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)

Single voxel proton MRS was used to study brain metabolism in the striatum of patients diagnosed with idiopathic Parkinson's disease (PD). Peak metabolite ratios in long echo time spectra were evaluated in 151 patient spectra and 97 age-matched control spectra collected at four participating institutions using identical hardware and clinical protocols. Combining data from all ages (27-83 years old) showed no significant difference between patient and control ratios. However, in an elderly subset of patients (51-70 years old), a significant decrease in striatal N-acetylaspartate (NAA)/choline (Cho) was observed. Also, a significant decrease in the mean NAA/Cho ratio was observed in patients versus controls for patients not being treated with Sinemet (Du Pont Pharm, Wilmington, DE) (hereafter referred to as levodopa/carbidopa). This result is consistent with the hypothesis that NAA may provide a reversible spectroscopic marker for neuronal dysfunction, although a prospective follow-up study will be needed to confirm this. Quantitation of MRS would be useful to exclude the possibility that a change in Cho levels affected the NAA/Cho ratios.
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PMID:Localized proton NMR spectroscopy in the striatum of patients with idiopathic Parkinson's disease: a multicenter pilot study. 759 61

Proton magnetic resonance spectroscopy, localised to the lentiform nucleus, was carried out in three ex-professional boxers who developed a parkinsonian syndrome, six patients with idiopathic Parkinson's disease, and six age matched controls. The three ex-boxers all showed a pronounced reduction in the absolute concentration of N-acetylaspartate compared with the patients with idiopathic Parkinson's disease and the control group. This reduction is likely to reflect neuronal loss occurring in the putamen and globus pallidus and supports the hypothesis that the extrapyramidal syndrome that may occur in ex-boxers is a distinct entity from idiopathic Parkinson's disease.
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PMID:Magnetic resonance spectroscopic study of parkinsonism related to boxing. 853 Sep 57

Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p < 0.02) compared with the NAA/creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrast, the IPD group had a normal NAA/creatine ratio (median, 1.82; range, 1.19-2.31; p > 0.05). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91-1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22-1.68; p < 0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p < 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy. 784 62

Water-suppressed chemical shift magnetic resonance imaging was used to detect neurochemical alterations in vivo in neurotoxin-induced rat models of Huntington's and Parkinson's disease. The toxins were: N-methyl-4-phenylpyridinium (MPP+), aminooxyacetic acid (AOAA), 3-nitropropionic acid (3-NP), malonate, and azide. Local or systemic injection of these compounds caused secondary excitotoxic lesions by selective inhibition of mitochondrial respiration that gave rise to elevated lactate concentrations in the striatum. In addition, decreased N-acetylaspartate (NAA) concentrations were noted at the lesion site over time. Measurements of lactate washout kinetics demonstrated that t1/2 followed the order: 3-NP approximately MPP+ >> AOAA approximately malonate, which parallels the expected lifetimes of the neurotoxins based on their mechanisms of action. Further increases in lactate were also caused by intravenous infusion of glucose. At least part of the excitotoxicity is mediated through indirect glutamate pathways because lactate production and lesion size were diminished using unilateral decortectomies (blockade of glutamatergic input) or glutamate antagonists (MK-801). Lesion size and lactate were also diminished by energy repletion with ubiquinone and nicotinamide. Lactate measurements determined by magnetic resonance agreed with biochemical measurements made using freeze clamp techniques. Lesion size as measured with MR, although larger by 30%, agreed well with lesion size determined histologically. These experiments provide evidence for impairment of intracellular energy metabolism leading to indirect excitotoxicity for all the compounds mentioned before and demonstrate the feasibility of small-volume metabolite imaging for in vivo neurochemical analysis.
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PMID:Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. 862 49

Recent advances in magnetic resonance spectroscopy(MRS) allow to assay noninvasively key molecules of brain metabolism in living patients. There are several reports of MRS in Parkinson's disease(PD) and multiple system atrophy(MSA). 1H-MRS of the striatum revealed the reduced NAA/Cr and Cho/Cr ratio in MSA patients and the preserved NAA/Cr and Cho/Cr ratio in PD patients. The reduced NAA/Cr ratio probably reflects striatal neuronal loss. 1H-MRS of the striatum showed increased Cho/Cr ratio in the "on" state compared with that in the "off" state in the PD patients. The increased Cho/Cr ratio may reflect some membrane alteration or change of choline metabolism in PD with the "wearing-off" phenomena. Although studies are still preliminary, MRS shows great possibility for aiding in the differential diagnosis of parkinsonism and it will contribute to a better understanding of the pathogenesis of PD and MSA.
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PMID:[Magnetic resonance spectroscopy in Parkinson's disease and multiple system atrophy]. 901 59

