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Citation: Tharu, N.S.; Alam, M.;
Ling, Y.T.; Wong, A.Y.; Zheng, Y.-P.
Combined Transcutaneous Electrical
Spinal Cord Stimulation and
Task-Specific Rehabilitation Improves
Trunk and Sitting Functions in People
with Chronic Tetraplegia.
Biomedicines 2023,11, 34. https://
doi.org/10.3390/biomedicines11010034
Academic Editor: Nicolas Guerout
Received: 5 December 2022
Revised: 19 December 2022
Accepted: 20 December 2022
Published: 23 December 2022
Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
biomedicines
Article
Combined Transcutaneous Electrical Spinal Cord Stimulation
and Task-Specific Rehabilitation Improves Trunk and Sitting
Functions in People with Chronic Tetraplegia
Niraj Singh Tharu 1, Monzurul Alam 1, * , Yan To Ling 1, Arnold YL Wong 2,3 and Yong-Ping Zheng 1 ,3 ,*
1Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China
2Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China
3Research Institute for Smart Ageing, The Hong Kong Polytechnic University, Hong Kong SAR, China
*Correspondence: md.malam@connect.polyu.hk (M.A); yongping.zheng@polyu.edu.hk (Y.-P.Z.)
Abstract:
The aim of this study was to examine the effects of transcutaneous electrical spinal cord
stimulation (TSCS) and conventional task-specific rehabilitation (TSR) on trunk control and sitting
stability in people with chronic tetraplegia secondary to a spinal cord injury (SCI). Five individuals
with complete cervical (C4–C7) cord injury participated in 24-week therapy that combined TSCS
and TSR in the first 12 weeks, followed by TSR alone for another 12 weeks. The TSCS was delivered
simultaneously at T11 and L1 spinal levels, at a frequency ranging from 20–30 Hz with
0.1–1.0 ms
.
pulse width biphasically. Although the neurological prognosis did not manifest after either treatment,
the results show that there were significant increases in forward reach distance (10.3
±
4.5 cm), right
lateral reach distance (3.7
±
1.8 cm), and left lateral reach distance (
3.0 ±0.9 cm
) after the combina-
tional treatment (TSCS+TSR). The stimulation also significantly improved the participants’ trunk
control and function in sitting. Additionally, the trunk range of motion and the electromyographic re-
sponse of the trunk muscles were significantly elevated after TSCS+TSR. The TSCS+TSR intervention
improved independent trunk control with significantly increased static and dynamic sitting balance,
which were maintained throughout the TSR period and the follow-up period, indicating long-term
sustainable recovery.
Keywords: transcutaneous electrical spinal cord stimulation; trunk control; sitting balance; tetraplegia;
spinal cord injury
1. Introduction
Spinal cord injury (SCI) often results in a permanent loss of motor, sensory, or au-
tonomic functions below the level of injury [
1
,
2
]. The worldwide annual incidence and
prevalence of SCI range from 8 to 246 and from 236 to 1298 per million people, respec-
tively [
3
]. Depending on the level of neurological damage, SCI may cause tetraplegia or
paraplegia [
4
]. One-third of people with SCI are found to have tetraplegia, and 50% of them
have a complete lesion [
5
], with C5 (cervical vertebrae) being the most commonly affected
level [
6
]. People with tetraplegia experience severe trunk muscle weakness that inhibits
sitting and trunk functions, thus restricting their overall functional activity [
7
]. In addition,
individuals with complete or incomplete tetraplegia have greater trunk impairment, which
results in more trunk instability and sitting imbalance than people with paraplegia [
8
,
9
],
and often struggle to perform the daily functions of sitting [
10
,
11
]. They are also more
prone to postural instability and fall-related injuries [
12
]. For people with tetraplegia, trunk
stability is more important than trunk mobility [
13
]. Individuals with tetraplegia report
significantly more limitations and restrictions in their activities of daily living (ADL) than
people with paraplegia [
14
]. Similarly, more than 60% of SCI survivors consider trunk
function to be an important factor for mobility and performing ADL [
15
]. Around 70–80%
Biomedicines 2023,11, 34. https://doi.org/10.3390/biomedicines11010034 https://www.mdpi.com/journal/biomedicines
Biomedicines 2023,11, 34 2 of 18
of people with SCI are wheelchair-bound, and consider trunk control an essential factor for
those with sitting difficulties [16].
Traditionally, SCI management focused on teaching compensatory skills. Recently, this
approach has gradually shifted toward neural restoration through the use of innovative,
intensive therapy strategies that successfully address physiological changes and regenera-
tion concepts [
17
,
18
]. Of various approaches (activity-based therapy, impairment-based
training, etc.), task-specific rehabilitation (TSR) has been shown to be more beneficial than
conventional rehabilitation for motor recovery in people with chronic SCI [
19
,
20
]. “The TSR
is a therapeutic approach that involves intensive practice of actions or functional tasks” [
21
],
which is based on the idea that motor output can be shaped and retrained in response
to specific sensory inputs [
22
]. It focuses on regaining muscular strength and improving
functional abilities through targeted and repeated specific exercises [
23
]. Motor or sensory
recovery is often restricted to minimal success in people with tetraplegia [
24
,
25
]. In addi-
tion, TSR has been observed to be advantageous for improving upper limb functions [
26
].
The locomotion ability was reported to be enhanced in individuals with incomplete SCI
using TSR strategies [
27
,
28
]. Although TSR has shown some benefits over conventional
rehabilitation, more studies are needed to confirm its efficacy [29,30].
It used to be believed that people with complete SCI would not experience motor
recovery below the lesion [
31
]. Yet prior research has indicated that individuals with com-
plete or incomplete SCI showed motor and sensory improvement with neuromodulation
treatment [
32
]. In addition, transcutaneous electrical spinal cord stimulation (TSCS) has
recently emerged as a potential treatment for SCI, among other neuromodulation tech-
niques [
33
,
34
]. It modulates the activity of neural pathways through spinal stimulation
to generate therapeutic benefits [
35
]. The TSCS produces an electric field that triggers the
neural connectome via sensory pathways in the dorsal roots, which provides subthreshold
excitation to interneurons and motor neurons distal to the injury. Motor neurons near the
threshold are then more rapidly triggered and produce volitional movement [
36
]. Previous
studies indicated that TSCS may decrease spasticity [
37
], modify neuronal connections [
38
],
assist in locomotion [
39
] and stepping [
40
], and initiate volitional movement [
41
]. Moreover,
TSCS produced immediate trunk self-control in people with chronic SCI with a more steady
and upright sitting position [
12
], and quickly restored the ability to sit up straight [
42
].
However, these studies on trunk control have only been conducted on people with para-
plegia or incomplete cervical SCI [
11
,
43
]. More research is warranted to investigate trunk
recovery in people with complete tetraplegia [42].
The current study aimed to investigate the effects of adding TSCS to TSR treatment on
trunk control and sitting function in people with tetraplegia following complete cervical SCI.
To achieve this aim, two specific objectives were set to investigate the (1) efficacy of TSCS
for improving trunk control and sitting function with TSR in people with tetraplegia; and
(2) effect of TSCS on motor and sensory functions of the study participants. We hypothesized
that the combined treatment (TSCS+TSR) could improve trunk and sitting functions in people
with complete chronic tetraplegia. To our knowledge, this is the first study to report the use of
TSCS for trunk control in people with complete cervical SCIs; the outcomes may be applicable
to people with various levels of neurological damage caused by SCI.
2. Methods
The study was approved by the Human Subjects Ethics Sub-Committee of The Hong
Kong Polytechnic University (Reference no: HSEARS20190201002-01).
2.1. Study Participants
Five individuals with chronic SCI with impaired trunk and sitting function were
recruited. Each participant had sustained a traumatic complete cervical SCI (Table 1).
Participant consent was obtained prior to the start of the experiment.
Biomedicines 2023,11, 34 3 of 18
Table 1. The demographic and clinical characteristics of the participants.
Participants Age Gender Time since Injury (Years) Type of Injury NLI AIS Category
P1 57 F 1.5 Traumatic C6 A
P2 55 F 19 Traumatic C7 A
P3 26 F 12 Traumatic C5 A
P4 40 M 12 Traumatic C5 A
P5 32 M 2 Traumatic C4 A
NLI, neurological level of injury; AIS, American Spinal Injury Association Impairment Scale.
As shown in Table 1, the mean age of the participants was 42.0 years (
SD = 13.7 years
,
range = 26–57 years), and the mean time since injury was 9.3 years (SD = 7.4 years,
range = 1.5–19 years
). Each participant had a traumatic cervical SCI based on the American
Spinal Injury Association Impairment Scale (AIS), and the injury level varied from C4–C7.
The inclusion criteria were people with SCI aged between 18 and 60 years; a cervical SCI
resulting in complete tetraplegia; injury duration of at least 1 year; an injury level between
C4–C8; absence of independent trunk control; being unable to sit independently; stable
respiratory functions; and no prior neuromodulation treatment. People were excluded if
they had received injections (Botox or Dysport) within the previous 6 months, had spasticity
(more than grade 1
+
based on the Modified Ashworth Scale), contracture, pressure injuries,
infections, or internal fixations at the site of the injury, transplants (cardiac pacemakers and
defibrillators), or had comorbidities (e.g., asthma, hypertension).
