帕金森氏病的神经保护性治疗

目前对帕金森氏病的神经保护性治疗的研究正方兴未艾。这被称之为帕金森氏病治疗的第 二次革命。帕金森氏病治疗的第一次革命是运用左旋多巴进行替代性治疗。本文就神经保护性治疗中神经元变性的可能发病机理,以及运用MAO-B抑制剂、DA受体激动剂、EAA受体拮抗剂等的动物实验和临床结果作一综述。     

神经组织移植治疗帕金森氏病的研究现状

近年来,神经组织移植治疗帕金森氏病的临床和实验研究已在许多国家广泛开展,并对移植中的某些问题进行了深入探讨,提出了一些新观点.本文就神经移植治疗帕金森氏病的机理,适应症、移植部位及手术方式等方面问题作一综述.     

GDNF治疗帕金森氏病研究进展

胶质细胞源性神经营养因子(glial-cell-line-derived neurotrophic factor ,GDNF)是黑质纹状体系统中重要的靶源性神经营养因子,对黑质多巴胺能神经元具有保护和修复作用.帕金森氏病(Parkinson's disease , PD)动物模型和临床试验均提示GDNF对帕金森病具有治疗价值.     

丘脑底核与帕金森氏病

帕金森氏病（ｐｏｒｋｉｎｓｏｎ＇ｓｄｉｓｅａｓｅ,ＰＤ）患者长期多巴胺治疗产生运动机能的波动和不自主的异常运动,治疗十分棘手。目前根据基底节生理功能的进展已向人们提供了多条新的治疗途径［１—４］。黑质—纹状体多巴胺能耗竭可能是由于丘脑底核（ｓｕｂｔｈ...     

氯氮平治疗帕金森氏病所致精神障碍3例报告

例１住院号３０６，女６１岁，工人。因步态不稳、四肢抖动２０年。病后就诊均诊断为帕金森氏病，并服安坦、美多巴等药物无效。近４年，出现精神异常，其诊断均符合ＣＣＭＤ－２－Ｒ中帕金森氏病所致精神障碍诊断标准，先后接受多种抗精神药物合并安坦治疗效果均不佳。后改用氯氮平（１００ｍｇ／日）合并安坦治疗，精神症状消失，躯体症状改善，能自理生活。随访近两年精神症状无复发。例２住院号９５５，女，４８岁，工人。因步态前倾，四肢强硬，抖动１６年。于８年前出院乱语、疑人害她、哭笑无常，求治于各地医院均诊断为帕金森氏病所…     

慢性丘脑刺激治疗帕金森氏病

随着立体定向和功能神经外科技术的发展,脑深部电极埋藏技术的应用,慢性丘脑电刺激治疗帕金森氏病的临床研究,相继在一些国家开展,并认为这一技术方法是治疗帕金森氏病较理想的方法之一。本文就慢性丘脑电刺激治疗帕金森氏病的简史、作用机理、技术方法、临床疗效观察、应用指征及并发症等作一简要综述。     

青少年帕金森氏病38例临床分析

分析了３８例青少年帕金森氏病的临床资料，发现青少年帕金森氏病与中老年帕金森氏病的临床表现有许多不同，震颤较轻，一般不累及智力及自主神经，病程长，对安坦反应好。     

青少年帕金森氏病的临床特征

本文对３６例青少年帕金森氏病进行了临床分析，认为青少年帕金森氏病是帕金森氏病的一种特殊类型。我国较西方国家多见。主要临床特征为：１、强直多于震颤；２、症状左右不对称，３、通常不累及智力，精神及自主神经；４、病情进展缓慢，病程较长；５、对左旋多巴，安坦均有良好疗效。     

帕金森氏病的脑内移植治疗进展

自1982年脑内移植治疗帕金森氏病(PD)在临床取得疗效以来,这一领域的研究迅猛发展。目前这项课题已发展成为神经科学的前沿和热点之一。各国学者先后将肾上腺髓质、胚胎黑质、交感神经节及培养的细胞系细胞植入脑内,以期恢复黑质纹状体多巴胺系统功能。特别是近年来开展的包被细胞及遗传修饰细胞移植,为PD治疗开辟了新途径。本文综述了该领域当前的现状及最新进展,提出了存在的问题和前景展望。     

