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)

In addition to motor symptoms, patients with Parkinson's disease (PD) show deficits in sensory processing. These deficits are thought to result from deficient gating of sensory information due to basal ganglia dysfunction in PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve sensory deficits in PD, e.g. STN-DBS normalizes the perception of urinary bladder filling in patients with PD. This study aimed at investigating how STN-DBS modulates the processing of urinary bladder information to elucidate the (patho-)physiology of sensory gating mechanisms in PD. Nine PD patients with bilateral STN-DBS switched on (STN-DBS ON) or off (STN-DBS OFF) were studied during dynamic bladder filling and an empty bladder condition (for control), while changes in regional cerebral blood flow (rCBF) were measured by PET. Urinary bladder filling led to an increased rCBF in the periaqueductal grey (PAG), the posterior thalamus, the insular cortex as well as in the right frontal cortex and the cerebellum bilaterally. A significant interaction between bladder condition and STN-DBS was observed in the posterior thalamus and the insular cortex, with enhanced modulation of these areas during STN-DBS ON compared to STN-DBS OFF. Furthermore, regression analyses revealed a modulation of the neural activity in the thalamus and the insular cortex by the PAG activity during STN-DBS ON only. Thus, STN-DBS led to a significant enhancement of afferent urinary bladder information processing. The data suggest that STN-DBS facilitates the discrimination of different bodily states by supporting sensory perception and the underlying neural mechanisms. Furthermore, this is the first imaging study, which shows an effect of STN-DBS on sensory gating in PD patients and its neural basis.
 ...
PMID:Improved sensory gating of urinary bladder afferents in Parkinson's disease following subthalamic stimulation. 1797 62

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.
 ...
PMID:Ambulatory monitoring of physical activities in patients with Parkinson's disease. 1807 46

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.
 ...
PMID:Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease. 1841 Sep 27

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.
 ...
PMID:[Functional models of movement disorders of basal ganglia origin and effects of functional neurosurgery]. 1821 Jul 85

Parkinson's disease (PD) patients with prior radio-frequency lesions in the internal segment of the globus pallidus (GPi, pallidotomy), whose symptoms have deteriorated, may be candidates for further invasive treatment such as subthalamic deep brain stimulation (STN DBS). Six patients with prior pallidotomy (five unilaterally; one bilaterally) underwent bilateral STN DBS. The microelectrode recordings (MERs, used intraoperatively for STN verification), ipsilateral and contralateral to pallidotomy, and MERs from 11 matched PD patients who underwent bilateral STN DBS without prior pallidotomy were compared. For each trajectory, average, variance and mean successive difference (MSD, a measure of irregularity) of the root mean square (RMS) of the STN MER were calculated. The RMS in trajectories ipsilateral to pallidotomy showed significant reduction of the mean average and MSD of STN activity when compared with trajectories from patients without prior pallidotomy. The RMS parameters contralateral to pallidotomy tend to lie between those ipsilateral to pallidotomy and those without prior pallidotomy. The average STN power spectral density of oscillatory activity was notably lower ipsilateral to pallidotomy than contralateral, or without prior pallidotomy. The finding that pallidotomy reduces STN activity and changes firing characteristics, in conjunction with the effectiveness of STN DBS despite prior pallidotomy, calls for reappraisal and modification of the current model of the basal ganglia (BG) cortical network. It highlights the critical role of direct projections from the BG to brain-stem structures and suggests a possible GPi-STN reciprocal positive-feedback mechanism.
 ...
PMID:Prior pallidotomy reduces and modifies neuronal activity in the subthalamic nucleus of Parkinson's disease patients. 1821 42

We examined the effect of bilateral subthalamic nucleus stimulation on levodopa-resistant balance impairment in 14 patients with Parkinson's disease and 18 matched controls. Instability was quantitatively assessed using standardized multidirectional dynamic posturography. Patients were tested after taking a suprathreshold dose of levodopa, both with stimulators turned on and off. Patients with stimulators turned off were more unstable than controls following backward directed perturbations. Overall, patients' instability did not improve with STN stimulation, and considerable inter-individual variability was noted. Of note, marked levodopa- resistant axial motor symptoms before surgery correlated with an adverse treatment effect. We conclude that STN stimulation does not alleviate levodopa-resistant postural instability in Parkinson's disease.
 ...
PMID:Subthalamic nucleus stimulation and levodopa-resistant postural instability in Parkinson's disease. 1827 10

