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Effectiveness of Thermal Stimulation for the Moderately to Severely Paretic Leg After Stroke: Serial Changes at One-Year Follow-Up
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Effectiveness of Thermal Stimulation for the Moderately to Severely Paretic Leg After Stroke: Serial Changes at One-Year Follow-Up Chung-Chao Liang, MD, Tsung-Cheng Hsieh, PhD, Chun-Hsiang Lin, PT, BS, Yu-Chun Wei, PT, BS, Jung Hsiao, PT, BS, Jia-Ching Chen, PT, MS ABSTRACT. Liang C-C, Hsieh T-C, Lin C-H, Wei Y-C, Hsiao J, Chen J-C. Effectiveness of thermal stimulation for the moderately to severely paretic leg after stroke: serial changes at one-year follow-up. Arch Phys Med Rehabil 2012;93:1903-10. Objective: To evaluate the serial changes of long-term effects
of thermal stimulation (TS) on acute stroke patients. Design: A prospective study with follow-up at 3, 6, and 12 months after TS to assess motor and balance function of the paretic leg of acute stroke patients. Setting: A general hospital rehabilitation department. Participants: Poststroke patients (N⫽30) with moderate to severe impairment of leg function. Interventions: In addition to receiving standard rehabilitation, eligible patients were randomly assigned to a TS group (5 thermal stimulations per week for 6wk) or a control group (3 consultations per week for 6wk). Main Outcome Measures: Fugl-Meyer lower extremity score, Medical Research Council Scale for the Lower Extremity, Berg Balance Scale, Modified Motor Assessment Scale, Functional Ambulation Classification, and Barthel Index were administered at baseline, after 4 and 6 weeks of treatment, and at the 3-, 6-, and 12-month follow-up. Results: No significant differences were found between the 2 groups at baseline. After TS, the Fugl-Meyer lower extremity score, Medical Research Council Scale for the Lower Extremity, Modified Motor Assessment Scale, and Functional Ambulation Classification were significantly better in the TS group, and the effects persisted for 3 months (P⬍.05). Significant differences were found between the 2 groups for the Berg Balance Scale and Barthel Index only at the 3-month follow-up (P⬍.05). However, all the effects except for the Fugl-Meyer lower extremity score had disappeared at the 6-month follow-up (P⬎.05). Conclusions: The long-term benefits of TS for patients with acute stroke may be sustained for 3 months but disappear by the 6-month and 1-year follow-up. Key Words: Follow-up studies; Lower extremity; Rehabilitation; Stroke. © 2012 by the American Congress of Rehabilitation Medicine
From the Department of Rehabilitation Medicine, Tzu Chi Buddhist General Hospital, Hualien (Liang, Lin, Wei, Hsiao, Chen); and the Departments of Medicine (Liang) and Physical Therapy (Lin, Chen), and the Institute of Medical Sciences (Hsieh), Tzu Chi University, Hualien, Taiwan. Supported by the Tzu Chi General Hospital through grant TCRD 100-38 Research Plan. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Jia-Ching Chen, PT, MS, Dept of Rehabilitation Medicine, Tzu Chi Buddhist General Hospital, 707 Chung Yang Rd, Sec 3, Hualien 970 Taiwan, e-mail: [email protected]. In-press corrected proof published online on Aug 14, 2012, at www.archives-pmr.org. 0003-9993/12/9311-00229$36.00/0 http://dx.doi.org/10.1016/j.apmr.2012.06.016
FTER A STROKE, MORE than half of patients have A moderate to severe impairment on admission, and many become confined to bed or a wheelchair. Shortening the 1,2
period of being wheelchair-bound or bedridden through early and rapid recovery of motor and walking functions is usually of great concern to the patient, the family, and the clinician.2-4 Various treatment techniques such as intensive exercise5 or cycling exercise,6,7 functional electrical stimulation,7-9 body weight support treadmill,4,10,11 and robotic gait trainer4,11-14 are integrated into rehabilitation programs to enhance recovery of motor and walking function of the paretic leg after acute or subacute stroke. Most studies have reported the immediate5,6,12 or short-term effects7,8,14; only a few have assessed the longterm effects.4,10,13,15,16 Repetitive sensory stimulation and mass motor practice can facilitate neuroplasticity and cortical reorganization in poststroke patients.17 As shown on functional magnetic resonance imaging, thermal stimulation (TS) activates larger areas of the brain than does tactile or mechanical stimulation, and the degree of activation is nearly identical to that of motor tasks.18,19 Recently, we have added an additional TS intervention to our rehabilitation programs. In earlier studies, we found that TS had the potential of facilitating paretic upper20 and lower limb21 recovery after acute stroke. Wu et al22 have also reported the beneficial effects on the paretic upper limbs of chronic stroke patients. Unfortunately, our studies and Wu’s study only addressed the immediate and short-term effects of TS. Compared with other training modalities commonly used in orthopedic rehabilitation, TS is simple, convenient, and inexpensive.20,23 However, its long-term effects on motor function recovery after stroke are still unknown. Therefore, we designed a study to examine the serial changes of long-term effects on motor and balance function of the lower extremity after additional TS intervention in the early phase of stroke. METHODS Participants All patients who had a stroke and were consecutively admitted to the Department of Rehabilitation Medicine at Tzu Chi List of Abbreviations BBS BI FAC FMA-LE GEE MMAS MRC-LE TS
Berg Balance Scale Barthel Index Functional Ambulation Classification Fugl-Meyer Assessment for the Lower Extremity generalized estimating equation Modified Motor Assessment Scale Medical Research Council Scale for the Lower Extremity thermal stimulation
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Buddhist General Hospital, Hualien, Taiwan, from December 2009 to January 2011 were recruited and screened for eligibility for the study. The main inclusion criteria were (1) a diagnosis of first-ever stroke within the last 4 weeks; (2) no history of cardiac or orthopedic disease before the stroke; (3) the ability to follow instructions by the therapist during the study; and (4) a motor deficit of the paretic leg that was less than Brunnstrom stage 4.24 The exclusion criteria were (1) a history of severe diabetes or sensory impairment attributable to peripheral vascular disease or neuropathy; (2) global aphasia; or (3) a previous psychological disorder. Of the 42 subjects recruited, 30 met the inclusion criteria and were randomly assigned either to a TS group (15 subjects) or a control group (15 subjects) by computer-generated random numbers held in sealed envelopes by an individual not involved with the study. Both groups received 40 minutes each of physical and occupational therapy once per day, 5 days per week, for 6 weeks. The TS group also received a 40-minute TS intervention session 5 times weekly for 6 weeks with the same physical therapist. Participants in the control group were visited 3 times per week for 6 weeks, for 20-minute discussion sessions provided by a therapist uninvolved in the study. The research protocol was approved by the ethics committee of Tzu Chi University and Medical Center. All subjects gave informed consent before participating in the study. Intervention The method and definition of TS intervention used in this study were reported in our previous study.21 During the intervention, patients lay comfortably supine or side-lying on a mat with 1 or 2 pillows under their head, and were able to see their lower limbs. The thermal agents were hot (70°C) and cold (0°C) packs wrapped with 2 to 3 layers of towels that buffered thermal conduction and modulated the temperature of the thermal agent, which was placed over the calf or foot. To keep the stimulated temperature as constant as possible (45°– 48°C for heat and 11°–15°C for cold), a thermometer was attached with paper tape on the stimulation site to record the skin temperature during hot and cold pack stimulation. Hot and cold stimulation were limited to 30 seconds (46.5°⫾4.1°C) and 45 seconds (15.5°⫾4.7°C), respectively.21 The hot pack was first placed on the nonparetic leg, and the patient was asked to be aware of the change in skin temperature