摘要:

AbstractRecent experimental reports concerning L‐dihydroxyphenylalanine (L‐DOPA) and aromatic L‐amino acid decarboxylase (AADC, L‐DOPA decarboxylase) are reviewed in this article. Both in vitro and in vivo data now suggest that L‐DOPA is an endogenous neuroactive compound that is released from neurons and acts as a neurotransmitter or neuromodulator in the brain. Administration of exogenous L‐DOPA affects dopamine receptor status, AADC activity, and mitochondrial oxidation in experimental animals. The type and severity of these effects depend on the duration of the treatment. These findings may partly explain the limited efficacy of L‐DOPA therapy in Parkinson's disease (PD). AADC also plays a controlling role in the central nervous system, being a regulatory enzyme in the synthesis of a putative neuromodulator 2‐phenylethylamine and other trace amines. Recent experimental findings on AADC activity and localisation are of importance because they suggest that striatal [18F]DOPA uptake used as an indicator of PD progression in positron emission tomography (PET) studies is likely to overestimate nigrostriatal integrity in advanced PD. Possible new PET tracers of presynaptic dopaminergic function are discussed

ISSN:0885-3185    

DOI:10.1002/mds.870100302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractStudies examining the mortality from Parkinson's disease have been reviewed to assess the impact of levodopa therapy. These include national mortality data taken from death certificate returns, cohort studies compring the deaths observed in a group of patients with those expected from population statistics, and case‐control studies comparing deaths in patients with those in a matched control group. It is concluded that the decrease in crude mortality rate in the early 1970s in several western countries was mirrored by a decrease in observed to expected mortality rates in cohort studies over the same period. The rise in crude mortality in the late 1970s and early 1980s paralleled an increase in observed to expected mortality in cohort studies. These trends are compatible with the hypothesis that levodopa delayed the death of a cohort of frail elderly parkinsonian patients who succumbed ∼5 years later, leading to an apparent “catch‐up” increment in national mortality data. Whilst crude mortality in England and Wales does not appear to be increasing as fast as before the introduction of levodopa, recent cohort and case‐control studies report mortality ratios comparable to those seen in the prelevodopa era. Further case‐control studies are required to determine the position with current treat

ISSN:0885-3185    

DOI:10.1002/mds.870100303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0885-3185    

DOI:10.1002/mds.870100304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe developed a teaching tape of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) to provide investigators with a visual document of three raters' interpretations of the scoring system for each item except rigidity. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordanceWranging between 0.97 and 0.62. We also provided full UPDRS ratings on sample patients that may be used for training and for multicenter studies to assure uniformity of rating. The study identified several items of the UPDRS motor examination for which written instructions were vague, including speech, action tremor, finger taps, rapid alternating movements, and postural stability. Future versions of the scale should address these problems and correct ambiguities. This project offers the first attempt to provide a visual analog for the UPDRS.

ISSN:0885-3185    

DOI:10.1002/mds.870100305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractTracking behavior in Parkinsonian patients and in a control group of elderly subjects was studied using a one‐dimensional pursuit tracking task. The most obvious abnormality in patients with Parkinson's disease is a tendency to restrict movements to a limited range, thus “clipping” the extreme deviations of the target, reflected by movement arrests, reduced amplitude gain, and decreased velocity gain. Most of the tracking parameters were selectively sensitive to parkinsonian as opposed to age‐related impairment of motor functions, the only exception being directional errors, which were more frequent in the old age group. Movement range and amplitude gain were related to general disability as reflected by the Hoehn and Yahr stage. Amplitude gain was also the single factor with the strongest influence on tracking error and was smaller for large target deviations in both groups. A reduction in target velocity caused a significant increase in amplitude gain, suggesting a compensatory strategy (amplitude/lag trade‐off) as one possible cause of low‐amplitude gain. Decreased peak velocity did not contribute significantly to tracking error. These findings suggest that reduced movement amplitude and slowness are independent phenomena, of which only the former has a significant influence on tracking performance in the task used. Patients with Parkinson's disease showed no impairment of motor learning o

ISSN:0885-3185    

DOI:10.1002/mds.870100306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractMolecular genetic studies of the cytochrome P450 system enzymeCYP2D6, which hydroxylates debrisoquine, have indicated an excess of mutant alleles in large series of patients with Parkinosn's disease (PD) when compared with controls. We have investigatedCYP2D6polymorphism in 91 patients with multiple system atrophy (MSA) in order to determine if this finding is specific to PD or if there is similar evidence of genetic susceptibility to neurotoxicity in MSA. The distribution ofCYP2D6alleles was not significantly different between MSA patients and controls, and there were fewer poor metabolisers in the MSA group than in the control group.

ISSN:0885-3185    

DOI:10.1002/mds.870100307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

Abstractn‐Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by‐products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n‐hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Park

ISSN:0885-3185    

DOI:10.1002/mds.870100308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractImpaired olfaction occurs in patients with idiopathic Parkinson's disease (PD), and Lewy bodies have been found in the olfactory bulb and tract. We now confirm the latter finding and show that this presence of Lewy bodies is associated with significant neuronal loss. A quantitative study of the anterior olfactory nucleus (AON) was performed in tissue obtained postmortem from seven patients with PD and seven age‐matched controls. Neuronal loss was seen in the PD bulb and tracts (p<0.01), and a strong correlation of neuronal loss with disease duration was detected (R = −0.87). The presence of Lewy bodies was confirmed with immunocytochemical staining for ubiquitin in all the PD ca

ISSN:0885-3185    

DOI:10.1002/mds.870100309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractStriatonigral degeneration (SND) is difficult to diagnose in vivo. The purpose of this study was to detect the best indicators for an early and reliable diagnosis of the disease. Eighteen patients clinically diagnosed as having SND were selected with rigorous inclusion criteria and compared to 18 patients with Parkinson's disease (PD) matched for age and disease duration. Apart from dysautonomia, the principal discriminant clinical features that distinguished SND from PD were the early appearance of the following symptoms and signs: (a) severe and atypical progressive parkinsonism characterized by bilateral bradykinesia and rigidity, slowness of gait, postural instability, and falls, and poor or absent response to adequate levodopa treatment; (b) increased tendon reflexes associated or not with frank pyramidal signs, severe dysarthria, and less consistently, dysphagia, stridor, antecollis, and stimulussensitive myoclonus, which, when present, are highly suggestive of the disease.

ISSN:0885-3185    

DOI:10.1002/mds.870100310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThere is evidence for a 37% deficiency of complex I activity in Parkinson's disease (PD), which appears to be specific for PD amongst parkinsonian syndromes and selective for the substantia nigra within the central nervous system. Rat studies have shown that, in the context of a normal nigrostriatal dopaminergic cell population,L‐dihydroxyphenylalanine (L‐dopa) causes a reversible 25% defect of complex I activity in nigral and striatal tissue. Analysis of striatal tissue from PD patients after prolonged exposure to highdoseL‐dopa does not show such a defect. Results of these and other studies suggest thatL‐dopa therapy does not cause complex I deficiency in PD striatum. However, it cannot be excluded that, in the particular environment of the PD substantia nigra,L‐dopa may enhance a preexisting complex

ISSN:0885-3185    

DOI:10.1002/mds.870100311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY