肌肉張力異常常見於上運動神經元疾病患者。其中痙攣常見於中風、脊髓損傷、腦外傷及腦性麻痺的病患，對病患運動功能造成影響而降低生活品質。許多動物模型被建立來研究其肌肉張力異常的機制及新治療技術的研發，然而適用於動物模型的量化評估系統缺乏以致於造成研究突破上的困難。在臨床上，儘管痙攣現象顯而易見，但是痙攣程度卻不易被量化。因此本研究目的在於發展使用於動物模型之肌肉張力評估平台，及發展適合臨床使用之張力評估系統。
在動物實驗方面，首先以多巴胺D2受體拮抗劑raclopride來建立帕金森氏症動物模型；再以我們所建立的微小化肌肉張力評估系統以及表面多點電極來量測不正常肌肉張力之情形。在施打藥物前及施打後五小時內，藉由節拍器指示以五種不同頻率（1/3，1/2，1，3/2，2赫茲）手動牽張大白鼠後肢踝關節，同時記錄其反應阻力；並記錄無外力干擾休息狀態下，大白鼠的自主運動肌電訊號。Catalepsy的評估採用行為測試，Bar test，依照同樣時序量測。在臨床實驗方面，我們首先利用可攜式牽張系統（Portable stretching device）結合肌電訊號來追蹤觀察施打肉毒桿菌素前後中風患者肘屈肌的痙攣情形。針對十位肘關節肌肉接受肉毒桿菌素的治療慢性中風患者進行痙攣的臨床量表（Modified Ashworth Scale, MAS），生物力學及肌電學的評估。在施打肉毒桿菌素之前、後各兩個星期，對病人進行評估；經由節拍器指示以不同的牽張頻率（1/3、1/2、1 和 3/2 赫茲）在一定的活動範圍內（60°），手動牽張肘關節，並同時記錄肘關節肌群的反應阻力及肌電訊號。然而可攜式牽張系統利用正弦波的評估方式無法區分出肌肉本身的變化對痙攣的影嚮，因此基於Modified Tardieu臨床評估的方式進而發展可攜式手動肌肉張力系統（Manual Spasticity Evaluator, MSE)來辨別中風患者及正常老年人肘關節的肌肉張力情形。利用MSE提供之即時視覺聽覺回饋，同一施測者分別對十二位慢性中風患者及九位平均年齡相仿之正常受試者進行不同速度之手動牽張測試（30°/s、90°/s、180°/s及270°/s）及MAS評估。基本生物力學參數（關節活動角度、反應阻力、關節剛性及能量散失）及神經反射參數（肌電訊號及Catch angle）分別被記錄並於兩組之間或不同速度之間作統計比較。
動物實驗結果顯示，施打藥物後不僅關節剛性增加，黏性也明顯增加（P<0.05）；肌電訊號強度也在施打藥物後明顯增強（P<0.05）。經由肌電訊號分析得知被施打藥物之大白鼠自主運動的情形與Bar test分數呈現顯著負相關，意指自主運動減少。施打raclopride後之大白鼠不只顯示運動不能的症狀，亦有僵直的情形發生。臨床施打肉毒桿菌之前跟施打之後第二週，用速度相依之黏性參數（Bω）和黏性，以及反射肌電訊號閾值來作為評估痙攣程度的參數。我們可以發現MAS分數、黏性元素及黏性等參數在施打肉毒桿菌素之後均呈現下降；而在較高牽張頻率所量到的肌電訊號閾值則為增加（P<0.05）。利用MSE評估中風及正常族群發現，中風患者有顯著關節活動度減小，關節剛性增加，較高的能量損失及在與正常族群相當的關節角度下產生較高的阻力（P<0.05）。並發現Catch angle的速度相依性，當牽張速度上升，Catch angle發生較晚。
本研究提供了適用於動物模型之肌肉張力評估平台，證實利用可攜式痙攣評估系統可以用來做為臨床量測在施打肉毒桿菌素之後肌肉張力亢進下降的變化。黏性參數和反射肌電訊號閾值可用在臨床上來量化痙攣肌肉施打肉毒桿菌素後的張力變化，然而對於肌肉內因性變化無法單獨評估。經由另一模式的可攜式手動評估量測系統，肌肉內因性改變及神經性改變對於痙攣的影響可以分別加以評估。

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.

