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)

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

We have previously shown that in patients with Parkinson's disease (PD), high-frequency stimulation (HFS) of the subthalamic nucleus (STN) modifies spinal excitability via subcortical reticulospinal routes. To investigate whether STN-HFS also modifies spinal excitability via transcortical routes in PD, 10 patients with PD (9 men, 1 woman; 58.3 +/- 8.3 years) were investigated in the medical OFF-state with or without STN-HFS. The H-reflex of the right soleus muscle was recorded during slight plantar flexion at 20% of maximum force. A conditioning transcranial stimulus was applied at 95% of active motor threshold to the contralateral primary motor leg area (M1) 0-5 ms after eliciting the H-reflex. The same paradigm was applied to 8 healthy individuals (5 men, 3 women; 50.8 +/- 3.0 years). Transcranial magnetic stimulation (TMS) facilitated the H-reflex amplitude in healthy controls. A facilitatory effect of the corticospinal input on the H-reflex was also found in patients with PD, but only with STN-HFS switched on. When STN-HFS was discontinued, the H-reflex was no longer facilitated by the TMS pulse. Accordingly, analysis of variance showed a main effect of stimulation (F = 11.15; P = 0.005), ISI (F = 6.1; P = 0.003), and an interaction between stimulation and group (PD vs. control) (F = 8.9; P = 0.01). STN-HFS restores the normal facilitatory drive of a transcranially evoked motor cortical response to the spinal motoneuron pool. In addition to subcortical routes, STN-DBS also alters spinal excitability via transcortical pathways.
 ...
PMID:Subthalamic nucleus stimulation restores corticospinal facilitation in Parkinson's disease. 1875 43

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.
 ...
PMID:Deep brain stimulation of the subthalamic nucleus and cognitive functions in Parkinson's disease. 1878 Jun 43

Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.
 ...
PMID:Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation. 1878 48

High-frequency stimulation of around 130 Hz delivered to the subthalamic nucleus (STN-DBS [deep brain stimulation]) is an effective treatment of Parkinson's disease (PD), but the mechanisms of its therapeutic effect remain obscure. Recently, it has been shown in anaesthetized rats that STN-DBS antidromically activates cortical neurons with coincident reduction of the cortical slow wave oscillations that occur in this preparation. Here we extend this work; recording the effect of STN-DBS upon cortical EEG and akinesia, in unanesthetized rats rendered cataleptic by acute dopaminergic blockade. STN-DBS-like stimulation resulted in a short latency, presumed antidromic, evoked potential in the cortex. In cataleptic animals, there was a significant increase in the power of beta oscillations in the electroencephalography which was reversed by stimulation that evoked the cortical response. We also observed a significant rescue of motor function, with the level of akinesia (bar test score) being inversely correlated to the amplitude of the evoked potential (R2 = 0.84). These data confirm that (probably antidromic) short latency cortical responses occur in the awake animal and that these are associated with reductions in abnormal cortical oscillations characteristic of PD and with improvements in akinesia. Our results raise the possibility that STN-DBS reduces PD oscillations and symptoms through antidromic cortical activation.
 ...
PMID:Cortical effects of subthalamic stimulation correlate with behavioral recovery from dopamine antagonist induced akinesia. 1878 34

Pathological gambling (PG) is defined by the DSM IV criteria as inappropriate, persistent, and maladaptive gambling behavior that has repercussions on family, personal, and professional life. It is classified as an impulse control disorder and is widely understood as a nonpharmacological addiction. PG has been reported as a complication in the treatment of Parkinson disease (PD). The prevalence of PG in PD has been reported to range between 1.7 and 7% compared to a prevalence of approximately 1% in the general population. Though there is no survey that indicates the prevalence of PG in Japanese PD patients, problematic gambling behaviors in PD are occasionally observed. In addition to PG other impulse control behaviors and punding (repetitive stereotyped behavior) are recognized as components of the dopamine dysregulation syndrome (DDS), which is characterized by the compulsive use of dopaminergic medications, including levodopa and subcutaneous apomorphine. Though PG can occur with DDS it often occurs in isolation. The vast majority of PG seen in PD is related to dopamine agonists (DA). With regard to the administration of oral DA, pramipexole may induce a higher degree of PG than other types of oral DA due to its disproportionate stimulation of dopamine D3 receptors. However, the differences between the observed effects of various classes of oral DA were insignificant. PG associated with levodopa mono-therapy is uncommon, but in the majority of cases levodopa is co-prescribed. Subthalamic nucleus deep brain stimulation (STN-DBS) was recently introduced to treat advanced PD. An improvement in PG symptoms following STN-DBS has been reported due to a marked decrease in dopaminergic medications. However, in some patients, PG developed following STN-DBS despite the significant reduction or discontinuation of DA. STN-DBS per se may be a potential initiator of PG. Younger age of PD onset, novelty seeking personality traits, history of alcohol abuse, and impulsivity traits were significant predictors of PG. Patients especially those with individual susceptibility to PG should be warned of the potential risks of PG before DA treatment is initiated.
 ...
PMID:[Pathological gambling and Parkinson disease]. 1880 38

