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

Limited data exist concerning the mechanisms that underlie the different motor features of Parkinson's disease (PD) and their course over time. Our aims were (1) to identify longitudinal changes in PD patients and (2) to determine the neural correlates of the changes in movement initiation and velocity that occur in the course the disease. Thirteen early stage PD patients were scanned twice off antiparkinsonian medication with H(2)15O PET. Imaging was performed at baseline and again after 2 years while the subjects performed a motor task that was kinematically controlled across time. Paced reaching movements were made towards targets that were presented in a predictable order. Measures of movement onset time (OT) and mean velocity (MV) were recorded during PET. OT and MV decreased significantly from baseline to follow-up. With advancing disease, increasing subcortical activation was detected in the pallidum bilaterally and in the left putamen. In the cortex, motor-related activation increased in the right pre-SMA, anterior cingulate cortex and the left postcentral gyrus. Progressive delays in movement initiation (OT) correlated with increases in the right dorsal premotor cortex (dPMC). Slowing of movement (MV) was associated with declining activation in the left dorsolateral prefrontal cortex and dPMC. Our data suggest that with advancing PD, motor performance is associated with the recruitment of brain regions normally involved in the execution of more complex tasks.
 ...
PMID:Correlates of movement initiation and velocity in Parkinson's disease: A longitudinal PET study. 1706 39

We used fMRI to investigate the neurofunctional basis of externally and internally timed movements in Parkinson's disease (PD) patients. Ten PD patients whose medication had been withheld for at least 18h and 11 age- and sex-matched healthy controls were scanned while performing continuation paradigm with a visual metronome. Compared with the controls, PD patients displayed an intact capability to store and reproduce movement frequencies but with a significantly increased movement latencies. No differences in BOLD response were found in both groups when comparing the continuation with the preceding synchronization phase and viceversa, except for activity in visually related regions. Relative to healthy controls during the synchronization phase, PD patients exhibited an overall signal increase in the cerebellum and frontostriatal circuit (putamen, SMA and thalamus) activity together with specific brain areas (right inferior frontal gyrus and insula cortex) that are also implicated in primary timekeeper processes. By contrast, in the continuation phase the only neural network involved to a greater extent by the PD group was the cerebello-thalamic pathway. The lack of neurofunctional differences between the two timing phases suggests that rhythmic externally and internally guided movements engage similar neural networks in PD and matched healthy controls. Moreover, between-group comparison indicates that PD patients OFF medication may compensate for their basal ganglia-cortical loop's dysfunction using different motor pathways involving cerebellum and basal ganglia relays during the two phases of rhythmic movement.
 ...
PMID:Functional changes in the activity of cerebellum and frontostriatal regions during externally and internally timed movement in Parkinson's disease. 1711 55

The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA) show pathological changes in Parkinson's disease (PD). We examined if PD patients show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA, or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented PD patients and 38 controls (18 male, 20 female) 65 years of age and older were examined using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination, Frontal Assessment Battery, and Geriatric Depression Scale. MRS was performed at 1.5 T. Voxels (8 cc; PRESS; TE = 80; TR = 1,600 ms) were placed mid-sagittally. Gray matter and white matter volumes were measured within voxels using SPM2. Spectra were analyzed using LC model to yield NAA/Cr and Cho/Cr. Demographic and cognitive measures did not differ between groups. Motor UPDRS was 17.7 +/- 8.8 for PD. Pre-SMA NAA/Cr was lower in PD (PD: 1.39 +/- 0.17; control: 1.47 +/- 0.16; P = 0.045) and correlated negatively with age (r = 0.39; P = 0.01), but not with UPDRS, disease duration, or dopamine equivalents. AC and PC NAA/Cr and Cho/Cr in any region did not differ (P > 0.05). In conclusion, pre-SMA NAA/Cr was selectively decreased in PD, consistent with neuronal dysfunction. This should be further examined as a biomarker of disease in PD.
 ...
PMID:Magnetic resonance spectroscopic evidence for presupplementary motor area neuronal dysfunction in Parkinson's disease. 1721 52

We treated a patient with levodopa-resistant akinesia with motor cortex stimulation (MCS), and she showed dramatic improvement more than 1 year. On admission, the patient presented severe akinesia and gait disturbance without tremor and rigidity, and did not respond to levodopa test. The patient was suspected pure akinesia and progressive supranuclear palsy. First, high-frequency rTMS of primary motor cortex was examined, and showed the dramatic improvement. Next, chronic subdural electrodes were implanted over the motor cortex bilaterally. One year after surgery, the Unified Parkinson's Disease Rating Scale had improved remarkably, and she could walk four times faster than before. The H2 15O PET study showed a significant increase of rCBF in the left SMA and right dorsolateral prefrontal cortex after bilateral MCS. MCS may be an alternative treatment for patients with akinesia, including those with PD, and particularly for levodopa-resistant patients, who respond well to rTMS.
 ...
PMID:Motor cortex stimulation for levodopa-resistant akinesia: case report. 1755 43

