Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both the striatal 18F-dopa uptake and brain glucose metabolism were studied by PET with 6-L-[18F]fluorodopa (FD) and [18F]fluorodeoxyglucose (FDG) in 9 patients with multiple system atrophy (MSA) and 15 patients with idiopathic Parkinson's disease (PD). Five of the 9 MSA patients were diagnosed as having olivopontocerebellar atrophy, whereas 2 had striatonigral degeneration and 2 demonstrated Shy-Drager syndrome. The FD uptake ratios to the occipital cortex in the MSA patients at 120 min after the administration of FD were 2.07 +/- 0.31 (mean +/- SD) and 1.96 +/- 0.29 in the caudate and the putamen, respectively, and decreased compared to those in the controls (2.72 +/- 0.11, 2.71 +/- 0.10). The same ratios in the PD patients were 2.07 +/- 0.36 and 1.74 +/- 0.24, respectively, which also decreased, but the decreased uptake in the putamen was more prominent. The caudate-putamen index (CPI)(%), which was calculated by a formula based on the difference in the uptakes in the caudate and putamen divided by the caudate uptake, indicated 5.6 +/- 4.6 in the MSA patients and 14.8 +/- 5.4 in the PD patients. The CPI for all PD patients was more than 7.0, which was the mean + 2SD for the controls, but the CPI for 3 MSA patients was more than 7.0 (accuracy: 88%). The glucose metabolic rates for each region in the PD patients showed no difference from the normal controls. The frontal and the temporal cortical glucose metabolism and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolism in the MSA patients decreased significantly in comparison to those in the controls. But, as the glucose metabolic rates in such regions of each patient overlapped in the two groups, the accuracy of the FDG study for differentiation was lower than that of the FD study. The putaminal glucose metabolic rates, for example, in 3 PD patients were less than 6.8 (mg/min/100 ml), which was the mean-2SD for the controls, while those in 3 MSA patients were more than 6.8 (accuracy: 75%). In addition, the combination of these two methods slightly improved the accuracy. The glucose metabolism is useful for evaluating the regional metabolic activity of the brain, and the FD study, which is specific to the dopamine system, seems to be more useful for differentiating between MSA and PD.
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PMID:Differentiating between multiple system atrophy and Parkinson's disease by positron emission tomography with 18F-dopa and 18F-FDG. 931 Jan 75

A 20-25% rate of antemortem misdiagnosis of idiopathic Parkinson's disease (PD) suggests that it may be difficult to clinically differentiate PD from other degenerative diseases of the central nervous system, such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA). Iodine-123 meta-iodobenzylguanidine ([123I] MIBG), an analogue of norepinephrine, is a tracer for functioning of sympathetic neurons. To investigate cardiac sympathetic function in PD, MSA, and PSP, [123I] MIBG myocardial scintigraphy was performed in 25 patients with PD, 25 patients with MSA, 14 patients with PSP, and 20 control subjects. In planar imaging studies, the heart-to-mediastinum average count ratio (H/M) was calculated for both early and delayed images. The mean value of H/M in patients with PD was significantly lower than in those with MSA, PSP, or no disease (p < 0.0001). Regardless of disease severity or intensity of anti-parkinsonian pharmacotherapy, mean values for H/M were always low in patients with PD. The mean values of H/M in patients with MSA and PSP were significantly lower than in controls (p < 0.01). There was no significant difference between the mean value of H/M in MSA with orthostatic hypotension (OH) and that in MSA without OH, and also there was no significant difference between the mean value of H/M in MSA with striatonigral degeneration and that in MSA with olivopontocerebellar atrophy. Although the mean value of H/M in PSP with amitriptyline treatment was significantly lower than that in PSP patients without amitriptyline treatment (p < 0.005), there was no significant difference between the mean value of H/M in PSP patients without amitriptyline treatment and that in controls. There was no correlation between H/M and disease duration in those three akinetic-rigid disorders that we have studied here. Thus, PD may have an abnormality of cardiac sympathetic function which has not been detected by previous cardiovascular autonomic studies. Particularly in early stages, [123I] MIBG myocardial scintigraphy may help to differentiate PD from MSA and PSP.
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PMID:[Iodine 123-labeled meta-iodobenzylguanidine myocardial scintigraphy in the cases of idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy]. 936 73