and learned to move the nonparetic leg away from the hot pack when the temperature became uncomfortable. Next, the hot pack was placed on the paretic leg 8 times, separated by 30-second intervals. During TS, the patient was encouraged to actively move the paretic leg as far as possible from the stimulus and was guided by the therapist when discomfort developed.21 If a motor response was not generated after the development of discomfort, or if the patient tolerated the maximum duration of stimulation, the leg was moved away from the stimulus by the therapist. Thus, the thermal agent produced a hot or cold sensation, followed by active or passive motion. When the skin temperature of the paretic leg dropped to baseline after 8 episodes of heat stimulation, an identical procedure was used with the cold pack. Once patients could control their leg movements, they were encouraged to perform them independently. If patients were unable to move the paretic leg at the beginning (antigravity), they could turn to initiate the movement in the side-lying position (gravity). A cycle of TS consisted of 8 applications each of hot and cold stimuli. Three such cycles were performed during each session. Therefore, approximately 48 minutes (8 ⫻ [30s ⫹ 30s] ⫻ 2 ⫻ 3) was required to complete a session of TS therapy. This duration was approximate because not all patients tolerated the full 30 Arch Phys Med Rehabil Vol 93, November 2012
seconds of stimulus. Adverse effects were assessed during and after TS. All patients in both groups completed their respective study interventions while in the hospital. After finishing the treatment protocol, most were discharged and continued outpatient rehabilitation programs. Assessments We tested all eligible patients with measures of demonstrated reliability, validity, and sensitivity to change during poststroke recovery. To do so, we selected the Fugl-Meyer Assessment for the Lower Extremity (FMA-LE),25 the Medical Research Council Scale for the Lower Extremity (MRC-LE),26,27 and the Functional Ambulation Classification (FAC) for gait ability28 as our primary outcome measures. Secondary outcome variables included the Berg Balance Scale (BBS),29 the Modified Motor Assessment Scale (MMAS),30 and the Barthel Index (BI).31 The FMA-LE measures impairment after stroke with a 3-point ordinal scale (0, cannot perform; 1, can partially perform; 2, can perform fully). The scale measures 17 items, with a scoring range from 0 to 34. It has been shown to have high test-retest reliability (total, .98 –.99; subtests, .87–1.00), interrater reliability, and construct validity.25 The MRC-LE is an ordinal scale with good to very good reliability (.80–.96) for measuring strength of muscle force, with scores from 0 (no muscle contraction) to 5 (normal strength). We used this scale to rate the paretic hip flexors, knee extensors, and ankle dorsiflexors (range, 0 –15).26,27 Gait ability was evaluated with the FAC. This measure is reliable and valid for determining the different levels of walking abilities, with a range of 0 (unable to walk) to 5 (near-normal walk).28 The BBS evaluates balance on 14 items (1 sitting, 13 standing) and is based on a 5-point ordinal scale of 0 to 4, with the total score ranging from 0 to 56. It has been reported to have high reliability (total, .85–.98) and validity (total, .82–.94).29,30 The MMAS contains 8 items, each graded on a 6-point scale, with a range from 0 to 48.31 The BI evaluates 10 basic activities of daily living and is scored from 0 to 100 in 5-point increments according to the degree of assistance required by the patient.32 The reliability and validity of MMAS and BI assessment have been well documented.31,32 All outcome measures were evaluated at baseline, at 4 and 6 weeks after the treatment, and at 3-, 6-, and 12-month follow-up by the same therapist, who was blinded for group allocation. Statistical Analysis Basic characteristics of all patients were compared with the Student t (parametric data), Mann-Whitney U (nonparametric
Table 1: Baseline Characteristics and Measurements for Patients in the TS and Control Groups (Nⴝ30) Variable
Age (y) Sex (male/female) Stroke onset to treatment (d) Type of stroke (infarction/ hemorrhage) Side of paresis (right/left) Brunnstrom stage (scale)
TS (n⫽15)
Control (n⫽15)
56.1⫾11.9 59.73⫾11.6 12/3 7/8 10.9⫾5.4 13.6⫾6.4 9/6 9/6 6/9 3 (2.0–3.0)
7/8 3 (2.0–3.0)
P
.410 (t) .13 (F) .22 (t) 1 (2) 1 (2) .46 (M)
NOTE. Values are mean ⫾ SD, n, median (interquartile range), or as otherwise indicated. Abbreviations: 2, chi-square test; F, Fisher exact test; M, MannWhitney U test; t, Student t test.
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Assessed for eligibility (n=42) n=12, excluded due to orthopedic problems or history of severe diabetes Randomized (n=30)
Complete 4 and 6
Thermal group
Control group
(n=15)
(n=15)
Thermal group
Control group
(n=15)
(n=15)
3-month follow-up
Thermal group
Control group
assessment (n=30)
(n=15)
6-month follow-up
Thermal group (n=13)
Control group (n=12)
assessment, analysis
(Two drop-out for loss
(Three drop-out for
with intention to treat
of contact, n=1;
loss of contact, n=2
refused, n=1)
and death, n=1)
weeks intervention and assessment
(n=30)
One-year follow-up
Thermal group (n=13)
(n=15)
Control group (n=12)
assessment, analysis with intention to treat (n=30) Fig 1. Flowchart showing the progress of patients participating in the follow-up study and dropouts.
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33 30
#
27
#
24
*
#
*
#
*
#
*
MRC-LE (scale)
FMA-LE (score)
Control group Thermal group
*
21
#
10
*
9
#
8
*
18
6
15
5
12
4
9
3
6
2
3
1
*
*
*
3m
6m
12m
*
*
6m
12m
0 w4
w6
3m
6m
12m
*
*
4.0 #
3.5
*
#
3.0 #
2.5
*
w1 BBS (score)
w1
FAC (scale)
#
11
7
0
w4
w6
55 #
50
*
45
*
40
*
35
*
30
2.0
25
1.5
20
1.0
15 10
0.5
5
0.0
0 w4
w6
3m
40
#
*
#
35 #
30
*
6m
12m
*
*
*
w1 BI (score)
w1 MMAS (score)
12
w4
w6
3m
100
#
90
*
*
*
3m
6m
12m
*
80
*
70
25
60
20
50
15
40 30
10
20
5
10
0
0 w1
w4
w6
3m
week
6m
12m
w1
w4
w6
week
Fig 2. Temporal changes of 6 measures (mean ⴞ SE) at weeks 4 and 6 and at 3-, 6-, and 12-month follow-up in the control and TS groups. *P<.05 significantly different vs first week within TS group; #P<.05 significantly different vs control group; adjusted for post hoc comparison based on Bonferroni method.
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THERMAL STIMULATION FOR STROKE PATIENTS, Liang
data), and chi-square or Fisher exact (nominal data) tests. All outcome variables were based on a repeated-measure design. Considering that the assumption of variance-covariance matrix of compound symmetry was probably unsatisfied as a result of the different lengths of the intervals between each of 2 neighbor time points (ie, wk 4, wk 6, 3mo, 6mo, and 12mo), we used the generalized estimating equation (GEE) method with unstructured variance-covariance matrix adjusted by the baseline of each outcome variable to identify the postintervention results between group and time effects of all measurements. A post hoc test with Bonferroni adjustment was used for controlling overall type I error. The level of statistical significance was set at P⬍.05 for all analyses. All data were analyzed as intention to treat using SPSS 18.0 statistics software.a RESULTS All 30 subjects completed the 6-week study protocol while hospitalized, and no adverse effects were reported. During the follow-up period, most patients continued outpatient rehabilitation programs at least twice a week. Two subjects, 1 in the TS group and 1 in the control group, reported a history of falling at the 6-month and 12-month follow-up, respectively, but none sustained severe physical injury. All subjects had data for all outcome measures at the 3-month point, but 2 in the TS group and 3 in the control group had withdrawn from the study at the 6-month and 12-month follow-up. The reasons given for dropping out were loss of contact and refusal to participate because of economic factors; 1 subject died. For the data on dropout subjects, we used the final evaluations as our data analysis. The data analysis was used as an intention to treat. No statistically significant differences were found between the 2 groups in any of the demographic data (table 1). The progress of subjects throughout the study is depicted in the flowchart in figure 1.
