- Email: [email protected]
Comparison of the Effect of Sensory-Level and Conventional Motor-Level Neuromuscular Electrical Stimulations on Quadriceps Strength After Total Knee Arthroplasty: A Prospective Randomized Single-Blind Trial
Accepted Manuscript Comparison of the effect of sensory-level and conventional motor-level neuromuscular electrical stimulation on quadriceps strength after total knee arthroplasty: a prospective randomized single-blind trial Yosuke Yoshida, MSc, Koki Ikuno, PhD, Koji Shomoto, PhD PII:
S0003-9993(17)30381-7
DOI:
10.1016/j.apmr.2017.05.005
Reference:
YAPMR 56908
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 28 September 2016 Revised Date:
3 May 2017
Accepted Date: 4 May 2017
Please cite this article as: Yoshida Y, Ikuno K, Shomoto K, Comparison of the effect of sensory-level and conventional motor-level neuromuscular electrical stimulation on quadriceps strength after total knee arthroplasty: a prospective randomized single-blind trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/j.apmr.2017.05.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Running head: Comparison of effect of sNMES and mNMES after TKA
RI PT
Title: Comparison of the effect of sensory-level and conventional motor-level neuromuscular electrical stimulation on quadriceps strength after total knee arthroplasty:
SC
a prospective randomized single-blind trial
M AN U
Author: Yosuke Yoshida, MSca,c, Koki Ikuno, PhD b,c, Koji Shomoto, PhD c
Institution: a Department of Rehabilitation Medicine, Yamato Kashihara Hospital, Nara, Japan
Japan c
TE D
Department of Rehabilitation Medicine, Nishiyamato Rehabilitation Hospital, Nara,
Department of Physical Therapy, Faculty of Health Science, Kio University, Nara,
AC C
Japan
EP
b
This trial was performed at the Yamatokashihara Hospital Total Arthroplasty Center between June 2014 and March 2015 participated in this trial.
This manuscript has not been published and is not under consideration for publication elsewhere.
ACCEPTED MANUSCRIPT
Acknowledgements: We thank research assistants Kazuhito Fujikawa for delivery of the intervention and the staff from the Department of Rehabilitation Medicine for their
RI PT
support. We also thank Akihiro Okuda for his guidance.
SC
Funding: No outside funding was utilized in this trial.
M AN U
Conflict of Interest: Authors declare no conflict of interest or financial benefit connected with this trial.
Yosuke Yoshida
TE D
Corresponding author:
Department of Rehabilitation Medicine, Yamato Kashihara Hospital
EP
81, Ishikawa-cho, Kashihara-city, Nara, 634-0045, Japan TEL : 81-744-27-1071
AC C
e-mail : [email protected]
Clinical trial registration number: All patients gave written consent after being clearly advised about the trial, which was approved by the Yamatokashihara Hospital Ethics Committee (H24-1). This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR 000011884).
ACCEPTED MANUSCRIPT Abstract
2
Objective: To compare sensory-level neuromuscular electrical stimulation (sNMES) and
3
conventional motor- level neuromuscular electrical stimulation (mNMSE ) in patients after
4
total knee arthroplasty (TKA).
5
Design: A prospective randomized single-blind trial.
6
Setting: A hospital total arthroplasty center: inpatients.
7
Participants: Patients with osteoarthritis (N=66, 85% women, mean age 73.5±6.3y) were
8
randomized to receive either sNMES applied to the quadriceps (the sNMES group),
9
mNMES (the mNMES group), or no stimulation (the Control group) in addition to a
M AN U
SC
RI PT
1
standard rehabilitation program.
11
Interventions: Each type of NMES was applied in 45 minute sessions, 5days/week, for 2
12
weeks.
13
Main Outcome Measures: Data for the quadriceps maximum voluntary isometric
14
contraction (MVIC), the leg skeletal muscle mass determined using multiple frequency
15
bioelectrical impedance analysis, the Timed Up and Go test, the 2-Minute Walk Test
16
(2MWT), the visual analogue scale, and the range-of-motion of the knee were measured
17
preoperative and at 2 and 4 weeks after TKA.
18
Results: The mNMES (P = 0.001) and sNMES groups (P = 0.028) achieved better MVIC
19
results than the Control group. The mNMES (P = 0.003) and sNMES groups (P = 0.046)
20
achieved better 2MWT results than the Control group. Some patients in the mNMES group
AC C
EP
TE D
10
1
ACCEPTED MANUSCRIPT dropped out of the experiment due to discomfort.
22
Conclusion: The mNMES significantly improved the muscle strength and functional
23
performance more than the standard program alone. The mNMES was uncomfortable for
24
some patients. The sNMES was comfortable and improved muscle strength and functional
25
performance more than the standard program alone.
SC
26
RI PT
21
Key words: sensory-level neuromuscular electrical stimulation, total knee arthroplasty,
28
muscle strength training
29
List of Abbreviations:
30
BIA Bioelectrical Impedance Analysis
31
BMI Body Mass Index
32
LSMM
33
TKA Total Knee Arthroplasty
34
MVIC
35
NMES
36
OA Osteoarthritis
37
ROM
38
TUG Timed Up and Go test
39
VAS
40
2MWT 2 Minute Walk Test
TE D
M AN U
27
EP
Leg Skeletal Muscle Mass
AC C
Maximum Voluntary Isometric Contraction Neuromuscular Electrical Stimulation
Range of Motion
Visual Analog Scale
2
ACCEPTED MANUSCRIPT Introduction
42
Total knee arthroplasty (TKA) is the gold standard treatment for end-stage knee
43
osteoarthritis (OA)1. TKA reliably reduces pain and improves self-reported functioning in
44
patients with end-stage OA2-4. Despite the well-documented success of this treatment, the
45
recovery of quadriceps muscle strength and full recovery from functional impairment are
46
rare in patients who have undergone TKA when compared with age- and gender-matched
47
individuals without knee pathology5,6. Furthermore, quadriceps muscle weakness is thought
48
to be caused predominantly by a central nervous system in the early postoperative period
49
after TKA7,8. Recently, neuromuscular electrical stimulation (NMES) has received research
50
attention in the form of several clinical trials8,9. The benefits of NMES also remain under
51
investigation in the Cochrane review10. The advantage of motor-level NMES (mNMES) is
52
that it evokes the muscle contraction, preventing quadriceps weakness and improving
53
physical performance in patients after TKA8,9. However, mNMES was found to be
54
uncomfortable for some patients and caused pain, thus accounting for the higher dropout
55
rate in these patients11. Meanwhile, sensory-level (no contraction) NMES (sNMES) has
56
been reported to activate the recruitment of the central nervous system by means of the
57
electrically evoked peripheral afferent nerves, leading to the enhancement of motor
58
activation 12. Maximizing the amount of afferent input via sNMES is not limited by muscle
59
fatigue, pain or discomfort13. Our hypothesis is that the addition of sNMES to standard
60
rehabilitation programs would accelerate patients’ recovery from quadriceps weakness and
AC C
EP
TE D
M AN U
SC
RI PT
41
3
ACCEPTED MANUSCRIPT physical functional disorder after TKA to the same degree as in mNMES. To the best of our
62
knowledge, no trials have yet compared the use of sNMES and mNMES in patients after
63
TKA. The aim of this trial was to assess the clinical outcomes of standard rehabilitation
64
programs plus sNMES after TKA compared to those of standard rehabilitation programs
65
plus mNMES or standard rehabilitation programs alone.
SC
66
RI PT
61
Methods
68
Study design and randomization
69
This trial was a prospective, randomized, controlled, single-blind trial. A statistician who
70
was uninvolved with the treatment provided computer-generated randomization lists. After
71
baseline evaluation was completed, each eligible patient was block randomized into three
72
groups to ensure equal enrollment among the groups. We calculated our target sample sizes
73
using the variance in the main outcome measures in our sample during the previous trial
74
analysis 14. This resulted in a target sample size of 22 in the sNMES and standard
75
rehabilitation programs14. This allowed us to detect an effect size of 0.7414. We recruited
76
patients until the target sample size was reached.
TE D
EP
AC C
77
M AN U
67
78
Patients
79
Ninety-five patients who had undergone TKA surgery at the Masked Hospital Total
80
Arthroplasty Center between June 2014 and March 2015 participated in this trial. All 4
ACCEPTED MANUSCRIPT patients had been operated on using a medial parapatellar approach, with a cemented
82
tricompartmental prosthesis with a fixed bearing (including resurfacing of the patella). The
83
implants used were all of the posterior-stabilized type. In accordance with usual practice,
84
the all patients received physical therapy from day 1 to 4 weeks after the TKA surgery at the
85
Total Arthroplasty Center. All patients had the following common clinical pathways in their
86
rehabilitation programs: lower extremity muscle exercises for the quadriceps, calf, and
87
hamstrings; passive knee range-of-motion (ROM) exercises; patellofemoral joint
88
mobilization; and exercise related to major activities of daily living, such as walking and
89
climbing stairs (40-60 min/day, 5-6 days/week, 4 weeks). Full weight bearing was allowed
90
from day 2 on. After a preoperative evaluation was completed, each eligible patient was
91
randomly allocated to one of three groups: standard rehabilitation programs plus sNMES af-
92
ter TKA (the sNMES group), standard rehabilitation programs plus mNMES (the mNMES
93
group), and standard rehabilitation programs alone (the Control group). Patients were
94
included if they were between the ages of 55 and 85 years and had undergone a primary
95
unilateral TKA for end-stage knee OA (Kellgren-Lawrence Grading Scale 3-4, medial
96
compartment). The exclusion criteria for inpatients included dependent prehospital living (a
97
Barthel Index of less than 100), a body mass index greater than 35 kg/m2, uncontrolled
98
hypertension, uncontrolled diabetes, significant neurologic or psychiatric impairments,
99
other unstable lower-extremity orthopedic conditions, inflammatory arthritis, contralateral
100
AC C
EP
TE D
M AN U
SC
RI PT
81
knee OA (as defined by a pain level of greater than 40/100 mm on the visual analogue scale 5
ACCEPTED MANUSCRIPT (VAS) while walking), an implanted cardiac pacemaker or cardiodefibrillator, dementia, and
102
cutaneous allergy. The investigation conformed to the principles outlined in the Declaration
103
of Helsinki. All patients gave written consent after being clearly advised about the trial,
104
which was approved by the Masked Hospital Ethics Committee (H24-1).