[1] Charles TC, Alloway KD. Spinal cord and peripheral nerves. Medical Neuroscience: Hayes Barton Press 1999:448.
[2] Latash ML. Spasticity. In: Latash ML, ed. Neurophysiological basis of movement. USA: Human kinetics 1998:213-28.
[3] Sanger TD. Hypertonia in children: how and when to treat. Curr Treat Options Neurol. 2005 Nov;7(6):427-39.
[4] Sanger TD, Delgado MR, Gaebler-Spira D, Hallett M, Mink JW. Classification and definition of disorders causing hypertonia in childhood. Pediatrics. 2003 Jan;111(1):e89-97.
[5] Lance JW. Symposium synopsis. In: Feldman RG, Young RR, Koella WP, eds. Spasticity: Disordered Motor Control. Chicago: Yearbook Meidcal 1980:485-94.
[6] Hankey GJ, Wardlaw JM. Neurologic diagnosis. In: Hankey GJ, Wardlaw JM, eds. Clinical Neurology. New York: Demos 2002:20.
[7] Rymer WZ, Katz RT. Mechanisms of spastic hypertonia. Phys Med Rehabil State Art Rev. 1994;8:441-54.
[8] Gottlieb GL, Agarwal GC, Penn R. Sinusoidal oscillation of the ankle as a means of evaluating the spastic patient. J Neurol Neurosurg Psychiatry. 1978 Jan;41(1):32-9.
[9] Meinders M, Price R, Lehmann JF, Questad KA. The stretch reflex response in the normal and spastic ankle: effect of ankle position. Arch Phys Med Rehabil. 1996 May;77(5):487-92.
[10] Mirbagheri MM, Barbeau H, Ladouceur M, Kearney RE. Intrinsic and reflex stiffness in normal and spastic, spinal cord injured subjects. Exp Brain Res. 2001 Dec;141(4):446-59.
[11] Rack PM, Ross HF, Thilmann AF. The ankle stretch reflexes in normal and spastic subjects. The response to sinusoidal movement. Brain. 1984 Jun;107 (Pt 2):637-54.
[12] Thilmann AF, Fellows SJ, Garms E. The mechanism of spastic muscle hypertonus. Variation in reflex gain over the time course of spasticity. Brain. 1991;114(Pt 1A):233-44.
[13] Zhang LQ, Wang G, Nishida T, Xu D, Sliwa JA, Rymer WZ. Hyperactive tendon reflexes in spastic multiple sclerosis: measures and mechanisms of action. Arch Phys Med Rehabil. 2000 Jul;81(7):901-9.
[14] Pandyan AD, Gregoric M, Barnes MP, Wood D, Van Wijck F, Burridge J, et al. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disabil Rehabil. 2005 Jan 7-21;27(1-2):2-6.
[15] Sheean G. The pathophysiology of spasticity. European Journal of Neurology. 2002;9(Suppl 1):3-9; dicussion 53-61.
[16] Kandel ER, Schwartz JH, Jessell TM. Spinal reflexes. Principles of Neural Science. 4 ed: McGraw-Hill 2000:713-36.
[17] Dietz V, Berger W. Normal and impaired regulation of muscle stiffness in gait: a new hypothesis about muscle hypertonia. Exp Neurol. 1983 Mar;79(3):680-7.
[18] Lee WA, Boughton A, Rymer WZ. Absence of stretch reflex gain enhancement in voluntarily activated spastic muscle. Exp Neurol. 1987 Nov;98(2):317-35.
[19] Sinkjaer T, Andersen JB, Nielsen JF. Impaired stretch reflex and joint torque modulation during spastic gait in multiple sclerosis patients. J Neurol. 1996 Aug;243(8):566-74.
