in
Nerve Transfer Surgery. J. Neurotrauma 2020, 37, 441–447. [CrossRef]
9. Gad, P.; Lee, S.; Terrafranca, N.; Zhong, H.; Turner, A.; Gerasimenko, Y.; Edgerton, V.R. Non-Invasive Activation of Cervical
Spinal Networks after Severe Paralysis. J. Neurotrauma 2018, 35, 2145–2158. [CrossRef]
10. Sutor, T.W.; Ghatas, M.P.; Goetz, L.L.; Lavis, T.D.; Gorgey, A.S. Exoskeleton Training and Trans-Spinal Stimulation for Physical
Activity Enhancement after Spinal Cord Injury (EXTra-SCI): An Exploratory Study. Front. Rehabil. Sci. 2022, 2, 789422. [CrossRef]
11. Hachmann, J.T.; Yousak, A.; Wallner, J.J.; Gad, P.N.; Edgerton, V.R.; Gorgey, A.S. Epidural spinal cord stimulation as an
intervention for motor recovery after motor complete spinal cord injury. J. Neurophysiol. 2021, 126, 1843–1859. [CrossRef]
12. Gill, M.L.; Grahn, P.J.; Calvert, J.S.; Linde, M.B.; Lavrov, I.A.; Strommen, J.A.; Beck, L.A.; Sayenko, D.G.; Van Straaten, M.G.;
Drubach, D.I.; et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia.
Nat. Med. 2018, 24, 1677–1682. [CrossRef]
13. Doucet, B.M.; Lam, A.; Griffin, L. Neuromuscular electrical stimulation for skeletal muscle function. Yale J. Biol. Med. 2012, 85,
201–215.
14. Bekhet, A.H.; Bochkezanian, V.; Saab, I.M.; Gorgey, A.S. The Effects of Electrical Stimulation Parameters in Managing Spasticity
after Spinal Cord Injury: A Systematic Review. Am. J. Phys. Med. Rehabil. 2019, 98, 484–499. [CrossRef]
15. Gorgey, A.S.; Dolbow, D.R.; Dolbow, J.D.; Gater, D.R. The Effects of Electrical Stimulation on Body Composition and Metabolic
Profile after Spinal Cord Injury—Part II. J. Spinal Cord Med. 2015, 38, 23–37. [CrossRef]
16. Dolbow, D.R.; Gorgey, A.S.; Ketchum, J.M.; Gater, D.R. Home-Based Functional Electrical Stimulation Cycling Enhances Quality
of Life in Individuals with Spinal Cord Injury. Top. Spinal Cord Inj. Rehabil. 2013, 19, 324–329. [CrossRef]
17. Gorgey, A.S.; Khalil, R.E.; Sutor, T.W.; Goldsmith, J.A.; Cifu, D.X. Employment of Neuromuscular Electrical Stimulation to
Examine Muscle and Bone Qualities after Spinal Cord Injury. J. Clin. Med. 2022, 11, 6681. [CrossRef]
18. Gorgey, A.S.; Lester, R.M.; Wade, R.C.; Khalil, R.E.; Khan, R.K.; Anderson, M.L.; Castillo, T. A feasibility pilot using telehealth
videoconference monitoring of home-based NMES resistance training in persons with spinal cord injury. Spinal Cord Ser. Cases
2017, 3, 17039. [CrossRef]
19. Martin, R.; Sadowsky, C.; Obst, K.; Meyer, B.; McDonald, J. Functional electrical stimulation in spinal cord injury: From theory to
practice. Top. Spinal Cord Inj. Rehabil. 2012, 18, 28–33. [CrossRef]
20. Dolbow, D.R.; Farkas, G.J.; Berg, A.S.; Welsch, M.A.; Gorgey, A.S.; Gater, D.R. Fat to lean mass ratio in spinal cord injury: Possible
interplay of components of body composition that may instigate systemic inflammation and metabolic syndrome. J. Spinal Cord
Med. 2022, 45, 833–839. [CrossRef]
21. Atkins, K.D.; Bickel, C.S. Effects of functional electrical stimulation on muscle health after spinal cord injury. Curr. Opin. Pharmacol.
