早期帕金森病诊断及治疗新进展-课件.pptVIP

徐评议 中山大学附属第一医院神经内科 早期帕金森病诊断及治疗新进展 共同特点: 老年, 进行性发展, 特定脑区和特定症状 中枢神经退行性病 帕金森病、老年性痴呆、多系统萎缩等 不同脑区退行性变 特定递质代谢障碍 中老年，隐匿，痴呆、震颤麻痹、运动障碍和病理性肌萎缩等 共同特征-不同区间神经元胞体或胞核内出现不同成份的异常蛋白沉积，神经元变性凋亡 中枢神经退行性病 In PD, the intracellular inclusion bodies called Lewe’s body in midbrain is a Golden standard for confirmed diagnosis of PD; while amyloid plaques and phosphored tau tangues are pathological hall marker for Alzheimer’s disease. Lewe’s body disease is wildly spread in cortex, and midbrain; in MSA, the neuronal loss is mainly present in nigro, striatum, pon, cellebrum, and spinal cord and vagus nuclei. 中枢神经退行性病的病理机制 Over 70 proteins have been identified in Lewy bodies ??-Crystallin; ?-Synuclein Calcium-calmodulin-dependent protein kinase II Calbindin D28K; Chondroitin sulfate; Chromogranin A Clusterin/apolipoprotein Cochaperone C terminus of Hsp-70-interacting protein Complement proteins (C3d, C4d, C7, and C9);Cyclin-dependent kinase 5 Cytochrome c; DJ-1; Dorfin; 14-3-3 protein Gelsolin-related amyloid protein Finnish type Heat-shock proteins 27, 40, 70, 60, 90, and 110P; hosphorylated IkBa; Lipids MAP-2; MAP-5/MAP-1b; Mitochondria Multicatalytic proteinase; MxA protein NEDD8; Neurofilaments; NFkB Omi/HtrA2P35nck5a; p62/sequestosome Pael-R; ROC1; Sphingomyelin Cu/Zn superoxide dismutase; Mn superoxide dismutase Synaptic vesicle-specific protein; Synphilin-1; Synaptophysin; Tau TorsinA; Tubulin; Tyrosine hydroxylase Ubiquitin; Ubiquitin C-terminal hydroxylase Shults, PNAS 2006; 103:1661 Savitt et al, JCI, 2006; 116:1744 帕金森病的临床病程 早期标记的发现期 Tolosa E et al, Lancet Neurology 2006 中枢神经变性病的不同临床特征 吞咽困难 发音困难 凝视麻痹 失用 步态不稳 跌倒 强直 运动迟缓 震颤 痴呆 植物神经功能障碍 帕金森背景 发病情况: 我国帕金森病(PD)＞200万↑.Zhang Z, et al. Lancet. 2005 无症状前10～20年，黑质多巴胺(DA)神经元大量变性 病理发展： 发病机制: 基因/环境/老化可能与大多数PD相关 替代疗法5～年后逐渐失效, 难以控制的不良反应;且DA神经元持续变性,需发展新的治疗方法，干预疾病发展 治疗现状: 发病机制不清:环境因素、遗传易感、老年背景 结果分析: Initial clinical diagnosis within 5 yrs of disease onset was correct in 65% of cases After a mean duration of 12 yrs, the final diagno