[20] Sinkjaer T, Magnussen I. Passive, intrinsic and reflex-mediated stiffness in the ankle extensors of hemiparetic patients. Brain. 1994 Apr;117 (Pt 2):355-63.
[21] Sinkjaer T, Toft E, Larsen K, Andreassen S, Hansen HJ. Non-reflex and reflex mediated ankle joint stiffness in multiple sclerosis patients with spasticity. Muscle Nerve. 1993 Jan;16(1):69-76.
[22] Hufschmidt A, Mauritz KH. Chronic transformation of muscle in spasticity: a peripheral contribution to increased tone. J Neurol Neurosurg Psychiatry. 1985 Jul;48(7):676-85.
[23] Booth CM, Cortina-Borja MJ, Theologis TN. Collagen accumulation in muscles of children with cerebral palsy and correlation with severity of spasticity. Dev Med Child Neurol. 2001 May;43(5):314-20.
[24] Feit H, Kawai M, Mostafapour AS. The role of collagen crosslinking in the increased stiffness of avian dystrophic muscle. Muscle Nerve. 1989 Jun;12(6):486-92.
[25] Singer BJ, Dunne JW, Singer KP, Allison GT. Velocity dependent passive plantarflexor resistive torque in patients with acquired brain injury. Clin Biomech (Bristol, Avon). 2003 Feb;18(2):157-65.
[26] Friden J, Lieber RL. Spastic muscle cells are shorter and stiffer than normal cells. Muscle & Nerve. 2003;27(2):157-64.
[27] Olsson MC, Kruger M, Meyer LH, Ahnlund L, Gransberg L, Linke WA, et al. Fibre type-specific increase in passive muscle tension in spinal cord-injured subjects with spasticity. J Physiol. 2006 Nov 15;577(Pt 1):339-52.
[28] Lieber RL, Runesson E, Einarsson F, Friden J. Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material. Muscle Nerve. 2003 Oct;28(4):464-71.
[29] Lorenc-Koci E, Wolfarth S, Ossowska K. Haloperidol-increased muscle tone in rats as a model of parkinsonian rigidity. Exp Brain Res. 1996 May;109(2):268-76.
[30] Kwon BK, Oxland TR, Tetzlaff W. Animal models used in spinal cord regeneration research. Spine. 2002 Jul 15;27(14):1504-10.
[31] Bose P, Parmer R, Thompson FJ. Velocity-dependent ankle torque in rats after contusion injury of the midthoracic spinal cord: time course. Journal of Neurotrauma. 2002;19(10):1231-49.
[32] Cenci MA, Whishaw IQ, Schallert T. Animal models of neurological deficits: how relevant is the rat? Nat Rev Neurosci. 2002 Jul;3(7):574-9.
[33] Dawson TM. New animal models for Parkinson's disease. Cell. 2000 Apr 14;101(2):115-8.
[34] Rodriguez Diaz M, Abdala P, Barroso-Chinea P, Obeso J, Gonzalez-Hernandez T. Motor behavioural changes after intracerebroventricular injection of 6-hydroxydopamine in the rat: an animal model of Parkinson's disease. Behav Brain Res. 2001 Jul;122(1):79-92.
[35] Dickinson SL, Longman DA, Slater P. A method for measuring drug-induced changes in limb muscle tone in the rat. Journal of Neuroscience Methods. 1982;5(1-2):195-200.
[36] Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995 Feb;12(1):1-21.
[37] Fischer DA, Ferger B, Kuschinsky K. Discrimination of morphine- and haloperidol-induced muscular rigidity and akinesia/catalepsy in simple tests in rats. Behav Brain Res. 2002;134:317-21.
[38] Wolfarth S, Kolasiewicz W, Ossowska K. Thalamus as a relay station for catalepsy and rigidity. Behav Brain Res. 1985 Dec;18(3):261-8.
