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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species and the onset of oxidative stress leading to oxidative damage to substantia nigra pars compacta. Extensive postmortem studies have provided evidence to support the involvement of oxidative stress in the pathogenesis of PD; in particular, these include alterations in brain iron content, impaired mitochondrial function, alterations in the antioxidant protective systems (most notably superoxide dismutase [SOD] and reduced glutathione [GSH]), and evidence of oxidative damage to lipids, proteins, and DNA. Iron can induce oxidative stress, and intranigral injections have been shown to induce a model of progressive parkinsonism. A loss of GSH is associated with incidental Lewy body disease and may represent the earliest biochemical marker of nigral cell loss. GSH depletion alone may not result in damage to nigral neurons but may increase susceptibility to subsequent toxic or free radical exposure. The nature of the free radical species responsible for cell death in PD remains unknown, but there is evidence of involvement of hydroxyl radical (OH.), peroxynitrite, and nitric oxide. Indeed, OH. and peroxynitrite formation may be critically dependent on nitric oxide formation. Central to many of the processes involved in oxidative stress and oxidative damage in PD are the actions of monoamine oxidase-B (MAO-B). MAO-B is essential for the activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenylpyridinium ion, for a component of the enzymatic conversion of dopamine to hydrogen peroxide (H2O2), and for the activation of other potential toxins such as isoquinolines and beta-carbolines. Thus, the inhibition of MAO-B by drugs such as selegiline may protect against activation of some toxins and free radicals formed from the MAO-B oxidation of dopamine. In addition, selegiline may act through a mechanism unrelated to MAO-B to increase neurotrophic factor activity and upregulate molecules such as glutathione, SOD, catalase, and BCL-2 protein, which protect against oxidant stress and apoptosis. Consequently, selegiline may be advantageous in the long-term treatment of PD.
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PMID:Oxidative stress and the pathogenesis of Parkinson's disease. 895 85

Lewy bodies have historically been considered a histopathologic hallmark of idiopathic Parkinson's disease. Recently, it has become clear that Lewy bodies play a role in neurodegenerative processes other than idiopathic Parkinson's disease, including diffuse Lewy body disease and diffuse Lewy bodies with concomitant Alzheimer's disease changes. It is likely that these processes represent a spectrum of neurodegenerative change in which Lewy bodies play a pivotal role. Although much is known and has been written regarding the histopathology and pathophysiology of Lewy body diseases, specific criteria for their diagnosis remain problematic. Within the spectrum of Lewy body disease, overlap in clinical presentation and histopathologic findings has caused some to dismiss attempts at subcategorizing Lewy body disease as artificial. We present, in brief, current information and theories concerning the pathology and pathogenesis of Lewy body disease.
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PMID:Lewy body disease. 896 51

In Parkinson's disease and other Lewy-body-associated disorders, the substantia nigra pars compacta undergoes degeneration, but the mechanism of cell death has not been previously described. The substantia nigra of normal and Alzheimer's disease cases were compared with substantia nigra from patients with Lewy-body-associated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's disease, and diffuse Lewy body disease) using in situ end labeling to detect fragmented DNA. In situ end-labeled neurons demonstrated changes resembling apoptosis: nuclear condensation, chromatin fragmentation, and formation of apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the substantia nigra of both normal and diseased cases; concomitant Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had significantly higher amounts of apoptotic-like changes than normal controls or Alzheimer patients. The finding of neuronal death by apoptosis may have relevance for the development of new treatment strategies for Parkinson's disease and related disorders.
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PMID:Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons. 900 29

The accuracy of the clinical diagnosis of corticobasal degeneration (CBD) is unknown. To determine its diagnostic accuracy, we presented 105 cases with known neuropathologic diagnoses, including CBD (n = 10), progressive supranuclear palsy (PSP, n = 24), Parkinson's disease (n = 15), diffuse Lewy body disease (n = 14), multiple system atrophy (n = 16), postencephalitic parkinsonism (n = 7), Pick's disease (n = 7), Creutzfeldt-Jakob disease (n = 4), Alzheimer's disease (n = 4), vascular parkinsonism (n = 3), and Whipple's disease (n = 1), as clinical vignettes to six neurologists unaware of the autopsy findings. Reliability was measured with the kappa statistics. The neurologists' clinical diagnoses were compared with clinicopathologic diagnoses for sensitivity, specificity, and positive predictive values at first and last clinic visits. The group reliability for the diagnosis of CBD significantly improved from moderate for the first visit (mean = 34 months after onset) to substantial for the last (68 months after onset). For the first visit, mean sensitivity for CBD was low (35%), but specificity was near-perfect (99.6%). For the last visit, mean sensitivity minimally increased (48.3%), and specificity remained stable. False-negative misdiagnoses mainly occurred with PSP. False-positive diagnoses were rare. The extremely low sensitivity of the clinical diagnosis of CBD suggests that this disorder is markedly underdiagnosed. Although the validity of the clinical diagnosis might have been improved if neurologists could have examined these patients, more important is that this disorder was misdiagnosed by the primary neurologists. In our data set, the best predictors for the diagnosis of CBD included limb dystonia, ideomotor apraxia, myoclonus, and asymmetric akinetic-rigid syndrome with late onset of gait or balance disturbances.
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PMID:Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. 900 6