The lentiform nucleus of five patients with idiopathic Parkinson's disease (IPD) was studied by quantitative magnetic resonance spectroscopy (MRS), both before and after administration of apomorphine, and the spectra were compared with those from a group of age-matched normal subjects. The concentrations of the three major metabolites, choline, creatine, and N-acetylaspartate (NAA), were quantified using tissue water content as an internal concentration reference. Glutamate concentration was assessed as the (glutamate + glutamine; GLX)/creatine peak area ratio. In normal subjects, the mean +/- SD concentrations of the the three metabolites were 2.4 +/- 0.4 mumol/g wet wt for choline, 11.5 +/- 0.8 mumol/g for creatine, and 14.7 +/- 2.8 mumol/g for NAA. The Glx/creatine ratio was 1.26 +/- 0.12. There was no significant difference in these parameters in the lentiform nucleus of patients with IPD either before or after apomorphine. The absence of detectable differences in IPD in this study implies that the changes in glutamate metabolism in the basal ganglia predicted by animal work are more subtle than those currently observable by MRS.
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PMID:Unchanged basal ganglia N-acetylaspartate and glutamate in idiopathic Parkinson's disease measured by proton magnetic resonance spectroscopy. 945 17

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.
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PMID:Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study. 927 May 74

We used proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the in vivo cortical and subcortical neuronal involvement in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration. This technique permitted the simultaneous measurement of compounds containing N-acetylaspartate (NA), choline (Cho), creatine-phosphocreatine (Cre) and lactate, from four 15-mm slices divided into 0.84-ml single-volume elements. The study included 12 patients with progressive supranuclear palsy, 10 with Parkinson's disease, nine with corticobasal degeneration and 11 age-matched normal control subjects. Regions of interest were selected from the brainstem, caudate, thalamus, lentiform nucleus, centrum semiovale, and from frontal, parietal, precentral, temporal and occipital cortices. Progressive supranuclear palsy patients, compared with control subjects, had significantly reduced NA/Cre in the brainstem, centrum semiovale, frontal and precentral cortex, and significantly reduced NA/Cho in the lentiform nucleus. Corticobasal degeneration patients, compared with control subjects, had significantly reduced NA/Cre in the centrum semiovale, and significantly reduced NA/Cho in the lentiform nucleus and parietal cortex. There were no significant differences between Parkinson's disease patients and control subjects, or between patients groups in any individual region of interest. In the parietal cortex of corticobasal degeneration patients, NA/Cho was significantly reduced contralateral to the most affected side. There were statistically significant group differences in the regional pattern of NA/Cre and NA/Cho reduction, comparing normal control subjects with all patient groups, Parkinson's disease with corticobasal degeneration, and Parkinson's disease with progressive supranuclear palsy. Although the occurrence of significant groups differences does not imply that it is possible to differentiate between individual patients using 1H-MRSI in progressive supranuclear palsy and corticobasal degeneration, detection of specific cortical and subcortical patterns of neuronal involvement is possible with this technique. We suggest that this regional pattern of neuronal involvement found in progressive supranuclear palsy and corticobasal degeneration may help in the diagnostic evaluation of affected individuals.
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PMID:Proton magnetic resonance spectroscopic imaging in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration. 931 38

Proton magnetic resonance spectroscopy (1H-MRS), localized to the lentiform nucleus, was carried out in 12 patients with idiopathic Parkinson's disease (IPD), seven patients with multiple-system atrophy (MSA), seven patients with progressive supranuclear palsy (PSP), and 10 healthy age-matched controls. The study assessed the level of N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), and choline (Cho) in the putamen and globus pallidus of these patients. NAA/Cho and NAA/Cr ratios were significantly reduced in MSA and PSP patients. No significant difference was found between IPD patients and controls. These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of MSA and PSP patients. 1H-MRS is a noninvasive technique that can provide useful information regarding striatal neuronal loss in basal ganglia of patients with atypical parkinsonian disorders and represents a potential tool for diagnosing these disorders.
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PMID:Proton magnetic resonance spectroscopy in Parkinson's disease and atypical parkinsonian disorders. 939 13

We used brain imaging to study long-term neurodegenerative and bioadaptive neurochemical changes in a primate model of Parkinson disease. We gradually induced a selective loss of nigrostriatal dopamine neurons, similar to that of Parkinson disease, by creating oxidative stress through infusion of the mitochondrial complex 1 inhibitor MPTP for 14+/-5 months. Repeated evaluations over 3 years by positron emission tomography (PET) demonstrated progressive and persistent loss of neuronal dopamine pre-synaptic re-uptake sites; repeated magnetic resonance spectroscopy (MRS) studies indicated a 23-fold increase in lactate and macromolecules in the striatum region of the brain for up to 10 months after the last administration of MPTP. By 2 years after the MPTP infusions, these MRS striatal lactate and macromolecule values had returned to normal levels. In contrast, there were persistent increases in striatal choline and decreases in N-acetylaspartate. Thus, these combined PET/MRS studies demonstrate patterns of neurochemical changes that are both dynamic and persistent long after selective dopaminergic degeneration.
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PMID:Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease. 980 56


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