[39] Lee TY, Fu MJ, Kuo TB, Lui PW, Chan SH. Power spectral analysis of electromyographic and systemic arterial pressure signals during fentanyl-induced muscular rigidity in the rat. Br J Anaesth. 1994 Mar;72(3):328-34.
[40] Hemsley KM, Crocker AD. Raclopride and chlorpromazine, but not clozapine, increase muscle rigidity in the rat: relationship with D2 dopamine receptor occupancy. Neuropsychopharmacology. 1999 Jul;21(1):101-9.
[41] Weinger MB, Bednarczyk JM. Atipamezole, an alpha 2 antagonist, augments opiate-induced muscle rigidity in the rat. Pharmacol Biochem Behav. 1994 Nov;49(3):523-9.
[42] Weinger MB, Segal IS, Maze M. Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat. Anesthesiology. 1989 Aug;71(2):242-9.
[43] Johnels B, Steg G. A mechanographic method for measurement of locomotor activity in rats. Effects of dopaminergic drugs and electric stimulation of the brainstem. Journal of Neuroscience Methods. 1982;6(1-2):17-27.
[44] Latash ML. Monosynaptic refexes. Neurophysiological basis of movement: Human Kinetics 1998:64-70.
[45] Latash ML. The skeletal muscle. Neurophysiological basis of movement. 1 ed: Human Kinetics 1998:26-34.
[46] Cutlip RG, Stauber WT, Willison RH, McIntosh TA, Means KH. Dynamometer for rat plantar flexor muscles in vivo. Med Biol Eng Comput. 1997 Sep;35(5):540-3.
[47] Kamper DG, Schmit BD, Rymer WZ. Effect of muscle biomechanics on the quantification of spasticity. Annals of Biomedical Engineering. 2001;29(12):1122-34.
[48] Wolfarth S, Lorenc-Koci E, Schulze G, Ossowska K, Kaminska A, Coper H. Age-related muscle stiffness: predominance of non-reflex factors. Neuroscience. 1997 Jul;79(2):617-28.
[49] Kolasiewicz W, Baran J, Wolfarth S. Mechanographic analysis of muscle rigidity after morphine and haloperidol: a new methodological approach. Naunyn Schmiedebergs Arch Pharmacol. 1987 Apr;335(4):449-53.
[50] Lee HM, Huang YZ, Chen JJ, Hwang IS. Quantitative analysis of the velocity related pathophysiology of spasticity and rigidity in the elbow flexors. J Neurol Neurosurg Psychiatry. 2002 May;72(5):621-9.
[51] Bakheit AM, Maynard VA, Curnow J, Hudson N, Kodapala S. The relation between Ashworth scale scores and the excitability of the alpha motor neurones in patients with post-stroke muscle spasticity. J Neurol Neurosurg Psychiatry. 2003 May;74(5):646-8.
[52] Cooper A, Musa IM, van Deursen R, Wiles CM. Electromyography characterization of stretch responses in hemiparetic stroke patients and their relationship with the Modified Ashworth scale. Clin Rehabil. 2005 Oct;19(7):760-6.
[53] Pandyan AD, Johnson GR, Price CI, Curless RH, Barnes MP, Rodgers H. A review of the properties and limitations of the Ashworth and modified Ashworth Scales as measures of spasticity. Clin Rehabil. 1999 Oct;13(5):373-83.
[54] Kumar RT, Pandyan AD, Sharma AK. Biomechanical measurement of post-stroke spasticity. Age Ageing. 2006 Jul;35(4):371-5.
[55] Haugh AB, Pandyan AD, Johnson GR. A systematic review of the Tardieu Scale for the measurement of spasticity. Disabil Rehabil. 2006 Aug 15;28(15):899-907.
[56] Scholtes VA, Becher JG, Beelen A, Lankhorst GJ. Clinical assessment of spasticity in children with cerebral palsy: a critical review of available instruments. Dev Med Child Neurol. 2006 Jan;48(1):64-73.
[57] Patrick E, Ada L. The Tardieu Scale differentiates contracture from spasticity whereas the Ashworth Scale is confounded by it. Clin Rehabil. 2006 Feb;20(2):173-82.
