Parkinson's disease as community health problem: study in Norwegian nursing homes. The Norwegian Study Group of Parkinson's Disease in the Elderly.

OBJECTIVE--To examine the extent of under-diagnosis and overdiagnosis of Parkinson''s disease and to determine quality of treatment in a defined population. DESIGN--Clinical evaluation of an elderly population. SETTING--40 Norwegian nursing homes. SUBJECTS--3322 residents of nursing homes, of whom 500 were selected by nursing staff for evaluation on the basis of a structured information programme on Parkinson''s disease and 269 were examined in detail by neurologists. MAIN OUTCOME MEASURES--Patients'' scores on clinical rating scales, diagnosis of parkinsonism, and effect of changing drug treatment. RESULTS--169 (5.1%) patients were found to have clinical idiopathic Parkinson''s disease, 31 of whom had not had the disease diagnosed previously. In addition, 31 patients without the disease were taking antiparkinsonian drugs unnecessarily. Eighty patients were judged to be receiving "optimal" treatment. In the remaining 58, the treatment was changed, and 36 patients showed a definite functional improvement after a 12 week observation period. CONCLUSIONS--The quality of life of many elderly patients with Parkinson''s disease could be improved by increasing medical and neurological services.     

帕金森病及运动障碍疾病门诊震颤患者的病因及临床表现分析

目的:总结帕金森病及运动障碍疾病门诊震颤患者的病因及临床表现,以提高门诊震颤患者的诊断率,降低误诊率,为门诊震颤诊断提供临床经验。方法:连续收集西京医院神经内科帕金森病及运动障碍疾病门诊自2015年5月至2016年7月收治的震颤患者进行横断面研究。采用SPSS19.0软件进行统计分析。结果:共纳入400例震颤患者,男性173例(43.3%),女性227例(56.8%),男女之比1:1.3,平均发病年龄54.0岁。40岁以下特发性震颤(ET)最多,41-60岁为帕金森病(PD),60岁以上帕金森病最多。震颤按临床表现形式分为静止性震颤85例(21.3%),动作性震颤137例(34.3%),混合性震颤178例(44.5%)。震颤按病因分类,占比例前三位的分别是:帕金森病(46.3%),特发性震颤(28.5%),心因性震颤(5.8%)。心因性震颤急性起病率及合并焦虑抑郁率最高,而PT画螺旋圈及书写阳性率明显低于其他病因组。结论:门诊震颤患者混合性震颤形式较多见,最常见病因为帕金森病、特发性震颤及心因性震颤;心因性震颤较其他病因所致震颤相比,急性起病率、合并焦虑抑郁率高,而画螺旋圈及书写阳性率低。震颤诊断应先明确震颤的临床特点,然后分析病因以确定诊断及治疗。     

Parkinson's disease.

In Parkinson''s disease there is degeneration of neurons in the substantia nigra, with consequent depletion of the neurotransmitter dopamine. The triad of tremor, rigidity and bradykinesia is the clinical hallmark. Drugs currently used for palliative therapy fall into three categories: anticholinergic agents, dopamine precursors (levodopa combined with extracerebral decarboxylase inhibitors) and artificial dopamine agonists. It has been argued, on theoretical grounds, that some drugs slow the progress of Parkinson''s disease, although no firm evidence has supported this. Treatment must be individualized, and more than one type of drug can be given concurrently after a careful build-up in dosage. We review the adverse effects of various drugs and consider new developments such as slow-release preparations, selective D-1 and D-2 agonists and transplants of dopaminergic cells into the brain. The treatment of Parkinson''s disease can be demanding, rewarding and sometimes frustrating, but it remains a most challenging exercise in pharmacotherapy.     

Comparisons of therapeutic effects of levodopa,levodopa and selegiline,and bromocriptine in patients with early,mild Parkinson's disease: three year interim report. Parkinson's Disease Research Group in the United Kingdom.