Figure 2 illustrates the longitudinal pattern of change on all the outcome measures at the 6 evaluation time points for both groups. Patients in both groups improved significantly over time (P⬍.05), and the patterns of recovery differed significantly between the 2 groups. Further, the FMA-LE, MRC-LE, FAC, BBS, and MMAS measures in the TS group deviated significantly from those in the control group between 4 weeks and 3 months, and the gap progressively narrowed from 6 months on. The results of comparisons between the 2 groups are summarized in table 2 and table 3 for the primary and secondary outcome measures, respectively. No statistically significant differences were found between the 2 groups in any of the outcome measures at baseline. Statistical comparison by means of repeated-measures analysis using the GEE method revealed no significant interaction effects between time and group. The changes in the primary outcomes for the FMA-LE, MRC-LE, and FAC all showed significant effects for both group and time (P⬍.05) (see table 2). After post hoc analysis, the MRC-LE, FAC, and MMAS in the TS group demonstrated better performance relative to the control group at 4 and 6 weeks and 3-month follow-up (P⬍.05). In addition, the BBS and BI in the TS group showed a nearly significant difference from those in the control group at 6 weeks (P⫽.05 and P⫽.054, respectively), and a significance difference at the 3-month follow-up (P⫽.038 and P⫽.031, respectively) (see table 3). Furthermore, the effect for the FMA-LE was maintained up to the 12-month follow-up. However, the effects for all outcomes except the FMA-LE had disappeared by the 6-month follow-up (see table 2). From our results comparing the TS group with the control group, we observed the optimal difference in MRC-LE at week 6, where the scales were 8.9⫾0.5 for the TS group and 6.3⫾0.6 for the control group. By using a 2-sided 5% level test and 15
Table 2: Effects of Group and Time on the Primary Outcome Measurements (Nⴝ30) Measurement
FMA-LE wk 1 wk 4 wk 6 3mo 6mo 12mo MRC-LE wk 1 wk 4 wk 6 3mo 6mo 12mo FAC wk 1 wk 4 wk 6 3mo 6mo 12mo
TS Group
Control Group
Mean Difference
Effect Size
Mean Difference of 95% CI
P*
8.9⫾4.6 19.0⫾0.9 22.2⫾1.1 24.6⫾1.1 25.6⫾1.1 26.2⫾1.1
9.2⫾5.2 13.4⫾1.0 16.1⫾1.1 18.7⫾1.2 20.5⫾1.2 21.9⫾1.3
–0.3 5.6⫾1.3 6.0⫾1.7 5.9⫾1.7 5.1⫾1.6 4.2⫾1.7
0.1 5.9 5.5 5.1 4.4 3.5
⫺4.0–3.4 3.1–8.2 2.8–9.3 2.6–9.2 2.0–8.2 0.9–7.6
.85 .000† .000† .000† .001† .013†
2.6⫾2.2 7.2⫾0.4 8.9⫾0.5 9.5⫾0.6 9.8⫾0.6 9.9⫾0.6
2.7⫾2.2 4.8⫾0.6 6.3⫾0.6 7.4⫾0.6 8.2⫾0.7 8.7⫾0.7
–0.13 2.4⫾0.7 2.6⫾0.8 2.1⫾0.8 1.6⫾0.9 1.2⫾0.9
0.1 4.7 4.7 3.5 2.5 1.8
⫺1.5–1.8 1.1–3.7 1.1–4.1 0.5–3.8 ⫺0.1–3.3 ⫺0.6–3.0
.87 .000† .001† .01† .07 .20
0.3⫾0.5 2.1⫾0.1 2.6⫾0.1 3.1⫾0.1 3.3⫾0.2 3.3⫾0.2
0.4⫾0.5 1.4⫾0.1 1.9⫾0.2 2.4⫾0.2 2.7⫾0.2 2.9⫾0.3
–0.1 0.7⫾0.2 0.7⫾0.2 0.7⫾0.2 0.5⫾0.3 0.5⫾0.3
0.3 7.0 4.4 4.4 3.0 1.6
⫺0.2–0.5 0.4–1.1 0.2–1.1 0.2–1.1 ⫺0.0–1.1 ⫺0.2–1.1
.46 .000† .005† .005† .058 .178
NOTE. Values are mean ⫾ SD or as otherwise indicated. Results were obtained from a GEE adjusted by the mean of each outcome measure at baseline. Abbreviation: CI, confidence interval. *P values at week 1 (baseline) were obtained by Student t test or Mann-Whitney U test if normality assumption was satisfied. P values at week 4, week 6, 3 months, 6 months, and 12 months were the adjusted P values obtained for post hoc comparison based on Bonferroni adjusted method. † P⬍.05, significant difference.
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THERMAL STIMULATION FOR STROKE PATIENTS, Liang Table 3: Effects of Group and Time on the Secondary Outcome Measurements (Nⴝ30)
Measurement
BBS wk 1 wk 4 wk 6 3mo 6mo 12mo MMAS wk 1 wk 4 wk 6 3mo 6mo 12mo BI wk 1 wk 4 wk 6 3mo 6mo 12mo
TS Group
Control Group
Mean Difference
Effect Size
Mean Difference of 95% CI
P*
8.1⫾10.4 30.9⫾2.5 24.0⫾3.8 43.1⫾1.8 44.8⫾1.9 45.1⫾1.8
8.7⫾7.9 24.0⫾3.8 29.7⫾3.9 34.5⫾3.7 37.5⫾3.3 39.5⫾3.2
–0.6 6.9⫾4.5 8.7⫾4.4 8.5⫾4.1 7.3⫾3.8 5.6⫾3.7
0.1 2.2 2.8 3.0 2.7 2.6
⫺6.3–7.5 ⫺2.0–15.7 ⫺0.0–17.4 0.5–16.6 ⫺0.1–14.8 ⫺1.7–12.9
.86 .129 .050 .038† .054 .132
11.7⫾6.1 26.2⫾1.9 30.0⫾1.8 32.6⫾1.6 33.1⫾1.6 33.7⫾1.7
12.0⫾5.5 20.3⫾1.6 23.8⫾1.8 27.2⫾1.8 29.9⫾1.1 31.5⫾2.2
–0.3 5.9⫾2.4 6.1⫾2.6 5.4⫾2.4 3.3⫾2.7 2.2⫾2.8
0.1 3.4 3.4 3.2 2.3 1.1
⫺4.0–4.7 1.1–10.6 1.1–11.1 0.6–10.2 ⫺2.0–8.5 ⫺3.2–7.6
.88 .016† .016† .026† .225 .429
30.3⫾11.1 65.0⫾4.0 76.7⫾3.7 85.0⫾3.1 87.0⫾3.0 88.0⫾3.0
27.7⫾14.3 55.0⫾4.5 64.7⫾5.0 74.0⫾4.1 78.7⫾3.9 80.3⫾4.3
2.7 10.0⫾6.1 12.0⫾6.2 11.0⫾5.4 8.30⫾4.9 7.7⫾5.3
0.2 2.4 2.7 3.0 2.4 1.5
⫺12.2–6.9 ⫺1.9–21.9 ⫺0.2–24.2 1.0–21.0 ⫺1.3–17.9 ⫺2.7–18.0
.57 .099 .054 .031† .089 .148
NOTE. Values are mean ⫾ SD or as otherwise indicated. Results were obtained from a GEE adjusted by the mean of each outcome measure at baseline. Abbreviation: CI, confidence interval. *P values at week 1 (baseline) were obtained by Student t test or Mann-Whitney U test if normality assumption was satisfied. P values at week 4, week 6, 3 months, 6 months, and 12 months were the adjusted P values obtained for post hoc comparison based on Bonferroni adjusted method. † P⬍.05, significant difference.
