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)

Subthalamic (STN) deep brain stimulation (DBS) is an effective treatment for advanced Parkinson's disease. We present a patient with significant gait problems due to Parkinson's disease (PD) who underwent STN DBS. Gait worsened after surgery despite significant improvement in parkinsonian signs, due to underlying spasticity previously overshadowed by his parkinsonian motor symptoms. This case illustrates an emergence of dysfunction in gait in a patient with otherwise improved function and reinforces the need for an interdisciplinary approach to care of these patients.
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PMID:Gait changes after deep brain stimulation for Parkinson's disease in a patient with cervical myelopathy. 1856 Jan 43

Bilateral symptoms and signs of Parkinson's disease (PD) are often improved by unilateral subthalamic nucleus deep brain stimulation (STN-DBS). However, the mechanism for such bilateral effects is unknown. This study was intended to examine effects of unilateral STN-DBS using positron emission computed tomography (PET) and to elucidate mechanisms for bilateral improvement achieved by unilateral stimulation.We conducted (18)F-fluorodeoxyglucose ((18)FDG) and (18)F-fluorodopa ((18)F-DOPA ) PET scans in PD patients whose bilateral limb symptoms and axial symptoms were improved by unilateral DBS. Two scans were performed in each PET study: when DBS was on and off. We compared those images using statistic parametric mapping (SPM) 99.The significant clinical improvement obtained by unilateral DBS was shown as improvements in bilateral motor limb, axial, and gait subscores of the Unified PD Rating Scale (UPDRS). Moreover, (18)FDG PET revealed significant metabolic increases in the ipsilateral ventrolateral thalamic areas and metabolic decrease at the contralateral globus pallidus interna (GPi). In contrast, (18)F-DOPA PET showed no significant differences between DBS on and off.Ipsilateral thalamic activation might induce ipsilateral motor cortical activation, which explains the improvement of contralateral limb symptoms. Furthermore, deactivation of the contralateral GPi might disinhibit the thalamus and contralateral motor cortex, which explains reduction of ipsilateral limb symptoms. These results suggest the mechanisms for bilateral improvement achieved by unilateral DBS.
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PMID:Mechanisms of unilateral STN-DBS in patients with Parkinson's disease : a PET study. 1856 67

Deep brain stimulation has been used for over a decade to relieve the symptoms of Parkinson's disease, although its mechanism of action remains poorly understood. To better understand the direct effects of DBS on central neurons, a computational model of a myelinated axon has been constructed which includes the effects of K(+) accumulation within the peri-axonal space. Using best estimates of anatomic and electrogenic model parameters for in vivo STN axons, the model predicts a functional block along the axon due to K(+) accumulation in the submyelin space. The functional block occurs for a range of model parameters: high stimulation frequencies (>130 Hz); high extracellular K(+) concentrations (>3 x 10(-3) M); low maximum Na(+)/K(+) ATPase current densities (<0.026 A m(-2)); low diffusion coefficients for K(+) diffusion out of the submyelin space (<2.4 x 10(-9) m(2) s(-1)); small periaxonal space widths of the myelin attachment sections (<2.7 x 10(-9) m) and perinodal/internodal sections (<8.4 x 10(-9) m). These results suggest that therapeutic DBS of the STN likely results in a functional block for many STN axons, although a subset of STN axons may also be activated at the stimulating frequency.
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PMID:Submyelin potassium accumulation may functionally block subsets of local axons during deep brain stimulation: a modeling study. 1856 5

The aim of this study was to investigate personality, by means of the Rorschach Psychodiagnostic test, in a consecutive series of fourteen patients with Parkinson's disease (PD) submitted to bilateral deep brain stimulation of the subthalamic nucleus (DBS STN). Patients were evaluated pre-operatively and 1 year after surgery. Patients were also assessed for motor disability and cognitive status. All the patients obtained a significant amelioration of motor symptoms and could reduce the dopaminergic treatment after surgery. No cognitive decline was observed comparing the pre- to the post-operative neuropsychological assessment. The comparison between pre- and post-operative Rorschach indexes showed no major modifications of personality structure. The results of the present explorative study suggest that DBS of STN does not result in relevant personality modifications in patients with Parkinson's disease.
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PMID:Does subthalamic stimulation induce personality modifications in Parkinson's disease? A Rorschach Test explorative study. 1857 80

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson's disease (PD) patients. The functional scheme of the basal ganglia (BG)-thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms.
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PMID:Increased bradykinesia in Parkinson's disease with increased movement complexity: elbow flexion-extension movements. 1861 34