2.2. Study Design
This was a case series study design where people with chronic tetraplegia underwent
two phases of treatment (first TSCS+TSR followed by TSR alone). The participants were
recruited through a convenience sampling method. The treatment frequency was divided
into three groups depending on the availability and schedules of the study participants:
(a) three sessions per week; (b) two sessions per week; and (c) one session per week. In
addition, participants P1, P2, and P4 attended three sessions per week, whereas P3 and P5
attended one session and two sessions per week, respectively. The outline of the study is
described in Figure 1.
Biomedicines 2022, 10, x FOR PEER REVIEW 3 of 19
Five individuals with chronic SCI with impaired trunk and sitting function were re-
cruited. Each participant had sustained a traumatic complete cervical SCI (Table 1). Par-
ticipant consent was obtained prior to the start of the experiment.
As shown in Table 1, the mean age of the participants was 42.0 years (SD = 13.7 years,
range = 26–57 years), and the mean time since injury was 9.3 years (SD = 7.4 years, range
= 1.5–19 years). Each participant had a traumatic cervical SCI based on the American Spi-
nal Injury Association Impairment Scale (AIS), and the injury level varied from C4–C7.
The inclusion criteria were people with SCI aged between 18 and 60 years; a cervical SCI
resulting in complete tetraplegia; injury duration of at least 1 year; an injury level between
C4–C8; absence of independent trunk control; being unable to sit independently; stable
respiratory functions; and no prior neuromodulation treatment. People were excluded if
they had received injections (Botox or Dysport) within the previous 6 months, had spas-
ticity (more than grade 1+ based on the Modified Ashworth Scale), contracture, pressure
injuries, infections, or internal fixations at the site of the injury, transplants (cardiac pace-
makers and defibrillators), or had comorbidities (e.g., asthma, hypertension).
Table 1. The demographic and clinical characteristics of the participants.
Participants Age Gender
Time since injury
(years)
Type of injury NLI AIS category
P1
57
F
1.5
Traumatic
C6
A
P2
55
F
19
Traumatic
C7
A
P3
26
F
12
Traumatic
C5
A
P4
40
M
12
Traumatic
C5
A
P5
32
M
2
Traumatic
C4
A
NLI, neurological level of injury; AIS, American Spinal Injury Association Impairment Scale.
2.2. Study design
This was a case series study design where people with chronic tetraplegia underwent
two phases of treatment (first TSCS+TSR followed by TSR alone). The participants were
recruited through a convenience sampling method. The treatment frequency was divided
into three groups depending on the availability and schedules of the study participants:
(a) three sessions per week; (b) two sessions per week; and (c) one session per week. In
addition, participants P1, P2, and P4 attended three sessions per week, whereas P3 and P5
attended one session and two sessions per week, respectively. The outline of the study is
described in Figure 1.
Figure 1. The outline of the study, divided into four phases: (i) The preparatory phase, in which
participants were enrolled and screened to ensure their eligibility for the study. During this period,
their response to TSCS was tested and optimal stimulation settings were determined. The visual
analog scale was used to record their response to the stimulation. After completing a baseline as-
sessment over a period of 2 weeks, the participants received two phases of therapy, each lasting for
12 weeks, with two half-way assessments completed every 6 weeks. (ii) Training phase 1, transcuta-
neous electrical spinal cord stimulation (TSCS) with task-specific rehabilitation (TSR); (iii) training
phase 2, TSR alone; and (iv) the follow-up phase, during which no therapy was performed, and
assessments were repeated 6 weeks following the completion of the TSR training period.
2.3. Experimental protocol
Figure 1.
The outline of the study, divided into four phases: (i) The preparatory phase, in which par-
ticipants were enrolled and screened to ensure their eligibility for the study. During this period, their
response to TSCS was tested and optimal stimulation settings were determined. The visual analog
scale was used to record their response to the stimulation. After completing a baseline assessment
over a period of 2 weeks, the participants received two phases of therapy, each lasting for
12 weeks
,
with two half-way assessments completed every 6 weeks. (ii) Training phase 1, transcutaneous
electrical spinal cord stimulation (TSCS) with task-specific rehabilitation (TSR); (iii) training phase 2,
TSR alone; and (iv) the follow-up phase, during which no therapy was performed, and assessments
were repeated 6 weeks following the completion of the TSR training period.
2.3. Experimental Protocol
The 12th free rib was palpated and followed to identify the T11 and T12 vertebrae.
The iliac crest was palpated and followed to the posterior superior iliac spine, and then to
the L1 and L2 levels. Two stimulation electrodes were then attached between T11–T12 and
L1–L2 spinous processes in the middle, targeting the spinal cord (hereinafter called T11
and L1 electrodes), while another two referencing electrodes were placed above the iliac
crests bilaterally. For the active electrodes, we utilized a pair of self-adhesive electrodes
Biomedicines 2023,11, 34 4 of 18
with a size of 3.2 cm (ValuTrode, Axelgaard Manufacturing Co., Ltd., Fallbrook, CA, USA)
and another pair of internally linked 6.0
×
9.0 cm self-adhesive rectangle-shaped electrodes
(Guangzhou Jetta Electronic Medical Device Manufacturing Co., Ltd., Guangdong, China)
as ground electrodes. The T11 and L1 regions of the study participants were stimulated
using two specifically designed constant current stimulators (DS8R, Digitimer, UK). In order
to activate the stimulators, a function generator (AFG1022, manufactured by Tektronix,
Inc., Beaverton, OR, USA) was used to produce a burst of 10 kHz, which was transmitted
at a frequency of 20–30 Hz [
41
]. The burst configuration was raised to 10 biphasic pulses
(
1.06 ms
burst duration, henceforth referred to as 1 ms), and the pulse lengths of each cycle
were maintained constant at 50
µ
s for both devices. The previous study of [
41
] showed
that a shorter pulse of 0.5 ms was more effective in improving functional movements. In
addition, it has been reported that short pulse durations (0.05–0.4 ms) preferentially activate
motor axons, while the use of longer pulse durations (0.5–1 ms) activates sensory axons [
43
].
Therefore, the short pulse duration of 0.05 msec. was chosen in the current study.
To determine the optimal stimulation intensity, the investigators used the Visual
Analog Scale to measure the pain intensity. The participants were asked to experience
involuntary extension of the trunk (straightening of the spine), and asked to feel when
the trunk became more stable in the presence of the stimulation. Based on the individual
participant’s response, he/she experienced the best trunk stability and tolerable stimulation
intensity, which ranged between 95–115 milliamperes (mA), depending on each individual’s
response. The other stimulation settings (such as frequency, carrier frequency, and burst
configuration) were kept constant for all the participants throughout the experiment. The
stimulation intensity varied between individual participants, which was set based on their
response as described above. During every treatment session, the participant was asked
to experience trunk extension with increased trunk stability in sitting as the intensity was
gradually increased. A previous study demonstrated that stimulation of the rostral portion
of the lumbar enlargement (corresponding to the T11–T12 vertebral level) at a frequency of
30 Hz could specifically facilitate voluntary movements, whereas stimulation delivered over
the caudal area of the lumbar enlargement (corresponding to the L1–L2 vertebral level) at a
frequency of 15 Hz would facilitate tonic extensor activity specific for postural control [
12
].
The 10 kHz carrier frequency was found to be suitable for stimulating the spinal circuits of
both injured and uninjured individuals [
44
]. Therefore, the above-mentioned parameters
were adopted for the stimulation settings. The TSR included spinal mobility exercises such
as flexion, extension, lateral flexion, and rotation, as well as static and dynamic seated
balancing exercises. The participants were trained in a variety of experimental settings and
positions, ranging from sitting in a wheelchair to lying on a bed to lying on a floor mat,
with the help and supervision of a physiotherapist.
For combinational treatment, after the placement of stimulating electrodes, the stim-
ulation parameters were set and the intensity gradually increased until the individual’s
maximum tolerance was reached. Then the participant was asked to perform various
task-specific exercises. Each session lasted for 45–60 min, divided into three sub-sessions of
15–20 min each. A break was given after each sub-session, and the stimulation was turned
off during the rest period. The participants were stimulated throughout each session, except
during the break. Because all participants in the present study had complete tetraplegia,
TSCS+TSR was delivered in the first 12 weeks to determine whether the combinational
treatment could improve trunk and sitting functions. Another 12 weeks of TSR alone was
followed to determine whether the functional gains could be maintained.
2.4. Outcome Measures
The functional assessment was conducted using the following outcome measures:
(1) Modified Functional Reach Test (mFRT) to determine the functional reach distance;
(2) Trunk Control Test (TCT) to assess static and dynamic balance (3) Function in Sitting
Test (FIST) to measure functional sitting balance; and (4) International Standards for Neuro-
logical Classification of Spinal Cord Injury (ISNCSCI) to assess sensory and motor levels
Biomedicines 2023,11, 34 5 of 18
on both the right and left sides, the neurological degree of damage, and the completeness
of the injury. The mFRT [
45
], TCT [
46
], and FIST [
47
] have proven reliability and validity
for assessing people with SCI. The TCT comprises 0–24 points and FIST 0–56 points, where
a higher score indicates improvement in function. Additionally, the trunk kinematics
(i.e., range of motion, ROM) were assessed using a motion capture system (Vicon Nexus
2.5.1, Vicon Nexus TM, Vicon Motion Systems Ltd., Yarnton, UK) (ROM), while surface
electromyography (EMG) (Model DE-2.1; Delsys USA, Inc., Boston, MA, USA) was used
to the measure muscle activity of four pairs of trunk muscles (rectus abdominis, external
oblique, erector spinae, and latissimus dorsi).
