PDF(Pubmed)
Abstract：
While cognitive impairment, which was previously considered a red flag against the clinical diagnosis of multiple system atrophy (MSA), is a common symptom of this rare neurodegenerative disorder, behavioral disorders are reported in 30 to 70% of MSA patients. They include anxiety, apathy, impaired attention, compulsive and REM sleep behavior disorders (RBD), and these conditions, like depression, are early and pervasive features in MSA, which may contribute to disease progression. Despite changing concepts of behavioral changes in this synucleinopathy, the underlying pathophysiological and biochemical mechanisms are poorly understood. While specific neuropathological data are unavailable, neuroimaging studies related anxiety disorders to changes in the cortico-limbic system, apathy (and depression) to dysfunction of prefrontal-subcortical circuits, and compulsive behaviors to impairment of basal ganglia networks and involvement of orbito-frontal circuits. Anxiety has also been related to α-synuclein (αSyn) pathology in the amygdala, RBD to striatal monoaminergic deficit, and compulsive behavior in response to dopamine agonist therapy in MSA, while the basic mechanisms of the other behavioral disorders and their relations to other non-motor dysfunctions in MSA are unknown. In view of the scarcity of functional and biochemical findings in MSA with behavioral symptoms, further neuroimaging and biochemical studies are warranted in order to obtain better insight into their pathogenesis as a basis for the development of diagnostic biomarkers and future adequate treatment modalities of these debilitating comorbidities.
摘要：
而认知障碍，以前被认为是多系统萎缩（MSA）临床诊断的危险信号，是这种罕见的神经退行性疾病的常见症状，据报道，30％至70％的MSA患者出现行为障碍。它们包括焦虑，冷漠,注意力受损，强迫性和快速眼动睡眠行为障碍（RBD），这些条件，比如抑郁症，是MSA的早期和普遍特征，这可能有助于疾病进展。尽管改变了这种突触核蛋白病行为变化的概念，潜在的病理生理和生化机制知之甚少。虽然没有具体的神经病理学数据，神经影像学研究将焦虑症与皮质-边缘系统的变化相关，对前额叶-皮质下回路功能障碍的冷漠（和抑郁），和强迫性行为对基底神经节网络的损害和额叶环路的参与。焦虑也与杏仁核中的α-突触核蛋白（αSyn）病理有关，RBD至纹状体单胺能缺陷，和对MSA多巴胺激动剂治疗的强迫行为，而MSA中其他行为障碍的基本机制及其与其他非运动障碍的关系尚不清楚。鉴于MSA中缺乏行为症状的功能和生化发现，需要进一步的神经影像学和生化研究,以便更好地了解其发病机制,作为开发诊断性生物标志物和未来这些衰弱合并症的适当治疗方式的基础.
