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)

The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each subscore of the motor section (UPDRS III) compresses a wide range of motor performance into a coarse-grained scale from 0 to 4; the assessment of performance can also be subjective. Quantitative digitography (QDG) is an objective, quantitative assessment of digital motor control using a computer-interfaced musical keyboard. In this study, we show that the kinematics of a repetitive alternating finger-tapping (RAFT) task using QDG correlate with the UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients with PD. We show that dopaminergic medication and an average of 9.5 months of bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) significantly improve UPDRS and QDG scores but may have different effects on certain kinematic parameters. This study substantiates the use of QDG to measure motor outcome in trials of PD therapeutics and shows that medication and B-STN DBS both improve fine motor control.
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PMID:Quantitative measurements of alternating finger tapping in Parkinson's disease correlate with UPDRS motor disability and reveal the improvement in fine motor control from medication and deep brain stimulation. 1600 1

In clinical conditions, high-frequency stimulation (HFS) of subthalamic (STN) neurons in Parkinson's disease is empirically applied at > or =100 Hz (130-185 Hz), with pulses of short duration (60-100 micros) and 1- to 3-mA amplitude. Other parameter values produce no effect or aggravate the symptoms. To gain a better understanding of the mechanisms that underlie the therapeutic action of HFS, we have compared the effects of different combinations of parameter values delivered by clinical stimulators on the activity of STN neurons recorded in whole cell patch-clamp configuration in slices. We showed that none of tested combinations of parameters silenced the neurons. Non-therapeutic combinations i.e., low-frequency pulses (10-50 Hz), even at large amplitude or width, further excited the STN neurons with respect to their spontaneous activity. In contrast, combinations in the therapeutic range (80-185 Hz, 90-200 micros, 500-800 microA) replaced the preexisting activity by spikes, time-locked to the stimuli and thus presenting a striking regularity. When increasing pulse width or amplitude in this high-frequency range, the dual effect was still present but the activity generated became more irregular. We propose that during HFS at clinically relevant parameters, STN neurons behave as stable oscillators entirely driven by the stimulation, giving an average stable STN output that overrides spontaneous activity and introduces high-frequency regular spiking in the basal ganglia network.
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PMID:Impact of high-frequency stimulation parameters on the pattern of discharge of subthalamic neurons. 1614 75

Here I introduce a dynamic model of the basal ganglia functions for the control of voluntary movement: information through major pathways in the cortico-basal ganglia loop, i. e., the cortico-STN-GPi/SNr "hyperdirect", cortico-striato-GPi/SNr "direct" and cortico-striato-GPe-STN-GPi/SNr "indirect" pathways, dynamically controls the activity of the thalamus and cortex and releases only the selected motor program at the selected timing. Based on the dynamic model, the pathophysiology of Parkinson's disease and the mechanism for the effectiveness of stereotaxic surgery can better be explained by an increase or decrease of disinhibition and inhibition in the thalamus and cortex in the temporal and spatial domains.
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PMID:A new approach to understand the pathophysiology of Parkinson's disease. 1622 31