2.5. Vicon Marker and EMG Electrode Placement
The placement of the Vicon reflective markers and EMG electrodes was performed
by an experienced physiotherapist. Specific bony landmarks were identified, and Vicon
markers were placed as follows (Figure 2A): anteriorly, at the acromia, sternum, right
and left anterior superior iliac spine (ASIS), and right and left patella; posteriorly, at the
cervical spinous process (C7), thoracic spinous process (T3, T8, T12), lumbar spinous
process (L2, L4), sacrum spinous process (S1), and right and left posterior superior iliac
spine (PSIS) [
12
,
48
]. The EMG electrodes over the rectus abdominis muscle were positioned
5 cm below the xiphoid process, while for the external oblique they were placed 5 cm
superior to the anterior superior iliac spine and 10 cm lateral to the umbilicus. Likewise,
electrodes for the latissimus dorsi were placed 2 cm inferior and lateral to the scapula’s
inferior angle, while those for the external oblique were placed 3 cm lateral to the L3 spinous
process [
49
]. The tested movements included trunk flexion, trunk extension, bilateral trunk
lateral flexion, and bilateral trunk rotation. Each movement was performed thrice, and
the best one was selected for data analysis. All assessments were conducted without
using TSCS. The placement of Vicon markers and a flexion movement performed in the
assessment are shown in Figure 2.
Biomedicines 2022, 10, x FOR PEER REVIEW 6 of 19
Figure 2. (A) Vicon markers positioned over the anatomical bony landmarks of a participant in a
normal straight sitting position; (B) a flexion movement performed during the assessment.
2.6. Data processing and analysis
The functional outcome scores were graphically and statistically analyzed through
GraphPad Prism version 9.0. Similarly, the kinesiologic and electrophysiologic data ac-
quired from Vicon and EMG were extracted, processed, and analyzed using MATLAB
(version 2016a, The MathWorks Inc., Natick, MA, USA). The sampling frequency was
2,000 Hz and the filters applied were 10 Hz to 40 Hz during data collection. Different
cutoff frequencies from 10 Hz to 50 Hz had been trialed, and 40 Hz was found to be the
best based on visual inspection. The descriptive analysis (mean ± SD) was calculated for
each phase. The trunk ROM angles were calculated by connecting selected markers at
specific landmarks (Figure 3). A Friedman one-way repeated measures ANOVA with
multiple comparisons was used to compare temporal differences in functional assessment
(mFRT, TCT, and FIST) and ROM among the baseline, post-TSCS+TSR, post-TSR, and the
final follow-up. The root mean square (RMS) value of EMG of each muscle was calculated
in microvolts (µV), and the above-mentioned repeated measures of ANOVA was used to
show significant improvements. In addition, Spearman correlation analysis was per-
formed to determine the correlation between these assessment parameters (mFRT, TCT,
FIST, EMG, and ROM). A p–value of 0.05 was set as the statistical level of significance.
Figure 3. The principle of data analysis process of Vicon data for trunk flexion movement: (i) The
erect sitting posture with knees in 90 degrees flexion and feet flat on the floor. For measuring flexion
angle (ii-a) segments C7, S1, and the midline connecting the left knee (LK) and right knee (RK), (ii-
b) an axis connecting the C7, S1 segments with a perpendicular line through the middle of the knees,
(ii-c) flexion movement was performed, and angle measured in degrees (θ). The participant was
allowed to take the required time to successfully and independently complete the movement.
Figure 2.
(
A
) Vicon markers positioned over the anatomical bony landmarks of a participant in a
normal straight sitting position; (B) a flexion movement performed during the assessment.
2.6. Data Processing and Analysis
The functional outcome scores were graphically and statistically analyzed through
GraphPad Prism version 9.0. Similarly, the kinesiologic and electrophysiologic data ac-
quired from Vicon and EMG were extracted, processed, and analyzed using MATLAB
Biomedicines 2023,11, 34 6 of 18
(version 2016a, The MathWorks Inc., Natick, MA, USA). The sampling frequency was
2000 Hz
and the filters applied were 10 Hz to 40 Hz during data collection. Different cutoff
frequencies from 10 Hz to 50 Hz had been trialed, and 40 Hz was found to be the best
based on visual inspection. The descriptive analysis (mean
±
SD) was calculated for each
phase. The trunk ROM angles were calculated by connecting selected markers at specific
landmarks (Figure 3). A Friedman one-way repeated measures ANOVA with multiple
comparisons was used to compare temporal differences in functional assessment (mFRT,
TCT, and FIST) and ROM among the baseline, post-TSCS+TSR, post-TSR, and the final
follow-up. The root mean square (RMS) value of EMG of each muscle was calculated in
microvolts (
µ
V), and the above-mentioned repeated measures of ANOVA was used to
show significant improvements. In addition, Spearman correlation analysis was performed
to determine the correlation between these assessment parameters (mFRT, TCT, FIST, EMG,
and ROM). A p–value of 0.05 was set as the statistical level of significance.
Biomedicines 2022, 10, x FOR PEER REVIEW 6 of 19
Figure 2. (A) Vicon markers positioned over the anatomical bony landmarks of a participant in a
normal straight sitting position; (B) a flexion movement performed during the assessment.
2.6. Data processing and analysis
The functional outcome scores were graphically and statistically analyzed through
GraphPad Prism version 9.0. Similarly, the kinesiologic and electrophysiologic data ac-
quired from Vicon and EMG were extracted, processed, and analyzed using MATLAB
(version 2016a, The MathWorks Inc., Natick, MA, USA). The sampling frequency was
2,000 Hz and the filters applied were 10 Hz to 40 Hz during data collection. Different
cutoff frequencies from 10 Hz to 50 Hz had been trialed, and 40 Hz was found to be the
best based on visual inspection. The descriptive analysis (mean ± SD) was calculated for
each phase. The trunk ROM angles were calculated by connecting selected markers at
specific landmarks (Figure 3). A Friedman one-way repeated measures ANOVA with
multiple comparisons was used to compare temporal differences in functional assessment
(mFRT, TCT, and FIST) and ROM among the baseline, post-TSCS+TSR, post-TSR, and the
final follow-up. The root mean square (RMS) value of EMG of each muscle was calculated
in microvolts (µV), and the above-mentioned repeated measures of ANOVA was used to
show significant improvements. In addition, Spearman correlation analysis was per-
formed to determine the correlation between these assessment parameters (mFRT, TCT,
FIST, EMG, and ROM). A p–value of 0.05 was set as the statistical level of significance.
Figure 3. The principle of data analysis process of Vicon data for trunk flexion movement: (i) The
erect sitting posture with knees in 90 degrees flexion and feet flat on the floor. For measuring flexion
angle (ii-a) segments C7, S1, and the midline connecting the left knee (LK) and right knee (RK), (ii-
b) an axis connecting the C7, S1 segments with a perpendicular line through the middle of the knees,
(ii-c) flexion movement was performed, and angle measured in degrees (θ). The participant was
allowed to take the required time to successfully and independently complete the movement.
Figure 3.
The principle of data analysis process of Vicon data for trunk flexion movement: (
i
) The
erect sitting posture with knees in 90 degrees flexion and feet flat on the floor. For measuring flexion
angle (
ii-a
) segments C7, S1, and the midline connecting the left knee (LK) and right knee (RK),
(
ii-b
) an axis connecting the C7, S1 segments with a perpendicular line through the middle of the
knees,
(ii-c) flexion
movement was performed, and angle measured in degrees (
θ
). The partici-
pant was allowed to take the required time to successfully and independently complete the move-
ment. Similarly, measurements for other movements are presented in the Supplementary Materials
(Supplementary Figure S1).
3. Results
3.1. Combinational Treatment Initiated Functional Improvements in Reaching, Trunk Control, and
Sitting Balance
As shown in Figure 4, the overall (mean
±
SD) forward reach distance (FRD) was
2.0 ±1.6 cm
at the baseline, which increased by 10.3
±
4.5 cm after TSCS+TSR (to
12.3 ±6.1 cm
),
and further slightly raised by 1.4
±
0.7 cm during TSR (to 13.7
±
6.8 cm), which was main-
tained throughout the follow-up period in the absence of any intervention (to 13.4
±
6.9 cm).
