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)

High frequency electrical stimulation by means of electrodes implanted into the brain (deep brain stimulation; DBS) recently has become an accepted technique for the treatment of several movement disorders and in particular for Parkinson's disease. Because the effects produced by DBS are similar to those produced by making a lesion in the same region, it has been proposed that the overall effect of DBS is to inhibit the neural activity in the region stimulated. However, whether this is actually the case is presently not known, but various mechanisms have been proposed in an attempt to explain how DBS could mimic the effects of a lesion. We describe the various mechanisms that have been proposed to account for the inhibition or disruption of the pathologic outflow by high-frequency DBS, ranging from depolarisation block to stimulation-evoked release of gamma-aminobutyric acid and describes preliminary findings that show that stimulation within these structures can result in inhibition.
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PMID:Mechanisms of deep brain stimulation. 1194 58

Currently, DBS is a commonly performed surgery for treatment of movement disorders, especially Parkinson's disease. Although nonablative and minimally invasive, this procedure may give rise to many complications and side effects, some of which are neither reversible nor adaptable. This study reviews the potential complications of DBS along the entire path of this procedure, from patient selection through the postoperative period. Although intraoperative complications such as paralysis and hematoma are rare, other serious complications due to the hardware, such as lead fracture, dislocation, and infection, are not uncommon. Complications or side effects as a result of chronic stimulation itself may be the most common. It is concluded that every member of the surgical team, including the referring neurologist, has an important role in the avoidance of such complications. Proper and careful patient selection, matching each patient to the specific DBS procedure appropriate for his/her symptom profile and suitable for his/her social and cognitive condition, along with experienced and careful intraoperative surgical routine, may be the best way to prevent the complications of DBS procedures.
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PMID:Complications of deep brain stimulation surgery. 1194 72

Parkinson's disease (PD) is caused by the degeneration of the dopaminergic neurons in the substantia nigra. Loss of dopaminergic innervation leads to hyperactivity in the internal segment of the globus pallidus (GPi), the main output nucleus of the basal ganglia and to a profound disturbance in the function of motor circuits. Lesions of the GPi (or in its upstream modulator, the subthalamic nucleus) can greatly improve the motor symptoms of PD presumably by reducing this pathological activity. Paradoxically, high-frequency electrical stimulation of the GPi (deep brain stimulation, DBS) mimics the effects of pallidotomy and has become an accepted therapeutic technique. The mechanisms underlying the beneficial effects of pallidal DBS are not known. Various mechanisms that might account for inhibiting or disrupting the pathological pallidal outflow by high-frequency DBS have been proposed ranging from depolarization block to stimulation-evoked release of GABA, and these are discussed.
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PMID:The globus pallidus, deep brain stimulation, and Parkinson's disease. 1206 8

Deep Brain Stimulation (DBS, chronic high frequency stimulation) is well established for Parkinson's disease and tremordominant movement disorders. Generalized dystonia is known as a type of movement disorder in which therapeutic options are very limited. A case of generalized dystonia is reported which was successfully treated by DBS in the Globus pallidus internus (GPI). A 26 years old male suffered from severe torsion dystonia of the lower limbs. The onset of symptoms was at age 7. It started with dystonia of the left foot. He very fast developed severe dystonia of the lower limbs. These complaints were initially treated by diazepam, later by baclofen (Lioresal ((R))) p.o em leader There was no L-DOPA response. Because of the rapid progression of the disease a cervical spinal cord stimulator was implanted with a transient success. Due to further progression of the disease the patient became wheelchair bounded and resistant for oral medication. Limited improvement of symptoms was achieved using continuous intrathecal administration of baclofen. Finally the patient was treated with 980 microgram intrathecal Baclofen (Lioresal ((R))) daily and up to 100 mg diazepam. Under these conditions the patient remained wheelchair bounded with severe lower limb dystonia. As an ultima ratio it was decided to treat the patient with stereotactic implantation of two electrodes (Medtronic 3387) and two neurostimulators (Medtronic ITREL ((R))II). The GPI was the bilateral target point. Intraoperative computerized tomography and ventriculography were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode positioning. Surgery was performed under sedation. Two weeks after surgery first improvement of symptoms was observed. Patient was able to stand with assistance. At the three months follow-up he could walk without assistance. Slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The oral medication has been continuously reduced. After 6 months it was stopped. The intrathecal administered baclofen was diminished to 250 microgram daily. At the 24 months follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (3,5 V, 400 microseconds 145 Hz for both sides). Deep Brain Stimulation of the Globus Pallidus internus is an alternative approach for severe cases of generalized dystonia.
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PMID:[Chronic high frequency deep brain stimulation of the globus pallidus internus for torsion dystonia]. 1209 79

