柏金遜綜合症背景

Background of Parkinsonism

1817年，詹姆士柏金遜醫生 (Dr. James Parkinson) 首次發表了一班患者病徵，包括行動緩慢、四肢僵硬、震顫及/或步履不穩。自此，這些臨床徵狀便歸類為「柏金遜綜合症」。我們知道柏金遜綜合症有很多原因，較為普遍的是原發性柏金遜病 (PD) 及偶發性腦小血管病 (SVD) 。其他病因則統稱為非典型柏金遜綜合症，包括較不普遍的腦神經退化疾病，例如多發性系統萎縮症。

暫時已知的柏金遜病理是腦內流失含有多巴胺的神經元，而至今仍未有有效的治療方法可以減慢或遏止多巴胺神經元的退化。一個可模仿柏金遜病的理想動物模型仍然缺乏，令科學家未能找出能保護腦神經的治療。我們亦知道當運動症狀出現時，約一半的多巴胺神經元已經流失。因此，最理想的是柏金遜病能早在運動症狀出現前斷症；例如快速眼動睡眠行為障礙 (RBD) 已被視為柏金遜病的其中一個最早期病徵。

柏金遜病及與腦小血管病有關的柏金遜綜合症的發病率隨著年紀而上升。估計全球現時有610萬名柏金遜病患者，而在中國及香港，則分別有170萬及12,000名患者。隨著人口老化，未來20年的患者人數更預計會上升兩倍；而腦小血管病的發病率將更高。中大腦神經科團隊的研究發現，約有三分一長者的腦內潛伏著腦小血管病，正正能解釋世界各地有很多長者都出現行動緩慢和步履不穩的情況。嚴重的腦小血管病不但使柏金遜患者行動更困難，更會大大增加患上認知障礙症及中風的風險。

然而，儘管腦小血管病十分普及，而且對人口老化社會帶來負面影響，有關此病的研究和公眾意識卻仍然不足，而一個理想的動物模型及針對腦小血管病病理的預防性治療更見缺乏。

In 1817, Dr. James Parkinson published the first series of subjects who presented with slow movement, rigidity of the limbs and body, tremor and/ or instability. Since then, the term “parkinsonism” is used to describe these clinical features. We now know that there are many causes for parkinsonism. The most common being idiopathic Parkinson’s Disease (PD) and sporadic cerebral Small Vessel Disease (SVD). Other causes may include less common neurodegenerative diseases (e.g. multiple system atrophy), which are commonly labelled as “atypical” parkinsonism.

A pathological feature of PD is a loss of neurons that contain dopamine. To date, there is still no effective treatment that can stop or slow down progressive degeneration of dopaminergic neurons. A good animal model mimicking PD is lacking, hindering the discovery of neuroprotective treatment. It is also well known that by the time motor symptoms appear, about 50% of dopaminergic neurons are already lost. Ideally, PD should be identified at an earlier stage before motor symptoms appear, e.g. rapid eye moment (REM) sleep behavioural disorder is now considered one of the earliest symptoms of PD.

The prevalence of PD and SVD parkinsonism increases with age. Currently, it was estimated that there are about 6.1 million, 1.7 million and 12,000 people having PD in the world, China and Hong Kong respectively. It was projected that people suffering from PD will at least double in the coming 2 decades due to the ageing population. In particular, the prevalence of SVD is even higher. Our team from Division of Neurology, CUHK has shown that about one third of the elderly harbour SVD in their brains, explaining a small step gait and unsteadiness experienced by many elderlies worldwide. More advanced SVD may give rise not only to more disabling parkinsonism but also dementia and stroke.

However, research interest and public awareness towards SVD have been very low, despite its high prevalence and negative impact on the ageing society, including the parkinsonism this disease induced. A good animal model for SVD is still lacking and specific preventive treatments targeting SVD pathophysiology are not available yet.