Statistical analysis showed significant improvements between the baseline and TSCS+TSR
(p= 0.025), TSR (p= 0.024), and follow-up (p= 0.026), respectively. For right lateral reach dis-
tance, the baseline mean
±
SD was 0.9
±
0.7 cm, which increased by 3.7
±
1.8 cm after the
introduction of TSCS+TSR (to 4.6
±
2.6 cm), followed by a further increment of
1.2 ±0.5 cm
during the TSR training period (to 5.8
±
3.0 cm), and then reduced to
5.7 ±3.0 cm
at the
final follow-up. Significant improvements were found between the baseline and TSCS+TSR
(p= 0.037), TSR (p= 0.029), and follow-up (p= 0.030), respectively. At the baseline, the left
lateral reach distance was 1.0
±
0.8 cm, which increased to 4.0
±
1.7 cm after TSCS+TSR,
and further increased to 4.5
±
1.96 cm throughout TSR, and then remained constant during
the follow-up period (4.5
±
2.0 cm). Significant improvements were observed between
the results of the baseline and TSCS+TSR (p= 0.014), TSR (p= 0.016), and follow-up
(p= 0.017), respectively.
As demonstrated in Figure 5A, the overall mean TCT score was 3.0
±
0.7 at the baseline,
which significantly increased to 11.6
±
3.4 after TSCS+TSR administration, which increased
further by 1.4
±
1.1 during TSR to 13.0
±
4.5, followed by a slight reduction to 12.8
±
4.1 at
the follow-up period. All these values of TCT were significantly greater than the baseline
values (p< 0.01). Likewise, the overall mean FIST score (Figure 5B) was 12.6
±
4.5 at the
baseline, which underwent the greatest increase, by 29.0
±
8.8, after TSCS+TSR, which
Biomedicines 2023,11, 34 7 of 18
further rose to 31.0
±
9.7 during TSR, with a minor decrease of 0.4
±
1.3 at the follow-up
period (to 30.6
±
8.4). All the FIST scores at the follow-ups were significantly larger than
the baseline values (p< 0.01). However, there was no significant difference in the TCT or
FIST scores between TSCS+TSR and TSR, between TSCS+TSR and follow-up, or between
TSR and follow-up.
Biomedicines 2022, 10, x FOR PEER REVIEW 7 of 19
Similarly, measurements for other movements are presented in the Supplementary Materials (Sup-
plementary Figure 1).
3. Results
3.1. Combinational treatment initiated functional improvements in reaching, trunk control, and
sitting balance
As shown in Figure 4, the overall (mean ± SD) forward reach distance (FRD) was 2.0
± 1.6 cm at the baseline, which increased by 10.3 ± 4.5 cm after TSCS+TSR (to 12.3 ± 6.1
cm), and further slightly raised by 1.4 ± 0.7 cm during TSR (to 13.7 ± 6.8 cm), which was
maintained throughout the follow-up period in the absence of any intervention (to 13.4 ±
6.9 cm). Statistical analysis showed significant improvements between the baseline and
TSCS+TSR (p = 0.025), TSR (p = 0.024), and follow-up (p = 0.026), respectively. For right
lateral reach distance, the baseline mean ± SD was 0.9 ± 0.7 cm, which increased by 3.7 ±
1.8 cm after the introduction of TSCS+TSR (to 4.6 ± 2.6 cm), followed by a further incre-
ment of 1.2 ± 0.5 cm during the TSR training period (to 5.8 ± 3.0 cm), and then reduced to
5.7 ± 3.0 cm at the final follow-up. Significant improvements were found between the
baseline and TSCS+TSR (p = 0.037), TSR (p = 0.029), and follow-up (p = 0.030), respectively.
At the baseline, the left lateral reach distance was 1.0 ± 0.8 cm, which increased to 4.0 ± 1.7
cm after TSCS+TSR, and further increased to 4.5 ± 1.96 cm throughout TSR, and then re-
mained constant during the follow-up period (4.5 ± 2.0 cm). Significant improvements
were observed between the results of the baseline and TSCS+TSR (p = 0.014), TSR (p =
0.016), and follow-up (p = 0.017), respectively.
As demonstrated in Figure 5A, the overall mean TCT score was 3.0 ± 0.7 at the base-
line, which significantly increased to 11.6 ± 3.4 after TSCS+TSR administration, which in-
creased further by 1.4 ± 1.1 during TSR to 13.0 ± 4.5, followed by a slight reduction to 12.8
± 4.1 at the follow-up period. All these values of TCT were significantly greater than the
baseline values (p < 0.01). Likewise, the overall mean FIST score (Figure 5B) was 12.6 ± 4.5
at the baseline, which underwent the greatest increase, by 29.0 ± 8.8, after TSCS+TSR,
which further rose to 31.0 ± 9.7 during TSR, with a minor decrease of 0.4 ± 1.3 at the follow-
up period (to 30.6 ± 8.4). All the FIST scores at the follow-ups were significantly larger
than the baseline values (p < 0.01). However, there was no significant difference in the TCT
or FIST scores between TSCS+TSR and TSR, between TSCS+TSR and follow-up, or be-
tween TSR and follow-up.
Figure 4. The increased functional scores of mFRT measured from the baseline. Statistical analysis
was conducted between the baseline with TSCS+TSR, TSR, and follow-up. (A) Forward reach dis-
tance, (B) right lateral reach distance, and (C) left lateral reach distance, respectively, measured for
each participant during the study. mFRT, Modified Functional Reach Test; TSCS, transcutaneous
electrical spinal cord stimulation; TSR, task-specific rehabilitation; F/U, follow-up; * p < 0.05, ** p <
0.01, all in comparison to the baseline value.
Figure 4.
The increased functional scores of mFRT measured from the baseline. Statistical analysis
was conducted between the baseline with TSCS+TSR, TSR, and follow-up. (
A
) Forward reach distance,
(
B
) right lateral reach distance, and (
C
) left lateral reach distance, respectively, measured for each
participant during the study. mFRT, Modified Functional Reach Test; TSCS, transcutaneous electrical
spinal cord stimulation; TSR, task-specific rehabilitation; F/U, follow-up; * p< 0.05, ** p< 0.01, all in
comparison to the baseline value.
Biomedicines 2022, 10, x FOR PEER REVIEW 8 of 19
Figure 5. The increased functional scores of (A) TCT (0–24 points) and (B) FIST (0–56 points) meas-
ured from the baseline for each participant during the study. Statistical analysis was conducted be-
tween the baseline with TSCS+TSR, TSR, and follow-up. TCT, Trunk Control Test; FIST, Function in
Sitting Test; TSCS, transcutaneous electrical spinal cord stimulation; TSR, task-specific rehabilita-
tion; F/U, follow-up; ⁎ p < 0.05, ** p < 0.01, all in comparison to the baseline value.
3.2. Increased trunk range of motion after TSCS+TSR treatment
Figure 6 shows that trunk flexion, extension, left lateral flexion, and bilateral rotation
ROM at TSCS+TSR, TSR, and the final follow-up were significantly higher than the re-
spective baseline values. However, the right trunk lateral flexion underwent significant
improvement in ROM only after TSCS+TSR. Specifically, the overall trunk flexion ROM
was 12.2° ± 4.7° at the baseline, which significantly increased to 23.1° ± 9.0° after
TSCS+TSR, followed by a 3.7° ± 0.4° reduction in motion after TSR (to 19.4° ± 9.37°), which
further decreased by 0.3° ± 1.7° to 19.1° ± 7.7° at the final follow-up. The trunk extension
ROM at the baseline was 5.7° ± 2.0°, which was significantly increased to 12.4° ± 4.5° after
TSCS+TSR, then back to 10.0° ± 4.0°, and then increased to 10.4° ± 3.9° at the follow-up.
Likewise, the trunk right lateral flexion was 5.8° ± 5.6° at the baseline, which significantly
increased to 9.1° ± 5.4° after TSCS+TSR, followed by a decrease to 8.4° ± 5.3° after TSR, and
then to 8.7° ± 5.1° at the follow-up. At the baseline, the left lateral flexion ROM increased
from 6.0° ± 2.8° to 9.8° ± 2.9° after TSCS+TSR, and then decreased to 8.8° ± 2.3° after TSR,
and further dropped to 8.2° ± 2.6° at the follow-up. The right rotation increased from 1.7°
± 2.3° at the baseline to 4.5° ± 2.7° after the TSCS+TSR, then dropped to 3.0° ± 2.2° after
TSR, followed by an increase to 4.1° ± 1.9° at the follow-up. The mean ± SD for left rotation
was 18.4° ± 10.1° at the baseline, which increased by 21.2° ± 3.3° to 39.6° ± 13.4° after
TSCS+TSR, followed by a decrease of 4.3° ± 0.2° to 35.3° ± 13.2° after TSR, and further
reduction to 31.8° ± 8.2° at the follow-up. However, no significant difference was observed
in any trunk ROMs between TSCS+TSR and TSR, between TSCS+TSR and follow-up, or
between TSR and follow-up.
Figure 5.
The increased functional scores of (
A
) TCT (0–24 points) and (
B
) FIST (0–56 points) measured
from the baseline for each participant during the study. Statistical analysis was conducted between
the baseline with TSCS+TSR, TSR, and follow-up. TCT, Trunk Control Test; FIST, Function in Sitting
Test; TSCS, transcutaneous electrical spinal cord stimulation; TSR, task-specific rehabilitation; F/U,
follow-up; * p< 0.05, ** p< 0.01, all in comparison to the baseline value.