RI PT
101
105 Interventions
107
Each NMES was applied for 2 weeks starting 2 weeks after the TKA surgery. The sNMES
108
was administered for sensory-level intensity, with a symmetrical biphasic current of 100 Hz,
109
pulse width of 1 msec, 45 min/day, and continuous stimulation, and was performed 5
110
days/week. The patients in the sNMES group reported mild paresthesia in the femoral nerve
111
area but no pain and no visible muscle contraction (10-15 mA). The mNMES was
112
administered for maximum tolerable intensity, with a symmetrical biphasic current of 100
113
Hz, pulse width of 1 msec, 30 min/day, and duty cycle of 10 sec on/20 sec off, and was
114
performed 5 days/week. The patients in the mNMES group gradually increased the
115
stimulation intensity as much as possible through the session to induce at least visible
116
muscle contraction and, if possible, passive knee extension movement (15-38 mA). If the
117
self-selected intensity did not result in visible contractions, the patient was excluded from
118
the trial. Each NMES intervention was applied before the standard rehabilitation programs
119
(voluntary muscle strength exercises) were begun. Each NMES interventions used an
120
electrical stimulation devicea. The surface self-adhesive electrodes (5×9 cm)b were placed
AC C
EP
TE D
M AN U
SC
106
6
ACCEPTED MANUSCRIPT on the femoral nerve trunk and the rectus femoris muscle, vastus lateralis muscle, and
122
vastus medialis muscle motor points (Figure 1). The femoral nerve trunk and motor points
123
were identified by pencil electrode. Applying the electrodes over the femoral nerve trunk
124
and the motor point of the muscle reduces the current threshold required and maximizes the
125
amount of afferent input 15,16.
RI PT
121
SC
126 Assessment
128
Quadriceps maximum voluntary isometric contraction (MVIC) was the main outcome
129
measure. Leg skeletal muscle mass (LSMM) using multiple frequency bioelectrical
130
impedance analysis (BIA), the Timed Up and Go test (TUG), the 2 Minute Walk Test
131
(2MWT), the VAS, and the ROM of the knee were the secondary outcome measures. All
132
outcome measures were measured preoperative and at 2 and 4 weeks (at the end of
133
treatment) after TKA surgery. MVIC was measured using a hand-held dynamometer with a
134
belt for fixationc, which has been found to be a valid method for measuring MVIC17,18. After
135
a warm-up and familiarization with the procedure, the patients sat at the end of the
136
examination table with a hip angle of 90° and a knee angle of 90°. We attached a force
137
sensor to the patient’s ankle (perpendicular to the longitudinal axis of the leg), 1 cm proximal
138
to the lateral malleolus. Three trials were performed, with 1 min of rest given between
139
subsequent trials, and the maximum value was adopted. The patient was asked to repeat the
140
trials if the difference in MVIC between two of the three trials was greater than 10%. All
AC C
EP
TE D
M AN U
127
7
ACCEPTED MANUSCRIPT MVIC measures were gravity compensated. LSMM was measured by multiple-frequency
142
BIAd. BIA is used to predict body composition using differences in electrical conductivity
143
that result from the biological characteristics of body tissue19. The segmental impedance
144
levels of the right and left arm, trunk, and right and left leg were measured. In
145
multi-frequency analysis, electrical current is passed through the body, and we measured the
146
body impedance. We measured LSMM using BIA in the involved leg. We performed this
147
measurement only after the TKA surgery so the implants would be accounted for in the
148
measurement. The data for MVIC and LSMM were used to calculate the body weight ratio.
149
The TUG measures the time required to rise from an armchair, walk 3 m, turn around, and
150
return to sitting in the same chair without physical assistance. The 2MWT measures the total
151
distance walked by an individual over 2 minutes. Patients were instructed to walk as quickly
152
as they felt safe and comfortable. Patients were permitted to use a T-cane. Knee pain was
153
quantified using the VAS. Patients rated the pain in and around the knee that had been
154
operated on immediately after the MVIC test using a ruler with a scale from 0 to 100 mm,
155
where 0 represented no pain and 100 represented the worst imaginable pain. The ROM of
156
passive knee flexion and extension was measured using a hand-held goniometer, which has
157
been found to be a valid method for quantifying knee movement. While the patient was lying
158
supine on a bed, a researcher aligned the stationary arm of the goniometer to the greater
159
trochanter and the moveable arm to the lateral malleolus. All outcome measures were
160
measured by a researcher who was blinded to the group allocation and data acquisition.
AC C
EP
TE D
M AN U
SC
RI PT
141
8
ACCEPTED MANUSCRIPT Statistical analysis
162
The baseline characteristics and outcome measures were compared among the three groups
163
using the chi square test and the one-way factorial analysis of variance (ANOVA). We
164
compared all outcome measures among the three groups (mNMES, sNMES and Control) at
165
three time points: (1) pre-operative (baseline), (2) pre-intervention (2 weeks after TKA) and
166
(3) post-intervention (4 weeks after TKA). All outcome measures were evaluated using
167
ANOVA among the three groups at the three time points. All tests were performed using a
168
significance level of 0.05. A post-hoc Newman-Keuls test was used to perform multiple
169
comparisons between groups (P = 0.05/2 = 0.025), if appropriate. We also calculated the
170
effect sizes between each groups at post-intervention for MVIC, which was proposed by
171
Cohen’s d. The effect sizes were interpreted as small (0.30–0.20), medium (around 0.50)
172
and large (above 0.80). All values are reported as means (SD), unless otherwise stated. Also,
173
we calculated the difference between the pre-operative measures and the post-intervention
174
measures divided by the pre-operative measures (Table 2, ⊿%). All statistical analyses
175
were performed with GraphPad Prism 5.
SC
M AN U
TE D
EP
AC C
176
RI PT
161
177
Results
178
Of the 95 patients who participated in this trial, 15 patients (16%) did not meet the inclusion
179
criteria and 3 patients (3%) did not consent to participate. At baseline, intervention-related
180
characteristics were obtained from 77 patients (81%). However, only 66 (69%) of them 9
ACCEPTED MANUSCRIPT completed the 4-week rehabilitation program. Evaluation was done for 22 patients in the
182
sNMES group (3 did not complete the program), 22 in the mNMES group (4 did not
183
complete the program), and 22 in the Control group (4 did not complete the program). The
184
reasons for not completing the program were deviation from the clinical pathways (7 cases)
185
and, in 3 patients in the mNMES group, ending the NMES training program prematurely
186
due to discomfort caused by the NMES stimulation. The patients in the sNMES group who
187
completed the entire NMES training program tolerated the NMES stimulation very well.
188
(Figure 2).
189
There were no statistically significant differences among the three groups in any of the
190
pre-operative characteristics (Table 1).
191
There were no statistically significant three-group differences in MVIC (P = 0.828), TUG
192
(P = 0.863), 2MWT (P =0.994), VAS (P = 0.401), knee-joint flex ROM (P = 0.538), or
193
knee-joint ext ROM (P =0.198) at the pre-operative point when accounting for baseline
194
measures (Table 2). Also, there were no statistically significant three-group differences in
195
MVIC (P = 0.854), LSMM (P = 0.951), TUG (P = 0.241), 2MWT (P = 0.453), VAS (P =
196
0.984), knee-joint flex ROM (P = 0.790), or knee-joint ext ROM (P = 0.414) at the
197
pre-intervention point (Table 2). However, there were statistically significant three-group
198
differences in MVIC (F = 5.924, P = 0.004) and 2MWT (F =4.202, P =0.019) at the
199
post-intervention point (Table 2). We observed that the MVIC results in the sNMES group
200
(P = 0.028; 95% confidence interval (CI), of difference, 0.01 to 0.09) and mNMES group (P
AC C
EP
TE D
M AN U
SC
RI PT
181
10
ACCEPTED MANUSCRIPT = 0.001; 95% CI of difference, 0.03 to 0.11) were significantly better at the
202
post-intervention point compared with the Control group. The effect size was also medium
203
(0.71) for MVIC between the sNMES group and the Control group measures. The effect
204
size was large (1.15) for MVIC between the mNMES group and Control group measures.
