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 sought to define the influence of ageing in clinical, cognitive, and quality-of-life outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We performed motor assessment (UPDRS), mood tests, cognitive, and quality of life evaluation (PDQ-39) on PD patients before surgery, and 12 and 24 months after, and we recorded adverse events. The variations of these parameters after surgery were correlated with age using regression statistical tests. Cerebral bleeding risk was evaluated by a nonparametric test. We enrolled 45 patients (mean age 60 +/- 9 years, range 40-73). No significant correlation was found between age and motor scores and PDQ-39 improvements at 12 months. At 24 months, there was a significant negative correlation between age and the improvement of three dimensions of PDQ 39 (mobility, activities of daily life, and cognition). Cognitive impairment showed no correlation, but apathy and depression were positively correlated with age. Significant statistical difference was observed between cerebral bleeding and age. STN-DBS is an effective treatment for elderly patients with advanced PD. A longer follow-up duration and a larger population seem necessary to better assess the quality of life perception in elderly patients and to determinate the real risk of hemorrage.
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PMID:Does ageing influence deep brain stimulation outcomes in Parkinson's disease? 1751 57

Chronic bilateral subthalamic stimulation leads to a spectacular clinical improvement in patients with motor complications. However, the post-operative body weight gain involved may limit the benefits of surgery and induce critical metabolic disorders. Twenty-four Parkinsonians (61.1 +/- 1.4 years) were examined 1 month before (M - 1) and 3 months after (M + 3) surgery. Body composition and energy expenditure (EE) were measured (1) over 36 h in calorimetric chambers (CC) with rigorous control of food intakes and activities [sleep metabolic rate, resting activities, meals, 3 or 4 sessions of 20 min on a training bicycle at 13 km/h and daily EE] and (2) in resting conditions (basal metabolic rate) during an acute L-dopa challenge (M - 1) or according to acute 'off' and 'on' stimulation (M + 3). Before surgery, EE was compared between the Parkinsonian patients and healthy subjects matched for height and body composition (metabolic rate during sleep, daily EE) or matched to predicted values (basal metabolic rate). Before surgery, in Parkinsonian men but not women, (1) daily EE was higher while sleep metabolic rate was lower compared to healthy matched men (+9.2 +/- 3.9 and -8.2 +/- 2.3%, respectively, P < 0.05) and (2) basal metabolic rate (L-dopa 'on') was higher than predicted basal metabolic rate (+11.5 +/- 4.0%, P < 0.05) but was further increased without L-dopa (+8.4 +/- 3.2% vs L-dopa 'on', P < 0.05). EE during daily activities was higher during 'off' periods compared to 'on' periods for both men (+19.3 +/- 3.3%, P < 0.0001) and women (+16.1 +/- 4.7%, P < 0.01). After surgery, there was a 3.4 +/- 0.6 kg (P < 0.0001) body weight increase together with fat mass (P < 0.0001) and fat-free mass (P < 0.05) in Parkinsonian men and a 2.6 +/- 0.8 kg (P < 0.05) body weight increase together with fat mass (P < 0.05) in Parkinsonian women. Sleep metabolic rate increased in men (+7.5 +/- 2.0%, P < 0.01) to reach control values but remained unchanged in women. Daily EE decreased significantly in both men and women (-7.3 +/- 2.2% and -13.1 +/- 1.7%, respectively, P < 0.01) but there was no correlation between daily EE changes and body weight gain. Parkinson's disease is associated with profound alterations in the central control of energy metabolism. Normalization of energy metabolism after DBS-STN implantation may favour body weight gain, of which quality was gender specific. As men gained primarily fat-free mass, a reasonable weight gain may be tolerated, in contrast with women who gained only fat. Other factors such as changes in free-living physical activity may help to limit body weight gain in some patients.
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PMID:Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation. 1753 33