3.2. Increased Trunk Range of Motion after TSCS+TSR Treatment
Figure 6shows that trunk flexion, extension, left lateral flexion, and bilateral rotation
ROM at TSCS+TSR, TSR, and the final follow-up were significantly higher than the re-
spective baseline values. However, the right trunk lateral flexion underwent significant
improvement in ROM only after TSCS+TSR. Specifically, the overall trunk flexion ROM was
12.2
◦±
4.7
◦
at the baseline, which significantly increased to 23.1
◦±
9.0
◦
after TSCS+TSR,
followed by a 3.7
◦±
0.4
◦
reduction in motion after TSR (to 19.4
◦±
9.37
◦
), which further de-
creased by 0.3
◦±
1.7
◦
to 19.1
◦±
7.7
◦
at the final follow-up. The trunk extension ROM at the
baseline was 5.7
◦±
2.0
◦
, which was significantly increased to 12.4
◦±
4.5
◦
after TSCS+TSR,
Biomedicines 2023,11, 34 8 of 18
then back to 10.0
◦±
4.0
◦
, and then increased to 10.4
◦±
3.9
◦
at the follow-up. Likewise, the
trunk right lateral flexion was 5.8
◦±
5.6
◦
at the baseline, which significantly increased to
9.1
◦±
5.4
◦
after TSCS+TSR, followed by a decrease to
8.4◦±5.3◦
after TSR, and then to
8.7
◦±
5.1
◦
at the follow-up. At the baseline, the left lateral flexion ROM increased from
6.0◦±2.8◦
to 9.8
◦±
2.9
◦
after TSCS+TSR, and then decreased to
8.8◦±2.3◦
after TSR,
and further dropped to 8.2
◦±
2.6
◦
at the follow-up. The right rotation increased from
1.7◦±2.3◦
at the baseline to 4.5
◦±
2.7
◦
after the TSCS+TSR, then dropped to
3.0◦±2.2◦
after TSR, followed by an increase to 4.1
◦±
1.9
◦
at the follow-up. The mean
±
SD for left
rotation was 18.4
◦±
10.1
◦
at the baseline, which increased by 21.2
◦±
3.3
◦
to
39.6◦±13.4◦
after TSCS+TSR, followed by a decrease of 4.3
◦±
0.2
◦
to 35.3
◦±
13.2
◦
after TSR, and further
reduction to 31.8
◦±
8.2
◦
at the follow-up. However, no significant difference was observed
in any trunk ROMs between TSCS+TSR and TSR, between TSCS+TSR and follow-up, or
between TSR and follow-up.
Biomedicines 2022, 10, x FOR PEER REVIEW 9 of 19
Figure 6. The trunk range of motion measured with Vicon for each participant during the study.
Statistical analysis was conducted between the baseline with TSCS+TSR, TSR and follow-up. (A)
Flexion, (B) extension, (C) right lateral flexion, (D) left lateral flexion, (E) right rotation, and (F) left
rotation, respectively. TSCS, transcutaneous electrical spinal cord stimulation; TSR, task-specific re-
habilitation; F/U, follow-up; * p < 0.05, ** p < 0.01, *** p < 0.001, non-significant (ns) p > 0.05, all in
comparison to the baseline value.
3.3. Elevated electromyographic response of the trunk muscles
The right latissimus dorsi (Rt LD) and left latissimus dorsi (Lt LD), as well as the right
erector spinae (Rt ES) and left erector spinae (Lt ES) during extension, and the right exter-
nal oblique (Rt EO) and left external oblique (Lt EO) during left rotation, exhibited the
significantly highest EMG amplitude at TSCS+TSR and TSR than the respective baseline
values in comparison to other trunk ROMs, i.e., flexion, bilateral lateral flexion, and right
rotation. However, there was no significant difference observed in the EMG response at
follow-up for Rt LD or Lt LD during extension, as well as for Rt EO and Lt EO for right
rotation and left rotation, and Rt ES during left lateral flexion, respectively, compared with
the baseline values (Table 2). The EMG responses of other trunk ROMs (excluding exten-
sion and left rotation) are presented in the Supplementary Materials (Supplementary Ta-
ble 1). Specifically, the EMG response for extension was 2.20 ± 1.60 µV for Rt LD and 2.57
± 1.81 µV for Lt LD at the baseline, which was significantly increased to 8.86 ± 6.04 µV (Rt
LD) and 9.94 ± 6.70 µV (Lt LD), respectively, after TSCS+TSR, which further reduced to
5.01 ± 3.71 µV (Rt LD) and 5.70 ± 4.86 µV (Lt LD) after TSR. In addition, the EMG values
remained almost unchanged after the follow-up for Rt LD (5.02 ± 3.03 µV) and Lt LD (6.07
± 4.45 µV) in comparison with the baseline value, similar for the subsequent descriptions.
Likewise, the EMG values during extension were 1.62 ± 0.95 µV (Rt ES) and 1.79 ± 1.25 µV
(Lt ES) at the baseline, and increased to 6.93 ± 6.32 µV (Rt ES) and 7.53 ± 5.47 µV (Lt ES),
respectively, after TSCS+TSR, followed by a further decrement to 4.11 ± 2.68 µV (Rt ES)
and 4.57 ± 3.02 µV (Lt ES) after TSR. Additionally, the EMG amplitude remained almost
unchanged after the follow-up for Rt ES (4.19 ± 2.58 µV) and Lt ES (4.69 ± 2.97 µV). For
left rotation, the EMG response was 1.55 ± 0.93 µV for Rt EO and 2.07 ± 1.17 µV for Lt EO
at the baseline, which significantly increased to 6.86 ± 3.94 µV (Rt EO) and 13.47 ± 7.49 µV
(Lt EO) after TSCS+TSR, respectively, and further reduced to 6.06 ± 3.38 µV (Rt EO) and
12.06 ± 6.73 µV (Lt EO) after TSR, which remained almost consistent after the follow-up
Figure 6.
The trunk range of motion measured with Vicon for each participant during the study. Sta-
tistical analysis was conducted between the baseline with TSCS+TSR, TSR and follow-up. (
A
) Flexion,
(
B
) extension, (
C
) right lateral flexion, (
D
) left lateral flexion, (
E
) right rotation, and (
F
) left rotation,
respectively. TSCS, transcutaneous electrical spinal cord stimulation; TSR, task-specific rehabilitation;
F/U, follow-up; * p< 0.05, ** p< 0.01, *** p< 0.001, non-significant (ns) p> 0.05, all in comparison to
the baseline value.
3.3. Elevated Electromyographic Response of the Trunk Muscles
The right latissimus dorsi (Rt LD) and left latissimus dorsi (Lt LD), as well as the right
erector spinae (Rt ES) and left erector spinae (Lt ES) during extension, and the right external
oblique (Rt EO) and left external oblique (Lt EO) during left rotation, exhibited the signifi-
cantly highest EMG amplitude at TSCS+TSR and TSR than the respective baseline values
in comparison to other trunk ROMs, i.e., flexion, bilateral lateral flexion, and right rotation.
However, there was no significant difference observed in the EMG response at follow-up for
Rt LD or Lt LD during extension, as well as for Rt EO and Lt EO for right rotation and left ro-
tation, and Rt ES during left lateral flexion, respectively, compared with the baseline values
(Table 2). The EMG responses of other trunk ROMs (excluding extension and left rotation)
are presented in the Supplementary Materials (
Supplementary Table S1
). Specifically, the
Biomedicines 2023,11, 34 9 of 18
EMG response for extension was 2.20
±
1.60
µ
V for Rt LD and
2.57 ±1.81 µV
for Lt LD at
the baseline, which was significantly increased to 8.86
±
6.04
µ
V (Rt LD) and
9.94 ±6.70 µV
(Lt LD), respectively, after TSCS+TSR, which further reduced to
5.01 ±3.71 µV
(Rt LD) and
5.70
±
4.86
µ
V (Lt LD) after TSR. In addition, the EMG values remained almost unchanged
after the follow-up for Rt LD (5.02
±
3.03
µ
V) and Lt LD (6.07
±
4.45
µ
V) in comparison
with the baseline value, similar for the subsequent descriptions. Likewise, the EMG values
during extension were 1.62
±
0.95
µ
V (Rt ES) and 1.79
±
1.25
µ
V (Lt ES) at the baseline,
and increased to 6.93
±
6.32
µ
V (Rt ES) and 7.53
±
5.47
µ
V (Lt ES), respectively, after
TSCS+TSR, followed by a further decrement to 4.11
±
2.68
µ
V (Rt ES) and
4.57 ±3.02 µV
(Lt ES) after TSR. Additionally, the EMG amplitude remained almost unchanged after
the follow-up for Rt ES (4.19
±
2.58
µ
V) and Lt ES (4.69
±
2.97
µ
V). For left rotation, the
EMG response was 1.55
±
0.93
µ
V for Rt EO and 2.07
±
1.17
µ
V for Lt EO at the baseline,
which significantly increased to 6.86
±
3.94
µ
V (Rt EO) and 13.47
±
7.49
µ
V (Lt EO) after
TSCS+TSR, respectively, and further reduced to 6.06
±
3.38
µ
V (Rt EO) and
12.06 ±6.73 µV
(Lt EO) after TSR, which remained almost consistent after the follow-up period for Rt EO
(5.84
±
3.40
µ
V) and Lt EO (11.19
±
6.23
µ
V), respectively. Furthermore, no significant
difference was observed in EMG amplitudes for any trunk ROMs between TSCS+TSR and
TSR, between TSCS+TSR and follow-up, or between TSR and follow-up.