205
Furthermore, there were no statistically significant differences between the sNMES group
206
and the mNMES group in MVIC at the post-intervention point (P = 0.38; 95% CI of
207
difference -0.22 to 0.57). The effect size was also small (0.30) between the sNMES group
208
and Control group measures. Also, we observed that the 2MWT results between the sNMES
209
group (P = 0.046; 95% CI of difference -2.48 to 29.96) and mNMES group (P = 0.003; 95%
210
CI of difference 6.52 to 30.25) were significantly better at the post-intervention point
211
compared with the Control group. However, there were also no statistically significant
212
differences between the sNMES group and the mNMES group in 2MWT (P = 0.49; 95% CI
213
of difference -18.0 to 8.7) at the post-intervention point. There were no statistically
214
significant three-group differences in LSMM (P = 0.733), TUG (P = 0.079), VAS (P =
215
0.200), knee-joint flex ROM (P =0.603), and knee-joint ext ROM (P =0.414) at the
216
post-intervention point, these assessments are adequately addressed with standard
217
postoperative rehabilitation programs. (Table 2).
AC C
EP
TE D
M AN U
SC
RI PT
201
218 219
Discussion
220
This trial compared the effects of sNMES and conventional mNMES in patients after TKA. 11
ACCEPTED MANUSCRIPT The results of this trial showed that patients in the sMNES and mNMES groups achieved
222
better results on muscle strength at 4 weeks after TKA surgery than did patients in the
223
Control group. Particularly, mNMES may facilitate quadriceps muscle strength gains more
224
rapidly than the control group, as the quadriceps strength reached 90% of preoperative
225
strength 4 weeks after TKA. Control groups showed quadriceps strength that was 63% of
226
the preoperative strength 4 weeks after TKA, despite engaging in postoperative
227
rehabilitation programs. In previous studies, a 40-50% reduction relative to preoperative
228
levels in the quadriceps strength was evident 4 weeks after TKA20,21, similar to the results of
229
our trial. However, there were no changes in the LSMM throughout this trial in all three
230
groups. The quadriceps weakness in the early postoperative period is primarily explained by
231
deficits in voluntary activation rather than by atrophy20,22. This weakness of the quadriceps
232
muscles is partly due to ongoing central nervous system inhibition that prevents the
233
quadriceps from being fully activated20,22. Central nervous system inhibition has been linked
234
to knee articular swelling, inflammation, pain, and receptor damage after TKA22. The use of
235
mNMES offers an effective approach for mitigating quadriceps muscle neural activation
236
deficits in the early period after TKA and restores normal quadriceps muscle function more
237
effectively than voluntary exercise alone7,8. Stevens-Lapsley et al23 showed that the
238
recovery of quadriceps muscle strength after TKA was positively correlated with
239
NMES-induced contraction intensity. It appears that high-intensity, maximally tolerated
240
NMES stimulations have proven to be more effective than lower-intensity stimulations.
AC C
EP
TE D
M AN U
SC
RI PT
221
12
ACCEPTED MANUSCRIPT However, three patients in the mNMES group dropped out due to discomfort caused by the
242
electrical stimulation. No patients dropped out of the sNMES group due to NMES
243
discomfort or pain. In this trial, we showed that sNMES may facilitate quadriceps muscle
244
strength gains more rapidly than voluntary exercise alone, as the quadriceps strength
245
reached 83% of preoperative strength 4 weeks after TKA in the sNMES group. In a
246
previous trial, the sNMES setting was reported to activate the recruitment of the central
247
nervous system through electrically evoked peripheral afferent nerves, leading to the
248
development of motor activation11. Even sensory levels of stimulation that target peripheral
249
afferent nerves can induce prolonged changes in the excitability of the human motor
250
cortex12,24. sNMES stimulation of the afferent nerves of the hand resulted in an increase in
251
the functional magnetic resonance imaging signal intensity in the primary and secondary
252
motor and somatosensory areas of the cortex25. Furthermore, the use of wide-pulse (1 ms)
253
and high-frequency (100 Hz) NMES produced significantly greater muscle strength
254
compared with narrow-pulse (0.05 ms) and low-frequency (25 Hz) stimulation, and this
255
strength enhancement was attributed to the invocation of the central nervous system by the
256
greater afferent input to the muscle12,26. As we used a wide-pulse and high-frequency setting
257
in the present trial, we can conclude that sNMES might facilitate quadriceps muscle
258
strength gains more rapidly than voluntary exercise alone. For patients who experience
259
NMES discomfort and pain, the sNMES setting is recommended.
260
Also, the sNMES and mNMES groups showed significantly improved physical function
AC C
EP
TE D
M AN U
SC
RI PT
241
13
ACCEPTED MANUSCRIPT (i.e., 2MWT) compared to the group receiving the standard rehabilitation program alone. In
262
previous trials, quadriceps weakness has become more profound and the quadriceps muscle
263
did not recover its physical function to the level of healthy adults after TKA5,6. In this trial,
264
there were no significant differences among the three groups in the VAS or ROM results at
265
4 weeks after TKA. Therefore, quadriceps muscle strength has the potential to impact
266
2MWT improvement. As quadriceps weakness has the potential to greatly impact physical
267
function, it is particularly important to improve quadriceps muscle strength early after TKA
268
5-6,20
269
after TKA. This is most likely due to a TUG ceiling effect, as the mean performance of the
270
mNMES group on this measure was 8.8 seconds at 4 weeks after TKA. The mean
271
performance on the TUG in this age group has been reported to be 9.0 seconds27, which
272
indicates that the mNMES group had recovered to normative levels on this measure at 4
273
weeks after TKA.
SC
M AN U
EP
TE D
. However, the differences in the TUG were no longer statistically significant 4 weeks
AC C
274
RI PT
261
275
Study limitations
276
The treating therapists were not blinded to their group assignments for the duration of the
277
trial. Also, follow-up data were not collected in this trial. Furthermore, the NMES settings
278
that were used differed in several ways (e.g., in terms of total stimulation time, quantity of
279
electric charge, on/off time, and ease of use) other than the presence or absence of muscle
280
contraction. Consequently the apparent difference in effectiveness maynot be attributed to 14
ACCEPTED MANUSCRIPT any single factor. Also, a sham stimulation group should be set up and placebo affects
282
should be considered. However, realistic placebo controls in an NMES trial might be
283
impractical because the use of sham devices is inevitably apparent to patients.
RI PT
281
284 Conclusions
286
The results of this trial show that patients in the mNMES group achieved better results on
287
muscle strength and functional performance measures at 4 weeks after TKA surgery than
288
did patients in the Control group. However, the conventional mNMES treatment was
289
uncomfortable for some patients. In such cases, we suggest that sNMES might be more
290
comfortable and may achieve greater quadriceps muscle strength than standard
291
rehabilitation programs. However, the ideal NMES settings (intensity, frequency,
292
wide-pulse) were not clarified in this trial. In further research, a more comfortable ideal
293
NMES setting should be determined.
EP
TE D
M AN U
SC
285
AC C
294 295
Suppliers
296
a. Intelect Mobile Stim, DJO Global, Vista, CA, USA
297
b. Axelgaard, PALS, Platinum, 5×9 cm, USA
298
c. µTas F-10, Anima Corp., JAPAN
299
d. Ito-InBody, Biospace Corp., Japan
300 15
ACCEPTED MANUSCRIPT References
302
1.
OECD. Health at a glance 2013:OECD indicators. OECD Publishing; 2013.
303
2.
Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of
RI PT
301
patients report long-term pain after total hip or knee replacement for osteoarthritis? A
305
systematic review of prospective studies in unselected patients. BMJ Open.
306
2012;2:e000435. 3.
Stevens-Lapsley JE, Schenkman ML, Dayton MR. Comparison of self-reported knee
M AN U
307
SC
304
308
injury and osteoarthritis outcome score to performance measures in patients after total
309
knee arthroplasty. PMR. 2011;3:541-549; quiz 549.
310
4.
Mizner RL, Petterson SC, Clements KE, Zeni JA Jr, Irrgang JJ, Snyder-Mackler L. Measuring functional improvement after total knee arthroplasty requires both
312
performance-based and patient-report assessments: a longitudinal analysis of outcomes.
313
J Arthroplasty. 2011;26:728-37.
EP
5.
Mizner RL, Petterson SC, Stevens JE, Vandenborne K, Snyder-Mackler L. Early
AC C
314
TE D
311
315
quadriceps strength loss after total knee arthroplasty. The contributions of muscle
316
atrophy and failure of voluntary muscle activation. J Bone Joint Surg Am.
317
2005;87:1047-53.
318
6.
arthroplasty compared to healthy adults. J Orthop Sports Phys Ther. 2010;40:559-67.
319 320
Bade MJ, Kohrt WM, Stevens-Lapsley JE. Outcomes before and after total knee
7.
Petterson SC, Barrance P, Buchanan T, Binder-Macleod S, Snyder-Mackler L. 16
ACCEPTED MANUSCRIPT 321
Mechanisms underlying quadriceps weakness in knee osteoarthritis. Med Sci Sports
322
Exerc. 2008;40:422-7. 8.
Kittelson AJ, Stackhouse SK, Stevens-Lapsley JE. Neuromuscular electrical
RI PT
323 324
stimulation after total joint arthroplasty: a critical review of recent controlled studies.
325
Eur J Phys Rehabil Med. 2013;49:909-20. 9.
Stevens-Lapsley JE, Balter JE, Wolfe P, Eckhoff DG, Kohrt WM. Early neuromuscular
SC
326
electrical stimulation to improve quadriceps muscle strength after total knee
328
arthroplasty: a randomized controlled trial. Phys Ther. 2012;92:210-26.
M AN U
327
10. Monaghan B, Caulfield B, O'Mathúna DP. Surface neuromuscular electrical stimulation
330
for quadriceps strengthening pre and post otal knee replacement. Cochrane Database
331
Syst Rev. 2010; 20:CD007177.