In patients with Parkinson's disease (PD), tetrapolar electrodes were implanted in the prelemniscal radiations (RAPRL) to treat tremor, rigidity and bradykinesia. Fifteen patients were implanted unilaterally and five patients bilaterally and followed-up for one year. The selection criteria included the presence of unilateral pronounced tremor and rigidity in patients implanted unilaterally or bilateral symptoms including severe bradykinesia in patients implanted bilaterally. In the operating room, the tremor decreased significantly or was abolished following the insertion of the electrode in the RAPRL. This effect was temporary and subsided when the stimulation was off. However, when the stimulator was turned on, the severity of the symptoms and signs decreased significantly. The post-implantation MRI confirmed that the electrode contacts used for stimulation were inserted in RAPRL, a group of fibers located between the red nucleus and subthalamic nucleus, above the substantia nigra, medially to the zona incerta and below the thalamus. The patients were evaluated using the UPDRS part III, before implantation and every 3 months during the first year. Global scores decreased significantly. The pre- and postoperative median values (range in round brackets) were as follows: tremor improved from 3 (2-16) to 1 (2-3) (p<0.001); rigidity was either abolished or decreased markedly from 2 (1-16) to 0 (0-4) (p< 0.001); bradykinesia improved from 2 (0-4) to 1 (0-2) (p<0.001). We conclude that RAPRL, an area anatomically different from STN, is a good target for electrical stimulation in order to treat effectively all the main symptoms of PD.
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PMID:Neuromodulation of prelemniscal radiations in the treatment of Parkinson's disease. 1769 3

Patients receiving oral levodopa, the standard treatment for Parkinson's disease (PD), eventually develop motor fluctuations and dyskinesias. Treatment options for patients with these symptoms include high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) or continuous dopaminergic stimulation (CDS). STN-DBS is the prevalent surgical therapy for PD and has shown efficacy, but behavioural disorders, including cognitive problems, depression and suicidality have been reported. CDS can be achieved with oral dopamine agonists with a long half-life, transdermal or subcutaneous delivery of dopamine agonists, or intestinal levodopa infusion. Of these, duodenal levodopa infusion appears to be the most promising option in terms of both efficacy and safety.
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PMID:Deep brain stimulation and continuous dopaminergic stimulation in advanced Parkinson's disease. 1770 31

Patients with advanced Parkinson's disease (PD) experience worsening motor fluctuations and dyskinesia. Management options include deep brain stimulation of the subthalamic nucleus (STN-DBS), subcutaneous apomorphine (in combination with oral levodopa) or continuous duodenal levodopa administration. We have used all three therapies at our clinic in Milan and report our experience. Apomorphine infusion reduced daily off time but did not improve dyskinesia; long-term treatment was associated with impulse control disorders. STN-DBS provided motor benefit, but was associated with behavioural changes including attempted suicide. Duodenal levodopa produced significant clinical benefit without behavioural changes and allowed patients to discontinue all other PD medications. Duodenal levodopa should be considered in PD patients with advanced disease.
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PMID:Continuous dopaminergic stimulation--from theory to clinical practice. 1770 32

Inconsistent response in freezing of gait (FOG) with levodopa treatment or STN DBS makes the pathogenesis difficult to understand. We studied brain areas associated with the expression of STN DBS effect on parkinsonian motor deficits and FOG. Ten Parkinson's disease patients with typical FOG were included. One month before STN DBS, we performed [(18)F]-deoxyglucose PET scans and measured the UPDRS motor and modified FOG (mFOG) scores during levodopa off and on periods. At two months after STN DBS, same rating scores were measured. The percentage improvement of mFOG and UPDRS motor scores by STN DBS during levodopa off period was calculated. We searched for brain areas in which glucose metabolism correlated with the improvement of mFOG and UPDRS motor scores by DBS. During levodopa off period, STN DBS improved the UPDRS motor scores by 32.3% and the mFOG scores by 56.6%. There was no correlation between the improvements of both scores. The improvement of UPDRS motor score by DBS correlated with the metabolic activities of rostral supplementary motor area (Brodmann's area 8; BA8), anterior cingulate cortex (BA32), and prefrontal cortex (BA9). On the other hand, there was a positive correlation between the improvement of mFOG score by DBS and the metabolic activity of the parietal, occipital, and temporal sensory association cortices. In conclusion, dysfunction of different cerebral cortical areas limits the beneficial effects of DBS on parkinsonian motor deficits and FOG.
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PMID:Different cerebral cortical areas influence the effect of subthalamic nucleus stimulation on parkinsonian motor deficits and freezing of gait. 1771 44