Oscillatory and coherent EEG activity is increasingly recognized as a fundamental hallmark of cortical integrative functions. We aimed to study deviations from the norm of different resting EEG parameters in Parkinson's disease (PD) patients. We compared spectral parameters of the resting EEG of PD patients (n=24, median age 67 years) to those of healthy controls (n=34, median age 62 years). On average, the patient group exhibited higher spectral power over the frequency range of 2-100 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 6-9 Hz theta band in all electrodes. Frontal electrodes contributed most to this difference in the 4-6 Hz theta, 12-18 Hz beta and 30-45 Hz gamma bands. On an individual basis, the combination of six spectral power band parameters discriminated between patient and control groups and 72% of all subjects were classified correctly. Using LORETA source analysis, the generators of this power difference were localized to fronto-insulo-temporal cortical areas in the theta and beta bands, and to interhemispheric frontal (supplementary motor area, SMA) and cingulate areas in the 30-45 Hz gamma band. We calculated spectral coherence between electrode pairs in a frontal, central and parietal region of interest (ROI). In the frontal ROI, coherence was enhanced significantly in the patient group in the theta, high beta and gamma bands. In the parietal ROI, patients showed lower coherence around 10 Hz. We demonstrate a deviation from the norm of different resting EEG parameters in PD patients. This evidence can be integrated in the context of a pathophysiological chain reaction initiated in the substantia nigra and resulting in a cortical aberrant dynamics rooted in enhanced dysrhythmic thalamocortical interactions.
 ...
PMID:Enhanced frontal low and high frequency power and synchronization in the resting EEG of parkinsonian patients. 1845 62

Although motor symptoms of Parkinson's disease (PD) are initially responsive to dopamine replacement therapy, nonresponsive features develop over time, suggesting that impaired dopaminergic function alone may not be wholly responsible for all the motor features of the disease. Previous studies suggest impaired function in the presupplementary motor area (pre-SMA) in PD. Our objective was to determine whether pre-SMA abnormalities are present in untreated patients with early disease. We measured N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in pre-SMA in 26 untreated patients with early PD (disease duration 3.0 +/- 2.0 yr) and 15 control subjects with single voxel magnetic resonance spectroscopy. Neither NAA/Cr nor Cho/Cr ratios differed significantly between groups. These observations suggest that, although pre-SMA function is impaired in moderately advanced PD, it is relatively spared in early disease. We suggest that pre-SMA dysfunction is in part responsible for the dopamine nonresponsive features associated with disease progression.
 ...
PMID:Intact presupplementary motor area function in early, untreated Parkinson's disease. 1870 78

BACKGROUND AND PURPOSE The antiakinetic effect of internal Globus pallidus deep brain stimulation (Gpi-DBS) in Parkinson's disease is not clear and not either how this effect is modulated by L-dopa. METHODS Left Gpi-DBS and/or L-dopa effect was studied with auditory paced right-handed sequential movements on (15)O-butanol positron emission tomography (PET) in five patients. Rest and for conditions during movements (DBS off/L-dopa off; DBS on/L-dopa off; DBS off/L-dopa on; DBS on/L-dopa on) were compared with statistical parametric mapping. RESULTS Gpi-DBS activated the right supplementary motor area/premotor (SMA/PMC), and right insular cortex (IC), and as L-dopa decreased the left sensorimotor cortex (M1/S1) activity. L-dopa increased the left ventrolateral thalamus (VLTH), and decreased the left superior parietal cortex (PC) activity. Gpi-DBS and L-dopa interaction showed right SMA/PMC, IC, and left PC activation, decrease of left VLTH, PMC, and dorsolateral prefrontal cortex (PFC) activity. CONCLUSIONS The improvement of bradykinesia with Gpi-DBS is secondary and contributed to the regress of M1/S1-related rigidity and compensatory SMA/PMC, and IC activation. L-dopa and Gpi-DBS alone each reduces M1/S1 overactivity. Interaction ignores this effect, moreover has akinetic effect in the left VLTH, PMC, and PFC. Motor improvement possibly related to left PC and compensatory right SMA/PMC, and IC activation.
 ...
PMID:Pallidal deep brain stimulation and L-dopa effect on PET motor activation in advanced Parkinson's disease. 1902 48