Table 2. The responses recorded from trunk muscles measured through EMG.
(A)
Study Timeline
Extension
Rt. ES Lt. ES Rt. LD Lt. LD
Mean ±SD p-Value Mean ±SD p-Value Mean ±SD p-Value Mean ±SD p-Value
Baseline 1.62 ±0.95 - 1.79 ±1.25 - 2.20 ±1.60 - 2.57 ±1.81 -
TSCS+TSR 6.93 ±6.32 * 7.53 ±5.47 * 8.86 ±6.04 *** 9.94 ±6.70 *
TSR 4.11 ±2.68 *** 4.57 ±3.02 *** 5.01 ±3.71 *** 5.70 ±4.86 *
Follow-up 4.19 ±2.58 *** 4.69 ±2.97 *** 5.02 ±3.03 ns 6.07 ±4.45 ***
(B)
Study timeline
Left rotation
Rt. EO Lt. EO
Mean ±SD p-Value Mean ±SD p-Value
Baseline 1.55 ±0.93 - 2.07 ±1.17 -
TSCS+TSR 6.86 ±3.94 * 13.47 ±7.49 *
TSR 6.06 ±3.38 * 12.06 ±6.73 *
Follow-up 5.84 ±3.40 * 11.19 ±6.23 *
LD, latissimus dorsi; ES, erector spinae; EO, external oblique; Rt, right; Lt, left; Lat, lateral; SD, standard deviation;
TSCS, transcutaneous electrical spinal cord stimulation; TSR, task-specific rehabilitation; * p< 0.05, *** p< 0.001,
non-significant (ns) p> 0.05, all in comparison with the baseline value.
3.4. Improvements of Trunk Control and Function in Sitting after Combinational Treatment
The functional improvements of trunk control and function in sitting were correlated
with each other (Figure 7), demonstrating a strong positive correlation between the TCT
and FIST after TSCS+TSR (R
2
= 0.916, p= 0.001). Similarly, the TCT and mFRT (R
2
= 0.774,
p= 0.017), TCT and EMG (R
2
= 0.743, p= 0.009), EMG and ROM (R
2
= 0.626, p= 0.004), and
FIST and EMG (R
2
= 0.746, p= 0.0125), respectively, exhibited mild positive correlations
after the TSCS+TSR. Conversely, FIST and mFRT (R
2
= 0.305, p= 0.009), EMG and mFRT
(R
2
= 0.233, p= 0.047), and TSR and TSCS+TSR (R
2
= 0.217, p= 0.094) displayed weak
correlations following TSCS+TSR.
3.5. Treatment Effect on Sensorimotor Recovery
The ISNCSCI underwent some changes in the sensorimotor scores, but the neurological
level of injury and AIS remained unchanged (Supplementary Table S2). Figure 8shows that
for ISNCSCI, a participant (P1) revealed an increase of 8 points and 18 points in response
to light touch and pinprick sensation (68/64 to 76/82), respectively, while P3 showed
Biomedicines 2023,11, 34 10 of 18
a 4-point elevation in response to pinprick sensation (64/64 to 64/68) after TSCS+TSR.
Moreover, throughout TSR and the follow-up period, the increased motor and sensory
scores remained unchanged. However, over the entire study period, there was no change
in ISNCSCI scores for P2, P4, or P5.
Biomedicines 2022, 10, x FOR PEER REVIEW 10 of 19
period for Rt EO (5.84 ± 3.40 µV) and Lt EO (11.19 ± 6.23 µV), respectively. Furthermore,
no significant difference was observed in EMG amplitudes for any trunk ROMs between
TSCS+TSR and TSR, between TSCS+TSR and follow-up, or between TSR and follow-up.
Table 2. The responses recorded from trunk muscles measured through EMG.
Study time-
line
Extension
Rt. ES
Lt. ES
Rt. LD
Lt. LD
Mean ± SD
p-value
Mean ± SD
p-value
Mean ± SD
p-value
Mean ± SD
p-value
Baseline
1.62 ± 0.95
-
1.79 ± 1.25
-
2.20 ± 1.60
-
2.57 ± 1.81
-
TSCS+TSR
6.93 ± 6.32
*
7.53 ± 5.47
*
8.86 ± 6.04
***
9.94 ± 6.70
*
TSR
4.11 ± 2.68
***
4.57 ± 3.02
***
5.01 ± 3.71
***
5.70 ± 4.86
*
Follow-up
4.19 ± 2.58
***
4.69 ± 2.97
***
5.02 ± 3.03
ns
6.07 ± 4.45
***
Study timeline
Left rotation
Rt. EO
Lt. EO
Mean ± SD
p-value
Mean ± SD
p-value
Baseline
1.55 ± 0.93
-
2.07 ± 1.17
-
TSCS+TSR
6.86 ± 3.94
*
13.47 ± 7.49
*
TSR
6.06 ± 3.38
*
12.06 ± 6.73
*
Follow-up
5.84 ± 3.40
*
11.19 ± 6.23
*
LD, latissimus dorsi; ES, erector spinae; EO, external oblique; Rt, right; Lt, left; Lat, lateral; SD, stand-
ard deviation; TSCS, transcutaneous electrical spinal cord stimulation; TSR, task-specific rehabilita-
tion; ⁎ p < 0.05, ⁎⁎ p < 0.01, ⁎⁎⁎ p < 0.001, non-significant (ns) p > 0.05, all in comparison with the
baseline value.
3.4. Improvements of trunk control and function in sitting after combinational treatment
The functional improvements of trunk control and function in sitting were correlated
with each other (Figure 7), demonstrating a strong positive correlation between the TCT
and FIST after TSCS+TSR (R2 = 0.916, p = 0.001). Similarly, the TCT and mFRT (R2 = 0.774,
p = 0.017), TCT and EMG (R2 = 0.743, p = 0.009), EMG and ROM (R2 = 0.626, p = 0.004), and
FIST and EMG (R2 = 0.746, p = 0.0125), respectively, exhibited mild positive correlations
after the TSCS+TSR. Conversely, FIST and mFRT (R2 = 0.305, p = 0.009), EMG and mFRT
(R2 = 0.233, p = 0.047), and TSR and TSCS+TSR (R2 = 0.217, p = 0.094) displayed weak cor-
relations following TSCS+TSR.
Figure 7. The correlation between the functional improvements regarding the Trunk Control Test
(TCT) and Function in Sitting Test (FIST).
(A)
(B)
Figure 7.
The correlation between the functional improvements regarding the Trunk Control Test
(TCT) and Function in Sitting Test (FIST).
Biomedicines 2022, 10, x FOR PEER REVIEW 11 of 19
3.5. Treatment effect on sensorimotor recovery
The ISNCSCI underwent some changes in the sensorimotor scores, but the neurolog-
ical level of injury and AIS remained unchanged (Supplementary Table 2). Figure 8 shows
that for ISNCSCI, a participant (P1) revealed an increase of 8 points and 18 points in re-
sponse to light touch and pinprick sensation (68/64 to 76/82), respectively, while P3
showed a 4-point elevation in response to pinprick sensation (64/64 to 64/68) after
TSCS+TSR. Moreover, throughout TSR and the follow-up period, the increased motor and
sensory scores remained unchanged. However, over the entire study period, there was no
change in ISNCSCI scores for P2, P4, or P5.
Figure 8. The International Standards for Neurological Classification of Spinal Cord Injury
(ISNCSCI) scores with light touch and pinprick sensory sub-scores obtained in this study.
3.6. The impact of treatment frequency on functional outcome
The frequency of treatment delivered to the study participants is illustrated in Figure
9, where P1, P2, and P4 received the intervention thrice per week with C6-, C7-, and C5-
level cervical cord injuries, respectively. P3, who attended once a week, had a SCI at the
C5 level. Furthermore, P5, who participated twice a week, had a C4 SCI. P1 and P2 im-
proved the most in regard to mFRT (forward reach), TCT, and FIST. Additionally, P4, who
attended the same treatment sessions as P1 and P2, presented with minimal improvement,
relative to P1 and P2, in comparison to the increased functional scores. Interestingly, P3
scored better than P5 in terms of the above functional outcome measures. However, their
injury levels differed from each other. Additionally, P3, who received fewer weekly ses-
sions, improved more than P4, although they had the same injury level. Furthermore, P1
and P2 were able to independently perform transfers from their wheelchairs to their beds
and vice versa, using a sliding board, under the supervision and assistance of caregivers.
They also reported feeling more secure and having less fear of falling.
Figure 8.
The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)
scores with light touch and pinprick sensory sub-scores obtained in this study.
3.6. The Impact of Treatment Frequency on Functional Outcome
The frequency of treatment delivered to the study participants is illustrated in Figure 9,
where P1, P2, and P4 received the intervention thrice per week with C6-, C7-, and C5-level
cervical cord injuries, respectively. P3, who attended once a week, had a SCI at the C5 level.