332
TE D
329
11. Petterson SC, Mizner RL, Stevens JE, et al. Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with
334
an imbedded prospective cohort. Arthritis Rheum. 2009;61:174-83.
336 337
AC C
335
EP
333
12. Collins DF. Central contributions to contractions evoked by tetanic neuromuscular electrical stimulation. Exerc Sport Sci Rev. 2007;35:102-9. 13. Sullivan JE, Hedman LD. A home program of sensory and neuromuscular electrical
338
stimulation with upper-limb task practice in a patient 5 years after a stroke. Phys Ther.
339
2004;84:1045-54.
340
14. Yoshida Y, Ikuno K, Shomoto K. Effects of sensory level neuromuscular electrical 17
ACCEPTED MANUSCRIPT stimulation in patients after total knee arthroplasty: a pilot quasi randomized trial.
342
Japanese Journal of Electrophysical Agents. 2014; 21:45-52. (in Japanese)
343
15. Robinson A, Snyder-Mackler L. Clinical Electrophysiology: Electrotherapy and
344
Electrophysiologic Testing. 3rd ed. Baltimore, MD: Williams & Wilkins; 2008.
RI PT
341
16. Bergquist AJ, Wiest MJ, Collins DF. Motor unit recruitment when neuromuscular
346
electrical stimulation is applied over a nerve trunk compared with a muscle belly:
347
quadriceps femoris. J Appl Physiol (1985). 2012;113:78-89.
M AN U
348
SC
345
17. Katoh M, Isozaki K. Reliability of isometric knee extension muscle strength
349
measurements of healthy elderly subjects made with a hand-held dynamometer and a
350
belt. J Phys Ther Sci. 2014;26:1855-9.
18. Martin HJ, Yule V, Syddall HE, Dennison EM, Cooper C, Aihie Sayer A. Is hand-held
352
dynamometry useful for the measurement of quadriceps strength in older people? A
353
comparison with the gold standard Bodex dynamometry. Gerontology. 2006;52:154-9.
EP
19. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. European consensus on definition and
AC C
354
TE D
351
355
diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age
356
Ageing. 2010;39:412-23.
357
20. Mizner RL, Petterson SC, Snyder-Mackler L. Quadriceps strength and the time course
358
of functional recovery after total knee arthroplasty. J Orthop Sports Phys Ther.
359
2005;35:424-36.
360
21. Stevens JE, Mizner RL, Snyder-Mackler L. Quadriceps strength and volitional 18
ACCEPTED MANUSCRIPT 361
activation before and after total knee arthroplasty for osteoarthritis. J Orthop Res.
362
2003;21:775-9.
364 365
22. Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms
RI PT
363
and treatment perspectives. Semin Arthritis Rheum. 2010;40:250-66.
23. Stevens-Lapsley JE, Balter JE, Wolfe P, et al. Relationship between intensity of
quadriceps muscle neuromuscular electrical stimulation and strength recovery after
367
total knee arthroplasty. Phys Ther. 2012;92:1187-96.
M AN U
SC
366
368
24. Kimberley TJ, Lewis SM, Auerbach EJ, Dorsey LL, Lojovich JM, Carey JR. Electrical
369
stimulation driving functional improvements and cortical changes in subjects with
370
stroke. Exp Brain Res. 2004;154:450-60.
25. Golaszewski S, Kremser C, Wagner M, Felber S, Aichner F, Dimitrijevic MM.
TE D
371
Functional magnetic resonance imaging of the human motor cortex before and after
373
whole-hand afferent electrical stimulation. Scand J Rehabil Med. 1999;31:165-73.
EP
372
26. Bergquist AJ, Wiest MJ, Collins DF. Motor unit recruitment when neuromuscular
375
electrical stimulation is applied over a nerve trunk compared with a muscle belly:
376
quadriceps femoris. J Appl Physiol. 2012;113:78-89.
377
AC C
374
27. Steffen TM, Hacker TA, Mollinger L. Age- and gender-related test performance in
378
community-dwelling elderly people: Six-Minute Walk Test, Berg Balance Scale, Timed
379
Up & Go Test, and gait speeds. Phys Ther. 2002;82:128-3.
380 19
ACCEPTED MANUSCRIPT Figure legends
382
Figure 1 Stimulation location. The channel-1 is connected to femoral nerve trunk and the
383
vastus lateralis muscle motor point. The channel-2 is connected to the rectus femoris and the
384
vastus medialis muscle motor point.
385
Figure 2
386
CONSORT flow chart to show the flow of patients through the trial.
SC
RI PT
381
M AN U
387 388
Titles of tables
389
Table 1
390
Baseline characteristics of trial patients.
TE D
391 Table 2
393
Outcome measures for mNMES group, sNMES group, and Control group at baseline and 2
394
and 4 weeks after TKA
396 397
AC C
395
EP
392
398 399 400 20
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
401
21
ACCEPTED MANUSCRIPT
mNMES group sNMES group
Control group
Total group P value
(n = 22)
(n = 22)
(n = 66)
Gender (F/M)
18 / 4
18 / 4
20 / 2
56 / 10
0.62a
Age (years)
75.9 (4.7)
71.6 (7.0)
72.5 (6.2)
73.5 (6.3)
0.07b
Height (m)
1.51 (0.05)
1.54 (0.06)
1.52 (0.07)
Weight (kg)
55.9 (8.3)
60.8 (6.3)
60.3 (9.6)
BMI (kg/m2)
24.6 (2.9)
25.4 (2.2)
25.8 (3.3)
112.0 (9.7)
113.0 (11.2)
110.3 (11.8)
111.6 (10.9)
0.54b
14.5 (4.7)
15.3 (8.0)
18.3 (6.9)
16.1 (6.8)
0.20b
26 / 30
0.64a
Knee joint ext ROM（－°） K-L Grading Scale （3/4）
9 / 13
7 / 15
1.52 (0.06)
0.22b
58.7 (8.5)
0.14b
25.3 (3.0)
0.40b
SC
ROM（°）
M AN U
Knee joint flex
RI PT
(n = 22)
10 / 12
AC C
EP
TE D
Table 1. Pre-operative characteristics of trial patients. Data are presented as means and standard deviations (in parentheses) or as numbers of patients. mNMES; motor-level neuromuscular electrical stimulation, sNMES; sensory-level neuromuscular electrical stimulation, F; females, M; males, BMI; body mass index, ROM; range of motion, K-L Grading Scale; Kellgren-Lawrence Grading Scale. a Chi square test, b one-way factorial analysis of variance.
ACCEPTED MANUSCRIPT
LSMM (kg / kg)
(3) Post-intervention
(baseline)
(2 weeks after TKA)
(4 weeks after TKA)
mNMES
0.29 (0.08)
0.13 (0.05)
0.26 (0.05)
sNMES
0.29 (0.10)
0.12 (0.04)
0.24 (0.07)
Control
0.30 (0.10)
0.13 (0.04)
p value
0.828
0.854
mNMES
Not measured
91.7 (11.4)
sNMES
Not measured
92.5 (14.6)
Control
Not measured
91.2 (13.9)
p value
VAS (mm)
13.5 (4.3)
sNMES
11.6 (4.5)
16.2 (6.9)
Control
12.2 (3.6)
p value
0.863
mNMES
114 (25)
sNMES
113 (31)
Control
113 (20)
p value
0.994
*
83 63
0.004
92.9 (12.3)
Not calculated
92.3 (13.8)
Not calculated
89.9 (121.6)
Not calculated
0.733
8.8 (1.8)
76
10.0 (13.1)
86
14.1 (4.5)
10.6 (2.7)
86
0.241
0.079
101 (17) 91 (32)
135 (16) 130 (25)
♯
*
119 115
95 (24)
116 (21)
0.453
0.019
25 (18)
53 (16)
20 (12)
80
29 (22)
54 (20)
29 (26)
101
20 (18)
53 (27)
31 (23)
153
0.401
0.984
0.200
mNMES sNMES Control p value
103
mNMES
112 (10)
85 (9)
121 (6)
108
sNMES
113 (11)
86 (8)
122 (4)
107
AC C
Knee joint
90
0.19 (0.07)
M AN U
11.6 (4.7)
TE D
2MWT (m)
mNMES
♯
EP
TUG (sec)
0.951
⊿ (%)
RI PT
(kgf / kg)
(2) Pre-intervention
SC
MVIC
(1) Pre-operative
Control
110 (12)
84 (9)
120 (5)
120
p value
0.538
0.790
0.603
mNMES
15 (5)
15 (7)
5 (4)
33
sNMES
16 (8)
18 (6)
5 (5)
33
Control
18 (7)
17 (7)
4 (4)
20
p value
0.198
0.414
0.507
flex ROM（°）
Knee joint
ext ROM（°）
ACCEPTED MANUSCRIPT Table 2. Outcome measures for mNMES group, sNMES group, and Control group at baseline and 2 and 4 weeks after TKA. Data are presented as means and standard deviations (in parentheses). MVIC; quadriceps maximum voluntary isometric contraction. LSMM; leg skeletal muscle mass, TUG; Timed Up and Go Test, 2MWT; 2-Minute Walk Test, VAS; visual analogue
RI PT
scale, ROM; range of motion. ⊿%; Difference between the pre-TKA surgery measures and the post-intervention measures divided by the pre-TKA surgery measures.
*Statistically significant improvements were observed for these variables when compared to Control group values (P<0.05).
SC
#Statistically significant improvements were observed for these variables when compared to
AC C
EP
TE D
M AN U
Control group values (P <0.01).
2
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 1. Stimulation location.