A higher than expected frequency of suicide has been reported among patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) for advanced Parkinson's disease (PD). We conducted a retrospective survey of 200 patients with PD who underwent STN DBS. Two patients (1%) committed suicide and four (2%) attempted suicide, despite clear motor improvements. Suicidal patients did not differ from non-suicidal patients with respect to age, disease duration or preoperative depressive and cognitive status. Suicidal behaviour was associated with postoperative depression and/or altered impulse regulation. Suicidal behaviour is a potential hazard of STN DBS, calling for careful preoperative assessment and close postoperative psychiatric and behavioural follow-up.
 ...
PMID:Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson's disease. 1864 12

The role of endogenous dopamine in severe Parkinson's disease is often underestimated. We report on a case of acute general motor worsening induced by the ingestion of fluphenazine in a parkinsonian patient successfully treated with STN DBS. Other etiologies were ruled out. Clinical improvement was gradual and fully reversible 4 days after discontinuation of the antidopaminergic drug. We suggest that residual striatal and extrastriatal dopaminergic pathways still play a paramount role in mediating central neurotrasmissions that may take part in STN DBS's mechanism of action.
 ...
PMID:Does dopamine still have a leading role in advanced Parkinson's disease after subthalamic stimulation? 1847 63

How deep brain stimulation (DBS) acts and how the brain responds to it remains unclear. To investigate the mechanisms involved, we analyzed changes in local field potentials from the subthalamic area (STN-LFPs) recorded through the deep brain macroelectrode during monopolar DBS of the subthalamic nucleus area (STN-DBS) in a group of eight patients (16 nuclei) with idiopathic Parkinson's disease. Monopolar STN-DBS was delivered through contact 1 and differential LFP recordings were acquired between contacts 0 and 2. The stimulating contact was 0.5 mm away from each recording contact. The power spectral analysis of STN-LFPs showed that during ongoing STN-DBS whereas the power of beta oscillations (8-20 Hz) and high beta oscillations (21-40 Hz) remained unchanged, the power of low-frequency oscillations (1-7 Hz) significantly increased (baseline=0.37+/-0.22; during DBS=7.07+/-15.10, p=0.0003). Despite comparable low-frequency baseline power with and without levodopa, the increase in low-frequency oscillations during STN-DBS was over boosted by pretreatment with levodopa. The low-frequency power increase in STN-LFPs during ongoing STN-DBS could reflect changes induced at basal ganglia network level similar to those elicited by levodopa. In addition, the correlation between the heart beat and the low-frequency oscillations suggests that part of the low-frequency power increase during STN-DBS arises from polarization phenomena around the stimulating electrode. Local polarization might in turn also help to normalize STN hyperactivity in Parkinson's disease.
 ...
PMID:Subthalamic local field potential oscillations during ongoing deep brain stimulation in Parkinson's disease. 1853 60

Ten years after the therapeutic revolution that emerged from the discovery of l-dopa, some pioneer teams led the rebirth of a new nonablative stereotaxical surgical treatment, which came from the interest of high frequency stimulation. Three targets were retained as the main location of a reversible functional inhibition: Vim, GPI and STN. The unilateral or bilateral stimulation, adjustable and possibly reversible, led to an exceptional medicosurgical collaboration, within expert dedicated places, based on the control of the Parkinson's disease's (PD) triad. The stimulation was initially applied to the most advanced forms of PD, after the medical control period of the motor performance, when the pejorative effects of the evolution settled and/or when side effects of the treatment appeared. Subsequently, the research of selection criterions and the strict control of the stereotaxical procedure during the per- and postoperatory period, with the collaboration of the patient and his family, progressively brought different teams to an earlier indication of this new treatment option, up to now reserved for fully medicosurgical concerted cases. Apparition of cognitive and postural decline as well as the known resistance stage to l-dopa tend to become a real contra-indication. Despite the initial relative weakness of controlled studies with limited number of patients, the multiplication of follow-up studies among high quality multicentric cohorts enabled the validation of practices respecting the differences related to the initial background of each different team. In Europe first, the prevalence of the subthalamic target is now to be generally admitted. A new objective is now imposing itself: trying to maintain the patient's quality of life, beyond the only motor benefit. The social adaptation of a young patient is now also taken into account. If this exemplary clinical research approach, efficient for a few highly selected patients, has not transformed the long-term prognostic of the PD, it will continue to improve the comprehension of this degenerative pathology and its extension. It still remains hopeful for the future in the actual constant technological progress, and that probably beyond the only PD.
 ...
PMID:[Deep brain stimulation and Parkinson's disease]. 1855 Jan 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>