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)

Freezing of Gait (FOG) is one of the most disabling and least understood symptoms in Parkinson's disease (PD), and is usually observed in the advanced stage of the disease. FOG can be experienced on turning, in narrow spaces, whilst reaching a destination, and in stressful situations. FOG is commonly observed in the "off" state, but it can also be observed in the "on" state. Dual tasking (cognitive load) aggravates FOG. Visual or auditory cues often resolve FOG. Analysis of gait revealed that the rhythm of stepping suddenly jumps into high frequency (4-5 Hz) in FOG (hastening), and that floor reaction forces are disregulated. Stride-to-stride variability is increased in FOG. Hastening phenomenon was reported not only in PD patients but also in patients with striatal lesions. The basal ganglia and its frontal projections may be one of the essential lesion sites for FOG.A recent study using single-photon emission tomography (SPECT) revealed enhanced lateral premotor cortex (PMC) activity during paradoxical gait in PD, suggesting that PMC can compensate for the impaired function of the medial frontal cortex when cued by visual input. Treatment of FOG includes behavioural, medical, and surgical approaches. Tricks of all kinds (including external cues) are effective therapeutic approaches. If FOG occurs predominantly in the "off" state, dopaminergic therapy can be increased. For "on" freezing or if "on" response is otherwise optimised, the dose of the dopaminergic agent may be manipulated, but it could lead to the deterioration of parkinsonism. Deep brain stimulation of the STN often alleviates FOG in the "off" state.
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PMID:Freezing of gait in Parkinson's disease. 1713 Dec 25

We report the case of a 60-year-old woman with Parkinson's disease and severe motor fluctuations. During OFF periods she presented both motor and non-motor symptoms, which ameliorated rapidly after each levodopa dose. After undergoing bilateral STN DBS, motor complications improved markedly while non-motor symptoms remained unchanged. Levodopa response is regarded as a good predictive factor for the prognosis of motor symptoms in PD patients undergoing surgery. However, our case suggests that its relation with the prognosis of non-motor symptoms might be different and remains to be addressed.
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PMID:Bilateral STN-DBS fails to improve non-motor fluctuations in a PD patient. 1723 5

Deep brain stimulation of the subthalamic nucleus (DBS STN) is an effective treatment method in advanced Parkinson's disease (PD) providing marked improvement of its major motor symptoms. In addition, non-motor effects have been reported including weight gain in PD patients after DBS STN. Using retrospective survey, we aimed to evaluate weight changes in our patients with advanced PD treated with DBS STN. We inquired 25 PD patients (16 men, 9 women), of mean age 55 (42-65) years, mean PD duration 15 (9-21) years, who previously received bilateral DBS STN. We obtained valid data from 23 patients. In the first survey, 1 to 45 months after DBS, weight gain was found in all patients comparing to pre-DBS period. The mean increase was 9.4 kg (from 1 to 25 kg). The patients' mean body mass index (BMI) increased from 23.7 to 27.0 kg/m2, i.e. by 3.3 kg/m2 (+2 to +6.1 kg/m2). In the repeated survey one year later, in 12 of the patients body weight moderately decreased, 3 did not change, and 6 patients further increased their weight. Possible explanations of body weight gain after DBS STN include a reduction of energy output related to elimination of dyskinesias, improved alimentation or direct influence on function of lateral hypothalamus by DBS STN.
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PMID:Increase in body weight is a non-motor side effect of deep brain stimulation of the subthalamic nucleus in Parkinson's disease. 1727 30

We prospectively evaluated 20 patients with Parkinson's disease (PD) preoperatively and 12 months after subthalamic nucleus-deep brain stimulation (STN-DBS). All patients had clinical (UPDRS III) and neuropsychological evaluations as well as brain perfusion SPECT-ECD. Clinical and cognitive data were compared with 12 matched PD patients who had not undergone surgery. STN-DBS patients improved in motor symptoms and reduced medications but selectively declined in category fluency (p<0.01). No clinical and cognitive changes were found in the control group at follow-up. Worsening fluency was associated with perfusion decrements in left dorsolateral prefrontal cortex, anterior cingulate cortex and ventral caudate nucleus (p<.001).
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PMID:Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: an ECD-SPECT study. 1729 55

