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)

Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an effective treatment option in advanced Parkinson's disease (PD). Recent animal studies showed an increase of neuronal firing in dopaminergic neurons under effective STN-DBS. Increased striatal dopamine levels may also contribute to the stimulation's mechanism of action in humans. We investigated the striatal dopamine release in 6 patients with advanced PD under effective bilateral STN-DBS with positron emission tomography (PET) of the reversible dopamine-D2/3-receptor ligand [(11)C]raclopride (RACLO). Although STN-DBS proved to be a highly effective treatment in these subjects, we found no significant difference of the striatal RACLO binding between the STN-DBS-on and -off condition. The changes of radioligand binding did not correlate with the patients' improvement in clinical rating scales or with the stimulation amplitudes. Therefore, our PET data in living parkinsonian humans do not provide evidence for an increased striatal dopamine concentration under effective STN-DBS. We conclude that the modulation of dopaminergic activity does not seem to play a crucial role for the stimulation's mechanisms of action in parkinsonian humans.
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PMID:Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans. 1251 99

Parkinson's disease (PD) is a progressive disturbances of movement that affects mainly the motor system. Prolonged pharmacological administration may result in insufficient control of symptoms and significant side effects. Deep brain stimulation (DBS), targeted at the STN, is a recent surgical procedure that, according to the symptoms response, allows modification of stimulation parameters; its effects are also reversible. In this paper management of surgical patients is reported. It includes patient selection, inclusion and exclusion criteria, postoperative clinical protocol. The evaluation rating scale such as UPDRS, Dyskinesias Rating Scale and Self-Reporting Questionnaire usually administrated on PD patients are analyzed. Surgical inclusion criteria are (1) idiopathic PD, (2) IV or V Hoehn-Yahr stage, (3) severe motor disability, and (4) no dementia or psychiatric abnormalities. Postoperative clinical protocol is analyzed and parameter of stimulation after surgery and at the follow up are reported. Generally DBS allows an improvement of rigidity and tremor; bradykinesia also improves with high frequency stimulation. Results obtained by continuous stimulation show a mean improvement of UPDRS of about 60% and a significant reduction in the drug intake.
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PMID:Surgery of Parkinson's disease: inclusion criteria and follow-up. 1277 12

Among all the extrapiramidal movement disorders Parkinson's disease (PD) is the one most often submitted to neurosurgical treatment. Technical advances in neurosurgery, neuroimaging and neurophysiology, as well as shortcomings of chronic Levodopa medication (i.e. on/off fluctuations, violent dyskinesia and painful dystonia) have greatly contributed to the renewed interest in the surgical treatment of PD. The attainment of a better understanding of the basal ganglia function and of PD pathophysiology has also encouraged centers to treat Parkinson's disease in recent years. This article presents the current model of PD and the rationale for using GPi, thalamus and STN as target sites in stereotactic surgery.
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PMID:[The currently accepted pathophysiological model underlying surgical management of Parkinson disease]. 1291 Aug 41

Chronic subthalamic nucleus high frequency stimulation (STN HFS) improves motor function in Parkinson's disease. However, its efficacy on cognitive function and the mechanisms involved are less known. The aim of this study was to assess the effects of STN HFS in hemiparkinsonian awake rats performing different specific motor tests and a cognitive operant task. Unilateral STN HFS applied in unilaterally DA-depleted rats decreased the apomorphine-induced circling behaviour and reduced catalepsy induced by the neuroleptic haloperidol. DA-depleted rats exhibited severe deficits in the operant task, among which the inability to perform the task was not alleviated by STN HFS. However, in a few animals showing less impairment, STN HFS significantly reduced the contralateral neglect induced by the lesion. These results are the first to demonstrate a beneficial effect of STN HFS applied in awake rats on basic motor functions. However, STN HFS appears to be less effective on impaired cognitive functions.
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PMID:High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats, but less efficiency in a choice reaction time task. 1292 21