The circuit-related consequences of activating the ventral pallidum (VP) are not well known, and lacking in particular is how these effects are altered in various neuropathological states. To help to address these paucities, this study investigated the brain regions affected by VP activation by quantifying neurons that stain for Fos-like immunoreactivity (ir). Fos-ir was assessed after intra-pallidal injections of the excitatory amino acid agonist, NMDA, or the GABA(A) antagonist, bicuculline in normal rats and in those rendered Parkinsonian-like by lesioning dopaminergic neurons with the neurotoxin, 6-OHDA. We hypothesized that activation of the VP will alter the activity state of brain regions associated with both the basal ganglia and limbic system, and that this influence would be modified in the Parkinsonian state. Blocking tonically activated GABA(A) receptors with bicuculline (50 ng/0.5 microl) elevated Fos-ir in the VP to 423% above the contralateral, vehicle-injected side. Likewise, intra-VP NMDA (0.23 microg or 0.45 microg/0.5 microl), dose-dependently increased the number of pallidal neurons expressing Fos-ir by 224 and 526%, respectively. At higher NMDA doses, the density of Fos-ir neurons was not elevated above control levels. This inverted U-shaped profile was mirrored by a VP output structure, the medial subthalamic nucleus (mSTN). The mSTN showed a 289% increase in Fos-ir neurons with intra-VP injections of 0.45 microg NMDA, and this response was halved following intra-VP injections of 0.9 microg NMDA. Of the 12 other brain regions measured, three showed VP NMDA-induced enhancements in Fos-ir: the frontal cortex, entopeduncular nucleus and substantia nigra pars reticulata, all regions associated with the basal ganglia. In a second study, we evaluated the NMDA activation profile in a rat model of Parkinson's Disease (PD) which was created by a unilateral injection of 6-OHDA into the rostral substantia nigra pars compacta. Comparisons of responses to intra-VP NMDA between the hemispheres ipsilateral and contralateral to the lesion revealed that Fos-ir cells in the pedunculopontine nucleus was reduced by 62%, whereas Fos-ir for the basolateral amygdala and STN was reduced by 32 and 42%, respectively. These findings support the concept that the VP can influence both the basal ganglia and the limbic system, and that that the nature of this influence is modified in an animal model of PD. As the VP regulates motivation and cognition, adaptations in this system may contribute to the mood and mnemonic disorders that can accompany PD.
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PMID:Fos expression following activation of the ventral pallidum in normal rats and in a model of Parkinson's Disease: implications for limbic system and basal ganglia interactions. 1866 73

The majority of patients with Parkinson's disease suffer from freezing of gait (FOG), which responds more or less to levodopa. Thalamic stimulation, mainly used in the treatment of tremor dominant Parkinson's disease is ineffective in FOG. GPi stimulation moderately improves FOG, but this effect may abate in the long term. STN stimulation was reported to improve levodopa-responsive FOG. In some patients, the benefit from levodopa is greater than that from STN stimulation, and levodopa and STN stimulation can have additive effects. On the contrary, STN stimulation is ineffective on levodopa-resistant FOG. In the few cases of levodopa-induced FOG, STN stimulation can indirectly be effective, thanks to a great decrease or arrest of levodopa. Stimulation of the pedunculopontine nucleus has recently been performed in small groups of patients suffering from both off- and on-levodopa gait impairments. The first results appear encouraging, but they need to be confirmed by controlled studies in larger series of patients.
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PMID:Deep brain stimulation effect on freezing of gait. 1866 17

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.
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PMID:Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease. 1869 9

Bilateral subthalamic (STN) deep brain stimulation (DBS) provides significant symptom relief for the majority of well-screened patients suffering with Parkinson's disease (PD). Implantation of stimulating electrodes bilaterally in a single session has become standard in most operating theaters worldwide. There is, however, limited evidence-based support for this approach. Although bilateral surgical procedures have been shown, using standardized clinical ratings, to provide greater motor benefits compared to unilateral procedures, bilateral procedures are more likely to be associated with increased acute and long-term complications including post-operative confusion, speech difficulties and cognitive dysfunction. Unilateral stimulation has been shown to provide significant benefits for appendicular and axial symptoms. The relative benefit of implanting one versus two sides and whether the degree of benefit associated with the second side is worth the potential risk of doing so have not been examined systematically. The relative magnitude of benefit associated with unilateral versus bilateral procedures is likely to vary from patient to patient, particularly in those patients with asymmetric symptomatology. As such, there are likely subsets of patients who do not require and therefore should not be exposed to the potential complications associated with bilateral simultaneous implantation. This review and commentary will outline our current understanding of the benefits associated with unilateral and bilateral STN DBS and discuss the role of unilateral or staged unilateral procedures as an alternative surgical approach for patients with advanced PD.
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PMID:Are two leads always better than one: an emerging case for unilateral subthalamic deep brain stimulation in Parkinson's disease. 1871 69

Deep brain stimulation of the subthalamic nucleus (DBS/STN) is an effective treatment for motor symptoms in advanced Parkinson's disease (PD). However, it is less clear how DBS/STN affects cognitive functions. We investigated 19 PD patients (13 male, 6 female, mean age 57 +/- 6, mean PD duration 15 +/- 4 years) who received bilateral DBS/STN. Neuropsychological assessment was done before the surgery and at least 12 months after DBS implantation. The patients were examined in their optimal motor status. Global cognitive performance measured by Mattis Dementia Rating Scale was not significantly changed after DBS STN. The performance in Wechsler Memory Scale III decreased in the subtest Logical Memory, in delayed recall (p < 0.05) and in recognition (p < 0.05). In Stroop Test, the performance worsened in the second (p < 0.05), and third condition (p < 0.01) measuring interference and ability to suppress automatic reactions. In conclusion, patients treated by DBS/STN tend to worsen in executive functions and in logical memory.
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PMID:Deep brain stimulation of the subthalamic nucleus and cognitive functions in Parkinson's disease. 1878 Jun 43


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