Over the last decade multiple system atrophy (MSA) has been confirmed as a distinct clinicopathological entity. For a long time, overlapping pathology in individual cases with striatonigral degeneration (SND), sporadic olivopontocerebellar atrophy (OPCA) or Shy-Drager syndrome (SDS) had often been a source of confusion. The recently discovered glial and neuronal inclusions indeed confirm that these three disorders represent manifestations of the same disease. Parkinsonism is the most frequent motor disorder of MSA. Early diagnosis of these patients is difficult but important, particularly in clinical trials of potential therapies. Patients with only parkinsonism (+/- autonomic failure) account for much of this diagnostic difficulty, particularly early on. Some features that have been associated with SND such as symmetry or absence of tremor are not helpful, and insistence on a poor levodopa response will miss a sizeable minority of patients. A number of further clinical 'red flags' may be helpful. MRI, MRS, PET and SPECT scanning, autonomic function tests and, especially, external sphincter EMG, may also help differentiate between idiopathic Parkinson's disease (IPD) and MSA. Available medical treatments are usually disappointing, so that good therapy services are all the more important. Better animal models of MSA and evaluation of novel treatment strategies are urgently required, and grafting techniques currently applied to IPD and Huntington's disease (HD) patients might be usefully combined in MSA. Epidemiological and case-control studies are needed to determine the prevalence, incidence and risk factors of MSA. The pathogenesis of MSA remains uncertain. Until the discovery of glial cytoplasmic inclusions (GCIs) previous studies had failed to identify abnormalities relevant to pathogenesis rather than reflecting secondary change. The abundance of GCIs points to a fundamental cytoskeletal alteration in glial cells that may eventually result in neuronal degeneration. Mechanisms of formation and distribution of GCIs as well as disordered glial-neuronal interactions should be studied in more detail in MSA brains.
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PMID:Parkinsonism. Multiple system atrophy. 942 75

MSA is a complex disorder, with regard to its pathology and cause as well as its clinical diagnosis and treatment. Although a number of clinical treatments may improve quality of life for these patients, given the widespread pathology present, symptomatic treatment, particularly that involving neurotransmitter replacement, is likely to remain difficult. Truly effective treatment for these patients is likely to depend on an understanding of the underlying pathogenic mechanisms and methods to halt or reverse disease progression. A firm understanding of the classification of these disorders is the first step to understanding the relevant pathogenic mechanisms. The finding of intracytoplasmic glial inclusion bodies provides a compelling piece of evidence that SND, OPCA, and SDS do, in fact, belong to one nosologic entity. These inclusions do not seem to be present in familial cases of OPCA; thus, they may provide a means to improve diagnostic specificity as well as sensitivity. With the ability to define clearly the entity of MSA, an understanding of the pathophysiology can be developed along with other degenerative neurologic diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease.
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PMID:Multiple system atrophy. 1009 84