EP
The channel-1 is connected to femoral nerve trunk and the vastus lateralis muscle motor point. The channel-2 is connected to the rectus femoris and the vastus medialis muscle motor point.
AC C
5
1
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 2. CONSORT flow chart to show the flow of patients through the trial.
S0003-9993(17)30381-7
DOI:
10.1016/j.apmr.2017.05.005
Reference:
YAPMR 56908
To appear in:
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
Received Date: 28 September 2016 Revised Date:
3 May 2017
Accepted Date: 4 May 2017
Please cite this article as: Yoshida Y, Ikuno K, Shomoto K, Comparison of the effect of sensory-level and conventional motor-level neuromuscular electrical stimulation on quadriceps strength after total knee arthroplasty: a prospective randomized single-blind trial, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi: 10.1016/j.apmr.2017.05.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Running head: Comparison of effect of sNMES and mNMES after TKA
RI PT
Title: Comparison of the effect of sensory-level and conventional motor-level neuromuscular electrical stimulation on quadriceps strength after total knee arthroplasty:
SC
a prospective randomized single-blind trial
M AN U
Author: Yosuke Yoshida, MSca,c, Koki Ikuno, PhD b,c, Koji Shomoto, PhD c
Institution: a Department of Rehabilitation Medicine, Yamato Kashihara Hospital, Nara, Japan
Japan c
TE D
Department of Rehabilitation Medicine, Nishiyamato Rehabilitation Hospital, Nara,
Department of Physical Therapy, Faculty of Health Science, Kio University, Nara,
AC C
Japan
EP
b
This trial was performed at the Yamatokashihara Hospital Total Arthroplasty Center between June 2014 and March 2015 participated in this trial.
This manuscript has not been published and is not under consideration for publication elsewhere.
ACCEPTED MANUSCRIPT
Acknowledgements: We thank research assistants Kazuhito Fujikawa for delivery of the intervention and the staff from the Department of Rehabilitation Medicine for their
RI PT
support. We also thank Akihiro Okuda for his guidance.
SC
Funding: No outside funding was utilized in this trial.
M AN U
Conflict of Interest: Authors declare no conflict of interest or financial benefit connected with this trial.
Yosuke Yoshida
TE D
Corresponding author:
Department of Rehabilitation Medicine, Yamato Kashihara Hospital
EP
81, Ishikawa-cho, Kashihara-city, Nara, 634-0045, Japan TEL : 81-744-27-1071
AC C
e-mail : [email protected]
Clinical trial registration number: All patients gave written consent after being clearly advised about the trial, which was approved by the Yamatokashihara Hospital Ethics Committee (H24-1). This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR 000011884).
ACCEPTED MANUSCRIPT Abstract
2
Objective: To compare sensory-level neuromuscular electrical stimulation (sNMES) and
3
conventional motor- level neuromuscular electrical stimulation (mNMSE ) in patients after
4
total knee arthroplasty (TKA).
5
Design: A prospective randomized single-blind trial.
6
Setting: A hospital total arthroplasty center: inpatients.
7
Participants: Patients with osteoarthritis (N=66, 85% women, mean age 73.5±6.3y) were
8
randomized to receive either sNMES applied to the quadriceps (the sNMES group),
9
mNMES (the mNMES group), or no stimulation (the Control group) in addition to a
M AN U
SC
RI PT
1
standard rehabilitation program.
11
Interventions: Each type of NMES was applied in 45 minute sessions, 5days/week, for 2
12
weeks.
13
Main Outcome Measures: Data for the quadriceps maximum voluntary isometric
14
contraction (MVIC), the leg skeletal muscle mass determined using multiple frequency
15
bioelectrical impedance analysis, the Timed Up and Go test, the 2-Minute Walk Test
16
(2MWT), the visual analogue scale, and the range-of-motion of the knee were measured
17
preoperative and at 2 and 4 weeks after TKA.
18
Results: The mNMES (P = 0.001) and sNMES groups (P = 0.028) achieved better MVIC
19
results than the Control group. The mNMES (P = 0.003) and sNMES groups (P = 0.046)
20
achieved better 2MWT results than the Control group. Some patients in the mNMES group
AC C
EP
TE D
10
1
ACCEPTED MANUSCRIPT dropped out of the experiment due to discomfort.
22
Conclusion: The mNMES significantly improved the muscle strength and functional
23
performance more than the standard program alone. The mNMES was uncomfortable for
24
some patients. The sNMES was comfortable and improved muscle strength and functional
25
performance more than the standard program alone.
SC
26
RI PT
21
Key words: sensory-level neuromuscular electrical stimulation, total knee arthroplasty,
28
muscle strength training
29
List of Abbreviations:
30
BIA Bioelectrical Impedance Analysis
31
BMI Body Mass Index
32
LSMM
33
TKA Total Knee Arthroplasty
34
MVIC
35
NMES
36
OA Osteoarthritis
37
ROM
38
TUG Timed Up and Go test
39
VAS
40
2MWT 2 Minute Walk Test
TE D
M AN U
27
EP
Leg Skeletal Muscle Mass
AC C
Maximum Voluntary Isometric Contraction Neuromuscular Electrical Stimulation
Range of Motion
Visual Analog Scale
2
ACCEPTED MANUSCRIPT Introduction
42
Total knee arthroplasty (TKA) is the gold standard treatment for end-stage knee
43
osteoarthritis (OA)1. TKA reliably reduces pain and improves self-reported functioning in
44
patients with end-stage OA2-4. Despite the well-documented success of this treatment, the
45
recovery of quadriceps muscle strength and full recovery from functional impairment are
46
rare in patients who have undergone TKA when compared with age- and gender-matched
47
individuals without knee pathology5,6. Furthermore, quadriceps muscle weakness is thought
48
to be caused predominantly by a central nervous system in the early postoperative period
49
after TKA7,8. Recently, neuromuscular electrical stimulation (NMES) has received research
50
attention in the form of several clinical trials8,9. The benefits of NMES also remain under
51
investigation in the Cochrane review10. The advantage of motor-level NMES (mNMES) is
52
that it evokes the muscle contraction, preventing quadriceps weakness and improving
53
physical performance in patients after TKA8,9. However, mNMES was found to be
54
uncomfortable for some patients and caused pain, thus accounting for the higher dropout
55
rate in these patients11. Meanwhile, sensory-level (no contraction) NMES (sNMES) has
56
been reported to activate the recruitment of the central nervous system by means of the
57
electrically evoked peripheral afferent nerves, leading to the enhancement of motor
58
activation 12. Maximizing the amount of afferent input via sNMES is not limited by muscle
59
fatigue, pain or discomfort13. Our hypothesis is that the addition of sNMES to standard
60
rehabilitation programs would accelerate patients’ recovery from quadriceps weakness and
AC C
EP
TE D
M AN U
SC
RI PT
41
3
ACCEPTED MANUSCRIPT physical functional disorder after TKA to the same degree as in mNMES. To the best of our
62
knowledge, no trials have yet compared the use of sNMES and mNMES in patients after
63
TKA. The aim of this trial was to assess the clinical outcomes of standard rehabilitation
64
programs plus sNMES after TKA compared to those of standard rehabilitation programs
65
plus mNMES or standard rehabilitation programs alone.
SC
66
RI PT
61
Methods
68
Study design and randomization
69
This trial was a prospective, randomized, controlled, single-blind trial. A statistician who
70
was uninvolved with the treatment provided computer-generated randomization lists. After
71
baseline evaluation was completed, each eligible patient was block randomized into three
72
groups to ensure equal enrollment among the groups. We calculated our target sample sizes
73
using the variance in the main outcome measures in our sample during the previous trial
74
analysis 14. This resulted in a target sample size of 22 in the sNMES and standard
75
rehabilitation programs14. This allowed us to detect an effect size of 0.7414. We recruited
76
patients until the target sample size was reached.
TE D
EP
AC C
77
M AN U
67
78
Patients
79
Ninety-five patients who had undergone TKA surgery at the Masked Hospital Total
80
Arthroplasty Center between June 2014 and March 2015 participated in this trial. All 4
ACCEPTED MANUSCRIPT patients had been operated on using a medial parapatellar approach, with a cemented
82
tricompartmental prosthesis with a fixed bearing (including resurfacing of the patella). The
83
implants used were all of the posterior-stabilized type. In accordance with usual practice,
84
the all patients received physical therapy from day 1 to 4 weeks after the TKA surgery at the
85
Total Arthroplasty Center. All patients had the following common clinical pathways in their
86
rehabilitation programs: lower extremity muscle exercises for the quadriceps, calf, and
87
hamstrings; passive knee range-of-motion (ROM) exercises; patellofemoral joint
88
mobilization; and exercise related to major activities of daily living, such as walking and
89
climbing stairs (40-60 min/day, 5-6 days/week, 4 weeks). Full weight bearing was allowed
90
from day 2 on. After a preoperative evaluation was completed, each eligible patient was
91
randomly allocated to one of three groups: standard rehabilitation programs plus sNMES af-
92
ter TKA (the sNMES group), standard rehabilitation programs plus mNMES (the mNMES
93
group), and standard rehabilitation programs alone (the Control group). Patients were
94
included if they were between the ages of 55 and 85 years and had undergone a primary
95
unilateral TKA for end-stage knee OA (Kellgren-Lawrence Grading Scale 3-4, medial
96
compartment). The exclusion criteria for inpatients included dependent prehospital living (a
97
Barthel Index of less than 100), a body mass index greater than 35 kg/m2, uncontrolled
98
hypertension, uncontrolled diabetes, significant neurologic or psychiatric impairments,
99
other unstable lower-extremity orthopedic conditions, inflammatory arthritis, contralateral
100
AC C
EP
TE D
M AN U
SC
RI PT
81
knee OA (as defined by a pain level of greater than 40/100 mm on the visual analogue scale 5
ACCEPTED MANUSCRIPT (VAS) while walking), an implanted cardiac pacemaker or cardiodefibrillator, dementia, and
102
cutaneous allergy. The investigation conformed to the principles outlined in the Declaration
103
of Helsinki. All patients gave written consent after being clearly advised about the trial,
104
which was approved by the Masked Hospital Ethics Committee (H24-1).
RI PT
101
105 Interventions
107
Each NMES was applied for 2 weeks starting 2 weeks after the TKA surgery. The sNMES
108
was administered for sensory-level intensity, with a symmetrical biphasic current of 100 Hz,
109
pulse width of 1 msec, 45 min/day, and continuous stimulation, and was performed 5
110
days/week. The patients in the sNMES group reported mild paresthesia in the femoral nerve
111
area but no pain and no visible muscle contraction (10-15 mA). The mNMES was
112
administered for maximum tolerable intensity, with a symmetrical biphasic current of 100
113
Hz, pulse width of 1 msec, 30 min/day, and duty cycle of 10 sec on/20 sec off, and was
114
performed 5 days/week. The patients in the mNMES group gradually increased the
115
stimulation intensity as much as possible through the session to induce at least visible
116
muscle contraction and, if possible, passive knee extension movement (15-38 mA). If the
117
self-selected intensity did not result in visible contractions, the patient was excluded from
118
the trial. Each NMES intervention was applied before the standard rehabilitation programs
119
(voluntary muscle strength exercises) were begun. Each NMES interventions used an
120
electrical stimulation devicea. The surface self-adhesive electrodes (5×9 cm)b were placed
AC C
EP
TE D
M AN U
SC
106
6
ACCEPTED MANUSCRIPT on the femoral nerve trunk and the rectus femoris muscle, vastus lateralis muscle, and
122
vastus medialis muscle motor points (Figure 1). The femoral nerve trunk and motor points
123
were identified by pencil electrode. Applying the electrodes over the femoral nerve trunk
124
and the motor point of the muscle reduces the current threshold required and maximizes the
125
amount of afferent input 15,16.
RI PT
121
SC
126 Assessment
128
Quadriceps maximum voluntary isometric contraction (MVIC) was the main outcome
129
measure. Leg skeletal muscle mass (LSMM) using multiple frequency bioelectrical
130
impedance analysis (BIA), the Timed Up and Go test (TUG), the 2 Minute Walk Test
131
(2MWT), the VAS, and the ROM of the knee were the secondary outcome measures. All
132
outcome measures were measured preoperative and at 2 and 4 weeks (at the end of
133
treatment) after TKA surgery. MVIC was measured using a hand-held dynamometer with a
134
belt for fixationc, which has been found to be a valid method for measuring MVIC17,18. After
135
a warm-up and familiarization with the procedure, the patients sat at the end of the
136
examination table with a hip angle of 90° and a knee angle of 90°. We attached a force
137
sensor to the patient’s ankle (perpendicular to the longitudinal axis of the leg), 1 cm proximal
138
to the lateral malleolus. Three trials were performed, with 1 min of rest given between
139
subsequent trials, and the maximum value was adopted. The patient was asked to repeat the
140
trials if the difference in MVIC between two of the three trials was greater than 10%. All
AC C
EP
TE D
M AN U
127
7
ACCEPTED MANUSCRIPT MVIC measures were gravity compensated. LSMM was measured by multiple-frequency
142
BIAd. BIA is used to predict body composition using differences in electrical conductivity
143
that result from the biological characteristics of body tissue19. The segmental impedance
144
levels of the right and left arm, trunk, and right and left leg were measured. In
145
multi-frequency analysis, electrical current is passed through the body, and we measured the
146
body impedance. We measured LSMM using BIA in the involved leg. We performed this
147
measurement only after the TKA surgery so the implants would be accounted for in the
148
measurement. The data for MVIC and LSMM were used to calculate the body weight ratio.
149
The TUG measures the time required to rise from an armchair, walk 3 m, turn around, and
150
return to sitting in the same chair without physical assistance. The 2MWT measures the total
151
distance walked by an individual over 2 minutes. Patients were instructed to walk as quickly
152
as they felt safe and comfortable. Patients were permitted to use a T-cane. Knee pain was
153
quantified using the VAS. Patients rated the pain in and around the knee that had been
154
operated on immediately after the MVIC test using a ruler with a scale from 0 to 100 mm,
155
where 0 represented no pain and 100 represented the worst imaginable pain. The ROM of
156
passive knee flexion and extension was measured using a hand-held goniometer, which has
157
been found to be a valid method for quantifying knee movement. While the patient was lying
158
supine on a bed, a researcher aligned the stationary arm of the goniometer to the greater
159
trochanter and the moveable arm to the lateral malleolus. All outcome measures were
160
measured by a researcher who was blinded to the group allocation and data acquisition.
AC C
EP
TE D
M AN U
SC
RI PT
141
8
ACCEPTED MANUSCRIPT Statistical analysis
162
The baseline characteristics and outcome measures were compared among the three groups
163
using the chi square test and the one-way factorial analysis of variance (ANOVA). We
164
compared all outcome measures among the three groups (mNMES, sNMES and Control) at
165
three time points: (1) pre-operative (baseline), (2) pre-intervention (2 weeks after TKA) and
166
(3) post-intervention (4 weeks after TKA). All outcome measures were evaluated using
167
ANOVA among the three groups at the three time points. All tests were performed using a
168
significance level of 0.05. A post-hoc Newman-Keuls test was used to perform multiple
169
comparisons between groups (P = 0.05/2 = 0.025), if appropriate. We also calculated the
170
effect sizes between each groups at post-intervention for MVIC, which was proposed by
171
Cohen’s d. The effect sizes were interpreted as small (0.30–0.20), medium (around 0.50)
172
and large (above 0.80). All values are reported as means (SD), unless otherwise stated. Also,
173
we calculated the difference between the pre-operative measures and the post-intervention
174
measures divided by the pre-operative measures (Table 2, ⊿%). All statistical analyses
175
were performed with GraphPad Prism 5.
SC
M AN U
TE D
EP
AC C
176
RI PT
161
177
Results
178
Of the 95 patients who participated in this trial, 15 patients (16%) did not meet the inclusion
179
criteria and 3 patients (3%) did not consent to participate. At baseline, intervention-related
180
characteristics were obtained from 77 patients (81%). However, only 66 (69%) of them 9
ACCEPTED MANUSCRIPT completed the 4-week rehabilitation program. Evaluation was done for 22 patients in the
182
sNMES group (3 did not complete the program), 22 in the mNMES group (4 did not
183
complete the program), and 22 in the Control group (4 did not complete the program). The
184
reasons for not completing the program were deviation from the clinical pathways (7 cases)
185
and, in 3 patients in the mNMES group, ending the NMES training program prematurely
186
due to discomfort caused by the NMES stimulation. The patients in the sNMES group who
187
completed the entire NMES training program tolerated the NMES stimulation very well.
188
(Figure 2).
189
There were no statistically significant differences among the three groups in any of the
190
pre-operative characteristics (Table 1).
191
There were no statistically significant three-group differences in MVIC (P = 0.828), TUG
192
(P = 0.863), 2MWT (P =0.994), VAS (P = 0.401), knee-joint flex ROM (P = 0.538), or
193
knee-joint ext ROM (P =0.198) at the pre-operative point when accounting for baseline
194
measures (Table 2). Also, there were no statistically significant three-group differences in
195
MVIC (P = 0.854), LSMM (P = 0.951), TUG (P = 0.241), 2MWT (P = 0.453), VAS (P =
196
0.984), knee-joint flex ROM (P = 0.790), or knee-joint ext ROM (P = 0.414) at the
197
pre-intervention point (Table 2). However, there were statistically significant three-group
198
differences in MVIC (F = 5.924, P = 0.004) and 2MWT (F =4.202, P =0.019) at the
199
post-intervention point (Table 2). We observed that the MVIC results in the sNMES group
200
(P = 0.028; 95% confidence interval (CI), of difference, 0.01 to 0.09) and mNMES group (P
AC C
EP
TE D
M AN U
SC
RI PT
181
10
ACCEPTED MANUSCRIPT = 0.001; 95% CI of difference, 0.03 to 0.11) were significantly better at the
202
post-intervention point compared with the Control group. The effect size was also medium
203
(0.71) for MVIC between the sNMES group and the Control group measures. The effect
204
size was large (1.15) for MVIC between the mNMES group and Control group measures.
205
Furthermore, there were no statistically significant differences between the sNMES group
206
and the mNMES group in MVIC at the post-intervention point (P = 0.38; 95% CI of
207
difference -0.22 to 0.57). The effect size was also small (0.30) between the sNMES group
208
and Control group measures. Also, we observed that the 2MWT results between the sNMES
209
group (P = 0.046; 95% CI of difference -2.48 to 29.96) and mNMES group (P = 0.003; 95%
210
CI of difference 6.52 to 30.25) were significantly better at the post-intervention point
211
compared with the Control group. However, there were also no statistically significant
212
differences between the sNMES group and the mNMES group in 2MWT (P = 0.49; 95% CI
213
of difference -18.0 to 8.7) at the post-intervention point. There were no statistically
214
significant three-group differences in LSMM (P = 0.733), TUG (P = 0.079), VAS (P =
215
0.200), knee-joint flex ROM (P =0.603), and knee-joint ext ROM (P =0.414) at the
216
post-intervention point, these assessments are adequately addressed with standard
217
postoperative rehabilitation programs. (Table 2).
