Quantification of Abnormal Muscle Tone in Animal Model and in Clinical Setting

博士 === 國立成功大學 === 醫學工程研究所碩博士班 === 96 === Spasticity is one of the abnormal muscle tone forms often hinders the functional performance of patients with upper motor neuron lesions such as stroke, spinal cord injury, traumatic brain injury, cerebral palsy etc. Various kinds of animal models have been e...

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Bibliographic Details
Main Authors: Yi-Ning Wu, 吳宜寧
Other Authors: Jia-Jin Chen
Format: Others
Language:en_US
Published: 2007
Online Access:http://ndltd.ncl.edu.tw/handle/08109513676221268193
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Summary:博士 === 國立成功大學 === 醫學工程研究所碩博士班 === 96 === Spasticity is one of the abnormal muscle tone forms often hinders the functional performance of patients with upper motor neuron lesions such as stroke, spinal cord injury, traumatic brain injury, cerebral palsy etc. Various kinds of animal models have been established for exploring the mechanism of abnormal muscle tone and the treatment intervention for abnormal muscle tone reduction. However there is a lack of appropriate evaluation platform in small animals. As for in clinics, although spasticity is generally agreed to be easy to recognize, it is not easy to quantify. Hence the aims of this study were to develop a miniature muscle tone evaluation system which could be used in animal models, as well as to validate the appropriate evaluation systems for clinical uses. For the animal study, a portable and miniature biomechanical stretching device was established to manually stretch the hind limb of awake rats with muscle rigidity induced by dopamine D2-receptor antagonist raclopride (5mg/Kg, i.p.). From the measured angular displacement angle and reactive torque of sinusoidal stretches at five varied frequencies, viscoelastic components of the muscle tone can be derived. In addition, non-invasive multielectrode was applied to record the tonic and phasic components of the gastrocnemius muscle electromyogram (EMG). The bar test score was also evaluated as the measure of catalepsy. In clinical human studies, we first utilized the portable stretching device combined with EMG for investigating the spasticity on the elbow flexors of stroke patients following botulinum toxin type A injection. Ten chronic post-stroke spastic patients were injected botulinum toxin type A in the main elbow flexor (i.e. biceps brachii). Spasticity was clinically evaluated with the Modified Ashworth Scale (MAS). The reactive resistance and reactive EMG of elbow joint induced at different stretching frequencies (1/3, 1/2, 1 and 3/2 Hz) through a 60 degrees range of motion were recorded following botulinum toxin type A treatment. The velocity-dependent viscous component (Bω) and the viscosity (B) as well as the reflex EMG threshold were used for evaluating the severity of spasticity at pre-injection as well as 2 weeks after injection. However the sinusoid method provided by portable stretching device can not differentiate the intrinsic property of muscle itself from the reflex component. Therefore a custom manual spasticity evaluator (MSE) developed based on modified Tardieu scale was used to evaluate spasticity and catch in twelve patients post stroke and nine healthy subjects. Elbow passive resistance torque, range of motion (ROM), stiffness and energy loss were measured at slow movement of 30˚/s. Spasticity and catch angle were evaluated at stretching velocities of 90˚/s, 180˚/s and 270˚/s with real-time audiovisual feedback and characterized systematically with four relevant variables (elbow flexion angle, velocity, torque, and torque change rate). The data of animal study showed not only increase in stiffness (p<0.05) but also increase in viscous components (p<0.05) that matched the time course of increased amplitude of EMG activity (p<0.05). Phasic contraction counts (PCC) of voluntary EMG exhibited a significantly negative correlation with the bar test scores (correlation coefficient= -0.78). These results confirm that akinesia induced by D2-receptor blockade also induces a rigidity that shares many features with human with Parkinson disease. In addition to decrease in clinical MAS scale, the viscous components and the viscosity of spastic elbow flexors were decreased and the EMG thresholds during higher stretching frequencies were increased after botulinum toxin type A intervention (p<0.05). By the MSE, compared with healthy controls, patients showed significantly higher resistance torque at comparable velocities (p<0.001) and the resistance torque increased more rapidly with increasing velocity (p=0.02). Biomechanically, patients post-stroke showed smaller ROM (p=0.0003), higher stiffness (p=0.0003), larger energy loss (p=0.005), and higher resistance at comparable angles (p=0.03).The catch angle was dependent on movement velocity and occurred significantly later with increasing velocity (p=0.02). These novel techniques for quantifying biomechanical and EMG parameters provide objective assessment methods for investigating the time-course changes of abnormal muscle tone in animal models that will be useful for evaluating novel treatments. Besides, the portable stretching device could be used for evaluating the treatment effect of spasticity reduction. Moreover, the intrinsic muscle property and reflex component contribute to spasticity could be evaluated by MSE.