帕金森氏症患者接受深層腦刺激術前後於行走跨越障礙物時之動作分析

Motion Analysis of Patients with Parkinson's Disease During Obstacle-Crossing Before and After Deep Brain Stimulation

陳冠州(Guan-Chou Chen)

指導教授 ： 呂東武

國立臺灣大學/工學院/醫學工程學研究所/碩士(2018年)

https://doi.org/10.6342/NTU201802671

摘要

帕金森氏症是一種慢性中樞神經系統退化疾病，主要原因為管控動作的基底核黑質緻密部分泌多巴胺不足所致，進而影響運動神經系統而出現動作異常，經常導致動作遲緩、肌肉僵直、靜止性震顫、姿勢不穩定等動作症狀，以至於在執行日常動作例如走路、跨越障礙物較為困難，也因常跨越失敗將導致跌倒與受傷。
帕金森氏症雖然可以透過藥物改善其症狀，但是長期服用藥物會出現藥效減退或異動症及藥物波動等副作用，因此手術的介入來輔助減緩疾病的症狀，深層腦刺激手術是目前認為最有效且最常見的手術，也有文獻指出對於手術後對於步態的改善，然而所用的評估工具多數為Hoehn and Yahr量表與統一帕金森氏症量表 (UPDRS)，此評估量表常見於臨床，然而整體上較為主觀，且少以運動學和動力學觀點切入探討；此外透過正子射出斷層掃描可以準確判斷多巴胺含量，但是無法即時回饋出患者對於日常生活的影響。帕金森氏症對於雙側動作表現影響之程度有所不同，且鮮少有文獻探討比較主要患側肢段與輕微患側肢段之術前與術後之差異以及與正常老年人跨越障礙物控制策略的比較。
因此，本研究透過立體攝影技術分析帕金森氏症患者在術前與術後對於跨越障礙物的運動學參數如關節角度與動力學參數如關節力矩的差異表現，並利用多目標最佳控制方法，探討帕金森氏症患者在接受深層腦刺激術前與術後、對於不同高度之障礙物與主要與次要患側的動作控制策略，並且與正常受試者進行比較，試圖了解深層腦刺激手術對於帕金森氏症患者的差異。
在本研究的結果指出，術後的跨越步寬有所下降與跨越速度有所上升的趨勢，並且都有明顯接近正常老年人，主要原因為帕金森氏症因多巴胺分泌不足所導致動作遲緩、肌肉僵直、靜止性震顫、姿勢不穩定等動作症狀在術後有所改善。此外，在本研究中患者以主要患側關節角度而言，術前與術後除了膝關節於橫狀面前腳跨越有達到顯著大於差異外，其餘皆沒有；比起正常老年人後腳跨越時，膝關節矢狀面大於術前、髖關節額狀面小於術前，踝關節矢狀面、髖關節額狀面皆大於術後，以及在前腳跨越時，踝關節橫狀面時有顯著小於術前之差異外，膝關節橫狀面大於術後與踝關節橫狀面小於術後。在關節力矩方面，術前與術後在任何關節任何平面於前腳跨越時皆沒有顯著差異；但是於後腳跨越時，比起正常老年人，無論是術前還是術後，髖關節額狀面、膝關節額狀面以及踝關節矢狀面皆小於正常老年人。相對次要患側關節角度而言，在後腳跨越時，術前與術後也僅有在膝關節於矢狀面有顯著差異；比起正常老年人後腳跨越時，髖關節額狀面顯著大於術前、膝關節矢狀面顯著小於術前，在前腳跨越時踝關節橫狀面有顯著小於術前；在術後方面，於膝關節、踝關節矢狀面後腳跨越時與膝關節、踝關節橫狀面前腳跨越時有顯著差異，比起現有的文獻有較大的差異，目前推測術前術後僅少有差異極有可能為術前與術後相隔時間過短所致。就整體跨越障礙物控制策略而言，正常老年人與術前和術後主要患側有顯著差異，而次要患側則無。對於手術前後而言，主要患側有顯著差異，而次要患側則無，並且由於帕金森氏症為一種退化性的疾病，隨著治療時機的拖延，病況會日益加劇，患者會因為動作呈現越來越僵直，導致控制策略逐漸採取較大能量權重、降低足部間隙進行跨越障礙物，增加跨越障礙物時被障礙物絆倒之風險。
結論，本研究提供帕金森氏症患者於深層腦刺激手術前後與正常老年人之跨越障礙物控制策略比較，並且討論帕金森氏症患者主要及次要患側的差異，透過控制策略並不會受到障礙物高度的影響，推測人體動作系統會依照執行一個特定形式的跨越動作，最後期盼多目標最佳控制方法可以做為評估復健效果的一個參考依據，並且可以用來評估以及預防病患跌倒的風險。

