1 Instrumented assessment of the effect of Botulinum Toxin-A in the medial 1 hamstrings in children with cerebral palsy 2 3 Bar-On L. PT MSc a,b , Aertbeliën E. Ir PhD c , Molenaers G. MD PhD a,d,e , Van 4 Campenhout A. MD a,d,e , Vandendoorent B. PT MSc b , Nieuwenhuys A. PT MSc a,b , 5 Jaspers E. PT PhD b,f , Hunaerts C. PT MSc a ; Desloovere K. PhD a, b 6 7 a Clinical Motion Analysis Laboratory, University Hospital Leuven, Pellenberg, 8 Belgium 9 b KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium 10 c KU Leuven Department of Mechanical Engineering, Leuven, Belgium 11 d KU Leuven Department of Development and Regeneration, Leuven, Belgium 12 e Department of Orthopedics, University Hospital Leuven, Pellenberg, Belgium 13 f Neural Control of Movement Lab, ETH Zurich, Switzerland 14 15 Acknowledgements 16 This work was made possible by a grant from the Doctoral Scholarships Committee 17 for International Collaboration with non EER-countries (DBOF) of the Katholieke 18 Universiteit Leuven, Belgium. This work was further supported by a grant from 19 Applied Biomedical Research from the Flemish agency for Innovation by Science and 20 technology (IWT-TBM: grant number 060799); and by an unrestricted educational 21 grant from Allergan, Inc. (USA). 22 23 24 25 26 27 28
24
Embed
hamstrings in children with cerebral palsy , Aertbeliën E ... · PDF file1 1 Instrumented assessment of the effect of Botulinum Toxin-A in the medial 2 hamstrings in children with
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Instrumented assessment of the effect of Botulinum Toxin-A in the medial 1
hamstrings in children with cerebral palsy 2
3
Bar-On L. PT MSca,b, Aertbeliën E. Ir PhDc, Molenaers G. MD PhDa,d,e, Van 4
Campenhout A. MDa,d,e, Vandendoorent B. PT MScb, Nieuwenhuys A. PT MSca,b, 5
Jaspers E. PT PhDb,f, Hunaerts C. PT MSca; Desloovere K. PhDa, b 6
7
a Clinical Motion Analysis Laboratory, University Hospital Leuven, Pellenberg, 8
Belgium 9
b KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium 10
c KU Leuven Department of Mechanical Engineering, Leuven, Belgium 11
d KU Leuven Department of Development and Regeneration, Leuven, Belgium 12
e Department of Orthopedics, University Hospital Leuven, Pellenberg, Belgium 13
f Neural Control of Movement Lab, ETH Zurich, Switzerland 14
15
Acknowledgements 16
This work was made possible by a grant from the Doctoral Scholarships Committee 17
for International Collaboration with non EER-countries (DBOF) of the Katholieke 18
Universiteit Leuven, Belgium. This work was further supported by a grant from 19
Applied Biomedical Research from the Flemish agency for Innovation by Science and 20
technology (IWT-TBM: grant number 060799); and by an unrestricted educational 21
grant from Allergan, Inc. (USA). 22
23
24
25
26
27
28
2
1. Introduction 29
30
Spasticity is characterized by a velocity-dependent increase in tonic stretch reflex [1] 31
with an accompanying increase in muscle resistance when a muscle is passively 32
stretched [2]. This definition, as well as the methods for spasticity assessment, has 33
been under much debate in the last decade. Nonetheless, neuromuscular tone 34
reduction remains an important treatment modality in children with cerebral palsy 35
(CP) [3]. For example, Botulinum Toxin type-A (BTX-A), injected intramuscularly, 36
causes a temporary reduction in reflex muscle activity by selectively blocking the 37
release of acetylcholine at the cholinergic nerve terminals. Whilst this has been found 38
effective to decrease spasticity in children with CP, there remains a large variability in 39
treatment response [4]. A comprehensive assessment of the effect of BTX-A on 40
spasticity could increase our knowledge of the pathology and improve our 41
understanding of this reported variability. 42
43
In children with CP, the effect of BTX-A is most commonly assessed with clinical 44
scales (Modified Ashworth-MAS [5], or Modified Tardieu Scale-MTS [6]). These 45
scales assess spasticity by subjectively interpreting the resistance felt during passive 46
stretch. Nonetheless, the perceived resistance may be a result of reflex muscle 47
activity as well as of changes in visco-elastic properties of the joint and muscle. The 48