Previous fMRI motor studies in Parkinson's disease (PD) have suggested that L-dopa may "normalize" areas of hypo- and hyperactivity. However, results from these studies, which were largely based on analyzing BOLD signal amplitude, have been conflicting. Examining only amplitude changes at distinct loci may thus be inadequate in fully capturing the activation changes induced by L-dopa. In this article, we extended prior analyses on the effects of L-dopa by investigating both amplitude and spatial changes of brain activation before and after L-dopa. Ten subjects with PD, both on and off medication, and ten healthy, age-matched controls performed a visuo-motor tracking task in which they sinusoidally squeezed a bulb at 0.25, 0.5, and 0.75 Hz. This task was contrasted with static squeezing to generate fMRI activation maps. To investigate the effects of L-dopa, we examined the amplitude and spatial variance of the BOLD response within anatomically-defined regions of interest (ROIs). L-dopa had significant main effects on the amplitude of BOLD signal in bilateral primary motor cortex and left SMA. In contrast, L-dopa-mediated spatial changes were apparent in bilateral cerebellar hemispheres, M1, SMA, and right prefrontal cortex. Moreover, L-dopa appeared to normalize the spatial distribution of ROI activation in PD to that of the controls. Specifically, L-dopa had a "focusing" effect on activity-an effect more pronounced than the typically-measured fMRI amplitude changes. This observation is consistent with modeling studies, which demonstrated that dopamine increases the signal-to-noise ratio at the neuronal level with a resultant focusing of representations at the macroscopic level.
 ...
PMID:Focusing effects of L-dopa in Parkinson's disease. 1958 87

Dynamic causal modelling (DCM) of functional magnetic resonance imaging (fMRI) data offers new insights into the pathophysiology of neurological disease and mechanisms of effective therapies. Current applications can be used both to identify the most likely functional brain network underlying observed data and estimate the networks' connectivity parameters. We examined the reproducibility of DCM in healthy subjects (young 18-48 years, n=27; old 50-80 years, n=15) in the context of action selection. We then examined the effects of Parkinson's disease (50-78 years, Hoehn and Yahr stage 1-2.5, n=16) and dopaminergic therapy. Forty-eight models were compared, for each of 90 sessions from 58 subjects. Model-evidences clustered according to sets of structurally similar models, with high correlations over two sessions in healthy older subjects. The same model was identified as most likely in healthy controls on both sessions and in medicated patients. In this most likely network model, the selection of action was associated with enhanced coupling between prefrontal cortex and the pre-supplementary motor area. However, the parameters for intrinsic connectivity and contextual modulation in this model were poorly correlated across sessions. A different model was identified in patients with Parkinson's disease after medication withdrawal. In "off" patients, action selection was associated with enhanced connectivity from prefrontal to lateral premotor cortex. This accords with independent evidence of a dopamine-dependent functional disconnection of the SMA in Parkinson's disease. Together, these results suggest that DCM model selection is robust and sensitive enough to study clinical populations and their pharmacological treatment. For critical inferences, model selection may be sufficient. However, caution is required when comparing groups or drug effects in terms of the connectivity parameter estimates, if there are significant posterior covariances among parameters.
 ...
PMID:Dynamic causal modelling of effective connectivity from fMRI: are results reproducible and sensitive to Parkinson's disease and its treatment? 2005 51

Spinal muscular atrophy, the most prevalent hereditary motor neuron disease, is caused by mutations in the survival motor neuron (SMN) 1 gene. A significant reduction in the encoded SMN protein leads to the degeneration of motor neurons. However, the molecular events leading to this process are not well understood. The present study uses a previously developed neuronal cell culture model of spinal muscular atrophy for a multiplex transcriptome analysis. Furthermore, gene expression analysis was performed on in vitro cell cultures, as well as tissue samples of spinal muscular atrophy patients and transgenic mice. RNA and subsequent Western blot protein analyses suggest that low SMN levels are associated with significantly lower alpha-synuclein expression. Examination of two genes related to vesicular transport showed a similar though less dramatic decrease in expression. The 140-amino acid protein alpha-synuclein, dominant mutations of which have previously been associated with an autosomal dominant form of Parkinson's disease, is strongly expressed in select neurons of the brain. Although not well understood, the physiologic functions of alpha-synuclein have been linked to synaptic vesicular neurotransmitter release and neuroprotection, suggesting a possible contribution to Smn-deficient motor neuron pathology. Furthermore, alpha-synuclein may be a genetic modifier or biomarker of spinal muscular atrophy.
 ...
PMID:Alpha-synuclein loss in spinal muscular atrophy. 2064 May 32


<< Previous 1 2 3 4 Next >>