Unilateral pallidotomy and bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) have demonstrated a positive effect on motor functions. However, further studies are needed of the unintended cognitive effects accompanying these new surgical procedures. We studied the consequences of unilateral pallidotomy and STN-DBS on cognitive function in a controlled comparative design. Sixteen consecutive PD patients were assessed before and 6 months after unilateral pallidotomy (n = 8) and bilateral STN-DBS (n = 8). The same assessments were performed in a control group of eight non-operated matched PD patients recruited from surgery candidates who refused operation. The neuropsychological battery consisted of test measuring memory, attention, arithmetic, problem solving and language, as well as visuospatial, executive and premotor functions. An analysis of variance (factors time and treatment) was applied. No statistically significant differences were found in the presurgical evaluation of clinical and demographic data for the three treatment groups. The controlled comparison between presurgical and postsurgical performance revealed no significant changes in the cognitive domains tested in the pallidotomy group. The STN-DBS group showed a selective significant worsening of semantic verbal fluency (p = 0.005). This controlled comparative study suggests that neither unilateral pallidotomy nor bilateral STN-DBS have global adverse cognitive consequences, but bilateral STN-DBS may cause a selective decrease in verbal fluency.
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PMID:Effects of pallidotomy and bilateral subthalamic stimulation on cognitive function in Parkinson disease. A controlled comparative study. 1292 9

STN-HFS is well known to improve patients with IPD. Because off-period dystonia mimics focal or generalized dystonia of other causes, we proposed bilateral STN-HFS to some patients with generalized dystonia. The aim of this study was to compare the efficacy of STN stimulation on off-period dystonia and generalized dystonia. From a larger series of patients with IPD, we selected 22 patients based on the presence of severe preoperative off-period dystonia rated > or = 3 in least one limb on a severity score ranging from 0 to 4. Four patients with generalized dystonia (Hallervorden-Spatz disease, n = 3; primary, n = 1) underwent bilateral STN-HFS. Dystonia of the four limbs was rated on video recordings in all patients before surgery and 3 months after surgery. In IPD, bilateral STN stimulation reduced the severity of off-period dystonia by 70% on the four limbs (preoperative mean severity score = 2.03 +/- 1.49; postoperative mean severity score = 0.60 +/- 0.78). In contrast, bilateral STN-HFS had no effect on generalized dystonia (preoperative mean severity score = 3.25 +/- 0.77; postoperative mean severity score = 3.12 +/- 0.62). Despite clinical similarities between off-period dystonia in Parkinson's disease and generalized dystonia in certain cases, the effect of chronic bilateral STN-HFS differs. STN stimulation is highly effective in off-period dystonia of IPD, whereas it does not improve generalized dystonia. The pathophysiologic mechanisms underlying dystonia in these two disorders are still unknown. Assuming that the mechanism of action of STN-HFS is similar regardless of the cause of dystonia, our findings suggest that the STN is not similarly involved in off-period dystonia of IPD and others dystonias.
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PMID:Off-period dystonia in Parkinson's disease but not generalized dystonia is improved by high-frequency stimulation of the subthalamic nucleus. 1450 88

The aim of the present study was to investigate the alteration of neuronal activities in the substantia nigra pars reticulata (SNpr) and globus pallidus (GP), after ipsilateral STN lesioning by kainic acid in the rat hemi-parkinsonian 6-hydroxydopamine (6-OHDA) model. In various rat Parkinson's disease (PD) models, an increase in the SNpr firing rate was observed, despite the occurrence of bursting patterns, and subthalamic lesion was found to reduce the mean firing rates and the percentage of bursting neurons in the SNpr. However, the relative proportion of bursting neurons, among all GP neurons, was slightly increased as a result of the subthalamic lesion. The significance of bursting activity in the SNpr and GP remains obscure. Further study is necessary to elucidate the pathophysiological mechanism behind Parkinson's disease.
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PMID:Effect of subthalamic lesion with kainic acid on the neuronal activities of the basal ganglia of rat parkinsonian models with 6-hydroxydopamine. 1451 46

Deep brain stimulation of the subthalamic nucleus (STN-DBS) reduces akinesia in Parkinson's disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L-dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS-items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L-dopa test than in the pure STN-DBS condition. Other akinesia items and the time for build-up of lifting force were equally improved in both conditions. This suggests that routine STN-DBS might not be equally effective on all aspects of fine motor functions.
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PMID:Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements. 1453 21

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow-up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow-up, STN-DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN-DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN-DBS beyond the first year after surgical procedure. Complications of STN-DBS comprise a wide range of psychiatric adverse events which, however, were temporary.
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PMID:Two-year follow-up of subthalamic deep brain stimulation in Parkinson's disease. 1463 76

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms induced by STN-DBS occurred in a previously psychiatrically healthy patient, focusing on the role of STN-DBS in influencing not only motor but also emotional behaviour.
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PMID:Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease. 1463 87


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