OBJECTIVE--To determine the optimum treatment for early Parkinson''s disease. DESIGN--An open, long term, prospective randomised trial conducted by the Parkinson''s Disease Research Group of the United Kingdom. SETTING--93 hospitals throughout the United Kingdom. SUBJECTS--782 patients with early Parkinson''s disease who were not receiving dopaminergic treatment. INTERVENTIONS--Patients allocated to treatment with levodopa/dopa decarboxylase inhibitor alone (arm 1), levodopa/decarboxylase inhibitor/selegiline in combination (arm 2), or bromocriptine (arm 3). MAIN OUTCOME MEASURES--Disability assessment as judged by improvement on Hoehn and Yahr, modified Webster, and North Western University disability scales. Adverse event profile and mortality ratios. RESULTS--Interim results indicate that all three treatment regimens led to improvement in baseline disabilities after 12 months'' treatment and that deterioration in control was apparent by three years. No significant differences were found between the results of treatment in arm 1 and arm 2, but both were significantly more effective than bromocriptine (arm 3) and had fewer early adverse reactions. The adjusted difference (95% confidence interval) in Webster rating for arm 3 v 1 was 0.93 points (0.27 to 1.50; p = 0.0058) and for arm 3 v 2 was 1.25 points (0.61 to 1.89; p = 0.0002). The incidence of dyskinesias and motor oscillations, however, was significantly lower in arm 3 (2% and 5%, respectively) than in arm 1 (27% and 33%, respectively) and arm 2 (34% and 35%, respectively). CONCLUSIONS--As there were no marked differences in functional improvement between the three groups the choice of treatment in the early stages of Parkinson''s disease may not be critical.     

Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early,mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom.

OBJECTIVE: To compare effectiveness of levodopa and levodopa combined with selegiline in treating early, mild Parkinson''s disease. DESIGN: Open, long term, prospective randomised trial. SETTING: 93 hospitals throughout United Kingdom. SUBJECTS: 520 patients with early Parkinson''s disease who were not receiving dopaminergic treatment. INTERVENTIONS: Treatment with levodopa and dopa decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in combination with selegiline (arm 2). MAIN OUTCOME MEASURES: Assessments of serial disability, frequency and severity of adverse events, and deaths from all causes. RESULTS: After average of 5-6 years'' follow up, mortality ratio in arm 2 compared with arm 1 was 1.57 (95% confidence interval 1.09 to 2.30), and difference in survival between the two arms was significant (log rank test, P = 0.015). Hazard ratio adjusted for age and sex was 1.49 (1.02 to 2.16), and after adjustment for other baseline factors it increased to 1.57 (1.07 to 2.31). Patients in arm 1 had slightly worse disability scores than those in arm 2, but differences were not significant. Functionally disabling peak dose dyskinesias and on/off fluctuations were more frequent in arm 2 than arm 1. During the trial the dose of levodopa required to produce optimum motor control steadily increased in arm 1 (median daily dose 375 mg at 1 year and 625 mg at 4 years), but median dose in arm 2 did not change (375 mg). CONCLUSIONS: Levodopa in combination with selegiline seemed to confer no clinical benefit over levodopa alone in treating early, mild Parkinson''s disease. Moreover mortality was significantly higher with combination treatment, casting doubts on its chronic use in Parkinson''s disease.     

Parkinson's disease in 1984: an update.

This update reviews several important topics in the field of Parkinson''s disease, including etiologic studies, the types and mechanisms of drug complications and their treatment, when and how to begin treatment, the association of dementia with Parkinson''s disease, and the development of the newer research tools. The recent discovery of a highly selective neurotoxin (MPTP) that causes parkinsonism in humans and other primates and the use of positron emission tomography in living patients should improve our understanding of the cause of cell death in Parkinson''s disease and assist in the development of more definitive treatment for this common, disabling neurologic condition.     

Relation between nicotine intake and Alzheimer's disease.

OBJECTIVE--To study the association between Alzheimer''s disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer''s disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer''s disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative risk of Alzheimer''s disease. RESULTS--89 of 193 patients with Alzheimer''s disease had a history of smoking compared with 102 of 195 controls. Among the patients and controls with a family history of dementia, smoking was significantly less common in those with dementia (40/95 with dementia v 55/96 controls; relative risk 0.35; 95% confidence interval 0.16 to 0.78). The risk of Alzheimer''s disease decreased with increasing daily number of cigarettes smoked before onset of disease (relative risk 0.3 in those smoking greater than 21/day v 1 in non-smokers). In six families in which the disease was apparently inherited as an autosomal dominant disorder, the mean age of onset was 4.17 years later in smoking patients than in non-smoking patients from the same family (p = 0.03). CONCLUSIONS--These findings suggest an inverse association between smoking and Alzheimer''s disease, although smoking cannot be advocated for other health reasons. We speculate that nicotine may have a role in the aetiology of both Alzheimer''s disease and Parkinson''s disease.     

