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Objective:The authors proposed an intraventricular 'floating' electrode inserted in the third ventricle (V3) adjacent to the ventromedian hypothalamus (VMH) in a freely moving Macaca fascicularis to modulate food intake (FI), body fat (BF), body weight (BW) and body mass index (BMI), as a potential treatment of obesity.Methods:Five adult Macaca fascicularis monkeys were implanted stereotactically in the V3 contiguous to the VMH with one deep brain stimulation (DBS) electrode. The study was divided in two phases: (a) acute 24 h-fasting trials: different electrical stimulation parameters were applied to a fasting primate to determine the best combination in reducing FI; and (b) chronic 8-week stimulation trials: three cycles of intraventricular-VMH DBS lasting 8-10 weeks were performed at 130 Hz, 80 Hz (most effective frequency reducing FI) and 30 Hz, respectively. BMI, BW, BF content, skinfolds and hormones were measured during baseline and at the end of each session of stimulation.Results:Acute 24 h-fasting trials: there was a decrease in FI in all subjects at 80 Hz, (11-19%, mean 15%). Chronic 8-week stimulation trials: a significant decrease in BW and BMI was observed in three out of four monkeys at 80 Hz (mean 8±4.4%). Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. The sham monkey remained stable. No significant adverse effects were recorded.Conclusion:The stimulation of the VMH region through an intraventricular approach might acutely modulate FI and induce a sustained decrease in BW and fat mass in normal non-human primate. [ABSTRACT FROM AUTHOR]

Stimulation of the subthalamic nucleus (STN) improves the cardinal features of Parkinson disease (PD). However, its efficacy on gait disorders is less satisfying in the long term. In recent years, the pedunculopontine (PPN) nucleus has emerged as a possible promising deep brain stimulation target for gait disorders in PD. In this review, we examine whether STN and PPN act synergistically or antagonistically. Results suggest that the combination of STN and PPN stimulations leads to a significant further improvement in gait as compared with STN stimulation alone, but additive effects on the classical motor triad are questionable. Thus, they highlight the specificity of STN stimulation over PPN's for the PD cardinal features and the specificity of PPN stimulation over STN for gait disorders. In addition, low-frequency stimulation of the PPN may improve alertness. The additive rather than potentiating effects of STN and PPN stimulations suggest that they may be mediated by distinct pathways. Nevertheless, considering the inconsistencies in published results regarding the influence of PPN stimulation on gait disorders, work is still needed before one can know whether it will convert into a standard surgical treatment and to decipher its place beside STN stimulation. [ABSTRACT FROM AUTHOR]

The article offers information on a medical research carried out on subthalamic neuronal firing in obsessive-compulsive disorder and Parkinson disease. In this disease, sensorimotor subthalamic neurons display high-frequency burst firing. It was seen whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops or not. The outcome showed that the subthalamic neuron discharge rate was low in patients with obsessive-compulsive disorder than in Parkinson disease.

We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk–benefit ratio. [ABSTRACT FROM PUBLISHER]

Objective: To study the pyramidal tract side effects (PTSEs) induced by the spread of current from the subthalamic nucleus (SIN) to the pyramidal tract (PT), in patients with parkinsonism undergoing SIN stimulation. Methods: 14 patients bilaterally implanted with tetrapolar electrodes were assessed. For each side separately, the threshold of adverse effects induced by monopolar stimulation delivered by the chronically used contact was detected. The voltage was progressively increased until the patient experienced discomfort. All the PTSEs induced at 130 Hz (high-frequency stimulation (HFS)) and 2 or 3 Hz (low-frequency stimulation (LFS)) were videotaped. By superimposing the preoperative and postoperative MR images, the minimum distance (R) from the centre of the used contact to the medial border of the PT were measured. Results: The progressive increase in voltage at HFS induced tonic motor contractions, mainly located in the face, in 27/28 electrodes. LFS induced synchronous rhythmic myoclonus in the same territory. PTSEs induced at threshold voltage by HFS were observed in the upper face at 13/28 electrodes (bilaterally in six cases) and in the contralateral lower face at five electrodes. A positive correlation was found between the stimulus intensity capable of eliciting motor contractions at HFS and R. Conclusions: HFS of the SIN preferentially activates the corticobulbar tract over the corticospinal tract. Therefore, cranial motor contractions need to be looked for during electrical parameter setting. The positive correlation between the electrical intensity threshold for PTSEs and R reflects the need for millimetre accuracy in electrode positioning. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation )DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. Methods: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. Results: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores )speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. Conclusion: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients. [ABSTRACT FROM AUTHOR]