2021, 60, 226–231. [CrossRef]
22. Bekhet, A.H.; Jahan, A.M.; Bochkezanian, V.; Musselman, K.E.; Elsareih, A.A.; Gorgey, A.S. Effects of Electrical Stimulation
Training on Body Composition Parameters after Spinal Cord Injury: A Systematic Review. Arch Phys. Med. Rehabil. 2022, 103,
1168–1178. [CrossRef]
23. Dolbow, D.R.; Credeur, D.; Lemacks, J.L.; Stokic, D.S.; Pattanaik, S.; Corbin, G.N.; Courtner, A.S. Electrically Induced Cycling and
Nutritional Counseling for Counteracting Obesity after Spinal Cord Injury: A Pilot Study. J. Spinal Cord Med. 2020, 44, 533–540.
[CrossRef]
24. Gorgey, A.S.; Mather, K.J.; Cupp, H.R.; Gater, D.R. Effects of Resistance Training on Adiposity and Metabolism after Spinal Cord
Injury. Med. Sci. Sports Exerc. 2012, 44, 165–174. [CrossRef]
25. Gorgey, A.S.; Shepherd, C. Skeletal muscle hypertrophy and decreased intramuscular fat after unilateral resistance training in
spinal cord injury: Case report. J. Spinal Cord Med. 2010, 33, 90–95. [CrossRef]
26. Gorgey, A.S.; Khalil, R.E.; Gill, R.; Gater, D.R.; Lavis, T.D.; Cardozo, C.P.; Adler, R.A. Low-Dose Testosterone and Evoked
Resistance Exercise after Spinal Cord Injury on Cardio-Metabolic Risk Factors: An Open-Label Randomized Clinical Trial. J.
Neurotrauma 2019, 36, 2631–2645. [CrossRef]
27. Ye, G.; Grabke, E.P.; Pakosh, M.; Furlan, J.C.; Masani, K. Clinical Benefits and System Design of FES-Rowing Exercise for
Rehabilitation of Individuals with Spinal Cord Injury: A Systematic Review. Arch. Phys. Med. Rehabil. 2021, 102, 1595–1605.
[CrossRef]
28. Kim, D.I.; Park, D.S.; Lee, B.S.; Jeon, J.Y. A six-week motor-driven functional electronic stimulation rowing program improves
muscle strength and body composition in people with spinal cord injury: A pilot study. Spinal Cord 2014, 52, 621–624. [CrossRef]
J. Clin. Med. 2023, 12, 3150 12 of 14

29. Jeon, J.Y.; Hettinga, D.; Steadward, R.D.; Wheeler, G.D.; Bell, G.; Harber, V. Reduced plasma glucose and leptin after 12 weeks
of functional electrical stimulation–rowing exercise training in spinal cord injury patients. Arch. Phys. Med. Rehabil. 2010, 91,
1957–1959. [CrossRef]
30. Wilbanks, S.R.; Bickel, C.S. Scapular stabilization and muscle strength in manual wheelchair users with spinal cord injury and
subacromial impingement. Top. Spinal Cord Inj. Rehabil. 2016, 22, 60–70. [CrossRef]
31. Gorgey, A.S.; Lai, R.E.; Khalil, R.E.; Rivers, J.; Cardozo, C.; Chen, Q.; Lesnefsky, E.J. Neuromuscular electrical stimulation
resistance training enhances oxygen uptake and ventilatory efficiency independent of mitochondrial complexes after spinal cord
injury: A randomized clinical trial. J. Appl. Physiol. 2021, 131, 265–276. [CrossRef]
32. Wade, R.C.; Gorgey, A.S. Skeletal muscle conditioning may be an effective rehabilitation intervention preceding functional
electrical stimulation cycling. Neural. Regen. Res. 2016, 11, 1232–1233. [CrossRef]
33. Dolbow, J.D.; Dolbow, D.R.; Gorgey, A.S.; Adler, R.R.; Gater, D.R. The Effects of Aging and Electrical Stimulation Exercise on Bone
after Spinal Cord Injury. Aging Dis. 2013, 4, 141–153.
