巴金森氏病病態生理及深腦刺激術的作用機轉

巴金森氏病是中老年人最常見的神經退化性疾病之一。巴金森氏病的病態生理關鍵變化在於病患中腦黑質細胞退化引起多巴胺等神經傳導物質分泌不足，造成調控運動的大腦－基底核迴路功能異常，進一步產生臨床上巴金森氏病的動作障礙症狀。位於大腦深部的視丘下核（subthalamic nucleus），是控制大腦－基底核迴路的重要結構。具有節律性及自發放電特性的視丘下核，有著獨特的電氣生理特性，在較負的膜電位狀況，視丘下核會由棘波式（spike mode）放電轉換成叢集式（burst mode）放電。視丘下核藉著分泌興奮性傳導物質的神經纖維，對基底核的輸出結構進行調控，並藉由其電生理特性影響運動功能。近年來對於巴金森氏病病態生理機轉的研究，發現視丘下核在大腦多巴胺缺乏的狀態下會出現叢集式放電表現增加的狀況，此一表現被視為巴金森氏病病態生理的特徵之一。利用高頻率電流刺激視丘下核，可以藉由改變視丘下核的電生理狀態，使實驗動物之巴金森氏病症狀獲得大幅度改善。這些動物試驗之研究成果，已促成人類巴金森氏病病患者接受視丘下核高頻率放電刺激治療的發展，而且成效卓著。此種治療即為臨床上利用視丘下核進行的深腦刺激術（deep brain stimulation, DBS），目前已成為中至重度巴金森氏病患者的重要治療方式。我們將由介紹大腦－基底核迴路和視丘下核的生理特性開始，至臨床上利用視丘下核刺激來治療巴金森氏病，並對視丘下核的基礎研究及臨床應用等方面作一簡要的介紹與回顧。

Parkinson's disease (PD) is one of the most common neurodegenerative disorders in the elderly. Pathophysiology of PD is closely related to the loss of midbrain dopaminergic neurons and subsequent dopamine deficiency-related aberrant cortico-basal ganglia circuit function, which further results in clinical motor symptoms of PD. Deeply seated subthalamic nucleus (STN) is a key structure in the control of cortico-basal ganaglia circuit. With the characteristics of a pacemaker and spontaneous discharge, STN can switch from spike firing to burst firing during membrane hyperpolarization. STN controls the output structures of basal ganglia through its glutamatergic fibers and influence the motor function by its electrophysiological property. Recent studies reveal that STN becomes markedly increasing in burst firing during parkinsonian dopamine deficiency state, and many researchers consider this increase in burst firing as a major pathophysiological hallmark of PD. By changing the electrophysiological status of STN through high frequency electrical stimulation, we can improve the parkinsonian motor symptoms significantly both in experimental animals and in human subjects suffering from PD. This treatment, currently named deep brain stimulation (DBS), has now become a standard treatment in PD patients. In this article, we first review the physiological function of cortico-basal ganglia circuit and STN, and then discuss about the basic and clinical aspects of STN in PD pathophysiology, followed by mechanism of DBS.