關鍵字

帕金森氏症 ； 異動症 ； 藥物波動 ； 深層腦刺激手術 ； 控制策略

並列摘要

Parkinson's disease (PD) is a chronic degenerative disease of the central nervous system. It’s mainly caused by the lack of the dopamine secretion in the substantia nigra pars. Substantia nigra pars play an essential role in the movement. If the controls of substantia nigra pars failure, dopamine may also cause insufficient secretion affecting the central nervous motor system and lead to abnormal movements, such as slow movement, muscle rigidity, resting tremor and unstable posture control. It may have difficulty to perform routine actions such as walking and obstacles crossing, and often falls and injuries due to failure crossing.
Although PD can improve its symptoms through medication, long-term of taking medicine may have side effects such as dyskinesia or motor fluctuation. The surgical intervention can help to alleviate the symptoms of the PD. Deep brain stimulation surgery (DBS) is currently considered the most effective and most common surgery; there are also evidence-based for the improvement of movement after surgery. However, most assessment tools are Hoehn and Yahr scale and the Unified Parkinson's Disease Rating Scale (UPDRS). It may have too intuitive issue to get rids of the human factors judgment. There are also using the positron emission tomography (PET) technique can accurately determine the dopamine content, but it cannot immediately give back the patient's impact on daily life. In real life, the grade of PD may affect the bilateral sides. There are much few kinds of literature discussing the control strategies of the major and minor side limbs before and after the surgery.
Therefore, in this study, three-dimensional motion capture system techniques were used to analyze the kinematics performance parameters, such as joint angle and kinetic performance parameters joint moment while crossing obstacles before and after surgery. In this study also used the multi-objective optimal control to investigate the control strategies of patients with PD of the major side and minor side effect before and after DBS. To find out if there are any crossing obstacles key factors between DBS operation for PD and healthy subjects.
In this study showed that patients might attend to use lesser crossing width and greater crossing speed after surgery close to the normal control. It's mainly because of the insufficient secretion of dopamine that affecting the central nervous motor system and lead to slow movement and muscle rigidity. Also, on the one hand in the major side of joints angle, only knee joint in the transverse plane has reached the significant difference in pre- and postoperative group while leading leg is crossed. Compared with healthy control in joint angles, during trailing leg is crossed, preoperative patients’ knee joint angle in the sagittal plane has lesser and hip joint angle in the frontal plane has greater than controls. In postoperative patients’ ankle joint angle is lesser in the sagittal plane and hip joint angle in the frontal plane than controls. While patients' leading leg is crossed, ankle joint in the transverse plane has significantly lesser in preoperative than controls; also the transverse plane of the knee joint angle is more celebrated and in the ankle joint angle is smaller in postoperative than controls. In the joint moment, there is no significant difference between pre-op and postoperative any joint in any plane while leading leg is crossed. Compared with controls, hip and knee joint moment in frontal plane and ankle joint moment in the sagittal plane has greater than in preoperative and postoperative while trailing leg is crossed.
On the other hand in the minor side of the joint angle, there is the only knee joint angle in the sagittal plane while trailing leg is crossed reached the significant difference. Compared with healthy control in joint angle, while trailing leg is crossed, hip joint angle in the frontal plane has significantly greater and knee joint angle in the sagittal plane markedly lesser than pre-operative patients. While leading leg is crossed, ankle joint angle in the transverse plane has the smaller joint angle in controls in preoperative. In postoperative patients’ both knee and ankle joint angle in the sagittal plane while trailing leg is crossed and knee, also ankle joint angle in the transverse plane while leading leg is crossed has reached a significant lesser in postoperative patients. There may have some inconsistencies in recent research. It estimated the reasons due to the short interval between preoperative and postoperative.
As far as the overall obstacle crossing control strategy is concerned, there is a significant difference between the normal elderly and the major side before and after surgery, while the minor side is not. For the pre- and post-operative, there is a significant difference in the main affected side, but not in the minor side, moreover because Parkinson's disease is a degenerative disease, the condition of rigidity will increase with the delay of treatment. The patient will appear to adopts a more significant energy weighting, reduces the foot clearance to cross the obstacle, it may increase the risk of being tripping by the obstacle when crossing.
In conclusion, in this study provides patients with Parkinson's disease before and after deep brain stimulation surgery obstacle crossing control strategies, also discusses the differences between the major side and the minor side of patients with Parkinson's disease. In this study found that patients with Parkinson's disease have different control strategies for obstacles crossing, but not affected by the height of the obstacles. It is speculated that the human body motion system will perform a specific form of cross-over action. Finally, the multi-target optimal control method can be used as a reference for evaluating the rehabilitation effect and can be used to assess and prevent the risk of falling of the patient.

並列關鍵字

Dyskinesia ； Motor fluctuation ； Deep brain stimulation ； Control strategies

參考文獻

1. Obeso JA, Rodríguez-Oroz MC, Rodríguez M, Arbizu J, Giménez-Amaya JM. The basal ganglia and disorders of movement: pathophysiological mechanisms. Physiology. 2002;17(2):51-5.

2. Nambu A, Tachibana Y, Kaneda K, Tokuno H, Takada M. Dynamic model of basal ganglia functions and Parkinson’s disease. The basal ganglia VIII: Springer; 2005. p. 307-12.

3. Fung H-C, Chen C-M, Hardy J, Singleton AB, Lee-Chen G-J, Wu Y-R. Analysis of the PINK1 gene in a cohort of patients with sporadic early-onset parkinsonism in Taiwan. Neuroscience letters. 2006;394(1):33-6.

4. Massano J, Bhatia KP. Clinical approach to Parkinson's disease: features, diagnosis, and principles of management. Cold Spring Harbor perspectives in medicine. 2012;2(6):a008870.

5. Rocha EM, De Miranda B, Sanders LH. Alpha-synuclein: pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurobiology of disease. 2018;109:249-57.