One to Two Year Treatment of Parkinson's Disease with Levodopa

One hundred patients with Parkinson''s disease were treated with levodopa for more than a year at UCLA Medical Center. They were examined at given intervals and their improvement was graded. The optimum therapeutic dose was attained by balancing side effects against relief of symptoms and ranged from 1.5 grams to 8.0 grams per day (average 4.3 grams). There is no doubt that levodopa is the most effective treatment now available for Parkinson''s disease. At the end of the first year, 60 percent of the patients improved 50 percent or better, and 10 percent were considered symptom-free. All major symptoms of this disease, including rigidity, akinesia and tremor, improved in variable degree.There were no serious abnormalities in the routine clinical laboratory tests. The comon side effects included nausea, vomiting and choreoathetoid dyskinesias. The side effects were not life threatening, but occasionally were major therapeutic challenges.Maximal benefits with minimal side effects were achieved only by careful adjustments of the levodopa dosage as the months went by. This needed careful management by the physician and cooperation by the patient. Anticholinergic medications or amantadine hydrochloride, sometimes both, usually supplemented the effect of the levodopa.     

Pathologie extrapyramidale : apport diagnostique de l’imagerie fonctionnelle et morphologique

Imaging of dopamine transporter (DatScan^®) confirms the existence of a presynaptic dopaminergic denervation in parkinsonian degenerative syndromes: Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. It helps to differentiate these diseases from parkinsonian syndromes without involvement of the presynaptic nigrostriatal pathway (drug-induced, psychogenic and sometimes vascular) or atypical tremor. This imagery also contributes to the diagnosis of dementia with Lewy bodies where there is a decrease in binding of this tracer. On the contrary it is not useful for differentiating Parkinson's disease from other degenerative parkinsonian syndromes. The study of post-synaptic dopaminergic system, which is not yet available in routine, could facilitate the distinction between these degenerative parkinsonian syndromes, as well as MIBG-I123 myocardial scintigraphy; MRI morphology revealed in these pathologies signal abnormalities within the basal ganglia and brainstem structures.     

盐酸普拉克索联合美多巴对老年帕金森病的临床疗效及对运动功能的影响

目的:研究盐酸普拉克索联合美多巴对老年帕金森病的临床疗效及对运动功能的影响。方法:选择2014年3月~2015年8月在我院进行诊治的老年帕金森病患者210例,随机分为观察组和对照组,对照组给予美多巴,观察组给予盐酸普拉克索联合美多巴,比较两组的临床疗效,治疗前后运动功能、生活质量的变化情况和不良反应的发生情况。结果:观察组的治疗有效率为85.71%,明显高于对照组的65.71%(P0.05);治疗12周后,观察组UPDRS评分与治疗前和对照组相比均明显降低(P0.05);治疗12周后,观察组生理、心理、独立性、社会关系和环境等方面的评分与治疗前和对照组相比均明显升高(P0.05);两组间恶心、呕吐、开关现象、精神症状等不良反应发生率相比无明显差异(P0.05)。结论:盐酸普拉克索联合美多巴对老年帕金森病疗效显著,能明显改善运动功能,且用药安全,值得推广应用。     

The nature of essential tremor

The literature concerning essential tremor is confusing. Some accounts describe tremor of a resting type and its accompaniment by other neurological abnormalities. Critical analysis of the pertinent literature leaves some question as to the validity of these observations.Clinical analysis of 34 patients with essential tremor, personally observed during a four-year period, reveals this to be a monosymptomatic condition. The tremor was usually of both a postural and action type and resting tremor was not observed. There were no other neurological abnormalities. Serious disability was infrequent and, when present, was related to upper limb tremor. Essential tremor should be readily distinguishable from other central nervous system diseases but it may be confused with Parkinson''s disease or cerebellar ataxia.     

