Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic stimulation of the ventral intermediate nucleus (Vim) of the thalamus is highly effective for the treatment of tremor. Patients with tremor associated with Parkinson's disease and essential tremor appear to respond best. Patients with cerebellar tremors may also respond but to a lesser extent. Although tremor is improved, Vim DBS does not substantially improve the daily living activities of patients with Parkinson's disease. This is related to the lack of effect on rigidity, bradykinesia, and gait and postural disturbances associated with Parkinson's. For this reason, the majority of patients with Parkinson's disease who require surgery are better treated with interventions in the globus pallidus or subthalamic nucleus, targets that allow improvement in all cardinal features of Parkinson's disease. In contrast, Vim DBS has unequivocal functional benefit in patients with essential tremor, this is likely to remain the major indication of this form of therapy. The mechanism of action of thalamic DBS is not understood and remains a research priority.
 ...
PMID:Vim thalamic stimulation for tremor. 1103 77

During the last decade, it has become increasingly clear that DBS represents a useful adjunct for therapies to control various symptoms of Parkinson's disease. The stimulation sites include the thalamic nucleus ventralis intermedius(Vim), globus pallidus internus(GPi) and subthalamic nucleus (STN). The clinical data of DBS therapy currently available from the literature, together with our own experience, are reviewed. The results of our double blinded evaluation of the effects of GPi and STN stimulation are also summarized. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvement of bradykinesia may often be induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. Two advantages of GPi and STN stimulation were identified in our double blinded evaluation. Firstly, the stimulation can supplement a reduced action of levodopa during the off-period. It thus improves the patient's daily activities through attenuation of the motor fluctuations. Secondly, the stimulation can replace part of the action of levodopa during the on-period. It thus attenuates dopa-induced dyskinesia through a reduced dose of medication. More importantly, the stimulation improves the daily activities in dopa-intolerant patients who are being administered a small dose of levodopa because of unbearable side effects. In addition, GPi stimulation has its own inhibitory effect on dopa-induced dyskinesia.
 ...
PMID:[Deep brain stimulation(DBS) therapy for parkkinson,s disease]. 1106 50

Dopamine depletion induces a series of changes in the basal ganglia motor circuit that underlie the origin of the cardinal features of Parkinson's disease. It has now been established that hyperactivity of the subthalamic nucleus (STN) is an essential feature of the parkinsonian state. This leads to increased excitatory driving onto the globus pallidum internum (GPi) and substantia nigra reticulata (SNr) which, in turn, overinhibits the motor projections to the thalamus and brainstem. The STN and GPi have become the preferred targets for surgery to treat PD. In keeping with the classic pathophysiologic model, physiologic and neuroimaging studies in patients have shown that lesioning or functional blockades (by deep brain stimulation, or DBS) of these nuclei increased cortical activation, in parallel with clinical improvements of bradykinesia. Neuronal recording during surgery has also shown tremor-related activity in both the STN and GPi. However, the pathophysiologic model of the basal ganglia needs further refinement to provide a more detailed explanation of the origin of both tremor and rigidity in Parkinson's disease and to explain the antidyskinetic effect of surgery of the GPi and STN.
 ...
PMID:Pathophysiologic basis of surgery for Parkinson's disease. 1118 78

The present study, the largest in the literature, was performed to assess the effectiveness and safety of unilateral subthalamic nucleus (STN) lesioning for Parkinson's disease (PD). From August 1999 to September 2000, 21 consecutive patients evaluated pre- and postoperatively by a single examiner were operated. Levodopa intake and dyskinesia, Hoehn & Yahr, Schwab & England and UPDRS motor scores were recorded. Stereotactic CT and MRI and the effects of macrostimulation were used to determine STN coordinates. A single radiofrequency lesion was made (60-75 degrees C/60"). Concomitant ipsilateral Vim/VOp lesions were made in 8 patients. Using a new technique, we were able to determine the territory of STN involved by the surgical lesion. The Wilcoxon and Mann-Whitney statistical tests were applied to evaluate the surgical results. All recorded parameters showed stable improvement after a mean follow up of 13.5 months. Recurrence occurred in two patients. Contralateral tremor arrest and decrease of rigidity and bradykinesia should be regarded as STN hallmarks to stimulation. Hyperintense lesions in the early-phase MRI seem to be a poor prognostic factor. Lateral territory lesioning correlates with better results. There was no significant difference between the cohorts with and without a Vim/VOp lesion. Dyskinesias happened in two patients (promptly abolished by a Vim/VOp lesion). Other complications were transient and/or rare. In conclusion, STN lesioning is a safe and very effective procedure to treat PD and probably an underutilized operation for those who can not afford the costs of DBS.
 ...
PMID:Unilateral subthalamic nucleus lesioning: a safe and effective treatment for Parkinson's disease. 1256 84

