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)

We report an unusual case of amyotrophic lateral sclerosis (ALS) marked by extensive cerebral amyloid-beta deposition in small and medium-size vessels, capillaries, and perivascular plaques in the cerebral cortex, and in most leptomeningeal vessels. Despite considerable cerebral amyloidosis, the patient remained cognitively intact until death. For comparison with other neuro-degenerative diseases and normal aging, we assessed the densities of amyloid-beta-immunoreactive cortical vessels and plaques in matched frontal and temporal lobe sections from archival uncomplicated cases of Alzheimer's disease (N=10), Pick's disease (PkD; N=4), Parkinson's disease (PD; N=6), Diffuse Lewy body disease (DLBD; N=7), progressive supranuclear palsy (PSP; N=5), multiple systems atrophy (MSA; N=4), ALS (N=7), or normal aging (N=10) by semi-quantitative grading (0 to 3+). Moderate (2+) or abundant (3+) cerebrovascular amyloid-beta immunoreactivity was detected in 8/10 AD, 3/7 DLBD, 3/6 PD, 1 each with PSP or PkD, and 2/10 controls. Moderate or abundant densities of amyloid-beta-immunoreactive diffuse plaques were detected in all cases of AD or DLBD, 4/6 with PD, 3/5 with PSP, and 2/10 controls. Moderate or abundant amyloid-beta-immunoreactive mature (dense core) plaques were present in all cases of AD or DLBD, and 3 each with PD or PSP. Importantly, amyloid-beta-immunoreactivity was not observed in the 4 MSA or 7 archival ALS cases. This study demonstrates that prominent amyloid-beta accumulation in cerebral vessels and plaques occurs frequently in AD, DLBD, PSP, and PD, but not in ALS or MSA, indicating that the case described is unique. The lack of cognitive impairment in the case presented argues against the idea that extensive amyloid-beta deposition in the brain causes dementia.
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PMID:Brain Accumulation of Amyloid-beta in Non-Alzheimer Neurodegeneration. 1221 3

Positron emission tomography (PET) and network analysis have been used to identify a reproducible pattern of regional metabolic covariation that is associated with idiopathic Parkinson's disease (PD). The activity of this PD-related pattern can be quantified in individual subjects and used to discriminate PD patients from atypical parkinsonians. Because PET is not commonly available, we sought to determine whether similar discrimination could be achieved using more routine single photon emission computed tomography (SPECT) perfusion methods. Twenty-three subjects with PD (age, 63 +/- 9 years), 22 subjects with multiple system atrophy (MSA; age, 64 +/- 7 years), and 20 age-matched healthy controls (age, 62 +/- 13 years) underwent SPECT imaging of regional cerebral perfusion with Tc-99m ethylene cysteinate dimer (ECD). Using network analysis, we determined whether a PD-related pattern existed in the SPECT data, and whether its expression discriminated PD from MSA patients. Additionally, we compared the accuracy of group discrimination achieved by this pattern with that of the PET-derived PD-related pattern applied to the SPECT data. Network analysis of the SPECT data identified a significant pattern characterized by relative increases in cerebellar, lentiform, and thalamic perfusion covarying with decrements in the frontal operculum and in the medial temporal cortex. Subject scores for this pattern discriminated PD patients from controls (P < 0.01) and from MSA patients (P < 0.03). Subject scores for the PET-derived PD-related pattern computed in the individual SPECT scans more accurately distinguished PD patients from controls (P < 0.005) and from MSA patients (P = 0.0002). A significant PD-related covariance pattern can be identified in SPECT perfusion data. Moreover, the disease related pattern identified previously with PET can be applied to individual SPECT perfusion scans to provide group discrimination between PD patients, healthy controls, and individuals with MSA. Because of significant individual subject overlap between groups, however, the clinical utility of this method in the differential diagnosis of Parkinsonism remains uncertain.
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PMID:Tc-99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism. 1246 66

The 42-amino-acid isoform of beta-amyloid Abeta42 in the cerebrospinal fluid (CSF) has recently been proposed as a biochemical marker for Alzheimer's disease (AD) and subcortical white-matter dementia (SWD). In both of these conditions, concentration of CSF-Abeta42 is reduced. We quantified CSF-Abeta42 from patients fulfilling strict clinical criteria for multiple system atrophy (MSA; n = 36), Parkinson's disease (PD; n = 48) and progressive supranuclear palsy (PSP; n = 15). The study groups were consecutively recruited among patients referred to a movement disorder unit, and 32 healthy, age-matched volunteers were used as controls. The CSF concentration of Abeta42 was significantly reduced in the MSA group (P < 0.001), whereas the PD and PSP groups did not differ from controls. On an individual basis, low content of Abeta42 was seen in 9 MSA patients regardless of age and disease duration. Three PD patients with long disease duration also had low concentrations but all PSP patients were normal. We conclude that the reduced CSF-Abeta42 concentration may be a clue to the pathogenesis of MSA. There is a decreased production, or more possible, an increased consumption of CSF-Abeta42. The analysis of this protein may also become a supplement to the clinical differentiation of parkinsonian syndromes in a movement disorder unit.
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PMID:Cerebrospinal fluid Abeta42 is reduced in multiple system atrophy but normal in Parkinson's disease and progressive supranuclear palsy. 1497 88