34. Sutor, T.W.; Kura, J.; Mattingly, A.J.; Otzel, D.M.; Yarrow, J.F. The Effects of Exercise and Activity-Based Physical Therapy on Bone
after Spinal Cord Injury. Int. J. Mol. Sci. 2022, 23, 608. [CrossRef]
35. Dolbow, D.R.; Gorgey, A.S.; Daniels, J.A.; Adler, R.R.; Gater, D.R., Jr. The Effects of Spinal Cord Injury and Exercise on Bone Mass:
A Literature Review. NeuroRehabilitation 2011, 29, 261–269. [CrossRef]
36. Craven, B.C.; Wiest, M.J.; Cervinka, T.; Eng, J.J. Bone Health Following Spinal Cord Injury. In Spinal Cord Injury Rehabilitation
Evidence; Version 7.0; Eng, J.J., Teasell, R.W., Miller, W.C., Wolfe, D.L., Townson, A.F., Hsieh, J.T.C., et al., Eds.; SCIRE: Vancouver,
BC, Canada, 2020; pp. 1–126. Available online: https://scireproject.com/wp-content/uploads/2022/02/BONE-CHAPTER-
FINAL-Nov.20-.20.pdf (accessed on 20 April 2023).
37. van der Scheer, J.W.; Goosey-Tolfrey, V.L.; Valentino, S.E.; Davis, G.M.; Ho, C.H. Functional electrical stimulation cycling exercise
after spinal cord injury: A systematic review of health and fitness-related outcomes. J. NeuroEngineering Rehabil. 2021, 18, 99.
[CrossRef]
38. Hamzaid, N.A.; Davis, G. Health and Fitness Benefits of Functional Electrical Stimulation-Evoked Leg Exercise for Spinal
Cord–Injured Individuals: A Position Review. Top. Spinal Cord Inj. Rehabil. 2009, 14, 88–121. [CrossRef]
39. Figoni, S.; Dolbow, D.R.; Crawford, C.; White, M.; Pattanaik, S. Does Aerobic Exercise Benefit Persons with Tetraplegia from
Spinal Cord Injury? J. Spinal Cord Med. 2021, 44, 690–703. [CrossRef]
40. Griffin, L.; Decker, M.J.; Hwang, J.Y.; Wang, B.; Kitchen, K.; Ding, Z.; Ivy, J.L. Functional electrical stimulation cycling improves
body composition, metabolic and neural factors in persons with spinal cord injury. J. Electromyogr. Kinesiol. 2009, 19, 614–622.
[CrossRef]
41. Farkas, G.J.; Burton, A.M.; McMillan, D.W.; Sneij, A.; Gater, D.R., Jr. The Diagnosis and Management of Cardiometabolic Risk and
Cardiometabolic Syndrome after Spinal Cord Injury. J. Pers. Med. 2022, 12, 1088. [CrossRef]
42. Farkas, G.J.; Gorgey, A.S.; Dolbow, D.R.; Berg, A.S.; Gater, D.R. Energy Expenditure, Cardiorespiratory Fitness, and Body
Composition Following Arm Cycling or Functional Electrical Stimulation Exercises in Spinal Cord Injury: A 16-Week Randomized
Controlled Trial. Top. Spinal Cord Inj. Rehabil. 2021, 27, 121–134. [CrossRef]
43. Nash, M.S.; Bilsker, M.S.; Kearney, H.M.; Ramirez, J.N.; Applegate, B.; Green, B.A. Effects of electrically-stimulated exercise and
passive motion on echocardiographically-derived wall motion and cardiodynamic functic in tetraplegic persons. Spinal Cord 1995,
33, 80–89. [CrossRef] [PubMed]
44. Alashram, A.R.; Annino, G.; Mercuri, N.B. Changes in spasticity following functional electrical stimulation cycling in patients
with spinal cord injury: A systematic review. J. Spinal Cord Med. 2022, 45, 10–23. [CrossRef] [PubMed]
45. Fang, C.Y.; Lien, A.S.; Tsai, J.L.; Yang, H.C.; Chan, H.L.; Chen, R.S.; Chang, Y.J. The Effect and Dose-Response of Functional
Electrical Stimulation Cycling Training on Spasticity in Individuals with Spinal Cord Injury: A Systematic Review with Meta-
Analysis. Front. Physiol. 2021, 12, 756200. [CrossRef]
46. Elgaddal, N.; Kramarow, K.A.; Reuben, C. Physical Activity among Adults Aged 18 and over: United States. 2020. Available
online: https://www.cdc.gov/nchs/products/databriefs/db443.htm (accessed on 11 November 2022).