Furthermore, P5, who participated twice a week, had a C4 SCI. P1 and P2 improved the
most in regard to mFRT (forward reach), TCT, and FIST. Additionally, P4, who attended
the same treatment sessions as P1 and P2, presented with minimal improvement, relative
to P1 and P2, in comparison to the increased functional scores. Interestingly, P3 scored
better than P5 in terms of the above functional outcome measures. However, their injury
levels differed from each other. Additionally, P3, who received fewer weekly sessions,
Biomedicines 2023,11, 34 11 of 18
improved more than P4, although they had the same injury level. Furthermore, P1 and P2
were able to independently perform transfers from their wheelchairs to their beds and vice
versa, using a sliding board, under the supervision and assistance of caregivers. They also
reported feeling more secure and having less fear of falling.
Biomedicines 2022, 10, x FOR PEER REVIEW 12 of 19
Figure 9. The increased functional scores based on treatment frequency obtained by the participants
(cervical cord injury level: C4, C5, C6, C7) during the functional assessment of Modified Functional
Reach Test (mFRT), Trunk Control Test (TCT), and Function in Sitting Test (FIST). A higher score
indicates an improvement in function.
4. Discussion
The present investigation examined the effects of combining TSCS and TSR treatment
on trunk control and sitting function in individuals with complete cervical SCI. The study
demonstrates that the combined intervention (TSCS+TSR) could improve trunk stability
along with static and dynamic sitting balance in people with complete tetraplegia. The
results substantiate that all participants trunk control and sitting function progressively
improved during TSCS+TSR, no matter whether they received one, two, or three treat-
ment sessions per week with an injury at C4, C5, C6, or C7 level. In addition, functional
improvements were maintained throughout the subsequent TSR and follow-up periods,
demonstrating positive long-term treatment effects. Our findings highlight that trunk re-
covery is possible even in people with chronic complete cervical SCI, and the functional
gains can be achieved using TSCS+TSR.
4.1. Functional reaching ability in sitting
TSCS+TSR can enhance the forward reaching ability of people with SCI, which is es-
sential in order for wheelchair users to accomplish everyday tasks [50]. The present study
reported an increase in FRD (10.3 ± 4.5 cm) after TSCS+TSR, which enabled the partici-
pants to reach objects placed in front of them. Additionally, the lateral reach distances also
increased to assist the maintenance of trunk balance. Prior research demonstrated that
implanted electrical stimulation in SCI individuals with thoracic-level injuries exhibited
improved FRD (5.5 ± 6.6 cm) in sitting [8]. Another study revealed that people with tho-
racic SCI receiving epidural stimulation displayed increased FRD, while lateral reach
lengths remained unchanged [51]. The current results support these findings; addition-
ally, the lateral reach distances also significantly increased. It has been previously revealed
that those with higher FRD exhibited greater sitting control and postural stability [50].
Likewise, the current investigation indicates that participants with increased FRD demon-
strated improved trunk and sitting function. This may assist clinicians to individualize
exercise regimens to improve the wheelchair-based ADL of people with SCI based on their
abilities [45]. Prior research showed that “off and on” epidural spinal cord stimulation
settings affected the reach lengths, where the individuals reaching abilities returned to
normal when the stimulator was switched off, but the FRD increased while the stimulator
was on [51]. However, the present study shows that the increased reaching distances
Figure 9.
The increased functional scores based on treatment frequency obtained by the participants
(cervical cord injury level: C4, C5, C6, C7) during the functional assessment of Modified Functional
Reach Test (mFRT), Trunk Control Test (TCT), and Function in Sitting Test (FIST). A higher score
indicates an improvement in function.
4. Discussion
The present investigation examined the effects of combining TSCS and TSR treatment
on trunk control and sitting function in individuals with complete cervical SCI. The study
demonstrates that the combined intervention (TSCS+TSR) could improve trunk stability
along with static and dynamic sitting balance in people with complete tetraplegia. The
results substantiate that all participants trunk control and sitting function progressively
improved during TSCS+TSR, no matter whether they received one, two, or three treatment
sessions per week with an injury at C4, C5, C6, or C7 level. In addition, functional
improvements were maintained throughout the subsequent TSR and follow-up periods,
demonstrating positive long-term treatment effects. Our findings highlight that trunk
recovery is possible even in people with chronic complete cervical SCI, and the functional
gains can be achieved using TSCS+TSR.
4.1. Functional Reaching Ability in Sitting
TSCS+TSR can enhance the forward reaching ability of people with SCI, which is
essential in order for wheelchair users to accomplish everyday tasks [
50
]. The present
study reported an increase in FRD (10.3
±
4.5 cm) after TSCS+TSR, which enabled the
participants to reach objects placed in front of them. Additionally, the lateral reach distances
also increased to assist the maintenance of trunk balance. Prior research demonstrated that
implanted electrical stimulation in SCI individuals with thoracic-level injuries exhibited
improved FRD (5.5
±
6.6 cm) in sitting [
8
]. Another study revealed that people with
thoracic SCI receiving epidural stimulation displayed increased FRD, while lateral reach
lengths remained unchanged [
51
]. The current results support these findings; additionally,
the lateral reach distances also significantly increased. It has been previously revealed
that those with higher FRD exhibited greater sitting control and postural stability [
50
].
Likewise, the current investigation indicates that participants with increased FRD demon-
strated improved trunk and sitting function. This may assist clinicians to individualize
Biomedicines 2023,11, 34 12 of 18
exercise regimens to improve the wheelchair-based ADL of people with SCI based on their
abilities [
45
]. Prior research showed that “off and on” epidural spinal cord stimulation settings
affected the reach lengths, where the individuals reaching abilities returned to normal when
the stimulator was switched off, but the FRD increased while the stimulator was on [
51
].
However, the present study shows that the increased reaching distances following TSCS+TSR
were maintained even in the absence of further stimulation during the follow-up period.
4.2. Trunk Control and Seated Postural Stability
While falls have been reported in up to 75% of people with SCI, lack of trunk control is
the predominant reason for falls in these individuals [
52
]. As trunk stability is a significant
contributor to falls, rehabilitation programs should aim to increase sitting balance [
52
].
Interestingly, the present results indicate that TSCS+TSR could improve static trunk control
in all participants, with the ability to sit independently with or without support of the upper
limbs, while dynamic trunk control was restored in two participants. Therefore, improved
trunk control could reduce the risk of falling from a wheelchair. Although a chest strap
is beneficial for stabilizing the trunk of individuals with paraplegia in a wheelchair, it is
only a temporary external method [
53
]. Given that TSCS+TSR could improve independent
sitting and trunk function with increased FRD in people with tetraplegia, this method may
complement or even replace traditional techniques such as chest straps, seating adjustments,
and other manual support. The promising results suggest that this intervention may
have the potential to help individuals with tetraplegia to turn in bed, which is critical in
preventing the development of pressure injuries.
Sitting stability is essential for the functioning of those who cannot stand. The inability
to complete transfer tasks may limit an individual’s independence in a wheelchair, thereby
interfering with ADL [
54
]. It was thought that a decrease or increase in trunk strength might
predict sitting balance in people with SCI, although this premise remains inconclusive [
10
].
Our outcomes show that individuals with a lower cervical SCI displayed greater recovery
in seated function, trunk strength, and sitting stability than those with a higher cervical SCI.
A recent study using TSCS also showed an immediate effect on the upright sitting ability of
SCI individuals that improved trunk stability and maintained sitting balance [
12
]. However,
participants in that study had less severe injuries, and the level of injury was lower than that of
our participants. That said, three of our participants reported improvements in their ability to
propel their wheelchairs. They switched from motorized wheelchairs to manual wheelchairs.
4.3. Trunk Muscle EMG Response and Range of Motion
TSCS can increase trunk muscle activity and active ROM. Individuals with SCI above
the L1 level experience trunk instability due to impaired trunk musculature [
55
]. A recent
study showed that TSCS significantly increased the EMG response of the ES, RA, and EO
muscles, which promoted trunk stability and sitting balance in people with chronic SCI [
12
].
These findings concur with those of the current study. Although invasive functional elec-
trical stimulation (FES) together with therapeutic exercise increased trunk muscle tone
and improved dynamic sitting stability, the effects reverted without FES [
56
]. Conversely,
our participants demonstrated increased EMG responses in ES, EO, LD, and trunk ROM
(maximum for flexion and rotation) following 12 weeks of TSCS+TSR. These effects per-
sisted even without further stimulation. Previous research showed that stimulating trunk
muscles with TSCS for thoracic-level SCI resulted in an increased mean trunk extension by
9.2
◦±
9.5
◦
in sitting [
8
], whereas the current study yielded an even greater increased mean
extension of 12.4
◦±
4.5
◦
. Collectively, these EMG changes may indicate the initial stage of
neuromuscular recovery [
36
], which may result in further functional improvements with
prolonged treatment. Interestingly, the right rotation (4.5
◦±
2.7
◦
) was significantly lower
than the left rotation (39.6
◦±
13.4
◦
). A prior study reported that an individual who had right
hand dominance before the SCI showed greater gains in relation to right hand function than
the left side after bimanual task-oriented training, likely due to hand dominance [
57
]. As such,
it was possible that hand dominance might contribute to the current findings. However, a
Biomedicines 2023,11, 34 13 of 18
recent study on sensorimotor and functional recovery between dominant and non-dominant
upper extremities showed no significant differences in outcomes [
58
]. Therefore, further
research is required to determine the veracity of this statement.