Although technological advances have reduced device-related complications, DBS surgery still carries a significant risk of transient and permanent complications. We report our experience in 86 patients and 149 DBS implants. Patients with Parkinson's disease, essential tremor and dystonia were treated. There were 8 perioperative, 8 postoperative, 9 hardware-related complications and 4 stimulation-induced side effects. Only 5 patients (6%) sustained some persistent neurological sequelae, however, 26 of the 86 patients undergoing 149 DBS implants in this series experienced some untoward event with the procedure. Although there were no fatalities or permanent severe disabilities encountered, it is important to extend the informed consent to include all potential complications.
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PMID:Complications of deep brain stimulation surgery. 1237 60

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

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.
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PMID:Unilateral subthalamic nucleus lesioning: a safe and effective treatment for Parkinson's disease. 1256 84

The mechanism by which chronic, high frequency, electrical deep brain stimulation (HF-DBS) suppresses tremor in Parkinson's disease is unknown. Rest tremor in subjects with Parkinson's disease receiving HF-DBS was recorded continuously throughout switching the deep brain stimulator on (at an effective frequency) and off. These data suggest that the stimulation induces a qualitative change in the dynamics, called a Hopf bifurcation, so that the stable oscillations are destabilized. We hypothesize that the periodic stimulation modifies a parameter affecting the oscillation in a time dependent way and thereby induces a Hopf bifurcation. We explore this hypothesis using a schematic network model of an oscillator interacting with periodic stimulation. The mechanism of time-dependent change of a control parameter in the model captures two aspects of the dynamics observed in the data: (1) a gradual increase in tremor amplitude when the stimulation is switched off and a gradual decrease in tremor amplitude when the stimulation is switched on and (2) a time delay in the onset and offset of the oscillations. This mechanism is consistent with these rest tremor transition data and with the idea that HF-DBS acts via the gradual change of a network property. (c) 2001 American Institute of Physics.
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PMID:Dynamics of Parkinsonian tremor during deep brain stimulation. 1277 15

In a previous H(2) (15)O/PET study of motor sequence learning, we used principal components analysis (PCA) of region of interest (ROI) data to identify performance-related activation patterns in normal subjects and patients with Parkinson's disease (PD). In the present study, we determined whether these patterns predicted learning performance in subsequent normal and untreated PD cohorts. Using a voxel-based PCA approach, we correlated the changes in network activity that occurred during antiparkinsonian treatment and their relationship to learning performance. We found that the previously identified ROI-based patterns correlated with learning performance in the prospective normal (P < 0.01) and untreated PD (P < 0.05) cohorts. Voxel analysis revealed that target retrieval was related to a network characterized by bilateral activation of the dorsolateral prefrontal, premotor and anterior cingulate cortex, the precuneus, and the occipital association areas as well as the right ventral prefrontal and inferior parietal regions. Target acquisition was associated with a different network involving activation of the caudate, putamen, and right dentate nucleus, as well as the left ventral prefrontal and inferior parietal areas. Antiparkinsonian therapy gave rise to changes in retrieval performance that correlated with network modulation (P < 0.01). Increases in network activation and learning performance occurred with internal pallidal deep brain stimulation (GPi DBS); decrements in these measures were present with levodopa. Our findings suggest that network analysis of activation data can provide stable descriptors of learning performance. Network quantification can provide an objective means of assessing the effects of therapy on cognitive functioning in neurodegenerative disorders.
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PMID:Learning networks in health and Parkinson's disease: reproducibility and treatment effects. 1281 35

The most effective treatment for late-stage Parkinson's disease is to electrically stimulate the subthalamic nucleus (STN) at high frequencies. Why this strategy works is unclear. The work by Do and Bean shows that the Na channels in STN neurons have distinctive features--like resurgence--that regulate their spiking behavior, providing new insights into the mechanism of DBS.
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PMID:"The little engine that could": voltage-dependent Na(+) channels and the subthalamic nucleus. 1284 36


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