47. Soriano, J.E.; Squair, J.W.; Cragg, J.J.; Thompson, J.; Sanguinetti, R.; Vaseghi, B.; Emery, C.A.; Grant, C.; Charbonneau, R.;
Larkin-Kaiser, K.A.; et al. A national survey of physical activity after spinal cord injury. Sci. Rep. 2022, 12, 4405. [CrossRef]
[PubMed]
48. Dolbow, D.R.; Gorgey, A.S.; Ketchum, J.M.; Moore, J.R.; Hackett, L.A.; Gater, D.R. Exercise Adherence during Home-Based
Functional Electrical Stimulation Cycling by Individuals with Spinal Cord Injury. Am. J. Phys. Med. Rehabil. 2012, 91, 922–930.
[CrossRef]
49. Tiu, C.; Ochoa, C.; Froehlich-Grobe, K. Qualitative analysis of perceived motivators and barriers to exercise in individuals with
spinal cord injury enrolled in an exercise study. Spinal Cord Ser. Cases 2022, 8, 74. [CrossRef]
50. Dolbow, D.R.; Figoni, S.F. Accommodation of Wheelchair-Reliant Individuals by Community Fitness Facilities. Spinal Cord 2015,
53, 515–519. [CrossRef]
51. Gorgey, A.S.; Khalil, R.E.; Gill, R.; Khan, R.; Adler, R.A. Effects of dose de-escalation following testosterone treatment and evoked
resistance exercise on body composition, metabolic profile, and neuromuscular parameters in persons with spinal cord injury.
Physiol. Rep. 2021, 9, e15089. [CrossRef]
J. Clin. Med. 2023, 12, 3150 13 of 14

52. Gorgey, A.S.; Khalil, R.E.; Alrubaye, M.; Gill, R.; Rivers, J.; Goetz, L.L.; Cifu, D.X.; Castillo, T.; Caruso, D.; Lavis, T.D.; et al.
Testosterone and long pulse width stimulation (TLPS) for denervated muscles after spinal cord injury: A study protocol of
andomized clinical trial. BMJ Open 2022, 12, e064748. [CrossRef]
53. Sadowsky, C.L.; Hammond, E.R.; Strohl, A.B.; Commean, P.K.; Eby, S.A.; Damiano, D.L.; Wingert, J.R.; Bae, K.T.; McDonald, J.W.,
3rd. Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord
injury. J. Spinal Cord Med. 2013, 36, 623–631. [CrossRef]
54. Kuhn, D.; Leichtfried, V.; Schobersberger, W. Four weeks of functional electrical stimulated cycling after spinal cord injury: A
clinical cohort study. Int. J. Rehabil. Res. 2014, 37, 243–250. [CrossRef]
55. Mazzoleni, S.; Battini, E.; Rustici, A.; Stampacchia, G. An integrated gait rehabilitation training based on Functional Electrical
Stimulation cycling and overground robotic exoskeleton in complete spinal cord injury patients: Preliminary results. IEEE Int.