4.4. TSCS and TSR for Sensorimotor Improvement
In recent years, TSCS has become increasingly popular as a treatment option for people
living with SCI. During locomotion training, TSCS has demonstrated exceptional gains
in motor performance that were previously believed to be unattainable for individuals
with chronic SCI [
59
]. Researchers have hypothesized that TSCS may have long-term
benefits even in cases of complete SCI [
12
,
42
]. The TSCS treatment has shown continual
improvements in locomotion [
60
], standing [
44
], upper extremity function [
61
], and sitting
posture [
12
,
42
] in individuals with SCI. A few studies have also reported the immediate
effects of TSCS on maintaining postural stability in people with SCI [
12
,
42
]. The present
study adds to the findings of previous studies [
12
,
42
] by demonstrating that TSCS+TSR
induced sustainable improvement in trunk function in people with complete tetraplegia.
Our findings may assist clinicians and rehabilitation experts in the planning of trunk
rehabilitation programs for individuals with complete tetraplegia to enhance patients’
trunk stability and sitting balance.
Furthermore, the effects of TSCS on the sensory functions of the study participants
revealed that pinprick and light touch sensations were improved, particularly in P1, with no
prognosis at the neurological level. This may be attributed to the fact that individuals with
SCI often reach a plateau in their spontaneous physical recovery approximately 1.5 years
after SCI [
62
]. While most of our participants were 2–19 years post-SCI, for P1, post-SCI
injury duration was 1.5 years. This could be one of the potential causes of the sensory im-
provement in P1 only. Further studies are needed to confirm this hypothesis. A prior study
reported similar outcomes, where no change in ISNCSCI scores was observed in individu-
als with complete SCI (AIS A) [
44
]. Some studies showed improvements in neurological
levels. However, the recovery was demonstrated in people with incomplete SCI [
61
,
63
].
Simultaneously, motor function improvements have been observed in individuals with
complete SCI, but evidence on clinical prognosis is lacking [61].
The present study also shows that people with complete tetraplegia are unlikely
to recover by TSR alone. This statement is supported by a review study evaluating the
effectiveness of TSR for improving independent sitting and standing function in people
with chronic SCI, which highlighted the minimal effect of TSR on functional recovery [
29
].
Indeed, little benefit to motor improvement has been reported in people with incomplete
SCI [
30
], and another review paper presented little evidence on the benefit of conventional
therapeutic exercise for increasing motor strength after SCI [
64
]. The current study findings
support the above statements, where no significant improvements were observed when the
TSR treatment was administered alone.
Research suggests that the combination of neuromodulation with a specific rehabilita-
tion approach may recover adequate function after SCI [
65
]. The current findings support
this notion, where significant improvements were seen after TSCS+TSR. Interestingly, the
findings indicate that TSCS with TSR increased trunk stability and improved sitting bal-
ance, which assisted the study participants to advance the functional tasks (such as being
able to perform rolling, accomplish transfer tasks, achieve progression in spinal mobility
functions, and maintain erect sitting posture) independently or with minimal assistance.
The impact of treatment frequency on functional outcome shows that improvement varied
between individuals. These differences in existing functional outcome may be related to
SCI level. Participants with lower tetraplegia had significantly more improvement than
those with higher tetraplegia, despite attending similar treatment sessions. Given that a
participant (P3) with lower cervical SCI, who attended fewer treatment sessions than an-
other participant (P1) with higher cervical SCI, had better improvements, it is possible that
improvement depends on the SCI level of neurological damage rather than the frequency
Biomedicines 2023,11, 34 14 of 18
of treatment. Future research should evaluate whether continuous intervention sessions
may yield further recovery.
4.5. Relationship between Functional Improvement of mFRT, TCT, and FIST
The TCT and FIST were found to have a stronger correlation than other assessment
parameters. Both TCT and FIST assessments have several trunk-based static and dynamic
balancing assessments. These activities provide a more stable sitting position [
46
,
66
].
Therefore, when the trunk control is increased, the sitting function will also improve. This
may explain their strong correlation in the current study. The mFRT did not show a strong
correlation with other outcome measures. Daily activities or functional movements require
a wide range of motions. Forward or lateral body movements alone may not accurately
reflect the functional ability of an individual [
16
]. A prior study also found no correlation
between mFRT and the mobility assessment of spinal cord independence measure III in
people with chronic SCI [
16
]. Similarly, the lack of correlation between ROM and other
functional assessment parameters in our study may be because SCI individual’s ability to
flex or extend their trunks had no effect on sitting stability [
10
]. Specifically, prolonged
sitting in a wheel chair may lead to the development of a C-shaped spinal sagittal profile
in people with SCI due to hyperkyphosis, hypolordosis, and a posterior pelvic tilt, which
could affect sitting stability [
9
,
67
]. In fact, trunk muscle strength and endurance [
68
],
pelvic alignment [
69
], and forward reaching ability together are the determinants of seated
performance [
70
]. Therefore, improved ROM alone may not result in the corresponding
improvement in sitting ability.
4.6. Study Limitations and Indications for Future Research
The research described herein has several limitations. First, the participants had vary-
ing levels of tetraplegia, which affected their ability to perform motor tasks to different
extents. Although motor improvements were observed in all of the study participants re-
gardless of the number of treatment sessions, greater functional gain was observed in those
with lower levels of tetraplegia. Second, the participants were recruited via convenience
sampling, which might lead to selection bias. Third, because one participant with C4 SCI
(AIS A) had a sudden increase in blood pressure, the training was hampered by the need
for frequent pauses to avoid autonomic dysreflexia. Fourth, one participant developed skin
rashes after stimulation, which required a week to recover, necessitating the suspension of
training for a week. To successfully complete all sessions, the treatment time was prolonged
for that participant. Fifth, because the data collection was performed by the same investigator,
there was a possibility of some bias. It was difficult to blind the participants because they
underwent the treatment. Given the difficulty of double blinding, we adopted single blinding,
where the rater was blinded in order to reduce the potential bias.
Despite our promising results, the mechanisms underlying the combined treatment
effects remain unknown. One possible mechanism could be that supraspinal adaptations
significantly improve balance performance following externally challenged balance training
which is facilitated by a feed-forward mechanism [
11
]. Since the posterior root reflexes
were not studied, the investigators did not know which structures were activated by the
stimulation and parameters used [
43
]. Future studies should investigate the mechanisms
and posterior root reflexes. Furthermore, future research should validate the current
findings in a larger sample from a wider geographic region. Randomized controlled
trial studies are warranted to compare the effects of TSCS+TSR and TSR alone under
different treatment regimens with adjustment for various confounders (e.g., body mass
index, duration of injury, residual upper limb function, and grasp function) in order to
inform clinical practice. Future work should also evaluate the effects of TSCS+TSR on the
quality of life of people with chronic complete cervical SCI.
Biomedicines 2023,11, 34 15 of 18
5. Conclusions
The current study demonstrates that 12 weeks of TSCS+TSR treatment significantly
improved functional reach distance and trunk muscle activation in multiple directions
among individuals with chronic complete cervical SCI. These improvements persisted even
after TSCS had been stopped for 18 weeks. The resulting increase in sitting balance may
reduce the risk of falling from a wheelchair and improve functional independence when
carrying out the purposeful tasks in sitting. The findings may be considered preliminary,
and future studies should determine the optimal treatment regimen and duration to attain
the maximum long-term treatment effects.
Supplementary Materials:
The following supporting information can be downloaded at: https://
www.mdpi.com/article/10.3390/biomedicines11010034/s1, Figure S1: The detailed analysis process
of Vicon involves connecting selected markers at specific anatomical landmarks; Table S1: The
responses recorded from trunk muscles measured through EMG; Table S2: The ISNCSCI classification
of the participants.
Author Contributions:
Conceptualization, N.S.T., M.A. and Y.-P.Z.; investigation, N.S.T., Y.T.L.,
A.Y.W. and M.A.; writing—original draft preparation, N.S.T.; writing—reviewing and editing, N.S.T.,
M.A., Y.T.L., A.Y.W. and Y.-P.Z.; project administration, Y.-P.Z.; funding acquisition, M.A. and Y.-P.Z.
All authors have read and agreed to the final version of the manuscript.
Funding:
The work was supported by The Hong Kong Polytechnic University (UAKB) and the
Telefield Charitable Fund (ZH3V).
Institutional Review Board Statement:
The study was conducted in accordance with the Declara-
tion of Helsinki, and approved by the Human Subjects Ethics Sub-Committee of The Hong Kong
Polytechnic University (Reference no: HSEARS20190201002-01).
Informed Consent Statement:
Informed consent was obtained from all subjects involved in the study.
Written informed consent has been obtained from the patient(s) to publish this paper if applicable.
Data Availability Statement:
The data generated from this work can be obtained from the corre-
sponding author upon reasonable request.
Acknowledgments:
We are grateful to the participants and their caregivers for their efforts and
commitment throughout the experiments. Our special thanks go to Lyn Wong for her support toward
the success of our research. We also thank Mohammad Akhlasur Rahman and Vaheh Nazari for
their valuable contributions in this study. This paper is an extended version of our conference paper
published in Artificial Organs, Volume 45, Issue 3, Page E42.
Conflicts of Interest: The authors declare no conflict of interest.
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