available clinical scales fail to distinguish between both components and are thus not 49
deemed sensitive or valid to quantitatively assess the effect of BTX-A on the stretch 50
reflex. Moreover, they have also been criticized for their low reproducibility and poor 51
accuracy [7,8]. As such, clinical scales have a limited ability to differentiate between 52
3
patients or to explain the response variability after treatment. Instrumented methods 53
could provide a more comprehensive assessment. 54
55
Electromyography (EMG) has been used in adults to quantify the effect of BTX-A on 56
the pathological response during passive muscle stretch [9,10]. Simultaneously 57
assessing muscular resistance using torque sensors provides an integrated (EMG 58
and torque) instrumented measurement method [11]. However, in children with CP, 59
clinically-applicable integrated approaches to assess the effect of BTX-A have only 60
been applied to the upper limb [12], whereas lower limb muscles are most commonly 61
treated. We therefore used an instrumented method, that integrates EMG and torque, 62
as described by Bar-On et al. [13]. The repeatability and discriminate validity to 63
measure spasticity in the medial hamstrings (MEH) in children with CP has previously 64
been shown [13,14]. However, it is yet to be determined whether this instrumented 65
assessment is sensitive to detect treatment efficacy and if it can help understand 66
variability in treatment outcome. 67
68
Therefore, the aim of this study was to quantify and understand the effects of BTX-A 69
injection in treating MEH spasticity in children with CP, using an integrated 70
assessment based on EMG and torque. 71
72
73
2. Method 74
75
Children aged 3-18 years and scheduled for BTX-A in the MEH (Mm. 76
Semitendinosus and Semimembranosus) were recruited from the multidisciplinary 77
4
clinic for patients with CP (University Hospital ***). The exclusion criteria were: 78
presence of ataxia or dystonia; severe muscle weakness (<2+ on the Manual Muscle 79
Test [15]); poor selectivity [6]; bone deformities or contractures hindering neutral 80
alignment; cognitive problems that could impede the measurements; previous lower 81
limb orthopedic surgery (soft tissue or bony procedures); intrathecal Baclofen pump 82
or selective dorsal rhizotomy. Minimal strength production and good selectivity were 83
required because a voluntary contraction was used as an individual reference to 84
evaluate surface EMG (sEMG) signals in previous studies with the same subject 85
group [13,14]. In the current study however, voluntary contractions were expected to 86
be influenced by the BTX-A injections and the normalized sEMG was thus not 87
analyzed. The University Hospitals’ ethical committee approved the experimental 88
protocol and all children’s parents signed an informed consent. 89
90
As part of a regular multilevel BTX-A treatment, muscles to inject and dosages were 91
selected based on standard multidisciplinary evaluation. Injection with BTX-A 92
(Botox®, Allergan Ltd, UK) was done under a short anesthesia and ultrasound was 93
used to confirm needle position. All children underwent casting for a period of 10 94
days (lower-leg with optional removable upper-part used as a knee-extension 95
device), intensive physical rehabilitation as well as orthotic management (day and 96
night) following the BTX-A injections. 97
98
2.1 Data acquisition 99
100
The set-up of the instrumented assessment for the MEH is presented in Figure 1. In 101
children with unilateral CP, only the affected side was tested. In children with bilateral 102
5
involvement, the most involved side was tested. This was defined as the side with the 103
highest MEH MAS-score or, in case of symmetrical MAS-scores, the most severe 104
MTS-score. All assessments were performed prior to injection and 14-70 days after 105
injection, by the same trained assessor. For more details regarding the measurement 106
method, the reader is referred to [13]. 107
108
Four repetitions of passive MEH muscle stretches over the full range of motion 109
(ROM) were carried out at three velocities. Firstly, the knee joint was moved at low 110