[58] Boyd R, Graham HK. Objective measurement of clinical findings in the use of botulinum toxin type A for the management of children with CP. Eur J Neurol. 1999;6(Suppl. 4):S23-S35.
[59] Mehrholz J, Wagner K, Meissner D, Grundmann K, Zange C, Koch R, et al. Reliability of the Modified Tardieu Scale and the Modified Ashworth Scale in adult patients with severe brain injury: a comparison study. Clin Rehabil. 2005 Oct;19(7):751-9.
[60] Hultborn H. Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients. J Rehabil Med. 2003 May(41 Suppl):46-55.
[61] Katz R. Presynaptic inhibition in humans: a comparison between normal and spastic patients. J Physiol Paris. 1999 Sep-Oct;93(4):379-85.
[62] Delwaide PJ. Electrophysiological testing of spastic patients: its potential usefulness and limitations. In: Delwaide PJ, Young RR, eds. Clinical neruophysiology in spasticity: Contribution to assessment and pathophysiology. Amsterdam: Elsevier 1985:185-203.
[63] Katz RT, Rovai GP, Brait C, Rymer WZ. Objective quantification of spastic hypertonia: correlation with clinical findings. Arch Phys Med Rehabil. 1992 Apr;73(4):339-47.
[64] Rymer WZ, Katz RT. Mechanical quantification of spastic hypertonia. Phys Med Rehabil State Art Rev. 1994;8:455-63.
[65] Chung SG, Van Rey E, Bai Z, Roth EJ, Zhang LQ. Biomechanic changes in passive properties of hemiplegic ankles with spastic hypertonia. Arch Phys Med Rehabil. 2004 Oct;85(10):1638-46.
[66] Schmit BD, Dewald JP, Rymer WZ. Stretch reflex adaptation in elbow flexors during repeated passive movements in unilateral brain-injured patients. Archives of Physical Medicine & Rehabilitation. 2000;81(3):269-78.
[67] Kamper DG, Rymer WZ. Quantitative features of the stretch response of extrinsic finger muscles in hemiparetic stroke. Muscle Nerve. 2000 Jun;23(6):954-61.
[68] Lee HM, Chen JJ, Ju MS, Lin CC, Poon PP. Validation of portable muscle tone measurement device for quantifying velocity-dependent properties in elbow spasticity. J Electromyogr Kinesiol. 2004 Oct;14(5):577-89.
[69] Prochazka A, Bennett DJ, Stephens MJ, Patrick SK, Sears-Duru R, Roberts T, et al. Measurement of rigidity in Parkinson's disease. Movement Disorders. 1997;12(1):24-32.
[70] Yeh CY, Chen JJ, Tsai KH. Quantifying the effectiveness of the sustained muscle stretching treatments in stroke patients with ankle hypertonia. J Electromyogr Kinesiol. 2007 Aug;17(4):453-61.
[71] Price R. Mechanical spasticity evaluation techniques. Crit Rev Phys Rehabil Med. 1990;2:65-73.
[72] Lin CC, Ju MS, Lin CW. The pendulum test for evaluating spasticity of the elbow joint. Arch Phys Med Rehabil. 2003 Jan;84(1):69-74.
[73] Bajd T, Bowman B. Testing and modelling of spasticity. J Biomed Eng. 1982 Apr;4(2):90-6.
[74] Bajd T, Vodovnik L. Pendulum testing of spasticity. J Biomed Eng. 1984 Jan;6(1):9-16.
[75] Bohannon RW. Variability and reliability of the pendulum test for spasticity using a Cybex II isokinetic dynamometer. Phys Ther. 1987 May;67(5):659-61.
[76] Levin MF, Hui-Chan C. Are H and stretch reflexes in hemiparesis reproducible and correlated with spasticity? J Neurol. 1993 Feb;240(2):63-71.
[77] Pierrot-Deseilligny E, Mazieres L. Spinal mechanisms underlying spasticity. In: Delwaide PJ, Young RR, eds. Clinical Neurophysiology in Spasticity. Amsterdam: Elsevier Science 1985:BV:63-76.