HFS has become a widely used method in functional neurosurgery. However, its mechanism is not well understood, and its cellular and molecular effects have not yet been investigated. The aim of the study was to understand which cellular events, unrelated to the network organization of cells or neurons, participate in the mechanism of action of HFS. In vitro cellular effects of high (HFS) and low (LFS) frequency electrical stimulation on prolactin secretion in GH3 cell lines (prolactinoma), as well as the catecholaminergic secretion on PC12 cells (pheochromocytoma) were investigated. Cells were cultured in dishes with integrated electrodes to deliver stimulation at the same parameters as those used in clinical conditions to treat advanced forms of Parkinson’s disease. Prolactin production was measured in GH3 using a Radio-Immuno-Assay. Dopamine, epinephrine and norepinephrine were measured in PC12 using Enzymo-immuno-assays. HFS for 24 hours reduced prolactin secretion by 40.3%, dopamine by 32.7%, epinephrine by 18.1% (non significant) and norepinephrine by 27.0%. LFS did not induce significant changes. These results suggest that HFS has an inhibitory impact on the cellular machinery responsible for hormone and neurotransmitter production. In this model of isolated cultured cells, network interactions and particularly presynaptic actions are discarded. HFS has inhibitory effects on cellular mechanisms responsible for the production and release of molecules participating in intercellular communication. This HFS-induced inhibition might participate in the lesion-like effect of therapeutic HFS in the basal ganglia during various movement disorders. [ABSTRACT FROM AUTHOR]

Background: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. Objective: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. Methods: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. Results: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001 ) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from €10 087 before surgery to €1673 after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at €36 904 over 2.2 years. Conclusions: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications. [ABSTRACT FROM AUTHOR]

Purpose. To determine the perfusion-sensitive characteristics of cerebral dural metastases and compare them with the data on meningiomas. Methods . Twenty-two patients presenting with dural tumor underwent conventional and dynamic susceptibility-contrast MR imaging: breast carcinoma metastases, two patients; colorectal carcinoma metastasis, one patient; lung carcinoma metastasis, one patient; Merkel carcinoma metastasis, one patient; lymphoma, one patient; meningiomas, 16 patients. The imaging characteristics were analyzed using conventional MR imaging. The cerebral blood volume (CBV) maps were obtained for each patient and the relative CBV (rCBV) in different areas was calculated using the ratio between the CBV in the pathological area (CBVp) and in the contralateral white matter (CBVn). Results. The differentiation between a meningioma and a dural metastasis can be difficult using conventional MR imaging. The rCBVs of lung carcinoma metastasis (1 case: 1.26), lymphoma (1 case: 1.29), breast carcinoma metastasis (2 cases: 1.50,1.56) and rectal carcinoma metastasis (1 case: 3.34) were significantly lower than that of meningiomas (16 cases: mean rCBV = 8.97±4.34, range 4–18). Merkel carcinoma metastasis (1 case: 7.56) showed an elevated rCBV, not different from that of meningiomas. Conclusion. Dural metastases are sometimes indistinguishable from meningiomas using conventional MR imaging. rCBV mapping can provide additional information by demonstrating a low rCBV which may suggest the diagnosis of metastasis. [ABSTRACT FROM AUTHOR]