We performed in vivo phosphorus magnetic resonance spectroscopy on the occipital lobes of 15 patients with multiple system atrophy (MSA; eight with olivopontocerebellar atrophy [OPCA] and seven with the striatonigral degeneration variant [SND]), 13 patients with idiopathic Parkinson's disease (PD), and 16 age-matched healthy subjects. The MSA group showed significantly reduced phosphocreatine (PCr), increased inorganic phosphate (Pi), and unchanged cytosolic free [Mg2+], and pH. We did not find any significant difference between the OPCA and SND variants. However, patients with PD showed significantly increased content of Pi, decreased cytosolic free [Mg2+], and unchanged [PCr] and pH. Comparing the MSA and PD groups, [PCr] was significantly lower in MSA than in PD, whereas cytosolic free [Mg2+] was significantly lower in PD. Despite a certain degree of overlap of [PCr] and [Mg2+] values between the two groups, by considering both variables at the same time it was possible to classify correctly 93% of cases by discriminant analysis. We conclude that phosphorus magnetic resonance spectroscopy discloses abnormal phosphate metabolite and ion contents in both MSA and PD, respectively, and may provide noninvasive diagnostic help to differentiate MSA from PD.
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PMID:Phosphorus magnetic resonance spectroscopy in multiple system atrophy and Parkinson's disease. 1034 65

Imaging of dopaminergic function is useful in the investigation of patients with Parkinson disease (iPD) and other extrapyramidal diseases. Using agents that bind to dopamine transporters ([123I]beta-CIT) and receptors ([123I]IBF SPECT), we investigated SPECT in 9 healthy volunteers and 24 patients for dopamine transporters as well as 15 patients for dopamine receptors. In beta-CIT SPECT studies, we examined 17 iPD patients (63.3 +/- 9.9 y/o), 3 multiple system atrophy (MSA) patients (OPCA type) (64.0 +/- 8.0 y/o), 2 vascular parkinsonism (VP) patients (71.0 +/- 0.0 y/o), 1 progressive supranuclear palsy (PSP) patient (69 y/o), 1 cortico-basal degeneration (CBD) patient (50 y/o) and nine healthy controls (39.1 +/- 9.3 y/o). For IBF SPECT studies 11 iPD patients (60.6 +/- 10.9 y/o), 3 MSA patients (2 OPCA type (50.5 +/- 3.5 y/o) and 1 SND type (65 y/o)) and 1 PSP patient (60 y/o) underwent SPECT scans after the injection of [123I]IBF. The specific to nonspecific striatal uptake ratio(St/Oc-1), ratio of putaminal uptake to caudatal uptake (Pu/Ca), and asymmetry indices (AI) were estimated. beta-CIT studies showed St/Oc-1 as follows; iPD: 2.66 +/- 1.09 (n = 17), VP: 5.73 and 7.39, MSA: 1.84 +/- 0.46 (n = 3), PSP: 2.34, CBD: 2.16. In all extrapyramidal diseases except VP, St/Oc-1 ratios were significantly lower than those in normal volunteers (6.46 +/- 1.08) (p < 0.01). Also in early-phase iPD patients (Yahr I-II), St/Oc-1 (3.16 +/- 1.49: n = 4) was significantly lower than those in normal volunteers (p < 0.01). In IBF studies, St/Oc-1 ratios were significantly higher in early-phase (Yahr I-II) iPD patients (1.82 +/- 0.25: n = 5) than those in late-phase (Yahr III-IV) iPD patients (1.38 +/- 0.32: n = 6) (p < 0.05). The Pu/Ca ratios in iPD patients (1.12 +/- 0.13) and MSA (OPCA type) patients (0.95 +/- 0.05) were higher than that in MSA (SND type) patient (0.78) and were lower than that in PSP patient (1.55). In conclusion, beta-CIT-SPECT is useful for the diagnosis of early-phase iPD patients and for differentiating VP from other extrapyramidal diseases. IBF-SPECT is useful for the diagnosis of the severity of iPD and has the possibility for ruling out MSA (SND type) or PSP from iPD. Both tracers are useful for investigating the pathophysiology of patients with iPD and other extrapyramidal diseases.
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PMID:[SPECT imaging using [123I]beta-CIT and [123I]IBF in extrapyramidal diseases]. 1264

