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进展性核上性麻痹经病理证实的两种不同临床表现型:Richardson综合征及PSP帕金森病

世界核心医学期刊文摘（眼科学分册） 2005年第10期1卷 1-2页

作者： Williams D.R. De Silva R. Paviour D.C. A.J. Lees 邢咏新 reta lila West on institute for neurological studies 46 Cleveland St London W1T 4JF United Kingdom Prof.

The clinical diagnosis of progressive supranuclear palsy(PSP) relies on the id entification of characteristic signsand symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagn ose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and t o compare the biochemical and genetic characteristics of these groups. In 103 co nsecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson’s syndrome (RS) a nd PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54%of all cases, an d were characterized by the early onset of postural instability and falls, supra nuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32 %) were characterized by asymmetric onset, tremor, a moderate initial therapeut ic response to levodopa and were frequently confused with Parkinson’s disease ( PSP-P). Fourteen cases (14%)-could not be separated according to these criter ia. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 year s, P < 0.001)-and age at death earlier (72.1 versus 75.5 years, P=0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basa l pons also differed significantly. In RS, the mean four-repeat: three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P< 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical su bgroups was not significant. There were no differences in apolipoprotein E genot ypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of case s in t

关键词：帕金森病 Richardson PSP 核上性麻痹表现型注视麻痹左旋多巴神经纤维缠结认知功能遗传特性

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影响帕金森病患者强迫使用多巴胺能药易感性的因素

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世界核心医学期刊文摘（神经病学分册） 2006年第3期2卷 36-36页

作者： Evans A.H. Lawrence A.D. Potts J. A.J. Lees 张殿增 reta lila weston institute of neurological studies Windeyer Building 46 Cleveland Street London W1T 4JF United Kingdom

Background: In the course of treatment, a small group of patients with Parkinson disease (PD) develop a harmful pattern of compulsive dopaminergic drug use, called the dopamine dysregulation syndrome (DDS). Individual factors may influence susceptibility. Objectives: To identify predisposing factors to DDS in a population of outpatients with PD. Methods: The authors compared clinical features, impulsive sensation seeking (ISS) personality traits, past experimental drug use, alcohol consumption, smoking behaviors, and depressive symptoms in 25 patients with DDS to an outpatient sample of 100 patients with PD who were not compulsively overusing dopaminergic medication. Results: Patients with DDS had a significantly younger age at disease onset, higher dopaminergic drug intake, greater past experimental drug use, more depressive symptoms, scored higher on ISS ratings, and tended to have higher alcohol intake. Using logistic regression analysis, we found that novelty seeking personality traits, depressive symptoms, alcohol intake, and age at PD onset were significant predictors of DDS. Conclusions: These factors may help to identify early patients who are more vulnerable to developing a pattern of compulsive dopaminergic drug use and help minimize its consequences.

关键词：帕金森病多巴胺能药失调综合征强迫性发病年龄人格特征饮酒量等级量表

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帕金森病与刺激寻求特质、吸烟、饮酒和摄入咖啡因之间的关系

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世界核心医学期刊文摘(神经病学分册) 2006年第8期 56-56页

作者： Evans A.H. Lawrence A.D. Potts J. A.J. Lees 刘凯 reta lila weston institute of neurological studies Windeyer Building 46 Cleveland Street London W1T 4JF United Kingdom Prof.

Background: An inverse relation exists between smoking and coffee intake and Parkinson’s disease (PD). The present study explored whether this is explained by low sensation seeking, a personality trait believed to characterise PD. Methods: A total of 106 non- demented patients with PD and 106 age and sex matched healthy controls completed a short version of Zuckerman’s Sensation Seeking Scale (SSS), the Geriatric Depression Scale, and the Trait Anxiety Inventory. Data were collected on past and current cigarette smoking, and participants also completed food frequency questionnaires to estimate current caffeine and alcohol intake. Results: Patients with PD had lower sensation seeking and higher depression and anxiety scores. They were also less likely to have ever smoked, and had lower caffeine and alcohol intakes. Analysis of the data using conditional logistic regression suggested that the inverse association of PD risk with sensation seeking was independent of smoking, and caffeine and alcohol intake. Moreover, low sensation seeking explained some of the apparent effect of caffeine and alcohol intake on PD. However, the effect of smoking was weakened only slightly when SSS was included in the regression model. Conclusion: This study raises the possibility that there is a neurobiological link between low sensation seeking traits- which might underlie the parkinsonian personality- and the hypothetical protective effect of cigarette smoking and caffeine consumption on PD.

关键词：帕金森病 PD 咖啡因嘌呤生物碱摄入

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Structures of α-synuclein filaments from human brains with Lewy pathology

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四川生理科学杂志 2022年第9期44卷 1669-1669页

作者： Yang Yang Medical Research Council Laboratory of Molecular Biology Cambridge UK Thermo Fisher Scientific Eindhoven The Netherlands Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis IN USA Department of Clinical and Movement Neurosciences Queen Square Institute of Neurology University College London London UK Queen Square Brain Bank for neurological Disorders Institute of Neurology University College London London UK

Parkinson's disease(PD)is the most common movement disorder,with resting tremor,rigidity,bradykinesia and postural instability being major symptoms(1).Neuropathologically,it is characterised by the presence of abundant filamentous inclusions ofα-synuclein in the form of Lewy bodies and Lewy neurites in some brain cells,including dopaminergic nerve cells of the substantia nigra(2).PD is increasingly recognised as a multisystem disorder,with cognitive decline being one of its most common non-motor *** patients with PD develop dementia more than 10 years after diagnosis(3).PD dementia(PDD)is clinically and neuropathologically similar to dementia with Lewy bodies(DLB),which is diagnosed when cognitive impairment precedes parkinsonian motor signs or begins within one year from their onset(4).In PDD,cognitive impairment develops in the setting of well-established *** PD and DLB,multiple system atrophy(MSA)is the third major synucleinopathy(5).It is characterised by the presence of abundant filamentousα-synuclein inclusions in brain cells,especially oligodendrocytes(Papp�Lantos bodies).We previously reported the electron cryo-microscopy(cryo-EM)structures of two types ofα-synuclein filaments extracted from the brains of individuals with MSA(6).Each filament type is made of two different *** we report that the cryo-EM structures ofα-synuclein filaments from the brains of individuals with PD,PDD and DLB are made of a single protofilament(Lewy fold)that is markedly different from the protofilaments of *** findings establish the existence of distinct molecular conformers of assembledα-synuclein in neurodegenerative disease.

关键词： markedly diagnosis rigidity

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