This study examined the cellular changes produced in the striatum by chronic L-DOPA treatment and prolonged subthalamic nucleus high-frequency stimulation (STN-HFS) applied separately, successively, or in association, in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease (PD). Only animals showing severe L-DOPA-induced dyskinesias (LIDs) were included, and STN-HFS was applied for 5 d at an intensity efficient for alleviating akinesia without inducing dyskinesias. L-DOPA treatment alone induced FosB/deltaFosB immunoreactivity, exacerbated the postlesional increase in preproenkephalin, reversed the decrease in preprotachykinin, and markedly increased mRNA levels of preprodynorphin and of the glial glutamate transporter GLT1, which were respectively decreased and unaffected by the dopamine lesion. STN-HFS did not affect per se the postlesion changes in any of these markers. However, when applied in association with L-DOPA treatment, it potentiated the positive modulation exerted by L-DOPA on all of the markers examined and tended to exacerbate LIDs. After 5 d of L-DOPA withdrawal, the only persisting drug-induced responses were an elevation in preprodynorphin mRNA levels and in the number of FosB/deltaFosB-immunoreactive neurons. Selective additional increases in these two markers were measured when STN-HFS was applied subsequently to L-DOPA treatment. These data provide the first evidence that STN-HFS exacerbates the responsiveness of striatal cells to L-DOPA medication and suggest that STN-HFS acts specifically through an L-DOPA-modulated signal transduction pathway associated with LIDs in the striatum. They point to striatal cells as a primary site for the complex interactions between these two therapeutic approaches in PD and argue against a direct anti-dyskinetic action of STN-HFS.
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PMID:High-frequency stimulation of the subthalamic nucleus potentiates L-DOPA-induced neurochemical changes in the striatum in a rat model of Parkinson's disease. 1732 35

It is now well established that subthalamic nucleus high-frequency stimulation (STN HFS) alleviates motor problems in Parkinson's disease. However, its efficacy for cognitive function remains a matter of debate. The aim of this study was to assess the effects of STN HFS in rats performing a visual attentional task. Bilateral STN HFS was applied in intact and in bilaterally dopamine (DA)-depleted rats. In all animals, STN HFS had a transient debilitating effect on all the variables measured in the task. In DA-depleted rats, STN HFS did not alleviate the deficits induced by the DA lesion such as omissions and latency to make correct responses, but induced perseverative approaches to the food magazine, an indicator of enhanced motivation. In sham-operated controls, STN HFS significantly reduced accuracy and induced perseverative behaviour, mimicking partially the effects of bilateral STN lesions in the same task. These results are in line with the hypothesis that STN HFS only partially mimics inactivation of STN produced by lesioning and confirm the motivational exacerbation induced by STN inactivation.
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PMID:Bilateral high-frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats. 1733 Dec 14

Acute and chronic behavioral effects of subthalamic stimulation (STN-DBS) for Parkinson's disease (PD) are reported in the literature. As the technique is relatively new, few systematic studies on the behavioral effects in long-term treated patients are available. To further study the putative effects of STN-DBS on mood and emotional processing, 15 consecutive PD patients under STN-DBS for at least 1 year, were tested ON and OFF stimulation while on or off medication, with instruments sensitive to short-term changes in mood and in emotional discrimination. After acute changes in experimental conditions, mood core dimensions (depression, elation, anxiety) and emotion discrimination processing remained remarkably stable, in the face of significant motor changes. Acute stimulator challenge in long-term STN-DBS-treated PD patients does not appear to provoke clinically relevant mood effects.
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PMID:Mood stability during acute stimulator challenge in Parkinson's disease patients under long-term treatment with subthalamic deep brain stimulation. 1739 45