Conf. Rehabil. Robot. 2017, 2017, 289–293. [CrossRef]
56. Gerasimenko, Y.; Gorodnichev, R.; Moshonkina, T.; Sayenko, D.; Gad, P.; Edgerton, V.R. Transcutaneous electrical spinal-cord
stimulation in humans. Ann. Phys. Rehabil. Med. 2015, 58, 225–231. [CrossRef] [PubMed]
57. Rehman, M.U.; Sneed, D.; Sutor, T.W.; Hoenig, H.; Gorgey, A.S. Optimization of Transspinal Stimulation Applications for Motor
Recovery after Spinal Cord Injury: Scoping Review. J. Clin. Med. 2023, 12, 854. [CrossRef]
58. Gad, P.; Gerasimenko, Y.; Zdunowski, S.; Turner, A.; Sayenko, D.; Lu, D.C.; Edgerton, V.R. Weight Bearing over-ground Stepping
in an Exoskeleton with Non-invasive Spinal Cord Neuromodulation after Motor Complete Paraplegia. Front. Neurosci. 2017,
11, 333. [CrossRef] [PubMed]
59. Shapkova, E.Y.; Pismennaya, E.V.; Emelyannikov, D.V.; Ivanenko, Y. Exoskeleton Walk Training in Paralyzed Individuals Benefits
from Transcutaneous Lumbar Cord Tonic Electrical Stimulation. Front. Neurosci. 2020, 14, 416. [CrossRef] [PubMed]
60. Hastings, S.; Zhong, H.; Feinstein, R.; Zelczer, G.; Mitrovich, C.; Gad, P.; Edgerton, V.R. A pilot study combining noninvasive
spinal neuromodulation and activity-based neurorehabilitation therapy in children with cerebral palsy. Nat. Commun. 2022,
13, 5660. [CrossRef]
61. Siu, R.; Brown, E.H.; Mesbah, S.; Gonnelli, F.; Pisolkar, T.; Edgerton, V.R.; Ovechkin, A.V.; Gerasimenko, Y.P. Novel Noninvasive
Spinal Neuromodulation Strategy Facilitates Recovery of Stepping after Motor Complete Paraplegia. J. Clin. Med. 2022, 11, 3670.
[CrossRef] [PubMed]
62. Barolat, G.; Myklebust, J.B.; Wenninger, W. Effects of spinal cord stimulation on spasticity and spasms secondary to myelopathy.
Appl. Neurophysiol. 1988, 51, 29–44. [CrossRef]
63. Dimitrijevic, M.R.; Illis, L.S.; Nakajima, K.; Sharkey, P.C.; Sherwood, A.M. Spinal cord stimulation for the control of spasticity in
patients with chronic spinal cord injury: II. Neurophysiologic observations. Cent. Nerv. Syst. Trauma 1986, 3, 145–152. [CrossRef]
64. Harkema, S.; Gerasimenko, Y.; Hodes, J.; Burdick, J.; Angeli, C.; Chen, Y.; Ferreira, C.; Willhite, A.; Rejc, E.; Grossman, R.G.; et al.
Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor
complete paraplegia: A case study. Lancet 2011, 377, 1938–1947. [CrossRef] [PubMed]
65. Angeli, C.A.; Edgerton, V.R.; Gerasimenko, Y.P.; Harkema, S.J. Altering spinal cord excitability enables voluntary movements
after chronic complete paralysis in humans. Brain 2014, 137 Pt 5, 1394–1409. [CrossRef] [PubMed]
66. Angeli, C.A.; Boakye, M.; Morton, R.A.; Vogt, J.; Benton, K.; Chen, Y.; Ferreira, C.K.; Harkema, S.J. Recovery of over-Ground
Walking after Chronic Motor Complete Spinal Cord Injury. N. Engl. J. Med. 2018, 379, 1244–1250. [CrossRef]
67. Wagner, F.B.; Mignardot, J.-B.; Le Goff-Mignardot, C.G.; Demesmaeker, R.; Komi, S.; Capogrosso, M.; Rowald, A.; Seanez, I.;
Caban, M.; Pirondini, E.; et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature 2018, 563,
65–71. [CrossRef] [PubMed]
68. Shah, P.K.; Lavrov, I. Spinal Epidural Stimulation Strategies: Clinical Implications of Locomotor Studies in Spinal Rats. Neurosci-
entist 2017, 23, 664–680. [CrossRef]
69. Gorgey, A.S.; Gill, S.; Holman, M.E.; Davis, J.C.; Atri, R.; Bai, O.; Goetz, L.; Lester, D.L.; Trainer, R.; Lavis, T.D. The feasibility of
using exoskeletal-assisted walking with epidural stimulation: A case report study. Ann. Clin. Transl. Neurol. 2020, 7, 259–265.