patients in each group, the power was 89% for detecting the true difference. DISCUSSION The main findings not only demonstrated that the TS group recovered significantly better than the control group in terms of the FMA-LE, MRC-LE, FAC, and MMAS, consistent with our previous study,21 but more importantly showed that the effects could be sustained to the 3-month follow-up. Furthermore, the primary outcomes for the FMA-LE could be maintained to the 12-month follow-up. We also found a significant difference in BBS and BI between the 2 groups only at the 3-month time point, but the effects disappeared at the 6-month and 12-month follow-up. Independence in daily living after stroke is often closely related to the ability to perform tasks such as moving from a sitting to a standing position, transferring, and walking. Although task-oriented repetitive training techniques have been favored in stroke rehabilitation,4,10-12 patients with moderate to severe status may have difficulty executing such tasks without a certain degree of muscle strength and voluntary movement control.6,11 Recovering some degree of paretic leg mobility and strength after stroke might greatly facilitate subsequent effective postural control and gait performance.2,11 Intensity and specificity appear to determine the effectiveness of therapeutic interventions.4,5,16 This study showed that TS may be a specifically valid treatment for the paretic leg in stroke, and the patients in the TS group obtained better effects on measures of the paretic leg in all our primary outcomes (see fig 2, table 2). The addition of TS to the standard rehabilitation program seemed to contribute more intensity and might initiate a positive feedback cycle and further motivate these patients to use the paretic leg more in upright activities in daily rehabiliArch Phys Med Rehabil Vol 93, November 2012
tation programs.21 Gradually, TS helped produce a greater cumulative effect of rehabilitation on paretic leg function. Although the mechanism of TS on stroke recovery is unclear, TS to the extremities of healthy subjects is associated with activation of various areas of the brain.18,19 Simultaneous activation of a large brain area enhances neural plasticity.17 Tracey et al33 also found bilateral widespread areas of brain activation during noxious hot and cold stimulation, suggesting the existence of a network associated with perception of noxious information, motor preparation, and response selection. Therefore, we suggest that TS in stroke patients may not only play a sensory stimulation role but also may force patients to respond to the strong stimulation, and to initiate motor preparation and drive motor response. The repetitive and enhanced sensory input by means of TS on the paretic leg after stroke may facilitate motor function recovery. As for the long-term benefits of TS, the training effects disappeared by the 6-month and 12-month follow-up. These results are similar to the findings of Kwakkel et al.16 In that study, the additional lower limb intervention was given to patients for 20 weeks, whereas in our study TS was applied for 6 weeks. Further investigation is warranted to show whether increasing the duration of intervention is enough to maintain the effects. Many studies1,2,16,34 have indicated that most walking and functional recovery occurs within or reaches a “plateau phase” 3 to 6 months after stroke. We found that patients in both groups improved in all outcomes over time and that greater improvement was observed in the TS group. However, after the 3-month follow-up, there were no significant differences in most outcomes between the 2 groups. This could be in part because most patients in both groups continued with their outpatient rehabilitation programs even after discharge. In addition, TS was mainly based on sensorimotor-specific treat-
THERMAL STIMULATION FOR STROKE PATIENTS, Liang
ment rather than on functionally oriented training and was administered only for 6 weeks. Another issue to consider is whether gradual deterioration in function associated with aging could affect functional improvements over the long-term.1,16,34 Significant differences in BBS and BI between the TS and control groups appeared only at the 3-month follow-up and had disappeared by the 6-month follow-up. Similar results were reported by Ng et al.13 It is possible that the BBS may not be sensitive enough to detect changes in early moderate to severe stroke.30 We found that the TS group performed significantly better than the control group on the 3-month BI. This seems to indicate that the early effects on the motor improvements in the TS group transferred to the daily activities later. However, the patients might have developed compensatory strategies with the unaffected limb, thus achieving some items of the BI in the chronic stage, resulting in an absence of detectable significance from 6 months on.1,35 Finally, unlike the other measures of functional performance, the significant effect for the FMA-LE was maintained between the TS and control groups up to 12 months. The FMA-LE25 is more detailed and specific than the MMAS30 and BI31 for evaluating impairment of the paretic leg after stroke. Thus, the patients in the TS group could more easily respond to the FMA-LE than could patients in the control group. Another possibility is that the difference in change in the FMA-LE between the 2 groups after 6 months was not sufficient to achieve the clinically significant change in functional performance because the compensatory strategies and plateau effects might have developed and were reflected on the MMAS and BI.
5.
6.
7.
8.
9.
10.
11. 12.
Study Limitations Since TS was added to the rehabilitation program of the TS group and, thus, treatment lasted longer in the TS group than in the control group, it is naturally difficult to evaluate to what extent the improved motor functions is attributable to the TS treatment or to the timing of treatment. Second, most patients continued outpatient programs after discharge, but we did not compare the frequency and duration of the outpatient programs between the 2 groups. Third, because of the small sample and because 5 subjects dropped out of the study after the 6-month follow-up, our conclusions need to be drawn with caution. CONCLUSIONS Six weeks of TS added to standard rehabilitation programs for acute stroke patients could facilitate motor and balance function recovery, and the effects could be sustained for at least 3 months. These thermal sessions might shorten the time a patient must be bedridden or wheelchair-bound after stroke. A large, robust study is needed to validate the long-term benefits of TS intervention. Acknowledgment: We thank all the members of the Department of Rehabilitation Medicine at Tzu Chi Buddhist General Hospital, Hualien, Taiwan, for their generous help. References 1. Skilbeck CE, Wade DT, Hewer RL, Wood VA. Recovery after stroke. J Neurol Neurosurg Psychiatry 1983;46:5-8. 2. Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Recovery of walking function in stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil 1995;76:27-32. 3. Bohannon RW, Horton MG, Wikholm JB. Importance of four variables of walking to patients with stroke. Int J Rehabil Res 1991;14:246-50. 4. Werner C, von Frankenberg S, Treig T, Konrad M, Hesse S. Treadmill training with partial body weight support and an elec-
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tromechanical gait trainer for restoration of gait in subacute stroke patients. a randomized crossover study. Stroke 2002;33:2895-901. Kawahira K, Shimodozono M, Ogata A, Tanaka N. Addition of intensive repetition of facilitation exercise to multidisciplinary rehabilitation promotes motor functional recovery of the hemiplegic lower limb. J Rehabil Med 2004;36:159-64. Katz-Leurer M, Sender I, Keren O, Dvir Z. The influence of early cycling training on balance in stroke patients at the subacute stage: results of a preliminary trial. Clin Rehabil 2006;20:398-405. Ambrosini E, Ferrante S, Pedrocchi A, Ferrigno G, Molteni F. Cycling induced by electrical stimulation improves motor recovery in postacute hemiparetic patients: a randomized controlled trial. Stroke 2011;42:1068-73. Yan T, Hui-Chan CW, Li LS. Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebocontrolled trial. Stroke 2005;36:80-5. Yavuzer G, Geler-Külcü D, Sonel-Tur B, Kutlay S, Ergin S, Stam HJ. Neuromuscular electric stimulation effect on lower-extremity motor recovery and gait kinematics of patients with stroke: a randomized controlled trial. Arch Phys Med Rehabil 2006;87:536-40. Franceschini M, Carda S, Agosti M, Antenucci R, Malgrati D, Cisari C. Walking after stroke: what does treadmill training with body weight support add to overground gait training in patients early after stroke? A single-blind, randomized, controlled trial. Stroke 2009;40:3079-85. Hesse S. Treadmill training with partial body weight support after stroke: a review. NeuroRehabilitation 2008;23:55-65. Husemann B, Müller F, Krewer C, Heller S, Koenig E. Effects of locomotion training with assistance of a robot-driven gait orthosis in hemiparetic patients after stroke: a randomized controlled pilot study. Stroke 2007;38:349-54. Ng MF, Tong RK, Li LS. A pilot study of randomized clinical controlled trial of gait training in subacute stroke patients with partial body-weight support electromechanical gait trainer and functional electrical stimulation: six-month follow-up. Stroke 2008;39:154-60. Hidler J, Nichols D, Pelliccio M, et al. Multicenter randomized clinical trial evaluating the effectiveness of the Lokomat in subacute stroke. Neurorehabil Neural Repair 2009;23:5-13. Nilsson L, Carlsson J, Danielsson A, et al. Walking training of patients with hemiparesis at an early stage after stroke: a comparison of walking training on a treadmill with body weight support and walking training on the ground. Clin Rehabil 2001;15:515-27. Kwakkel G, Kollen BJ, Wagenaar RC. Long term effects of intensity of upper and lower limb training after stroke: a randomised trial. J Neurol Neurosurg Psychiatry 2002;72:473-9. Johansson BB. Sensory stimulation and neuroplasticity. Brain plasticity and stroke rehabilitation. The Willis lecture. Stroke 2000;31:223-30. Gelnar PA, Krauss BR, Sheehe PR, Szeverenyi NM, Apkarian AV. A comparative fMRI study of cortical representations for thermal painful, vibrotactile and motor performance tasks. NeuroImage 1999;10:460-82. Davis KD, Kwan CL, Crawley AP, Mikulis DJ. Functional MRI study of thalamic and cortical activation evoked by cutaneous heat, cold, and tactile stimuli. J Neurophysiol 1998;80:1533-46. Chen JC, Liang CC, Shaw FZ. Facilitation of sensory and motor recovery by thermal intervention for the hemiplegic upper limb in acute stroke patients: a single-blind randomized clinical trial. Stroke 2005;36:2665-9. Chen JC, Lin CH, Wei YC, Hsiao J, Liang CC. Facilitation of motor and balance recovery by thermal intervention for the paretic lower limb of acute stroke: a single-blind randomized clinical trial. Clin Rehabil 2011;25:823-32. Arch Phys Med Rehabil Vol 93, November 2012
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22. Wu HC, Lin YC, Hsu MJ, Liu SM, Hsieh CL, Lin JH. Effect of thermal stimulation on upper extremity motor recovery 3 months after stroke. Stroke 2010;41:2378-80. 23. Salcido R, Musick DW, Erdman F. The Erdman therapy: a treatment utilizing hot and cold therapy. Am J Phys Med Rehabil 2003;82:972-8. 24. Brunnström S. Movement therapy in hemiplegia. New York: Harper and Row; 1970. 25. Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther 1983;63:1606-10. 26. Medical Research Council. Aids to the examination of the peripheral nervous system. London: Her Majesty’s Stationery Office; 1976. Memorandum No. 45. 27. Gregson JM, Leathley MJ, Moore AP, Smith TL, Sharma AK, Watkins CL. Reliability of measurements of muscle tone and muscle power in stroke patients. Age Ageing 2000;29:223-8. 28. Viosca E, Martínez JL, Almagro PL, Gracia A, González C. Proposal and validation of a new functional ambulation classification scale for clinical use. Arch Phys Med Rehabil 2005;86:1234-8. 29. Berg K, Wood-Dauphinee S, Williams JI. The Balance Scale: reliability assessment with elderly residents and patients with acute stroke. Scand J Rehabil Med 1995;27:27-36.