Parkinson's disease (PD) is one of the major neurological diseases affecting elderly subjects. Presumed prevalence of PD is 80-100 per 100 thousands and it is estimated that there are approximately 100 thousands patients in Japan. From a statistic on age distribution of patients visiting doctors, it is estimated that patients with ages at 75-79(639/100,000) and 80-84(632/100,000) are highest in number. Juvenile parkinsonism is a syndrome with parkinsonian motor symptoms and dystonia developing before and after ten years of age. Reports on this syndrome have been accumulated in Japan and gene abnormality in a enzyme relating to dopamine metabolism was discovered in the hereditary progressive dystonia with marked diurnal fluctuation (Segawa). Among symptomatic parkinsonism, cerebrovascular parkinsonism is mainly due to multiple infarction in the basal ganglia or Binswanger's disease in Japan, and both conditions develops parkinsonism, pseudobulbar palsy and dementia progressively. Diffuse Lewy body disease and a unique type of progressive supranuclear palsy presenting a disorder designated "pure akinesia" were studied mainly in Japan. In drug therapies of PD, it has been argued why the maintenance dose of levodopa or dopamine agonists was generally low in Japan. In addition to constitution and drug metabolism, attitude of Japanese people to worry side effects more than merit with beneficial effects by a drug may have inevitably lead to low maintenance dose. Development of new drugs have been undertaken in parallel with US and Europe. Talipexole hydrochloride has been on market in Japan recently, but MAO-B inhibitors and COMT inhibitors are in final stages to wait evaluations by the governmental committee.
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PMID:[Clinical characteristics and trends in research of Parkinson's disease and parkinsonism in Japan]. 901 16

I reviewed the clinical symptoms and neuropathologic findings of diffuse Lewy body disease (DLBD). The cardinal symptoms of DLBD are parkinsonian symptoms and dementia. Parkinsonian symptoms are similar to those of Parkinson's disease except for lower frequency and mild degree of tremor. Dementia becomes the initial symptom especially in elderly patients, and is composed of symptoms of cortical dementia. As neuropathologic findings, there are cortical Lewy bodies mainly observed in the temporal cortex, insular cortex, cingulate cortex, and amygdala with or without senile changes, besides brain stem findings as Parkinson's disease. For prompt diagnosis of DLBD, we should pay more attention to the clinical and neuropathologic symptoms and signs of this disease, which may be encountered more frequently in the future.
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PMID:[Diffuse Lewy body disease]. 901 39

Parkinsonism occurs frequently in the patients with Alzheimer type dementia (ATD). The frequency ranges from 9% to 100% of ATD patients, depending on samples, clinical instruments and stages of illness. Several studies have described that rigidity and hypokinesia are the most prevalently observed signs of parkinsonism, and that resting tremor is less. The clinical progress of patients with parkinsonism is more rapid than those of patients without parkinsonism. Patients with parkinsonism are frequently associated with psychiatric symptoms such as depression and delusion. The pathogenesis of parkinsonism in ATD remains to be elucidated, but it should be noted that some cases with parkinsonism correlates with Parkinson's disease pathologic condition, and some have diffuse Lewy body disease.
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PMID:[Parkinsonism in Alzheimer's disease]. 901 40

To determine at the tissue level whether the proteasome (Ps), a unique nonlysosomal protease, is involved in the metabolism of ubiquitinated proteins, we examined for the first time the immunocytochemical localizations of both Ps and ubiquitin (Ub) in sections of various abnormal structures that are known to be ubiquitinated in various neurodegenerative diseases and in the elderly. Concomitant increases of Ps and Ub were observed at the sites of most dystrophic neurites in Alzheimer disease (AD) and parkinsonism-dementia complex on Guam (PDC) and in Lewy bodies in Parkinson's disease and diffuse Lewy body disease, but not in neurofibrillary tangles in AD or PDC, in filamentous inclusions within anterior horn cells in sporadic motor neuron disease, or in eosinophilic granules in the olivary nucleus of the elderly. These results at the tissue level indicated that Ps is involved in the metabolism of some, but not all, ubiquitinated proteins and structures in various neurodegenerative disorders. This suggests that the involvement of Ps in the metabolism of ubiquitinated structures differs in different cases and at different stages of disease. These results and our previous immunocytochemical studies of lysosomal cathepsin proteases suggest that both nonlysosomal and lysosomal systems are involved in the metabolism of various ubiquitinated proteins and that their involvements differ in different structures and at different stages of degeneration of the structures.
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PMID:Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly. 903 65