We assessed the usefulness of routine MRI for the differential diagnosis of Parkinson's disease (PD) with "atypical" parkinsonian syndromes in everyday clinical practice. We studied routinely performed MRI in PD (n = 32), multiple system atrophy (MSA, n = 28), progressive supranuclear palsy (PSP, n = 30), and corticobasal degeneration (CBD, n = 26). From a preliminary analysis of 26 items, 4 independent investigators rated 11 easily recognizable MRI pointers organized as a simple scoring system. The frequency, severity and inter-rater agreement were determined. The total severity score was subdivided into "cortical", "putaminal", "midbrain", and "pontocerebellar" scores. The frequency of putaminal involvement (100%) and vermian cerebellar atrophy (45%) was significantly higher in MSA, but that of cortical atrophy (50%), midbrain atrophy and 3(rd) ventricle enlargement (75%) was higher in PSP and CBD. The median total score fairly differentiated "atypical" parkinsonian syndromes from PD (positive predictive value-PPV-90%). However, the median total score was unable to differentiate atypical parkinsonian syndromes each other. The "cortical" score distinguished CBD and PSP from MSA with a fair PPV (>90%). The PPV of the "putaminal" score was high (70%) for the differential diagnosis of MSA with PSP and CBD. The "midbrain" score was significantly higher in PSP and CBD compared to MSA. These results are in accordance with the underlying pathology found in these disorders and demonstrate that a simple MRI scoring procedure may help the neurologist to differentiate primary causes of parkinsonism in everyday practice.
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PMID:Routine MRI for the differential diagnosis of Parkinson's disease, MSA, PSP, and CBD. 1258 75

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.
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PMID:Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. 1453 16

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.
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PMID:123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. 1459 60

Atrophy of frontal lobe, midbrain, pons, and cerebellum was studied in 16 patients with progressive supranuclear palsy (PSP), 14 with multiple system atrophy of striatonigral type (MSA-P), 20 with idiopathic Parkinson's disease (IPS), and 12 age-matched healthy controls using axial T2-weighted MR images (1.5 Teslar). With <16 mm, the PSP group showed significantly lower anteroposterior midbrain diameters than the IPS, MSA-P, and control groups. We conclude that measurement of the anteroposterior diameter of the midbrain with axial T2-weighted MRI is a useful feature and should be incorporated into the diagnostic criteria for PSP. In addition to the typical slit hyperintensity in margin of putamen and decreased signal intensity in dorsolateral putamen, we found cerebellar atrophy in 64% of patients with MSA-P. Before now, this was considered a typical sign of multiple system atrophy of cerebellar type (MSA-C). The use of this feature in the differential diagnosis of both types of multiple system atrophy is debatable.
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PMID:[Differentiation of atypical Parkinson syndrome and delineation from idiopathic Parkinson syndrome with routine magnetic resonance tomography]. 1477 Feb 82

We have recently shown that diffusion-weighted magnetic resonance (MR) imaging (DWI) discriminates patients with the Parkinson variant of multiple system atrophy (MSA-P) from those with Parkinson's disease (PD) by regional apparent diffusion coefficients (rADC) in the putamen. Because rADCs measured in one direction may underestimate diffusion-related pathologic processes, we investigated the diffusivity in different brain areas by trace of diffusion tensor (Trace(D)) in a new cohort of patients with MSA-P and PD. We studied 11 MSA-P, 17 PD patients, and 10 healthy volunteers matched for age and disease duration. Regional ADCs in three orthogonal directions and Trace(D) values were determined in selected brain regions including the basal ganglia, gray matter, white matter, substantia nigra, and pons. MSA-P patients had significantly higher putaminal and pallidal rTrace(D) values as well as rADCs in y- and z-direction than both PD patients and healthy volunteers. Moreover, putaminal Trace(D) discriminated completely MSA-P from both PD and healthy volunteers. The rADCs in the y- and z-direction provided a complete or near complete separation. In conclusion, our study confirms the results of previous studies of our group that patients with MSA-P show an increased putaminal diffusivity due to neuronal loss and gliosis. Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD.
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PMID:Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease. 1505 May 69

We examined the role of a striatal lesion in the development of L-DOPA-induced abnormal involuntary movements (AIMs) using the double lesion rat model of striatonigral degeneration (SND), the underlying neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA-P), in comparison to a Parkinson's disease (PD) rat model. L-DOPA administration reliably induced AIMs in SND and PD rats in a dose-dependent fashion. AIMs occurred significantly earlier in SND compared to PD rats. There was a mild, but significant, transient increase of orolingual AIMs during the first week of low-dose L-DOPA treatment in SND. Whereas L-DOPA significantly improved contralateral forelimb akinesia in PD rats, there was no beneficial effect in SND rats. Striatal FosB/Delta FosB up-regulation in SND and PD rats correlated with the severity of L-DOPA-induced dyskinesias. Pulsatile L-DOPA administration in the double lesion SND rat model replicates salient features of the human disease MSA-P, including loss of the anti-akinetic L-DOPA response and induction of dyskinesias with transient orolingual predominance.
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PMID:Effects of pulsatile L-DOPA treatment in the double lesion rat model of striatonigral degeneration (multiple system atrophy). 1505 71

We investigated whether cerebrospinal fluid (CSF) analysis discriminates between idiopathic Parkinson's disease (PD; n = 35) and multiple system atrophy (MSA; n = 30). The median CSF concentration of the neurotransmitter metabolites 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) was reduced significantly (49-70%) in MSA compared to PD. In contrast, several brain-specific proteins (tau, neuron-specific enolase, myelin basic protein) were elevated (130-230%) in MSA compared with those in PD. A combination of CSF tau and MHPG discriminated PD from MSA (adjusted odds ratios: tau, 27.2; MHPG, 0.14). Our data suggest that the more progressive and widespread neurodegenerative nature of MSA, as compared with PD, is reflected in the composition of CSF. We propose that CSF analysis may become part of the diagnostic work-up of patients with parkinsonian syndromes.
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PMID:Cerebrospinal fluid analysis differentiates multiple system atrophy from Parkinson's disease. 1513 23


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