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30. Mao HF, Hsueh IP, Tang PF, Sheu CF, Hsieh CL. Analysis and comparison of the psychometric properties of three balance measures for stroke patients. Stroke 2002;33:1022-7. 31. Loewen SC, Anderson BA. Reliability of the Modified Motor Assessment Scale and the Barthel Index. Phys Ther 1988;68: 1077-81. 32. Quinn TJ, Langhorne P, Stott DJ. Barthel Index for stroke trials: development, properties, and application. Stroke 2011; 42:1146-51. 33. Tracey I, Becerra L, Chang I, et al. Noxious hot and cold stimulation produce common pattern of brain activation in human: a functional magnetic resonance imaging study. Neurosci Lett 2000; 288:159-62. 34. Verheyden G, Nieuwboer A, De Wit L, et al. Time course of trunk, arm, leg, and functional recovery after ischemic stroke. Neurorehabil Neural Repair 2008;22:173-9. 35. Tangeman PT, Banaitis DA, Williams AK. Rehabilitation of chronic stroke patients: changes in functional performance. Arch Phys Med Rehabil 1990;71:876-80. Supplier a. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.
ORIGINAL ARTICLE
Effectiveness of Thermal Stimulation for the Moderately to Severely Paretic Leg After Stroke: Serial Changes at One-Year Follow-Up Chung-Chao Liang, MD, Tsung-Cheng Hsieh, PhD, Chun-Hsiang Lin, PT, BS, Yu-Chun Wei, PT, BS, Jung Hsiao, PT, BS, Jia-Ching Chen, PT, MS ABSTRACT. Liang C-C, Hsieh T-C, Lin C-H, Wei Y-C, Hsiao J, Chen J-C. Effectiveness of thermal stimulation for the moderately to severely paretic leg after stroke: serial changes at one-year follow-up. Arch Phys Med Rehabil 2012;93:1903-10. Objective: To evaluate the serial changes of long-term effects
of thermal stimulation (TS) on acute stroke patients. Design: A prospective study with follow-up at 3, 6, and 12 months after TS to assess motor and balance function of the paretic leg of acute stroke patients. Setting: A general hospital rehabilitation department. Participants: Poststroke patients (N⫽30) with moderate to severe impairment of leg function. Interventions: In addition to receiving standard rehabilitation, eligible patients were randomly assigned to a TS group (5 thermal stimulations per week for 6wk) or a control group (3 consultations per week for 6wk). Main Outcome Measures: Fugl-Meyer lower extremity score, Medical Research Council Scale for the Lower Extremity, Berg Balance Scale, Modified Motor Assessment Scale, Functional Ambulation Classification, and Barthel Index were administered at baseline, after 4 and 6 weeks of treatment, and at the 3-, 6-, and 12-month follow-up. Results: No significant differences were found between the 2 groups at baseline. After TS, the Fugl-Meyer lower extremity score, Medical Research Council Scale for the Lower Extremity, Modified Motor Assessment Scale, and Functional Ambulation Classification were significantly better in the TS group, and the effects persisted for 3 months (P⬍.05). Significant differences were found between the 2 groups for the Berg Balance Scale and Barthel Index only at the 3-month follow-up (P⬍.05). However, all the effects except for the Fugl-Meyer lower extremity score had disappeared at the 6-month follow-up (P⬎.05). Conclusions: The long-term benefits of TS for patients with acute stroke may be sustained for 3 months but disappear by the 6-month and 1-year follow-up. Key Words: Follow-up studies; Lower extremity; Rehabilitation; Stroke. © 2012 by the American Congress of Rehabilitation Medicine
From the Department of Rehabilitation Medicine, Tzu Chi Buddhist General Hospital, Hualien (Liang, Lin, Wei, Hsiao, Chen); and the Departments of Medicine (Liang) and Physical Therapy (Lin, Chen), and the Institute of Medical Sciences (Hsieh), Tzu Chi University, Hualien, Taiwan. Supported by the Tzu Chi General Hospital through grant TCRD 100-38 Research Plan. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Jia-Ching Chen, PT, MS, Dept of Rehabilitation Medicine, Tzu Chi Buddhist General Hospital, 707 Chung Yang Rd, Sec 3, Hualien 970 Taiwan, e-mail: [email protected]. In-press corrected proof published online on Aug 14, 2012, at www.archives-pmr.org. 0003-9993/12/9311-00229$36.00/0 http://dx.doi.org/10.1016/j.apmr.2012.06.016
FTER A STROKE, MORE than half of patients have A moderate to severe impairment on admission, and many become confined to bed or a wheelchair. Shortening the 1,2
period of being wheelchair-bound or bedridden through early and rapid recovery of motor and walking functions is usually of great concern to the patient, the family, and the clinician.2-4 Various treatment techniques such as intensive exercise5 or cycling exercise,6,7 functional electrical stimulation,7-9 body weight support treadmill,4,10,11 and robotic gait trainer4,11-14 are integrated into rehabilitation programs to enhance recovery of motor and walking function of the paretic leg after acute or subacute stroke. Most studies have reported the immediate5,6,12 or short-term effects7,8,14; only a few have assessed the longterm effects.4,10,13,15,16 Repetitive sensory stimulation and mass motor practice can facilitate neuroplasticity and cortical reorganization in poststroke patients.17 As shown on functional magnetic resonance imaging, thermal stimulation (TS) activates larger areas of the brain than does tactile or mechanical stimulation, and the degree of activation is nearly identical to that of motor tasks.18,19 Recently, we have added an additional TS intervention to our rehabilitation programs. In earlier studies, we found that TS had the potential of facilitating paretic upper20 and lower limb21 recovery after acute stroke. Wu et al22 have also reported the beneficial effects on the paretic upper limbs of chronic stroke patients. Unfortunately, our studies and Wu’s study only addressed the immediate and short-term effects of TS. Compared with other training modalities commonly used in orthopedic rehabilitation, TS is simple, convenient, and inexpensive.20,23 However, its long-term effects on motor function recovery after stroke are still unknown. Therefore, we designed a study to examine the serial changes of long-term effects on motor and balance function of the lower extremity after additional TS intervention in the early phase of stroke. METHODS Participants All patients who had a stroke and were consecutively admitted to the Department of Rehabilitation Medicine at Tzu Chi List of Abbreviations BBS BI FAC FMA-LE GEE MMAS MRC-LE TS
Berg Balance Scale Barthel Index Functional Ambulation Classification Fugl-Meyer Assessment for the Lower Extremity generalized estimating equation Modified Motor Assessment Scale Medical Research Council Scale for the Lower Extremity thermal stimulation
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Buddhist General Hospital, Hualien, Taiwan, from December 2009 to January 2011 were recruited and screened for eligibility for the study. The main inclusion criteria were (1) a diagnosis of first-ever stroke within the last 4 weeks; (2) no history of cardiac or orthopedic disease before the stroke; (3) the ability to follow instructions by the therapist during the study; and (4) a motor deficit of the paretic leg that was less than Brunnstrom stage 4.24 The exclusion criteria were (1) a history of severe diabetes or sensory impairment attributable to peripheral vascular disease or neuropathy; (2) global aphasia; or (3) a previous psychological disorder. Of the 42 subjects recruited, 30 met the inclusion criteria and were randomly assigned either to a TS group (15 subjects) or a control group (15 subjects) by computer-generated random numbers held in sealed envelopes by an individual not involved with the study. Both groups received 40 minutes each of physical and occupational therapy once per day, 5 days per week, for 6 weeks. The TS group also received a 40-minute TS intervention session 5 times weekly for 6 weeks with the same physical therapist. Participants in the control group were visited 3 times per week for 6 weeks, for 20-minute discussion sessions provided by a therapist uninvolved in the study. The research protocol was approved by the ethics committee of Tzu Chi University and Medical Center. All subjects gave