We have previously introduced a concept of a probabilistic functional atlas (PFA) to overcome limitations of the current electronic stereotactic brain atlases: anatomical nature, spatial sparseness, inconsistency and lack of population information. The PFA for the STN has already been developed. This work addresses construction of the PFA for the ventrointermediate nucleus (PFA-VIM). The PFA-VIM is constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients. The data contain the positions of the chronically implanted electrodes and their best contacts. For each patient, the intercommissural distance, height of the thalamus and width of the third ventricle were measured. An algorithm was developed to convert these data into the PFA-VIM, and to present them on axial, coronal and sagittal planes and in 3-D. The PFA-VIM gives a spatial distribution of the best contacts, and its probability is proportional to best contact concentration in a given location. The region with the highest probability corresponds to the best target. The PFA-VIM is calculated with 0.25-mm3 resolution from 107 best contacts in two situations: with and without lateral compensation against the width of the third ventricle. For the PFA-VIM compensated laterally, the anterior, lateral and dorsal coordinates of the mean value are (in mm) 6.24, 13.83, 1.68 for the left VIM and 6.54, -13.84, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts (P) are: 6.25, 14.25, 1.75, P = 16, for the left VIM, and 6.0, -14.0, 1.00, P = 18, for the right VIM. The coordinate system origin is at the posterior commissure. For the PFA-VIM not compensated laterally, the coordinates of the mean value are 6.24, 13.99, 1.68 for the left VIM and 6.53, -14.13, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts are 5.58, 13.67, 1.33, P = 14, for the left VIM, and 6.36, -14.03, 1.11, P = 17, for the right VIM. The PFA-VIM atlas overcomes several limitations of the current anatomical atlases and can improve targeting of thalamotomies and thalamic stimulations. It is dynamic and can easily be extended with new cases.
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PMID:A probabilistic functional atlas of the VIM nucleus constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients. 1642 83

We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved complete daily on-time without dyskinesia at 12 months significantly. In conclusion, our study demonstrates the efficacy of chronic STN-DBS on motor features in a selected population of advanced PD patients. In addition to clinical assessments, patients' diaries serve as an essential tool to evaluate the functional motor status after STN-DBS.
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PMID:Chronic stimulation of the subthalamic nucleus increases daily on-time without dyskinesia in advanced Parkinson's disease. 1646 Sep 86

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.
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PMID:Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease. 1646 36

The involvement of the subthalamic nucleus in physiological and pathological motor behaviour has now largely been established. Clinical observations in patients suffering from Parkinson disease treated with Deep Brain Stimulation of the STN show that these patients can suffer from postoperative changes in non-motor behaviour mainly involving alterations in cognitive functions. The involvement of the STN in cognition has initially been demonstrated by non-human studies investigating the effects of STN lesions and stimulations on cognitive parameters. In the present review, we discuss the findings of these preclinical studies on cognitive parameters and outline the anatomical and functional place of the STN in the basal ganglia cognitive circuit.
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PMID:The subthalamic nucleus: From response selection to execution. 1647 94

We report the therapeutic effects of deep brain stimulation (DBS) in 2 patients with Parkinson's disease (PD) with severe end of dose dyskinesia that was resistant to medical therapy. In both patients, severe, end of day ballistic dyskinesias occurred when the last levodopa dose of the day was wearing off. Globus pallidus (GPi) DBS in 1 case and subthalamic (STN) DBS in the second case produced full resolution of end of day dyskinesia.
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PMID:End of day dyskinesia in advanced Parkinson's disease can be eliminated by bilateral subthalamic nucleus or globus pallidus deep brain stimulation. 1663 40

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B-STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory-deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B-STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N(subset) = 23; P < 0.001 for both); (3) B-STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B-STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003).
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PMID:Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in Parkinson's disease, whereas medication does not. 1667 Oct 73

DBS is a safe and effective option for the treatment of patients with advanced PD. To ensure a successful outcome, however, it is important to select the appropriate candidates. The ideal candidate has idiopathic PD, suffers from complications of chronic levodopa therapy despite optimal medical management, and has no cognitive impairment or active psychiatric issues. Although the exact mechanism of how DBS exerts its effects remains under investigation, it is clearly apparent that bilateral stimulation of either the GPi or STN effectively helps the motor symptoms of PD. While many surgical centers favor stimulation of the STN over the GPi, there is accumulating evidence that STN stimulation may result in adverse non-motor outcomes such as depression. Future studies will be needed in order to determine the best site of stimulation, the exact mechanisms of DBS, and the long-term outcomes of both motor and non-motor symptoms. As our understanding of these components becomes clearer, we will be able to optimize the treatment and management for those whose lives are affected by Parkinson's disease.
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PMID:Deep brain stimulation for Parkinson's disease: patient selection and motor outcomes. 1667 11


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