An effect of subthalamic nucleus deep brain stimulation (STN-DBS) on cognition has been suspected but long-term observations are lacking. The aim of this study was to evaluate the long-term cognitive profile and the incidence of dementia in a cohort of Parkinson's disease (PD) patients treated by STN-DBS. 57 consecutive patients were prospectively assessed by the mean of a neuropsychological battery over 3 years after surgery. Dementia (DSM-IV) and UPDRS I to IV were recorded. 24.5% of patients converted to dementia over 3 years (incidence of 89 of 1,000 per year). This group of patients cognitively continuously worsened over 3 years up to fulfilling dementia criteria (PDD). The rest of the cohort remained cognitively stable (PD) over the whole follow-up. Preoperative differences between PDD and PD included older age (69.2 +/- 5.8 years; 62.6 +/- 8 years), presence of hallucinations and poorer executive score (10.1 +/- 5.9; 5.5 +/- 4.4). The incidence of dementia over 3 years after STN-DBS is similar to the one reported in medically treated patients. The PDD presented preoperative risk factors of developing dementia similar to those described in medically treated patients. These observations suggest dementia being secondary to the natural evolution of PD rather than a direct effect of STN-DBS.
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PMID:Long-term cognitive profile and incidence of dementia after STN-DBS in Parkinson's disease. 1744 91

Subthalamic nucleus deep brain stimulation (STN-DBS) is effective in advanced Parkinson's disease (PD), but its effects on the levodopa response are unclear. We studied the levodopa response after long-term STN-DBS, STN-DBS efficacy and predictive value of preoperative levodopa response to long-term DBS benefit in 33 PD patients with bilateral STN-DBS. Patients were assessed using the Unified Parkinson's Disease Rating Scale preoperatively (with and without medications) and postoperatively (without medications or stimulation, with only medications or stimulation, and with both medications and stimulation). Levodopa response significantly decreased postoperatively by 31.1% at 3 years and 32.3% at 5 years, possibly related to the reduction in medication requirement, direct STN stimulation effect or PD progression. STN-DBS alone significantly improved motor scores (37.2% at 3 years and 35.1% at 5 years) and activities of daily living scores (27.1% at 3 years and 19.2% at 5 years). Anti-PD drugs were significantly reduced by 47.9% at 3 years and 39.8% at 5 years. However, the magnitude of the preoperative response to levodopa did not predict DBS benefit at 3 and 5 years.
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PMID:Levodopa response in long-term bilateral subthalamic stimulation for Parkinson's disease. 1816 52

The rate model regarding the development of movement disorders of basal ganglia origin suggests that hyperkinetic and hypokinetic disorders occur as a result of changes in the firing rates in the GPi and SNr, which in turn suppress thalamocortical output. Dopamine depletion in Parkinson's disease increases basal ganglia output, then decreases thalamocortical output, leading to bradykinesia. This model, however, cannot explain a lack of deterioration of parkinsonian signs following thalamic coagulation surgery. Instead of the rate model, the beta oscillation hypothesis has been proposed, explaining that synchronized oscillation in the beta frequency in the basal ganglia disturbs initiation of voluntary movement. We observed that effective high-frequency STN stimulation in parkinsonian monkeys was associated with increase in the firing rate and the pattern shift from irregular burst firing to regular high-frequency firing in the projecting sites. High-frequency neural activation by deep brain stimulation is supposed to cancel lower frequency oscillation including beta oscillation, leading to improvement of bradykinesia. Our observation supports the significance of the neural activity pattern, rather than the tonic activity level, in the development of movement disorders. The rate model cannot explain the improvement of ballismus and chorea by pallidotomy because pallidotomy increases the disinhibition of the thalamocortical projection, which should increase the movements. We observed repetitive bursts or pauses of neuronal firing of the globus pallidus synchronized to ballistic movements in patients with hemiballism or chorea, suggesting that phasic neuronal driving in the basal ganglia is important as their pathophysiology.
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PMID:[Functional models of movement disorders of basal ganglia origin and effects of functional neurosurgery]. 1749 32


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