This is an open, prospective, longitudinal study designed to compare two cohorts of patients with advanced Parkinson's disease during 1 year, one undergoing bilateral subthalamic stimulation (STN-DBS) and the other receiving the best medical treatment (BMT), with respect to the clinical effects observed and the medical expenses produced. Assessments were done by using clinical measures and a generic health related quality of life scale. A questionnaire was used to collect direct healthcare resources. As a measure of cost-effectiveness, we calculated life years gained adjusted by health-related quality of life (QALY) and the incremental cost-effectiveness ratio (ICER). Clinical and demographic variables of both groups were comparable at baseline. Total UPDRS scores improved from 50.5 +/- 3.6 to 28.5 +/- 3.8 in STN-DBS patients and worsened from 44.3 +/- 3.3 to 54.2 +/- 4 in the control group. Pharmacological costs in the operated patients were 3,799 +/- 940 euro, while in the BMT group the costs were 13,208 +/- 4,966 euro. Other medical costs were 1,280 +/- 720 euro in the STN-DBS group and 4,017 +/- 2,962 euro in BMT patients. Nondirect medical costs were 4,079 +/- 1,289 in operated patients and 2,787 +/- 1,209 euro in the BMT group. Mean QALYs were 0.7611 +/- 0.03 in STN-DBS and 0.5401 +/- 0.06 in BMT patients. In STN-DBS patients, the ICER needed to obtain an improvement of one point in the total UPDRS score was of 239.8 euro and the ICER/QALY was of 34,389 euro. Cost-effectiveness parameters were mostly related to the degree of clinical improvement and the reduction of pharmacological costs after STN-DBS. An ICER of 34,389 euro/QALY is within appropriate limits to consider subthalamic stimulation as an efficient therapy.
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PMID:Prospective comparative study on cost-effectiveness of subthalamic stimulation and best medical treatment in advanced Parkinson's disease. 1772 47

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is a powerful approach for treating the motor symptoms of Parkinson's disease (PD). It results in clinical improvement in patients with PD, further reducing the l-3,4-dihydroxyphenylalanine (L-DOPA) requirement and thus L-DOPA-induced dyskinesia. However, it remains unclear how STN-HFS modifies the response to L-DOPA. We investigated the effect of STN-HFS on striatal extracellular concentrations of dopamine and its metabolites following acute L-DOPA administration in intact or partially dopaminergic denervated (DA-PL) rats. L-DOPA treatment significantly increased striatal dopamine levels in intact and DA-PL animals, with the maximal effect observed 1 h after L-DOPA injection. This increase was more pronounced in DA-PL rats (ipsilateral to the lesion) than in intact animals. It remained fairly stable 1 h after the maximal effect of L-DOPA and then decreased towards basal values. STN-HFS in intact rats had no effect on the maximal L-DOPA-induced increase in striatal extracellular dopamine concentration or the return to basal values, the profiles observed being similar to those for non-stimulated intact animals. Conversely, STN-HFS amplified the L-DOPA-induced increase in striatal dopamine levels during the stimulation period (1 h) in DA-PL rats and this increase was sustained throughout the post-stimulation period (2.5 h), without the return to basal levels observed in stimulated intact and non-stimulated rats. These new neurochemical data suggest that STN-HFS interferes with L-DOPA effects, probably synergically, by stabilizing dopamine levels in the striatum and shed light on the mechanisms of STN-HFS in PD.
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PMID:High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats. 1782 36

A case is described of a patient with levodopa responsive parkinsonism, dyskinesia, and off periods who underwent bilateral deep brain stimulation of the subthalamic nuclei (DBS-STN) with good result. As the disease progressed, the patient fit diagnostic criteria for progressive supranuclear palsy parkinsonism (PSP-P). Benefit of DBS for the parkinsonian phenomena is still apparent 4 years later. That DBS-STN provided targeted symptom relief in this unusual patient suggests that the parkinsonism of PSP-P and that of Parkinson's disease (PD) may share a common pathophysiologic mechanism. The presence of dystonic features in this illness raises the possibility that the globus pallidus might also have been an effective target.
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PMID:Subthalamic stimulation improves levodopa responsive symptoms in a case of progressive supranuclear palsy. 1782 99

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.
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PMID:Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. 1792 54


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