[78] Powers RK, Marder-Meyer J, Rymer WZ. Quantitative relations between hypertonia and stretch reflex threshold in spastic hemiparesis. Annals of Neurology. 1988;23(2):115-24.
[79] O'Dwyer NJ, Ada L, Neilson PD. Spasticity and muscle contracture following stroke. Brain. 1996 Oct;119 (Pt 5):1737-49.
[80] Ibrahim IK, Berger W, Trippel M, Dietz V. Stretch-induced electromyographic activity and torque in spastic elbow muscles. Differential modulation of reflex activity in passive and active motor tasks. Brain. 1993 Aug;116 (Pt 4):971-89.
[81] Chen JJ, Wu YN, Huang SC, Lee HM, Wang YL. The use of a portable muscle tone measurement device to measure the effects of botulinum toxin type a on elbow flexor spasticity. Arch Phys Med Rehabil. 2005 Aug;86(8):1655-60.
[82] Caligiuri MP. Portable device for quantifying parkinsonian wrist rigidity. Movement Disorders. 1994;9(1):57-63.
[83] Wiegner AW, Watts RL. Elastic properties of muscles measured at the elbow in man: I. Normal controls. J Neurol Neurosurg Psychiatry. 1986 Oct;49(10):1171-6.
[84] Zhang LQ, Chung SG, Bai Z, Xu D, van Rey EM, Rogers MW, et al. Intelligent stretching of ankle joints with contracture/spasticity. IEEE Trans Neural Syst Rehabil Eng. 2002 Sep;10(3):149-57.
[85] Brashear A, Gordon MF, Elovic E, Kassicieh VD. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. N Engl J Med. 2002;347:395-99.
[86] Ellenbroek B, Schwarz M, Sontag KH, Jaspers R, Cools A. Muscular rigidity and delineation of a dopamine-specific neostriatal subregion: tonic EMG activity in rats. Brain Res. 1985;345(1):132-40.
[87] Sawner KA, LaVigne MJ. Brunnstrom's movement therapy in hemiplegia: a neurophysiological approach. 2nd ed. Philadelphia: J. B. Lippincott Company 1992.
[88] Pisano F, Miscio G, Del Conte C, D. P, Candeloro E, Colombo R. Quantitative measures of spasticity in post-stroke patients. Clinical Neurophysiology. 2000;111:1015-22.
[89] Zhang LQ, Shiavi R, Hunt MA, Chen JJ. Clustering analysis and pattern discrimination of EMG linear envelopes. IEEE Transactions on Biomedical Engineering. 1991;38(8):777-84.
[90] Park HS, Peng Q, Zhang LQ. Causality-based portable control system desgin for tele-assessment of elbow joint spasticity. Rehabilitation Robotics, 2005 ICORR 2005 9th International Conference on; 2005; Chicago; 2005. p. 303-6.
[91] Peng Q, Shah P, Selles RW, Gaebler-Spira DJ, Zhang LQ. Measurement of ankle spasticity in children with cerebral palsy using a manual spasticity evaluator. Conf Proc IEEE Eng Med Biol Soc. 2004;7:4896-9.
[92] Burstein AH, Wright TM. Fundamentals of orthopaedic biomechanics. Baltimore: Williams&Wilkins 1994.
[93] Hemsley KM, Crocker AD. Atropine reduces raclopride-induced muscle rigidity by acting in the ventral region of the striatum. Eur J Pharmacol. 2002 Jan 11;434(3):117-23.
[94] Alcock SJ, Hemsley KM, Crocker AD. Atropine acts in the ventral striatum to reduce raclopride-induced catalepsy. Eur J Pharmacol. 2001 Jul 27;424(3):179-87.
[95] Fowler SC, Liou JR. Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not. Psychopharmacology (Berl). 1998 Nov;140(1):81-90.