AC C
EP
TE D
M AN U
SC
RI PT
201
218 219
Discussion
220
This trial compared the effects of sNMES and conventional mNMES in patients after TKA. 11
ACCEPTED MANUSCRIPT The results of this trial showed that patients in the sMNES and mNMES groups achieved
222
better results on muscle strength at 4 weeks after TKA surgery than did patients in the
223
Control group. Particularly, mNMES may facilitate quadriceps muscle strength gains more
224
rapidly than the control group, as the quadriceps strength reached 90% of preoperative
225
strength 4 weeks after TKA. Control groups showed quadriceps strength that was 63% of
226
the preoperative strength 4 weeks after TKA, despite engaging in postoperative
227
rehabilitation programs. In previous studies, a 40-50% reduction relative to preoperative
228
levels in the quadriceps strength was evident 4 weeks after TKA20,21, similar to the results of
229
our trial. However, there were no changes in the LSMM throughout this trial in all three
230
groups. The quadriceps weakness in the early postoperative period is primarily explained by
231
deficits in voluntary activation rather than by atrophy20,22. This weakness of the quadriceps
232
muscles is partly due to ongoing central nervous system inhibition that prevents the
233
quadriceps from being fully activated20,22. Central nervous system inhibition has been linked
234
to knee articular swelling, inflammation, pain, and receptor damage after TKA22. The use of
235
mNMES offers an effective approach for mitigating quadriceps muscle neural activation
236
deficits in the early period after TKA and restores normal quadriceps muscle function more
237
effectively than voluntary exercise alone7,8. Stevens-Lapsley et al23 showed that the
238
recovery of quadriceps muscle strength after TKA was positively correlated with
239
NMES-induced contraction intensity. It appears that high-intensity, maximally tolerated
240
NMES stimulations have proven to be more effective than lower-intensity stimulations.
AC C
EP
TE D
M AN U
SC
RI PT
221
12
ACCEPTED MANUSCRIPT However, three patients in the mNMES group dropped out due to discomfort caused by the
242
electrical stimulation. No patients dropped out of the sNMES group due to NMES
243
discomfort or pain. In this trial, we showed that sNMES may facilitate quadriceps muscle
244
strength gains more rapidly than voluntary exercise alone, as the quadriceps strength
245
reached 83% of preoperative strength 4 weeks after TKA in the sNMES group. In a
246
previous trial, the sNMES setting was reported to activate the recruitment of the central
247
nervous system through electrically evoked peripheral afferent nerves, leading to the
248
development of motor activation11. Even sensory levels of stimulation that target peripheral
249
afferent nerves can induce prolonged changes in the excitability of the human motor
250
cortex12,24. sNMES stimulation of the afferent nerves of the hand resulted in an increase in
251
the functional magnetic resonance imaging signal intensity in the primary and secondary
252
motor and somatosensory areas of the cortex25. Furthermore, the use of wide-pulse (1 ms)
253
and high-frequency (100 Hz) NMES produced significantly greater muscle strength
254
compared with narrow-pulse (0.05 ms) and low-frequency (25 Hz) stimulation, and this
255
strength enhancement was attributed to the invocation of the central nervous system by the
256
greater afferent input to the muscle12,26. As we used a wide-pulse and high-frequency setting
257
in the present trial, we can conclude that sNMES might facilitate quadriceps muscle
258
strength gains more rapidly than voluntary exercise alone. For patients who experience
259
NMES discomfort and pain, the sNMES setting is recommended.
260
Also, the sNMES and mNMES groups showed significantly improved physical function
AC C
EP
TE D
M AN U
SC
RI PT
241
13
ACCEPTED MANUSCRIPT (i.e., 2MWT) compared to the group receiving the standard rehabilitation program alone. In
262
previous trials, quadriceps weakness has become more profound and the quadriceps muscle
263
did not recover its physical function to the level of healthy adults after TKA5,6. In this trial,
264
there were no significant differences among the three groups in the VAS or ROM results at
265
4 weeks after TKA. Therefore, quadriceps muscle strength has the potential to impact
266
2MWT improvement. As quadriceps weakness has the potential to greatly impact physical
267
function, it is particularly important to improve quadriceps muscle strength early after TKA
268
5-6,20
269
after TKA. This is most likely due to a TUG ceiling effect, as the mean performance of the
270
mNMES group on this measure was 8.8 seconds at 4 weeks after TKA. The mean
271
performance on the TUG in this age group has been reported to be 9.0 seconds27, which
272
indicates that the mNMES group had recovered to normative levels on this measure at 4
273
weeks after TKA.
SC
M AN U
EP
TE D
. However, the differences in the TUG were no longer statistically significant 4 weeks
AC C
274
RI PT
261
275
Study limitations
276
The treating therapists were not blinded to their group assignments for the duration of the
277
trial. Also, follow-up data were not collected in this trial. Furthermore, the NMES settings
278
that were used differed in several ways (e.g., in terms of total stimulation time, quantity of
279
electric charge, on/off time, and ease of use) other than the presence or absence of muscle
280
contraction. Consequently the apparent difference in effectiveness maynot be attributed to 14
ACCEPTED MANUSCRIPT any single factor. Also, a sham stimulation group should be set up and placebo affects
282
should be considered. However, realistic placebo controls in an NMES trial might be
283
impractical because the use of sham devices is inevitably apparent to patients.
RI PT
281
284 Conclusions
286
The results of this trial show that patients in the mNMES group achieved better results on
287
muscle strength and functional performance measures at 4 weeks after TKA surgery than
288
did patients in the Control group. However, the conventional mNMES treatment was
289
uncomfortable for some patients. In such cases, we suggest that sNMES might be more
290
comfortable and may achieve greater quadriceps muscle strength than standard
291
rehabilitation programs. However, the ideal NMES settings (intensity, frequency,
292
wide-pulse) were not clarified in this trial. In further research, a more comfortable ideal
293
NMES setting should be determined.
EP
TE D
M AN U
SC
285
AC C
294 295
Suppliers
296
a. Intelect Mobile Stim, DJO Global, Vista, CA, USA
297
b. Axelgaard, PALS, Platinum, 5×9 cm, USA
298
c. µTas F-10, Anima Corp., JAPAN
299
d. Ito-InBody, Biospace Corp., Japan
300 15
ACCEPTED MANUSCRIPT References
302
1.
OECD. Health at a glance 2013:OECD indicators. OECD Publishing; 2013.
303
2.
Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of
RI PT
301
patients report long-term pain after total hip or knee replacement for osteoarthritis? A
305
systematic review of prospective studies in unselected patients. BMJ Open.
306
2012;2:e000435. 3.
Stevens-Lapsley JE, Schenkman ML, Dayton MR. Comparison of self-reported knee
M AN U
307
SC
304
308
injury and osteoarthritis outcome score to performance measures in patients after total
309
knee arthroplasty. PMR. 2011;3:541-549; quiz 549.
310
4.
Mizner RL, Petterson SC, Clements KE, Zeni JA Jr, Irrgang JJ, Snyder-Mackler L. Measuring functional improvement after total knee arthroplasty requires both
312
performance-based and patient-report assessments: a longitudinal analysis of outcomes.
313
J Arthroplasty. 2011;26:728-37.
EP
5.
Mizner RL, Petterson SC, Stevens JE, Vandenborne K, Snyder-Mackler L. Early
AC C
314
TE D
311
315
quadriceps strength loss after total knee arthroplasty. The contributions of muscle
316
atrophy and failure of voluntary muscle activation. J Bone Joint Surg Am.
317
2005;87:1047-53.
318
6.
arthroplasty compared to healthy adults. J Orthop Sports Phys Ther. 2010;40:559-67.
319 320
Bade MJ, Kohrt WM, Stevens-Lapsley JE. Outcomes before and after total knee
7.
Petterson SC, Barrance P, Buchanan T, Binder-Macleod S, Snyder-Mackler L. 16
ACCEPTED MANUSCRIPT 321
Mechanisms underlying quadriceps weakness in knee osteoarthritis. Med Sci Sports
322
Exerc. 2008;40:422-7. 8.
Kittelson AJ, Stackhouse SK, Stevens-Lapsley JE. Neuromuscular electrical
RI PT
323 324
stimulation after total joint arthroplasty: a critical review of recent controlled studies.
325
Eur J Phys Rehabil Med. 2013;49:909-20. 9.
Stevens-Lapsley JE, Balter JE, Wolfe P, Eckhoff DG, Kohrt WM. Early neuromuscular
SC
326
electrical stimulation to improve quadriceps muscle strength after total knee
328
arthroplasty: a randomized controlled trial. Phys Ther. 2012;92:210-26.
M AN U
327
10. Monaghan B, Caulfield B, O'Mathúna DP. Surface neuromuscular electrical stimulation
330
for quadriceps strengthening pre and post otal knee replacement. Cochrane Database
331
Syst Rev. 2010; 20:CD007177.
332
TE D
329
11. Petterson SC, Mizner RL, Stevens JE, et al. Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with
334
an imbedded prospective cohort. Arthritis Rheum. 2009;61:174-83.