informed consent before participating in the study. Intervention The method and definition of TS intervention used in this study were reported in our previous study.21 During the intervention, patients lay comfortably supine or side-lying on a mat with 1 or 2 pillows under their head, and were able to see their lower limbs. The thermal agents were hot (70°C) and cold (0°C) packs wrapped with 2 to 3 layers of towels that buffered thermal conduction and modulated the temperature of the thermal agent, which was placed over the calf or foot. To keep the stimulated temperature as constant as possible (45°– 48°C for heat and 11°–15°C for cold), a thermometer was attached with paper tape on the stimulation site to record the skin temperature during hot and cold pack stimulation. Hot and cold stimulation were limited to 30 seconds (46.5°⫾4.1°C) and 45 seconds (15.5°⫾4.7°C), respectively.21 The hot pack was first placed on the nonparetic leg, and the patient was asked to be aware of the change in skin temperature and learned to move the nonparetic leg away from the hot pack when the temperature became uncomfortable. Next, the hot pack was placed on the paretic leg 8 times, separated by 30-second intervals. During TS, the patient was encouraged to actively move the paretic leg as far as possible from the stimulus and was guided by the therapist when discomfort developed.21 If a motor response was not generated after the development of discomfort, or if the patient tolerated the maximum duration of stimulation, the leg was moved away from the stimulus by the therapist. Thus, the thermal agent produced a hot or cold sensation, followed by active or passive motion. When the skin temperature of the paretic leg dropped to baseline after 8 episodes of heat stimulation, an identical procedure was used with the cold pack. Once patients could control their leg movements, they were encouraged to perform them independently. If patients were unable to move the paretic leg at the beginning (antigravity), they could turn to initiate the movement in the side-lying position (gravity). A cycle of TS consisted of 8 applications each of hot and cold stimuli. Three such cycles were performed during each session. Therefore, approximately 48 minutes (8 ⫻ [30s ⫹ 30s] ⫻ 2 ⫻ 3) was required to complete a session of TS therapy. This duration was approximate because not all patients tolerated the full 30 Arch Phys Med Rehabil Vol 93, November 2012
seconds of stimulus. Adverse effects were assessed during and after TS. All patients in both groups completed their respective study interventions while in the hospital. After finishing the treatment protocol, most were discharged and continued outpatient rehabilitation programs. Assessments We tested all eligible patients with measures of demonstrated reliability, validity, and sensitivity to change during poststroke recovery. To do so, we selected the Fugl-Meyer Assessment for the Lower Extremity (FMA-LE),25 the Medical Research Council Scale for the Lower Extremity (MRC-LE),26,27 and the Functional Ambulation Classification (FAC) for gait ability28 as our primary outcome measures. Secondary outcome variables included the Berg Balance Scale (BBS),29 the Modified Motor Assessment Scale (MMAS),30 and the Barthel Index (BI).31 The FMA-LE measures impairment after stroke with a 3-point ordinal scale (0, cannot perform; 1, can partially perform; 2, can perform fully). The scale measures 17 items, with a scoring range from 0 to 34. It has been shown to have high test-retest reliability (total, .98 –.99; subtests, .87–1.00), interrater reliability, and construct validity.25 The MRC-LE is an ordinal scale with good to very good reliability (.80–.96) for measuring strength of muscle force, with scores from 0 (no muscle contraction) to 5 (normal strength). We used this scale to rate the paretic hip flexors, knee extensors, and ankle dorsiflexors (range, 0 –15).26,27 Gait ability was evaluated with the FAC. This measure is reliable and valid for determining the different levels of walking abilities, with a range of 0 (unable to walk) to 5 (near-normal walk).28 The BBS evaluates balance on 14 items (1 sitting, 13 standing) and is based on a 5-point ordinal scale of 0 to 4, with the total score ranging from 0 to 56. It has been reported to have high reliability (total, .85–.98) and validity (total, .82–.94).29,30 The MMAS contains 8 items, each graded on a 6-point scale, with a range from 0 to 48.31 The BI evaluates 10 basic activities of daily living and is scored from 0 to 100 in 5-point increments according to the degree of assistance required by the patient.32 The reliability and validity of MMAS and BI assessment have been well documented.31,32 All outcome measures were evaluated at baseline, at 4 and 6 weeks after the treatment, and at 3-, 6-, and 12-month follow-up by the same therapist, who was blinded for group allocation. Statistical Analysis Basic characteristics of all patients were compared with the Student t (parametric data), Mann-Whitney U (nonparametric
Table 1: Baseline Characteristics and Measurements for Patients in the TS and Control Groups (Nⴝ30) Variable
Age (y) Sex (male/female) Stroke onset to treatment (d) Type of stroke (infarction/ hemorrhage) Side of paresis (right/left) Brunnstrom stage (scale)
TS (n⫽15)
Control (n⫽15)
56.1⫾11.9 59.73⫾11.6 12/3 7/8 10.9⫾5.4 13.6⫾6.4 9/6 9/6 6/9 3 (2.0–3.0)
7/8 3 (2.0–3.0)
P
.410 (t) .13 (F) .22 (t) 1 (2) 1 (2) .46 (M)
NOTE. Values are mean ⫾ SD, n, median (interquartile range), or as otherwise indicated. Abbreviations: 2, chi-square test; F, Fisher exact test; M, MannWhitney U test; t, Student t test.
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Assessed for eligibility (n=42) n=12, excluded due to orthopedic problems or history of severe diabetes Randomized (n=30)
Complete 4 and 6
Thermal group
Control group
(n=15)
(n=15)
Thermal group
Control group
(n=15)
(n=15)
3-month follow-up
Thermal group
Control group
assessment (n=30)
(n=15)
6-month follow-up
Thermal group (n=13)
Control group (n=12)
assessment, analysis
(Two drop-out for loss
(Three drop-out for
with intention to treat
of contact, n=1;
loss of contact, n=2
refused, n=1)
and death, n=1)
weeks intervention and assessment
(n=30)
One-year follow-up
Thermal group (n=13)
(n=15)
Control group (n=12)
assessment, analysis with intention to treat (n=30) Fig 1. Flowchart showing the progress of patients participating in the follow-up study and dropouts.
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33 30
#
27
#
24
*
#
*
#
*
#
*
MRC-LE (scale)
FMA-LE (score)
Control group Thermal group
*
21
#
10
*
9
#
8
*
18
6
15
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4
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6
2
3
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*
*
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*
*
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12m
0 w4
w6
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6m
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*
*
4.0 #
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2.5
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w1 BBS (score)
w1
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7
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w6
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50
*
45
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2.0
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0 w4
w6
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*
#
35 #
30
*
6m
12m
*
*
*
w1 BI (score)
w1 MMAS (score)
12
w4
w6
3m
100
#
90
*
*
*
3m
6m
12m
*
80
*
70
25
60
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40 30
10
20
5
10
0
0 w1
w4
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week
6m
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w4
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week
Fig 2. Temporal changes of 6 measures (mean ⴞ SE) at weeks 4 and 6 and at 3-, 6-, and 12-month follow-up in the control and TS groups. *P<.05 significantly different vs first week within TS group; #P<.05 significantly different vs control group; adjusted for post hoc comparison based on Bonferroni method.