A 59-year-old woman with levodopa-responsive parkinsonism complicated by motor fluctuations and generalized levodopa dyskinesia underwent bilateral subthalamic deep brain stimulation (STN DBS) 7 years after symptom onset. DBS improved levodopa-responsive upper extremity bradykinesia but aggravated speech, swallowing, and gait. Motor fluctuations were not improved and levodopa dose remained unchanged. Pulse generators were turned off. Clinical features and brain MRI in this case were indicative of multiple system atrophy (MSA). STN DBS is not recommended for patients with MSA.
 ...
PMID:Adverse effects of subthalamic nucleus DBS in a patient with multiple system atrophy. 1287 10

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.
 ...
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

To determine whether the degree to which a patient with Parkinson's disease expects therapeutic benefit from subthalamic nucleus-deep brain stimulation (STN-DBS) influences the magnitude of his or her improved motor response, 10 patients with idiopathic Parkinson's and bilateral STN-DBS were tested after a 12-hour period off medication and stimulation. Four consecutive UPDRS III scores were performed in the following conditions: (a) stimulation OFF, patient aware; (b) stimulation OFF, patient blind; (c) stimulation ON, patient aware; and (d) stimulation ON, patient blind. Statistical significance (P = 0.0001) was observed when comparing main effect ON versus OFF (mean ON: 32.55; mean OFF: 49.15). When the stimulation was OFF, patients aware of this condition had higher UPDRS motor scores than when they were blinded (mean: 50.7 vs. 47.6). With the stimulation ON, UPDRS motor scores were lower when the patients were aware of the stimulation compared with when they were blinded (mean: 30.6 vs. 34.5). The interaction between these levels was significant (P = 0.049). This variation was important for bradykinesia and was not significant for tremor and rigidity. The authors conclude that the information about the condition of the stimulation enhanced the final clinical effect in opposite directions. The results presented support the role of expectation and placebo effects in STN-DBS in Parkinson's disease patients.
 ...
PMID:Expectation and the placebo effect in Parkinson's disease patients with subthalamic nucleus deep brain stimulation. 1672 50

Currently, no study of subthalamic nucleus (STN) stimulation has compared continuous stimulation with a period of short-term stimulation, which is frequently employed in the clinic and in research studies. Therefore, this study examined the effects of STN stimulation over 90 min (short) and greater than 3 months (long) on the cardinal signs of Parkinson's disease. The 90 min time period immediately followed a 12 hour withdrawal from both STN stimulation and medication. Ten PD patients who received STN stimulation were studied. Bradykinesia, rigidity, and tremor were evaluated using the UPDRS and motor control measures which included peak velocity (bradykinesia), work (rigidity), and amplitude (tremor). Results showed no difference between 90 min and greater than 3 months of STN stimulation for the UPDRS or motor control measures. This finding confirms that the treatment efficacy that is derived from a relatively short time course of stimulation generalizes to longer time periods of high frequency STN stimulation that patients experience in their daily lives. As such, it is reasonable to evaluate the effect of DBS after 90 min of stimulation in clinical trials and research studies.
 ...
PMID:Effect of short and long term STN stimulation periods on parkinsonian signs. 1831 27

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.
 ...
PMID:Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease. 1869 9

BACKGROUND AND PURPOSE The antiakinetic effect of internal Globus pallidus deep brain stimulation (Gpi-DBS) in Parkinson's disease is not clear and not either how this effect is modulated by L-dopa. METHODS Left Gpi-DBS and/or L-dopa effect was studied with auditory paced right-handed sequential movements on (15)O-butanol positron emission tomography (PET) in five patients. Rest and for conditions during movements (DBS off/L-dopa off; DBS on/L-dopa off; DBS off/L-dopa on; DBS on/L-dopa on) were compared with statistical parametric mapping. RESULTS Gpi-DBS activated the right supplementary motor area/premotor (SMA/PMC), and right insular cortex (IC), and as L-dopa decreased the left sensorimotor cortex (M1/S1) activity. L-dopa increased the left ventrolateral thalamus (VLTH), and decreased the left superior parietal cortex (PC) activity. Gpi-DBS and L-dopa interaction showed right SMA/PMC, IC, and left PC activation, decrease of left VLTH, PMC, and dorsolateral prefrontal cortex (PFC) activity. CONCLUSIONS The improvement of bradykinesia with Gpi-DBS is secondary and contributed to the regress of M1/S1-related rigidity and compensatory SMA/PMC, and IC activation. L-dopa and Gpi-DBS alone each reduces M1/S1 overactivity. Interaction ignores this effect, moreover has akinetic effect in the left VLTH, PMC, and PFC. Motor improvement possibly related to left PC and compensatory right SMA/PMC, and IC activation.
 ...
PMID:Pallidal deep brain stimulation and L-dopa effect on PET motor activation in advanced Parkinson's disease. 1902 48


1 2 3 Next >>