[CrossRef]
70. Formento, E.; Minassian, K.; Wagner, F.; Mignardot, J.B.; Le Goff, C.G.; Rowald, A.; Bloch, J.; Micera, S.; Capogrosso, M.; Courtine,
G. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nat.
Neurosci. 2018, 21, 1728–1741. [CrossRef]
71. Anderson, K.D. Targeting Recovery: Priorities of the Spinal Cord-Injured Population. J. Neurotrauma 2004, 21, 1371–1383.
[CrossRef]
72. Snoek, G.J.; IJzerman, M.J.; Hermens, H.J.; Maxwell, D.; Biering-Sørensen, F. Survey of the needs of patients with spinal cord
injury: Impact and priority for improvement in hand function in tetraplegics. Spinal Cord 2004, 42, 526–532. [CrossRef]
73. Anderson, K.D.; Fridén, J.; Lieber, R.L. Acceptable benefits and risks associated with surgically improving arm function in
individuals living with cervical spinal cord injury. Spinal Cord 2008, 47, 334–338. [CrossRef] [PubMed]
74. Simpson, L.A.; Eng, J.J.; Hsieh, J.T.C.; Wolfe, D.L.; Team SCIRESR. The Health and Life Priorities of Individuals with Spinal Cord
Injury: A Systematic Review. J. Neurotrauma 2012, 29, 1548–1555. [CrossRef] [PubMed]
75. Jung, H.Y.; Lee, J.; Shin, H.I. The natural course of passive tenodesis grip in individuals with spinal cord injury with preserved
wrist extension power but paralyzed fingers and thumbs. Spinal Cord 2018, 56, 900–906. [CrossRef]
J. Clin. Med. 2023, 12, 3150 14 of 14

76. Harvey, L.; Baillie, R.; Ritchie, B.; Simpson, D.; Pironello, D.; Glinsky, J. Does three months of nightly splinting reduce the
extensibility of the flexor pollicis longus muscle in people with tetraplegia? Physiother. Res. Int. 2007, 12, 5–13. [CrossRef]
77. Bersch, I.; Fridén, J. Role of Functional Electrical Stimulation in Tetraplegia Hand Surgery. Arch. Phys. Med. Rehabil. 2016, 97
(Suppl. S6), S154–S159. [CrossRef]
78. Bersch, I.; Koch-Borner, S.; Fridén, J. Electrical stimulation-a mapping system for hand dysfunction in tetraplegia. Spinal Cord
2018, 56, 516–522. [CrossRef]
79. Bersch, I.; Krebs, J.; Fridén, J. A Prediction Model for Various Treatment Pathways of Upper Extremity in Tetraplegia. Front.
Rehabil. Sci. 2022, 3, 889577. [CrossRef]
80. Bersch, I.; Fridén, J. Upper and lower motor neuron lesions in tetraplegia: Implications for surgical nerve transfer to restore hand
function. J. Appl. Physiol. 2020, 129, 1214–1219. [CrossRef] [PubMed]
81. Chandrasekaran, S.; Davis, J.; Bersch, I.D.A.; Goldberg, G.; Gorgey, A.S. Electrical stimulation and denervated muscles after
spinal cord injury. Neural Regen. Res. 2020, 15, 1397–1407.
82. Zijdewind, I.; Gant, K.; Bakels, R.; Thomas, C.K. Do Additional Inputs Change Maximal Voluntary Motor Unit Firing Rates after
Spinal Cord Injury? Neurorehabilit. Neural Repair 2012, 26, 58–67. [CrossRef]
83. Thomas, C.K.; Häger, C.K.; Klein, C.S. Increases in human motoneuron excitability after cervical spinal cord injury depend on the
level of injury. J. Neurophysiol. 2017, 117, 684–691. [CrossRef] [PubMed]

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