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THERMAL STIMULATION FOR STROKE PATIENTS, Liang
data), and chi-square or Fisher exact (nominal data) tests. All outcome variables were based on a repeated-measure design. Considering that the assumption of variance-covariance matrix of compound symmetry was probably unsatisfied as a result of the different lengths of the intervals between each of 2 neighbor time points (ie, wk 4, wk 6, 3mo, 6mo, and 12mo), we used the generalized estimating equation (GEE) method with unstructured variance-covariance matrix adjusted by the baseline of each outcome variable to identify the postintervention results between group and time effects of all measurements. A post hoc test with Bonferroni adjustment was used for controlling overall type I error. The level of statistical significance was set at P⬍.05 for all analyses. All data were analyzed as intention to treat using SPSS 18.0 statistics software.a RESULTS All 30 subjects completed the 6-week study protocol while hospitalized, and no adverse effects were reported. During the follow-up period, most patients continued outpatient rehabilitation programs at least twice a week. Two subjects, 1 in the TS group and 1 in the control group, reported a history of falling at the 6-month and 12-month follow-up, respectively, but none sustained severe physical injury. All subjects had data for all outcome measures at the 3-month point, but 2 in the TS group and 3 in the control group had withdrawn from the study at the 6-month and 12-month follow-up. The reasons given for dropping out were loss of contact and refusal to participate because of economic factors; 1 subject died. For the data on dropout subjects, we used the final evaluations as our data analysis. The data analysis was used as an intention to treat. No statistically significant differences were found between the 2 groups in any of the demographic data (table 1). The progress of subjects throughout the study is depicted in the flowchart in figure 1.
Figure 2 illustrates the longitudinal pattern of change on all the outcome measures at the 6 evaluation time points for both groups. Patients in both groups improved significantly over time (P⬍.05), and the patterns of recovery differed significantly between the 2 groups. Further, the FMA-LE, MRC-LE, FAC, BBS, and MMAS measures in the TS group deviated significantly from those in the control group between 4 weeks and 3 months, and the gap progressively narrowed from 6 months on. The results of comparisons between the 2 groups are summarized in table 2 and table 3 for the primary and secondary outcome measures, respectively. No statistically significant differences were found between the 2 groups in any of the outcome measures at baseline. Statistical comparison by means of repeated-measures analysis using the GEE method revealed no significant interaction effects between time and group. The changes in the primary outcomes for the FMA-LE, MRC-LE, and FAC all showed significant effects for both group and time (P⬍.05) (see table 2). After post hoc analysis, the MRC-LE, FAC, and MMAS in the TS group demonstrated better performance relative to the control group at 4 and 6 weeks and 3-month follow-up (P⬍.05). In addition, the BBS and BI in the TS group showed a nearly significant difference from those in the control group at 6 weeks (P⫽.05 and P⫽.054, respectively), and a significance difference at the 3-month follow-up (P⫽.038 and P⫽.031, respectively) (see table 3). Furthermore, the effect for the FMA-LE was maintained up to the 12-month follow-up. However, the effects for all outcomes except the FMA-LE had disappeared by the 6-month follow-up (see table 2). From our results comparing the TS group with the control group, we observed the optimal difference in MRC-LE at week 6, where the scales were 8.9⫾0.5 for the TS group and 6.3⫾0.6 for the control group. By using a 2-sided 5% level test and 15
Table 2: Effects of Group and Time on the Primary Outcome Measurements (Nⴝ30) Measurement
FMA-LE wk 1 wk 4 wk 6 3mo 6mo 12mo MRC-LE wk 1 wk 4 wk 6 3mo 6mo 12mo FAC wk 1 wk 4 wk 6 3mo 6mo 12mo
TS Group
Control Group
Mean Difference
Effect Size
Mean Difference of 95% CI
P*
8.9⫾4.6 19.0⫾0.9 22.2⫾1.1 24.6⫾1.1 25.6⫾1.1 26.2⫾1.1
9.2⫾5.2 13.4⫾1.0 16.1⫾1.1 18.7⫾1.2 20.5⫾1.2 21.9⫾1.3
–0.3 5.6⫾1.3 6.0⫾1.7 5.9⫾1.7 5.1⫾1.6 4.2⫾1.7
0.1 5.9 5.5 5.1 4.4 3.5
⫺4.0–3.4 3.1–8.2 2.8–9.3 2.6–9.2 2.0–8.2 0.9–7.6
.85 .000† .000† .000† .001† .013†
2.6⫾2.2 7.2⫾0.4 8.9⫾0.5 9.5⫾0.6 9.8⫾0.6 9.9⫾0.6
2.7⫾2.2 4.8⫾0.6 6.3⫾0.6 7.4⫾0.6 8.2⫾0.7 8.7⫾0.7
–0.13 2.4⫾0.7 2.6⫾0.8 2.1⫾0.8 1.6⫾0.9 1.2⫾0.9
0.1 4.7 4.7 3.5 2.5 1.8
⫺1.5–1.8 1.1–3.7 1.1–4.1 0.5–3.8 ⫺0.1–3.3 ⫺0.6–3.0
.87 .000† .001† .01† .07 .20
0.3⫾0.5 2.1⫾0.1 2.6⫾0.1 3.1⫾0.1 3.3⫾0.2 3.3⫾0.2
0.4⫾0.5 1.4⫾0.1 1.9⫾0.2 2.4⫾0.2 2.7⫾0.2 2.9⫾0.3
–0.1 0.7⫾0.2 0.7⫾0.2 0.7⫾0.2 0.5⫾0.3 0.5⫾0.3
0.3 7.0 4.4 4.4 3.0 1.6
⫺0.2–0.5 0.4–1.1 0.2–1.1 0.2–1.1 ⫺0.0–1.1 ⫺0.2–1.1
.46 .000† .005† .005† .058 .178
NOTE. Values are mean ⫾ SD or as otherwise indicated. Results were obtained from a GEE adjusted by the mean of each outcome measure at baseline. Abbreviation: CI, confidence interval. *P values at week 1 (baseline) were obtained by Student t test or Mann-Whitney U test if normality assumption was satisfied. P values at week 4, week 6, 3 months, 6 months, and 12 months were the adjusted P values obtained for post hoc comparison based on Bonferroni adjusted method. † P⬍.05, significant difference.
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THERMAL STIMULATION FOR STROKE PATIENTS, Liang Table 3: Effects of Group and Time on the Secondary Outcome Measurements (Nⴝ30)
Measurement
BBS wk 1 wk 4 wk 6 3mo 6mo 12mo MMAS wk 1 wk 4 wk 6 3mo 6mo 12mo BI wk 1 wk 4 wk 6 3mo 6mo 12mo
TS Group
Control Group
Mean Difference
Effect Size
Mean Difference of 95% CI
P*
8.1⫾10.4 30.9⫾2.5 24.0⫾3.8 43.1⫾1.8 44.8⫾1.9 45.1⫾1.8
8.7⫾7.9 24.0⫾3.8 29.7⫾3.9 34.5⫾3.7 37.5⫾3.3 39.5⫾3.2
–0.6 6.9⫾4.5 8.7⫾4.4 8.5⫾4.1 7.3⫾3.8 5.6⫾3.7
0.1 2.2 2.8 3.0 2.7 2.6
⫺6.3–7.5 ⫺2.0–15.7 ⫺0.0–17.4 0.5–16.6 ⫺0.1–14.8 ⫺1.7–12.9
.86 .129 .050 .038† .054 .132
11.7⫾6.1 26.2⫾1.9 30.0⫾1.8 32.6⫾1.6 33.1⫾1.6 33.7⫾1.7
12.0⫾5.5 20.3⫾1.6 23.8⫾1.8 27.2⫾1.8 29.9⫾1.1 31.5⫾2.2
–0.3 5.9⫾2.4 6.1⫾2.6 5.4⫾2.4 3.3⫾2.7 2.2⫾2.8
0.1 3.4 3.4 3.2 2.3 1.1
⫺4.0–4.7 1.1–10.6 1.1–11.1 0.6–10.2 ⫺2.0–8.5 ⫺3.2–7.6
.88 .016† .016† .026† .225 .429
30.3⫾11.1 65.0⫾4.0 76.7⫾3.7 85.0⫾3.1 87.0⫾3.0 88.0⫾3.0
27.7⫾14.3 55.0⫾4.5 64.7⫾5.0 74.0⫾4.1 78.7⫾3.9 80.3⫾4.3
2.7 10.0⫾6.1 12.0⫾6.2 11.0⫾5.4 8.30⫾4.9 7.7⫾5.3
0.2 2.4 2.7 3.0 2.4 1.5
⫺12.2–6.9 ⫺1.9–21.9 ⫺0.2–24.2 1.0–21.0 ⫺1.3–17.9 ⫺2.7–18.0
.57 .099 .054 .031† .089 .148
NOTE. Values are mean ⫾ SD or as otherwise indicated. Results were obtained from a GEE adjusted by the mean of each outcome measure at baseline. Abbreviation: CI, confidence interval. *P values at week 1 (baseline) were obtained by Student t test or Mann-Whitney U test if normality assumption was satisfied. P values at week 4, week 6, 3 months, 6 months, and 12 months were the adjusted P values obtained for post hoc comparison based on Bonferroni adjusted method. † P⬍.05, significant difference.