Nine Parkinson's disease (PD), seven olivopontocerebellar atrophy (OPCA) patients and two age-matched control groups learned a linear arm movement-scaling task over 2 days, requiring movements proportional in length to visually presented target-bars. Scaling was acquired through knowledge of results (KR concerning the direction and magnitude of errors) following every second acquisition trial. Initial acquisition of both groups was significantly worse than their respective controls (poorer movement scaling), but rapidly improved to nearly identical levels. Retention for the PD group's movement scaling was as good as controls initially, but markedly poorer after 24 h. The OPCA group did not show this deficit. Both patient groups extrapolated accurately to longer, previously unpracticed target distances (no KR provided), suggesting an unimpaired capacity to generate and use an internal representation of the movement scaling. They also rapidly learned a new scaling relationship when the gain was changed. Overall, the learning of this movement-scaling task was not adversely affected in OPCA, and the impairment was restricted primarily to longer-term retention in PD. The study suggests that: (1) the ability to acquire movement scaling in a task that requires conscious use of error feedback and no new coordination may depend little on the cerebellum, and (2) the basal ganglia may participate in longer-term storage of scaling information.
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PMID:Motor learning processes in a movement-scaling task in olivopontocerebellar atrophy and Parkinson's disease. 1289 95

Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
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PMID:The neuropsychiatry of Parkinson's disease and related disorders. 1555 Feb 93

Glial cytoplasmic inclusions (GCIs) are characteristic protein deposits in multiple system atrophy (MSA), which are composed of abnormally phosphorylated, partially insoluble alpha-synuclein. In addition, recent studies have shown abnormal widespread accumulation of alpha-synuclein in neurons and neuronal processes, and in several regions including the thalamus and cerebral cortex in MSA. Combined alpha-synuclein and rab3a immunoprecipitation assays have shown alpha-synuclein/rab3a binding in the cerebellum and pons (in which GCIs were present) and in the cerebral cortex (area 8) (in which GCIs were absent) in MSA cases, but not in the cerebellum and cerebral cortex in age-matched controls. Similar findings were found in MSA-C and MSA-P cases (olivopontocerebellar atrophy and striatonigral degeneration types, respectively), thus indicating possible abnormal interactions of alpha-synuclein and rab3a in diseased brains. Abnormal alpha-synuclein binding to rab3a was also found in the substantia nigra but not in the cerebral cortex in Parkinson's disease. These findings suggest membrane and synaptic vesicle trafficking as vulnerable targets in MSA. Since rab3a is a member of the Ras super-family of small (21-25 kDa) GTP-binding proteins which is involved in the regulation of the internal trafficking, exocytosis and neurotransmission, and vesicle endocytosis, the present findings might suggest membrane and synaptic vesicle trafficking as vulnerable targets in MSA.
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PMID:Alpha-synuclein binding to rab3a in multiple system atrophy. 1585 72

Although the current guidelines for the clinical diagnosis of multiple system atrophy (MSA) do not require structural or functional brain imaging, investigations utilizing positron emission tomography (PET) have been helpful diagnostically in differentiating between MSA and primary autonomic failure; idiopathic Parkinson's disease; and sporadic olivopontocerebellar atrophy. These investigations have demonstrated different patterns of cerebral glucose utilization and of nigrostriatal projection abnormalities among these disorders and between the cerebellar and parkinsonian forms of MSA. Most of the studies have focused upon patients with well-established disease and none have examined the utility of PET imaging in early stage patients with follow-up of clinical course and autopsy verification to ensure accuracy of diagnosis and to determine the sensitivity and specificity of PET techniques for diagnosis. Recent PET studies have revealed denervation of myocardial post-ganglionic sympathetic neurons in some MSA patients, indicating that this disorder can affect the peripheral autonomic as well as the central nervous system. Investigations utilizing ligands to quantify central nervous system dopaminergic and cholinergic terminals have begun to provide insight into the neurochemical disorders that may underlie two of the sleep disturbances common in MSA, rapid eye movement sleep behavior disorder and obstructive sleep apnea.
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PMID:Functional imaging with positron emission tomography in multiple system atrophy. 1608 7


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