velocity (LV) during 5s, followed by a movement at intermediate, medium velocity 111
(MV) during 1s, and finally at high velocity (HV), which was performed as fast as 112
possible. The interval between repetitions was 7s in order to avoid post-activation 113
depression of the electrophysiological response. 114
115
2.2 Data analysis 116
117
A 6th order zero-phase Butterworth bandpass filter ranging from 20-500Hz was 118
applied to filter the raw sEMG signal. The root mean square envelope of the sEMG 119
(RMS-EMG) signal was computed using a low-pass 30Hz 6th order zero-phase 120
Butterworth filter on the squared raw signal. EMG onset, ROM, maximum angular 121
velocity (VMAX), and the net internal joint torque were computed as previously 122
described [13]. 123
124
Repetitions were excluded when passive stretches were performed out of plane, at 125
inconsistent velocities, in case of poor quality sEMG signal (loss of signal, low signal-126
to-noise ratio or obvious artifacts), or when there was indication of antagonist 127
6
activation (rectus femoris sEMG activity). All data analyses were carried out with 128
MATLAB® Software 7.6.0 R2010a. 129
130
2.3 Outcome parameters 131
132
ROM was determined during LV; VMAX during all velocities. All other parameters were 133
calculated at each velocity and were extracted from the RMS-EMG and the computed 134
torque signals. Average RMS-EMG, expressed in mV, was computed as the square 135
root of the area underneath the RMS-EMG time curve, divided by the duration of the 136
time interval considered. The time interval started 200ms prior to the time 137
corresponding to VMAX and ended at the time corresponding to 90% of the full ROM. 138
From the computed torque signal, four instrumented spasticity parameters were 139
developed. Firstly, the amount of work required to stretch the muscle was calculated 140
as the integral of the net internal torque from the joint position at VMAX to 90% of the 141
ROM (referred to as ‘work’ and expressed in J). Torque was additionally analyzed at 142
70° knee flexion, an angle that corresponded to the overall mid-ROM of all children 143
(‘torque’, expressed in Nm). The angle of catch (AOC) was defined as the angle that 144
corresponded to the time of minimum power after maximum power and was 145
expressed as a percentage of the ROM [14]. Finally, the value of the power at the 146
AOC was used to quantify catch severity [14] (‘AOC power’, expressed in W). The 147
AOC and AOC power were calculated from the first HV stretch following the 148
procedure described in [14]. All other parameters were calculated by taking the 149
average of 2-4 repetitions per velocity. To provide a measure of the severity of 150
spasticity, the absolute change between MV and LV (MV-LV) and between HV and 151
7
LV (HV-LV) was also calculated for every parameter (except ROM, AOC, and AOC 152
power). 153
154
155
2.4 Statistical analysis 156
157
All parameters were checked for normal distribution using the Kolmogorov-Smirnov 158
test with p>0.1 indicating a normal distribution. To ensure that the velocity of passive 159
stretches was performed consistently between measurement sessions, VMAX at each 160
velocity was first compared between sessions using a paired samples t-test, or in 161
case of non-normal distributions, a Wilcoxon Matched Pairs Test (WMPT). Next, to 162
evaluate the sensitivity of the parameters to treatment with BTX-A, the average 163
change between pre- and post-treatment sessions was calculated. It was 164
hypothesized that ROM, AOC, and AOC power would increase and that RMS-EMG, 165
torque, and work parameters would decrease post-treatment. Average change 166
between pre- and post-treatment sessions was interpreted in view of the minimal 167
detectable change (MDC). MDC values were calculated from the standard error of 168
measurement (SEM) values reported by Bar-On et al. [13,14] (MDC=SEM*1.645*√2) 169
[16] (Supplementary Material 1). Those parameters whose average change 170
exceeded the MDC were compared between sessions using a paired samples t-test, 171
or a WMPT, as appropriate. 172
173
Finally, to explore the relationships between different outcome parameters, Pearson 174