[96] Hillegaart V, Ahlenius S. Effects of raclopride on exploratory locomotor activity, treadmill locomotion, conditioned avoidance behaviour and catalepsy in rats: behavioural profile comparisons between raclopride, haloperidol and preclamol. Pharmacol Toxicol. 1987;60:350-4.
[97] Marin C, Parashos SA, Kapitzoglou-Logothetis V, Peppe A, Chase TN. D1 and D2 dopamine receptor-mediated mechanisms and behavioral supersensitivity. Pharmacol Biochem Behav. 1993 May;45(1):195-200.
[98] Wadenberg ML, Seeman P. Clozapine pre-treatment enhances raclopride catalepsy. Eur J Pharmacol. 1999 Jul 14;377(1):R1-2.
[99] Watts RL, Wiegner AW, Young RR. Elastic properties of muscles measured at the elbow in man: II. Patients with parkinsonian rigidity. J Neurol Neurosurg Psychiatry. 1986 Oct;49(10):1177-81.
[100] Nigg BM, Macintosh BR, Mester J. Biomechanics and Biology of Movement. 1 ed: Human Kinetics 2000.
[101] Cantello R, Gianelli M, Civardi C, Mutani R. Parkinson's disease rigidity: EMG in a small hand muscle at "rest". Electroencephalogr Clin Neurophysiol. 1995;97(5):215-22.
[102] Parr-Brownlie LC, Hyland BI. Bradykinesia induced by dopamine D2 receptor blockade is associated with reduced motor cortex activity in the rat. J Neurosci. 2005;25:5700-9.
[103] Goldberg JA, Boraud T, Maraton S, Haber SN, Vaadia E, Bergman H. Enhanced synchrony among primary motor cortex neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. J Neurosci. 2002;22:4639-53.
[104] Singer B, Dunne J, Allison G. Reflex and non-reflex elements of hypertonia in triceps surae muscles following acquired barin injury: implications for rehabilitation. Disability and Rehabilitation. 2001;23:749-57.
[105] Johnson GR. Outcome measures of spasticity. Eur J Neurol. 2002 May;9 Suppl 1:10-6; discussion 53-61.
[106] Mackey AH, Walt SE, Lobb G, Stott NS. Intraobserver reliability of the modified Tardieu scale in the upper limb of children with hemiplegia. Dev Med Child Neurol. 2004 Apr;46(4):267-72.
[107] Powers RK, Campbell DL, Rymer WZ. Stretch reflex dynamics in spastic elbow flexor muscles. Ann Neurol. 1989 Jan;25(1):32-42.
[108] Starsky AJ, Sangani SG, McGuire JR, Logan B, Schmit BD. Reliability of biomechanical spasticity measurements at the elbow of people poststroke. Arch Phys Med Rehabil. 2005 Aug;86(8):1648-54.
[109] Bakheit AM, Pittock S, Moore AP, Wurker M, Otto S, Erbguth F, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke. Eur J Neurol. 2001 Nov;8(6):559-65.
[110] Bakheit AM, Thilmann AF, Ward AB, Poewe W, Wissel J, Muller J, et al. A randomized, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo in upper limb spasticity after stroke. Stroke. 2000;31(10):2402-6.
[111] Dietz V, Trippel M, Berger W. Reflex activity and muscle tone during elbow movements in patients with spastic paresis. Ann Neurol. 1991 Dec;30(6):767-79.
[112] Ahlberg A, Moussa M, Al-Nahdi M. On geographical variations in the normal range of joint motion. Clin Orthop Relat Res. 1988 Sep(234):229-31.
[113] Allander E, Bjornsson OJ, Olafsson O, Sigfusson N, Thorsteinsson J. Normal range of joint movements in shoulder, hip, wrist and thumb with special reference to side: a comparison between two populations. Int J Epidemiol. 1974 Sep;3(3):253-61.
[114] Gunal I, Kose N, Erdogan O, Gokturk E, Seber S. Normal range of motion of the joints of the upper extremity in male subjects, with special reference to side. J Bone Joint Surg Am. 1996 Sep;78(9):1401-4.