La maladie de Parkinson et les syndromes parkinsoniens apparentés

Parkinson's disease represents the main cause of parkinsonian syndrome with precise clinical criteria and a prolonged sensitivity to the dopaminergic treatments. In a systematic way, in front of any parkinson's syndrome, an iatrogenic origin must be required (neuroleptic therapy). Other atypical degenerative parkinsonian syndromes include: multiple system atrophy and dementia with Lewy bodies within the group of synucleinopathy; progressive supranuclear palsy and corticobasal degeneration within the group of tauopathy. These diseases are distinguished in particular from the Parkinson's disease by the weak one, even the absence of reactivity with the dopaminergic treatment resulting in particular from postsynaptic lesions. The clinical and paraclinic characteristics of these various pathologies will be developed in this article like their therapeutic approach.     

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study.

OBJECTIVE--To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. DESIGN--Population based cross sectional study. SETTING--Ommoord, a suburb of Rotterdam. SUBJECTS--7528 participants of the Rotterdam study aged 55-106 years. RESULTS--474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer''s disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson''s disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. CONCLUSIONS--The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer''s disease. In this study an inverse dose-response relation was found between education and dementia--in particular, Alzheimer''s disease.     

基于益生菌治疗帕金森病的研究进展

帕金森病是常见的神经退行性疾病,其发病原因至今尚未明确,目前的治疗方法价格昂贵、效果差且副作用大。帕金森病患者常见胃肠道功能障碍,帕金森病和肠道菌群之间的关联已得到实验证实,患者有望通过益生菌改善肠道菌群达到治疗的目的。工程益生菌的出现使得人们可以按照自己的意愿改造益生菌,提高其稳定性和靶向性,展现出其特有的应用潜力。本文将从益生菌治疗帕金森病的研究现状出发,阐述益生菌治疗帕金森病的可能机制,进一步分析工程益生菌治疗帕金森病的可行性,为该疾病的安全治疗提供新的思路。     

The Impact of Autonomic Dysfunction on Survival in Patients with Dementia with Lewy Bodies and Parkinson's Disease with Dementia

Introduction

Autonomic dysfunction is a well-known feature in neurodegenerative dementias, especially common in α-synucleinopathies like dementia with Lewy bodies and Parkinson''s disease with dementia. The most common symptoms are orthostatic hypotension, incontinence and constipation, but its relevance in clinical practice is poorly understood. There are no earlier studies addressing the influence of autonomic dysfunction on clinical course and survival. The aim of this study was to investigate the frequency of the three most common features of autonomic dysfunction and analyze how it affects survival.

Methods

Thirty patients with dementia with Lewy bodies and Parkinson''s disease with dementia were included in this prospective, longitudinal follow-up study. Presence of incontinence and constipation was recorded at baseline. Blood pressure was measured at baseline, after 3 months and after 6 months according to standardized procedures, with 5 measurements during 10 minutes after rising. Orthostatic hypotension was defined using consensus definitions and persistent orthostatic hypotension was defined as 5 or more measurements with orthostatic hypotension. Difference in survival was analyzed 36 months after baseline.

Results

There was a high frequency of persistent orthostatic blood pressure (50%), constipation (30%) and incontinence (30%). Patients with persistent orthostatic hypotension had a significantly shorter survival compared to those with no or non-persistent orthostatic hypotension (Log rank x² = 4.47, p = 0.034). Patients with constipation and/or urinary incontinence, in addition to persistent orthostatic hypotension, had a poorer prognosis compared to those with isolated persistent orthostatic hypotension or no orthostatic hypotension (Log rank x² = 6.370, p = 0.041).

Discussion

According to our findings, the identification of autonomic dysfunction seems to be of great importance in clinical practice, not only to avoid falls and other complications, but also as a possible predictor of survival.     

抗氧化剂依达拉奉联合葛根素用于帕金森病治疗的临床观察

目的:观察西药抗氧化剂依达拉奉联合中药葛根素在帕金森病治疗中的效果及安全评价。方法:选取2011年8月-2013年12月哈尔滨医科大学附属第四医院神经内科收治的帕金森病人80例,随机均分为实验组和对照组。实验组给予口服美多巴,同时静滴依达拉奉和葛根素,对照组仅予口服美多巴治疗,疗程2周,治疗前后比较UPDRS评分、不良反应,观察血清氧化酶学指标的变化。结果:治疗后,实验组的四项UPDRS评分改善均显著优于对照组,且实验组不良反应亦显著低于对照组;两组患者的血清氧化酶学指标检测与治疗前比有明显改善,差异均具有统计学意义(P0.05)。结论:在口服美多巴治疗基础上,联合应用依达拉奉和葛根素,对帕金森病的治疗显示出更好的效果,并有利于减轻药物的不良反应,可能跟调控抗氧化酶有关。     

Integrative Network Analysis Unveils Convergent Molecular Pathways in Parkinson's Disease and Diabetes

Background

Shared dysregulated pathways may contribute to Parkinson''s disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson''s disease and type 2 diabetes are linked at the molecular level.

Methods and Findings

Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson''s disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson''s disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson''s disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson''s disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.

Conclusions

These results provide the first evidence that Parkinson''s disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that increased expression of APP in blood may modulate the neurodegenerative phenotype in type 2 diabetes patients.     

Rasagiline Ameliorates Olfactory Deficits in an Alpha-Synuclein Mouse Model of Parkinson's Disease

Impaired olfaction is an early pre-motor symptom of Parkinson''s disease. The neuropathology underlying olfactory dysfunction in Parkinson''s disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson''s disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson''s disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson''s disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson''s disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson''s disease.     

Características Neuropsicológicas y Aproximación Diagnóstica a la Demencia Parkinson y a la Demencia por Cuerpos de Lewy

When approaching the neurophysiological characteristics and diagnostic approach to Parkinson's disease dementia (PDD) and Lewy body dementia (LBD), the first idea that comes to mind is that both types of dementia fall within the group of subcortical dementias, with the practical implications that this observation entails. We should therefore leave our knowledge of Alzheimer's dementia and other cortical dementias to one side as, in most cases, these forms of dementia do not correspond clinically or diagnostically to subcortical dementias. Therefore, the clinical and therapeutic approach of PDD and LBD differs from that of cortical dementias in form, if not in essence.     

A型肉毒毒素耳后注射治疗帕金森病合并神经性耳鸣患者的疗效探讨

摘要 目的：探讨A型肉毒毒素耳后注射治疗帕金森病合并神经性耳鸣患者的疗效。方法：收集2016年3月至2021年6月苏州大学附属第二医院耳鼻喉科或神经内科门诊就诊或住院的帕金森病患者,追问病史,发现部分患者有单侧或双侧耳鸣症状,并进行电测听+声导抗检查回报,其中有73 %患者有神经性听力下降,根据治疗方法将其分为A型肉毒毒素耳后注射组（实验组,22例）和地塞米松耳后注射组（对照组,22例）,A型肉毒毒素注射组予以100U A型肉毒毒素耳垂后方自上而下3个点注射,地塞米松注射组予以5 mg地塞米松耳垂后方自上而下3个点注射,对比两组鸣残疾评估量表（THI）评分、耳鸣评价量表（TEQ）评分、治疗总有效率、汉密尔顿焦虑量表（HAMA）和汉密尔顿抑郁量表（HAMD）评分、匹兹堡睡眠质量指数（PSQI）评分。结果：两组治疗前THI和TEQ评分比较无差异（P>0.05）,两组治疗后THI和TEQ评分均有所降低,且实验组均低于对照组（P<0.05）;实验组治疗后1周、治疗后4周、治疗后14周治疗总有效率为63.64 %、81.82 %、90.91 %,对照组治疗总有效率分别为63.64 %、63.64 %、72.73 %,两组治疗总有效率比较无差异（P>0.05）,但实验组略高于对照组;两组治疗前HAMA、HAMD评分比较无差异（P>0.05）,两组治疗后14周HAMA、HAMD评分均有多下降,且实验组均低于对照组（P<0.05）;两组治疗前入睡时间、睡眠时间、睡眠质量、睡眠效率、睡眠障碍、日间功能障碍、安眠药物评分以及总分比较无差异（P>0.05）,两组治疗后14周上述各项评分均有所降低,且实验组均低于对照组（P<0.05）。结论：A型肉毒毒素耳后注射治疗帕金森病合并神经性耳鸣患者,可改善耳鸣症状,提高临床治疗效果,缓解焦虑抑郁情绪,改善睡眠质量,值得临床不断深入研究。