336 337
AC C
335
EP
333
12. Collins DF. Central contributions to contractions evoked by tetanic neuromuscular electrical stimulation. Exerc Sport Sci Rev. 2007;35:102-9. 13. Sullivan JE, Hedman LD. A home program of sensory and neuromuscular electrical
338
stimulation with upper-limb task practice in a patient 5 years after a stroke. Phys Ther.
339
2004;84:1045-54.
340
14. Yoshida Y, Ikuno K, Shomoto K. Effects of sensory level neuromuscular electrical 17
ACCEPTED MANUSCRIPT stimulation in patients after total knee arthroplasty: a pilot quasi randomized trial.
342
Japanese Journal of Electrophysical Agents. 2014; 21:45-52. (in Japanese)
343
15. Robinson A, Snyder-Mackler L. Clinical Electrophysiology: Electrotherapy and
344
Electrophysiologic Testing. 3rd ed. Baltimore, MD: Williams & Wilkins; 2008.
RI PT
341
16. Bergquist AJ, Wiest MJ, Collins DF. Motor unit recruitment when neuromuscular
346
electrical stimulation is applied over a nerve trunk compared with a muscle belly:
347
quadriceps femoris. J Appl Physiol (1985). 2012;113:78-89.
M AN U
348
SC
345
17. Katoh M, Isozaki K. Reliability of isometric knee extension muscle strength
349
measurements of healthy elderly subjects made with a hand-held dynamometer and a
350
belt. J Phys Ther Sci. 2014;26:1855-9.
18. Martin HJ, Yule V, Syddall HE, Dennison EM, Cooper C, Aihie Sayer A. Is hand-held
352
dynamometry useful for the measurement of quadriceps strength in older people? A
353
comparison with the gold standard Bodex dynamometry. Gerontology. 2006;52:154-9.
EP
19. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. European consensus on definition and
AC C
354
TE D
351
355
diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age
356
Ageing. 2010;39:412-23.
357
20. Mizner RL, Petterson SC, Snyder-Mackler L. Quadriceps strength and the time course
358
of functional recovery after total knee arthroplasty. J Orthop Sports Phys Ther.
359
2005;35:424-36.
360
21. Stevens JE, Mizner RL, Snyder-Mackler L. Quadriceps strength and volitional 18
ACCEPTED MANUSCRIPT 361
activation before and after total knee arthroplasty for osteoarthritis. J Orthop Res.
362
2003;21:775-9.
364 365
22. Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms
RI PT
363
and treatment perspectives. Semin Arthritis Rheum. 2010;40:250-66.
23. Stevens-Lapsley JE, Balter JE, Wolfe P, et al. Relationship between intensity of
quadriceps muscle neuromuscular electrical stimulation and strength recovery after
367
total knee arthroplasty. Phys Ther. 2012;92:1187-96.
M AN U
SC
366
368
24. Kimberley TJ, Lewis SM, Auerbach EJ, Dorsey LL, Lojovich JM, Carey JR. Electrical
369
stimulation driving functional improvements and cortical changes in subjects with
370
stroke. Exp Brain Res. 2004;154:450-60.
25. Golaszewski S, Kremser C, Wagner M, Felber S, Aichner F, Dimitrijevic MM.
TE D
371
Functional magnetic resonance imaging of the human motor cortex before and after
373
whole-hand afferent electrical stimulation. Scand J Rehabil Med. 1999;31:165-73.
EP
372
26. Bergquist AJ, Wiest MJ, Collins DF. Motor unit recruitment when neuromuscular
375
electrical stimulation is applied over a nerve trunk compared with a muscle belly:
376
quadriceps femoris. J Appl Physiol. 2012;113:78-89.
377
AC C
374
27. Steffen TM, Hacker TA, Mollinger L. Age- and gender-related test performance in
378
community-dwelling elderly people: Six-Minute Walk Test, Berg Balance Scale, Timed
379
Up & Go Test, and gait speeds. Phys Ther. 2002;82:128-3.
380 19
ACCEPTED MANUSCRIPT Figure legends
382
Figure 1 Stimulation location. The channel-1 is connected to femoral nerve trunk and the
383
vastus lateralis muscle motor point. The channel-2 is connected to the rectus femoris and the
384
vastus medialis muscle motor point.
385
Figure 2
386
CONSORT flow chart to show the flow of patients through the trial.
SC
RI PT
381
M AN U
387 388
Titles of tables
389
Table 1
390
Baseline characteristics of trial patients.
TE D
391 Table 2
393
Outcome measures for mNMES group, sNMES group, and Control group at baseline and 2
394
and 4 weeks after TKA
396 397
AC C
395
EP
392
398 399 400 20
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
401
21
ACCEPTED MANUSCRIPT
mNMES group sNMES group
Control group
Total group P value
(n = 22)
(n = 22)
(n = 66)
Gender (F/M)
18 / 4
18 / 4
20 / 2
56 / 10
0.62a
Age (years)
75.9 (4.7)
71.6 (7.0)
72.5 (6.2)
73.5 (6.3)
0.07b
Height (m)
1.51 (0.05)
1.54 (0.06)
1.52 (0.07)
Weight (kg)
55.9 (8.3)
60.8 (6.3)
60.3 (9.6)
BMI (kg/m2)
24.6 (2.9)
25.4 (2.2)
25.8 (3.3)
112.0 (9.7)
113.0 (11.2)
110.3 (11.8)
111.6 (10.9)
0.54b
14.5 (4.7)
15.3 (8.0)
18.3 (6.9)
16.1 (6.8)
0.20b
26 / 30
0.64a
Knee joint ext ROM（－°） K-L Grading Scale （3/4）
9 / 13
7 / 15
1.52 (0.06)
0.22b
58.7 (8.5)
0.14b
25.3 (3.0)
0.40b
SC
ROM（°）
M AN U
Knee joint flex
RI PT
(n = 22)
10 / 12
AC C
EP
TE D
Table 1. Pre-operative characteristics of trial patients. Data are presented as means and standard deviations (in parentheses) or as numbers of patients. mNMES; motor-level neuromuscular electrical stimulation, sNMES; sensory-level neuromuscular electrical stimulation, F; females, M; males, BMI; body mass index, ROM; range of motion, K-L Grading Scale; Kellgren-Lawrence Grading Scale. a Chi square test, b one-way factorial analysis of variance.
ACCEPTED MANUSCRIPT
LSMM (kg / kg)
(3) Post-intervention
(baseline)
(2 weeks after TKA)
(4 weeks after TKA)
mNMES
0.29 (0.08)
0.13 (0.05)
0.26 (0.05)
sNMES
0.29 (0.10)
0.12 (0.04)
0.24 (0.07)
Control
0.30 (0.10)
0.13 (0.04)
p value
0.828
0.854
mNMES
Not measured
91.7 (11.4)
sNMES
Not measured
92.5 (14.6)
Control
Not measured
91.2 (13.9)
p value
VAS (mm)
13.5 (4.3)
sNMES
11.6 (4.5)
16.2 (6.9)
Control
12.2 (3.6)
p value
0.863
mNMES
114 (25)
sNMES
113 (31)
Control
113 (20)
p value
0.994
*
83 63
0.004
92.9 (12.3)
Not calculated
92.3 (13.8)
Not calculated
89.9 (121.6)
Not calculated
0.733
8.8 (1.8)
76
10.0 (13.1)
86
14.1 (4.5)
10.6 (2.7)
86
0.241
0.079
101 (17) 91 (32)
135 (16) 130 (25)
♯
*
119 115
95 (24)
116 (21)
0.453
0.019
25 (18)
53 (16)
20 (12)
80
29 (22)
54 (20)
29 (26)
101
20 (18)
53 (27)
31 (23)
153
0.401
0.984
0.200
mNMES sNMES Control p value
103
mNMES
112 (10)
85 (9)
121 (6)
108
sNMES
113 (11)
86 (8)
122 (4)
107
AC C
Knee joint
90
0.19 (0.07)
M AN U
11.6 (4.7)
TE D
2MWT (m)
mNMES
♯
EP
TUG (sec)
0.951
⊿ (%)
RI PT
(kgf / kg)
(2) Pre-intervention
SC
MVIC
(1) Pre-operative
Control
110 (12)
84 (9)
120 (5)
120
p value
0.538
0.790
0.603
mNMES
15 (5)
15 (7)
5 (4)
33
sNMES
16 (8)
18 (6)
5 (5)
33
Control
18 (7)
17 (7)
4 (4)
20
p value
0.198
0.414
0.507
flex ROM（°）
Knee joint
ext ROM（°）
ACCEPTED MANUSCRIPT Table 2. Outcome measures for mNMES group, sNMES group, and Control group at baseline and 2 and 4 weeks after TKA. Data are presented as means and standard deviations (in parentheses). MVIC; quadriceps maximum voluntary isometric contraction. LSMM; leg skeletal muscle mass, TUG; Timed Up and Go Test, 2MWT; 2-Minute Walk Test, VAS; visual analogue
RI PT
scale, ROM; range of motion. ⊿%; Difference between the pre-TKA surgery measures and the post-intervention measures divided by the pre-TKA surgery measures.
*Statistically significant improvements were observed for these variables when compared to Control group values (P<0.05).
SC
#Statistically significant improvements were observed for these variables when compared to
AC C
EP
TE D
M AN U
Control group values (P <0.01).
2
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
Figure 1. Stimulation location.
EP
The channel-1 is connected to femoral nerve trunk and the vastus lateralis muscle motor point. The channel-2 is connected to the rectus femoris and the vastus medialis muscle motor point.
AC C
5
1
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
Figure 2. CONSORT flow chart to show the flow of patients through the trial.