Treatment of Parkinson's disease with NADH

It has earlier been claimed that clinical improvement of patients with Parkinson's disease is obtained by treatment with NADH. This has to be verified by double-blind, clinical studies and measurement of biochemical effects of the treatment. In a double blind study five patients with clinically moderate Parkinson's disease were treated with NADH, 25 mg, given intravenously once a day for four days. Then they were given 25 mg NADH intramuscularly after 2 and 4 weeks. Disability scores were determined before each treatment and two weeks after the final injection. A control group (n = 4) with the same degree of Parkinson's disease obtained sodium chloride with the same schedule. According to the Unified Parkinson's Disease Rating Scale a tendency to clinical improvement was seen after the iv infusions in both treatment and placebo groups. However, the changes were not statistically significant, and no changes occurred during the following weeks. No changes were found neither in the study nor the control group regarding cerebrospinal fluid concentrations of dynorfin, metenkefalin, somatostatin, hydroxy-methoxy-phenylglycol, homovanillic acid and 5-hydroxyindole acetic acid. The results indicate that no great changes are obtained after short-term treatment of parkinsonian patients with NADH, neither clinically nor biochemically.     

New strategies in the treatment of early Parkinson's disease

Over recent years I have been studying whether dopamine agonist treatment alone, or in early combination with levodopa, might institute a better long-term treatment in Parkinson's disease than levodopa alone. Indeed, early combination of levodopa with bromocriptine, pergolide or lisuride has indicated that this kind of treatment results in better management of Parkinson's disease with fewer fluctuations in disability, especially end-of-dose disturbances and dyskinesias, than treatment with levodopa alone. Furthermore, similar results were obtained by using lisuride in combination with selegiline and levodopa. However, during long-term treatment the changes in parkinsonian disability were equal in all treatment groups with or without selegiline. Thus, the possible efficacy of selegiline in slowing down the progression of Parkinson's disease requires further investigations. As a new treatment strategy it appears advisable to initiate the dopaminergic treatment in early Parkinson's disease by using initially selegiline and a dopamine agonist and by adding levodopa when the therapeutic response is insuifficient. Another alternative would be to start with selegiline alone, then add a dopamine agonist and, finally, levodopa.     

Dopamine agonists and neuroprotection in Parkinson's disease

Dopamine agonists are effective in reversing the motor symptoms of Parkinson's disease (PD). They have also shown that they can delay or prevent the onset of motor complications associated with levodopa use. Recent attention has focused on the possible role for dopamine agonists in neuroprotection. Numerous studies have demonstrated that a variety of dopamine agonists can protect dopaminergic neuronal function in several toxin model systems. Pramipexole in particular has shown efficacy in reducing toxicity to MPTP, MPP, rotenone and 6-hydroxydopamine. Recent studies in early PD using imaging parameters as a surrogate marker of dopaminergic neuronal integrity have shown that pramipexole and ropinirole can apparently retard the rate of cell loss. These observations are of considerable interest, but additional studies are required to confirm a neuroprotective function for these dopamine agonists.     

帕金森病与阿尔茨海默病

普遍认为帕金森病和阿尔茨海默病是两个独立的、有着显著判别的疾病。但是,相当数量为证据表明,二者具有相互重叠的临床和神经病理特征、相似的病因和病变发生机制。因此,现在有人认为这两种疾病的部分病例可能是同一种神经元退行性变疾病的不同表现形式。本文拟对此作一介绍。     

左旋多巴在帕金森病治疗中的地位及进展

数十年来,左旋多巴曾为帕金森病(PD)治疗带来革命性的改变,并始终作为PD治疗的金标准享有及其重要的地位。然而,伴随其治疗产生的运动并发症却成为困扰医患的一大难题。近年来,随着对运动并发症机制的研究,越来越多的证据表明持续性多巴胺能刺激(CDS)可在产生良好疗效的同时降低运动并发症的风险,故其被作为PD治疗的新理念备受关注。为此,大量研究致力于开发能形成CDS状态的左旋多巴新制剂,从而探寻出提高疗效与降低运动并发症之间的平衡点。文中就左旋多巴治疗PD的回顾及进展予以介绍。     

Progress in neuroprotection in Parkinson's disease

Slowing or aborting the progress of neurodegeneration in Parkinson's disease (PD) remains the most important unmet need of this disorder. There are several recent developments in trial design and also in drugs under investigation for possible neuroprotective effect. Emphasis has been placed on clinical as opposed to imaging end-points and these include change in a clinical rating scale, e.g. United Parkinson's disease Rating Scale (UPDRS), or time to additional therapy. The introduction of the delayed-start, or wash-in, trial design adds an additional dimension to drug evaluation for neuroprotection. Compounds that have been recently tested in clinical trial include the monoamine oxidase-B inhibitor rasagiline, the anti-apoptotic agents TCH346 and CEP1347, and the promitochondrial agent creatine. The dopamine agonists have been evaluated for a neuroprotective effect using imaging end-points. Perhaps the most important and simplest concept for neuroprotection has been the theory that early dopaminergic support for the degenerating dopaminergic system per se provides significant long-term clinical benefit for PD patients.     