The difficulty in differentiating progressive supranuclear palsy (PSP, also called Steele-Richardson-Olszewski syndrome) from other related disorders was the incentive for a study to determine the clinical features that best distinguish PSP. Logistic regression and classification and regression tree analysis (CART) were used to analyse data obtained at the first visit from a sample of 83 patients with a clinical history of parkinsonism or dementia confirmed neuropathologically, including PSP (n = 24), corticobasal degeneration (n = 11), Parkinson's disease (PD, n = 11), diffuse Lewy body disease (n = 14). Pick's disease (n = 8) and multiple system atrophy (MSA, n = 15). Supranuclear vertical gaze palsy, moderate or severe postural instability and falls during the first year after onset of symptoms classified the sample with 9% error using logistic regression analysis. The CART identified similar features and was also helpful in identifying particular attributes that separate PSP from each of the other disorders. Unstable gait, absence of tremor-dominant disease and absence of a response to levodopa differentiated PSP from PD. Supranuclear vertical gaze palsy, gait instability and the absence of delusions distinguished PSP from diffuse Lewy body disease. Supranuclear vertical gaze palsy and increased age at symptom-onset distinguished PSP from MSA. Gait abnormality, severe upward gaze palsy, bilateral bradykinesia and absence of alien limb syndorme separated PSP from corticobasal degeneration. Postural instability successfully classified PSP from Pick's disease. The present study may help to minimize the difficulties neurologists experience when attempting to classify these disorders at early stages.
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PMID:Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? A clinicopathological study. 905 98

We report a 85-year-old woman who had an onset of gait disturbance at 80 years of the age. She had a dizzy spell when she was 80-year-old. She was evaluated at another hospital where paroxysmal tachycardia and sinus arrest lasting as long as 5.8 seconds were found. She was diagnosed as having sick sinus syndrome and a pace maker was inserted. She had a gradual onset of disturbance of gait shortly after the above dizzy spell. She became unable to walk fast and her steps became small. Neurologic examination at age 83 revealed small step gait with freezing episodes. Retropulsion was present. No motor weakness or origidity was noted. She had no tremor. Mentally she was alert and sound. Cranial nerves were essentially normal. Cranial CT scan revealed slight diffuse low density change in the bilateral cerebral white matter. She was treated with amantadine HCI and levodopa with carbidopa. Her gait and balance showed some improvement. She developed pneumonia and worsening of her gait when she was 85 years of the age, and she was admitted again to our hospital. She was mentally alert and sound but she showed marked freezing of gait with loss of postural reflex; she would have fallen down unless supported upon standing. Cranial nerves were again essentially normal. Her hospital course was complicated by pneumonia, DIC, and renal failure. She expired suddenly on the 10th day of her last admission. She was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had vascular parkinsonism due to lacunar state. However, paucity of vascular changes in her CT scan remained as a question. Other participants thought that she had nigral cell loss secondary to her aging and circulatory disturbance which would have been caused by her sick sinus syndrome. Post-mortem examination revealed marked loss of nigral pigmented cells; the cell loss was diffusely seen in the substantia nigra. Neurofibrillary tangles were seen in the remaining neurons. In addition, gliosis was noted in the globus pallidus and the subthalamic nucleus, however, neuronal loss was very mild in those nuclei. In the superior colliculus, neuronal loss was mild, however, gliosis was seen. No clear neuronal loss was observed in the locus coeruleus, however, Lewy bodies were seen in the remaining neurons. Furthermore, Lewy bodies were also found in the substantia sigra. It was thought that she had progressive supranuclear play (PSP). Question was whether or not she was complicated by Parkinson's disease. Clinically, she had no rigidity or tremor. Pathologically, locus coeruleus did not show neuronal loss. Therefore, incidental Lewy body disease was raised as a possibility. Finally, it should be pointed out that she had no oculomotor disturbance or dementia, yet she had PSP. Her clinical features were those of pure akinesia. Pathologic changes were also relatively mild except for those in the substantia nigra. Possibility of post-encephalitic parkinsonism without encephalitis was also discussed, however, over all distribution of her pathologic changes was more consistent with PSP.
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PMID:[A 85-year-old woman with the onset of progressive gait disturbance at 80 years of the age]. 912 48


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