Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

BACKGROUND: Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS: At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS: Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

Effect of electrical stimulation of the cervical spinal cord on blood flow following subarachnoid hemorrhage.

OBJECT: Cervical spinal cord stimulation (SCS) increases global cerebral blood flow (CBF) and ameliorates cerebral ischemia according to a number of experimental models as well as some anecdotal reports in humans. Nonetheless, such stimulation has not been systematically applied for use in cerebral vasospasm. In the present study the authors examined the effect of cervical SCS on cerebral vasoconstriction in a double-hemorrhage model in rats. METHODS: Subarachnoid hemorrhage (SAH) was induced with 2 blood injections through an indwelling catheter in the cisterna magna. Spinal cord stimulation was applied 90 minutes after induction of the second SAH (Day 0) or on Day 5 post-SAH. Measurements of the basilar artery (BA) diameter and cross-sectional area and regional CBF (using laser Doppler flowmetry and (14)C-radiolabeled N-isopropyl-p-iodoamphetamine hydrochloride) were obtained and compared between SAH and sham-operated control rats that did not receive SCS. RESULTS: At Day 0 after SAH, there were slight nonsignificant decreases in BA diameter and cross-sectional area (89 +/- 3% and 81 +/- 4%, respectively, of that in controls) in no-SCS rats. At this time point, BA diameter and crosssectional area were slightly increased (116 +/- 6% and 132 +/- 9%, respectively, compared with controls, p < 0.001) in SCS-treated rats. On Day 5 after SAH, no-SCS rats had marked decreases in BA diameter and cross-sectional area (64 +/- 3% and 39 +/- 4%, respectively, compared with controls, p < 0.001) and corrugation of the vessel wall. These changes were reversed in rats that had received SCS (diameter, 110 +/- 9% of controls; area, 106 +/- 4% of controls; p < 0.001). Subarachnoid hemorrhage reduced CBF at Days 0 and 5 post-SAH, and SCS increased flows at both time points, particularly in regions supplied by the middle cerebral artery. CONCLUSIONS: Data in this study showed that SCS can reverse BA constriction and improve global CBF in this SAH model. Spinal cord stimulation may represent a useful adjunct in the treatment of vasospasm.

Mechanisms of spinal cord stimulation in ischemia.

OBJECT: The goal of this study was to assess the duration of neuroprotection after SCS. Nearly 40 years after the first description of spinal cord stimulation (SCS), the mechanisms underlying its physiological effects remain unclear. It is known that SCS affects activity in the nervous system on a broad scale. Local neurohumoral changes within the dorsal horn of the spinal cord have been described, as have changes in cortical activation in a number of brain regions. Spinal cord stimulation has even been found to have profound effects on sympathetic vascular tone, a discovery that has led to its use in ameliorating blood flow in the limbs, heart, and brain. METHODS: In an effort to delineate the limits of neuroprotection offered by SCS, the authors have studied its use in an experimental model of permanent middle cerebral artery (MCA) occlusion in rats. The investigators applied SCS in a delayed fashion 3, 6, or 9 hours after MCA occlusion. The results are reported and mechanisms underlying the physiological effects of SCS are reviewed, with particular attention being paid to the effect of SCS on cerebral blood flow in the setting of cerebral ischemia. CONCLUSIONS: The authors found that SCS applied as late as 6 hours postischemia significantly reduces stroke volumes, whereas SCS applied 9 hours after ischemia fails to reduce stroke injury.

Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients.

PURPOSE: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients. METHODS: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21-58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial. RESULTS: Baseline PSGs: One of 16 patients had an apnea-hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels. CONCLUSIONS: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.