The effect of onset age on the clinical features of Parkinson's disease

Many clinicians view age at onset as an important determinant of clinical phenotype in Parkinson's disease (PD) and this has been reinforced by the identification of Mendelian genes that account for some cases of younger onset PD. A systematic review of OVID Medline for articles relevant to the relationship between clinical features and age at onset in PD published in English between 1950–2007 was performed. There are very few prospective community based studies which focus on the relationship between age at onset and the features of PD and a variety of case definitions are used in the literature. Most studies of young onset PD are based on specialist clinic referral series. The available evidence suggests that PD patients with a younger age at onset have: (i) a slower disease progression, (ii) an increased rate of dystonia at onset and during treatment, (iii) a lower rate of dementia and (iv) an increased rate of dyskinesias in response to l -DOPA treatment. The majority of the available studies do not report patient genotype data, but it is probably that the clinical heterogeneity of PD will be further refined with detailed clinico-genetic studies.     

New therapies for Parkinson's disease

In the last decade there has been a surge of new therapeutic strategies for the treatment of Parkinson's disease along with a change of concepts about how the disease should be treated. The gold standard remains levodopa preparations, which have a rapid and dramatic symptomatic effect by replenishing the reduced dopamine levels in caudate and putamen nuclei. However, keeping in mind the complications that may emerge following long-term treatment, its initiation should possibly be delayed to the more advanced stages of the illness, especially in younger patients, in favour of dopamine agonists monotherapy. The adverse reactions that become prominent and disabling in late stages of the disease, i. e., dyskinesias, response fluctuations, and psychiatric side effects, can currently be managed by novel pharmacological as well as surgical strategies. Future therapies will focus on transplantation of dopaminergic embryonic tissue, gene therapy, and neuroprotective treatments. Received: 22 December 2000 / Accepted: 5 January 2001     

Epidemiology of Parkinson's disease

The incidence of Parkinson syndrome in North America is 20.5/10⁵, adjusted to 1970 US population, and there has been no significant change between 1935 and 1979. The composition of different Parkinson variants in the general population, however, has altered remarkably during recent decades. Arteriosclerotic Parkinsonism is very rarely diagnosed now, post-encephalitic Parkinsonism is extinct and drug induced Parkinsonism, first identified in the 1950s, is now the second most common variant in the combined community and institutionalised population survey. There has been a trend to higher incidence of Parkinson's disease in recent decades and it is predicted that the incidence would rise further if the current population survival trends continue. There is no race or gender difference for the risk of Parkinson's disease. Survival in Parkinson's disease has increased since the widespread use of levodopa. The prevalence rate of Parkinson syndrome in North America is estimated at 300/105. Increased risk of Parkinson's disease in essential tremor patients and the reported protective effect of smoking are artifactual. Twin studies show a concordance rate of 10.5% in monozygotic and 10.8% in dizygotic twins, indicating against a major genetic basis for Parkinson's disease. Several large Parkinson's disease families with autosomal dominant inheritance are well documented. In one such family, linkage to chromosome 4 is reported and mutation in the a-synuclein gene has been identified. In several other families, linkage to that region was not detected. These families are believed to inherit a Parkinson's disease susceptibility trait.     

Clozapine for the treatment of psychosis in Parkinson's disease: a review

The occurrence of psychosis is frequent during the evolution of Parkinson's disease. The reduction of therapeutics or the use of classical neuroleptics may improve the symptoms, but usually worsens parkinsonism. Clozapine is an atypical neuroleptic with only few extrapyramidal effects, which has been proposed at low dose in this indication since 1985. A review of the literature, about more than 200 patients shows good results in approximately 90% without worsening of extrapyramidal symptoms. Some patients even noted an improvement of their motor state while treated by clozapine alone or as dopatherapy was secondarily increased. More controversial results were obtained in demented or depressed patients. Sedation is one of the most frequently encountered side-effect but rarely necessitates the withdrawal of clozapine. Even if the risk of agranulocytosis is slight, regular blood cell counts must be done.