The intra-laminar (IL) thalamic complex, composed of centromedian (CM) and parafascicular (Pf) nucleus, is a strategic crossroad for the activity of the basal ganglia and is recently regaining its position has a putative neurosurgical target for Parkinsonian syndromes. The multi-target approach we have encouraged since the late nineties has allowed the combined implantation of a standard target (the subthalamic nucleus-STN or the internal pallidus-GPi) plus an innovative one (CM/Pf) in well-identified Parkinson's disease (PD) patients; hence, it is possible to study, in the same PD patients, the specific target-mediated effects on different clinical signs. Here, we focus on the potential usefulness of implanting the CM/Pf complex when required in the management of contra-lateral tremor (resistant to standard deep brain stimulation-DBS - in STN - , n=2) and disabling involuntary movements, partially responsive to GPi-DBS (n=6). When considering global UPDRS scores, CM/Pf-DBS ameliorate extra-pyramidal symptoms but not as strongly as STN (or GPi) does. Yet, CM/Pf acts very powerfully on tremor and contributes to the long-term management of l-Dopa-induced involuntary movements. The lack of cognitive deficits and psychic impairment associated with the improvement of their quality of life, in our small cohort of CM/Pf implanted patients, reinforces the notion of CM/Pf as a safe and attractive area for surgical treatment of advanced PD, possibly affecting not only motor but also associative functions.
 ...
PMID:Multi-target strategy for Parkinsonian patients: the role of deep brain stimulation in the centromedian-parafascicularis complex. 1881 14

Conflicting research suggests that deep brain stimulation surgery, an effective treatment for medication-refractory Parkinson's disease (PD), may lead to selective cognitive declines. We compared cognitive performance of 22 PD patients who underwent unilateral DBS to the GPi or STN to that of 19 PD controls at baseline and 12 months. We hypothesized that compared to PD controls, DBS patients would decline on tasks involving dorsolateral prefrontal cortex circuitry (letter fluency, semantic fluency, and Digit Span Backward) but not on other tasks (Vocabulary, Boston Naming Test), and that a greater proportion of DBS patients would fall below Reliable Change Indexes (RCIs). Compared to controls, DBS patients declined only on the fluency tasks. Analyses classified 50% of DBS patients as decliners, compared to 11% of controls. Decliners experienced less motor improvement than non-decliners. The present study adds to the literature through its hypothesis-driven method of task selection, inclusion of a disease control group, longer-term follow-up and use of Reliable Change. Our findings provide evidence that unilateral DBS surgery is associated with verbal fluency declines and indicate that while these changes may not be systematically related to age, cognitive or depression status at baseline, semantic fluency declines may be more common after left-sided surgery. Finally, use of Reliable Change highlights the impact of individual variability and indicates that fluency declines likely reflect significant changes in a subset of patients who demonstrate a poorer surgical outcome overall.
 ...
PMID:Cognitive declines one year after unilateral deep brain stimulation surgery in Parkinson's disease: a controlled study using reliable change. 1882 Nov 80

Although bilateral subthalamic deep brain stimulation (STN DBS) provides greater relief from the symptoms of Parkinson's disease (PD) than unilateral STN DBS, it has been suggested that unilateral STN DBS may be a reasonable treatment option in selected patients, especially those with highly asymmetric PD. In previous studies on the effect of unilateral STN DBS, the asymmetry of PD symptoms was not prominent and the mean follow-up durations were only 3 to 12 months. In this study, we report our findings in a series of 8 patients with highly asymmetric PD who were treated with unilateral STN DBS and were followed for 24 months. Serial changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and subscores in the ipsilateral, contralateral, and axial body parts were analyzed. Unilateral STN DBS improved the UPDRS motor score and the contralateral subscore in the on-medication state for 5 nonfluctuating patients and in the off-medication state for 3 fluctuating patients. However, the ipsilateral subscore progressively worsened and reversed asymmetry became difficult to manage, which led to compromised medication and stimulator adjustment. At 24 months, all the patients were considering the second-side surgery. Our results suggest that bilateral STN DBS should be considered even in highly asymmetric PD.
 ...
PMID:Two-year follow-up on the effect of unilateral subthalamic deep brain stimulation in highly asymmetric Parkinson's disease. 1900 87

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


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