patients in each group, the power was 89% for detecting the true difference. DISCUSSION The main findings not only demonstrated that the TS group recovered significantly better than the control group in terms of the FMA-LE, MRC-LE, FAC, and MMAS, consistent with our previous study,21 but more importantly showed that the effects could be sustained to the 3-month follow-up. Furthermore, the primary outcomes for the FMA-LE could be maintained to the 12-month follow-up. We also found a significant difference in BBS and BI between the 2 groups only at the 3-month time point, but the effects disappeared at the 6-month and 12-month follow-up. Independence in daily living after stroke is often closely related to the ability to perform tasks such as moving from a sitting to a standing position, transferring, and walking. Although task-oriented repetitive training techniques have been favored in stroke rehabilitation,4,10-12 patients with moderate to severe status may have difficulty executing such tasks without a certain degree of muscle strength and voluntary movement control.6,11 Recovering some degree of paretic leg mobility and strength after stroke might greatly facilitate subsequent effective postural control and gait performance.2,11 Intensity and specificity appear to determine the effectiveness of therapeutic interventions.4,5,16 This study showed that TS may be a specifically valid treatment for the paretic leg in stroke, and the patients in the TS group obtained better effects on measures of the paretic leg in all our primary outcomes (see fig 2, table 2). The addition of TS to the standard rehabilitation program seemed to contribute more intensity and might initiate a positive feedback cycle and further motivate these patients to use the paretic leg more in upright activities in daily rehabiliArch Phys Med Rehabil Vol 93, November 2012
tation programs.21 Gradually, TS helped produce a greater cumulative effect of rehabilitation on paretic leg function. Although the mechanism of TS on stroke recovery is unclear, TS to the extremities of healthy subjects is associated with activation of various areas of the brain.18,19 Simultaneous activation of a large brain area enhances neural plasticity.17 Tracey et al33 also found bilateral widespread areas of brain activation during noxious hot and cold stimulation, suggesting the existence of a network associated with perception of noxious information, motor preparation, and response selection. Therefore, we suggest that TS in stroke patients may not only play a sensory stimulation role but also may force patients to respond to the strong stimulation, and to initiate motor preparation and drive motor response. The repetitive and enhanced sensory input by means of TS on the paretic leg after stroke may facilitate motor function recovery. As for the long-term benefits of TS, the training effects disappeared by the 6-month and 12-month follow-up. These results are similar to the findings of Kwakkel et al.16 In that study, the additional lower limb intervention was given to patients for 20 weeks, whereas in our study TS was applied for 6 weeks. Further investigation is warranted to show whether increasing the duration of intervention is enough to maintain the effects. Many studies1,2,16,34 have indicated that most walking and functional recovery occurs within or reaches a “plateau phase” 3 to 6 months after stroke. We found that patients in both groups improved in all outcomes over time and that greater improvement was observed in the TS group. However, after the 3-month follow-up, there were no significant differences in most outcomes between the 2 groups. This could be in part because most patients in both groups continued with their outpatient rehabilitation programs even after discharge. In addition, TS was mainly based on sensorimotor-specific treat-
THERMAL STIMULATION FOR STROKE PATIENTS, Liang
ment rather than on functionally oriented training and was administered only for 6 weeks. Another issue to consider is whether gradual deterioration in function associated with aging could affect functional improvements over the long-term.1,16,34 Significant differences in BBS and BI between the TS and control groups appeared only at the 3-month follow-up and had disappeared by the 6-month follow-up. Similar results were reported by Ng et al.13 It is possible that the BBS may not be sensitive enough to detect changes in early moderate to severe stroke.30 We found that the TS group performed significantly better than the control group on the 3-month BI. This seems to indicate that the early effects on the motor improvements in the TS group transferred to the daily activities later. However, the patients might have developed compensatory strategies with the unaffected limb, thus achieving some items of the BI in the chronic stage, resulting in an absence of detectable significance from 6 months on.1,35 Finally, unlike the other measures of functional performance, the significant effect for the FMA-LE was maintained between the TS and control groups up to 12 months. The FMA-LE25 is more detailed and specific than the MMAS30 and BI31 for evaluating impairment of the paretic leg after stroke. Thus, the patients in the TS group could more easily respond to the FMA-LE than could patients in the control group. Another possibility is that the difference in change in the FMA-LE between the 2 groups after 6 months was not sufficient to achieve the clinically significant change in functional performance because the compensatory strategies and plateau effects might have developed and were reflected on the MMAS and BI.
5.
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11. 12.
Study Limitations Since TS was added to the rehabilitation program of the TS group and, thus, treatment lasted longer in the TS group than in the control group, it is naturally difficult to evaluate to what extent the improved motor functions is attributable to the TS treatment or to the timing of treatment. Second, most patients continued outpatient programs after discharge, but we did not compare the frequency and duration of the outpatient programs between the 2 groups. Third, because of the small sample and because 5 subjects dropped out of the study after the 6-month follow-up, our conclusions need to be drawn with caution. CONCLUSIONS Six weeks of TS added to standard rehabilitation programs for acute stroke patients could facilitate motor and balance function recovery, and the effects could be sustained for at least 3 months. These thermal sessions might shorten the time a patient must be bedridden or wheelchair-bound after stroke. A large, robust study is needed to validate the long-term benefits of TS intervention. Acknowledgment: We thank all the members of the Department of Rehabilitation Medicine at Tzu Chi Buddhist General Hospital, Hualien, Taiwan, for their generous help. References 1. Skilbeck CE, Wade DT, Hewer RL, Wood VA. Recovery after stroke. J Neurol Neurosurg Psychiatry 1983;46:5-8. 2. Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Recovery of walking function in stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil 1995;76:27-32. 3. Bohannon RW, Horton MG, Wikholm JB. Importance of four variables of walking to patients with stroke. Int J Rehabil Res 1991;14:246-50. 4. Werner C, von Frankenberg S, Treig T, Konrad M, Hesse S. Treadmill training with partial body weight support and an elec-
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22. Wu HC, Lin YC, Hsu MJ, Liu SM, Hsieh CL, Lin JH. Effect of thermal stimulation on upper extremity motor recovery 3 months after stroke. Stroke 2010;41:2378-80. 23. Salcido R, Musick DW, Erdman F. The Erdman therapy: a treatment utilizing hot and cold therapy. Am J Phys Med Rehabil 2003;82:972-8. 24. Brunnström S. Movement therapy in hemiplegia. New York: Harper and Row; 1970. 25. Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther 1983;63:1606-10. 26. Medical Research Council. Aids to the examination of the peripheral nervous system. London: Her Majesty’s Stationery Office; 1976. Memorandum No. 45. 27. Gregson JM, Leathley MJ, Moore AP, Smith TL, Sharma AK, Watkins CL. Reliability of measurements of muscle tone and muscle power in stroke patients. Age Ageing 2000;29:223-8. 28. Viosca E, Martínez JL, Almagro PL, Gracia A, González C. Proposal and validation of a new functional ambulation classification scale for clinical use. Arch Phys Med Rehabil 2005;86:1234-8. 29. Berg K, Wood-Dauphinee S, Williams JI. The Balance Scale: reliability assessment with elderly residents and patients with acute stroke. Scand J Rehabil Med 1995;27:27-36.
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