Jurg L. Jaggi

Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy

Summary:  Purpose: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open‐label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data.

Predictors of outcome after anterior temporal lobectomy Positron emission tomography

We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fishers exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.

Deep brain stimulation in the treatment of obesity

Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brains reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.

Subthalamic nucleus deep brain stimulation for severe idiopathic dystonia: impact on severity, neuropsychological status, and quality of life

OBJECT Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN). METHODS Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally. RESULTS Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery. CONCLUSIONS Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.

Deep Brain Stimulation for Epilepsy

SummaryMany patients who suffer from medically refractory epilepsy are not candidates for resective brain surgery. Success of deep brain stimulation (DBS) in relieving a significant number of symptoms of various movement disorders paved the way for investigations into this modality for epilepsy. Open-label and small blinded trials have provided promising evidence for the use of DBS in refractory seizures, and the first randomized control trial of DBS of the anterior thalamic nucleus is currently underway. There are multiple potential targets, because many neural regions have been implicated in seizure propagation. Thus, it is difficult as yet to make any definitive judgments about the efficacy of DBS for seizure control. Future study is necessary to identify a patient population for whom this technique would be indicated, the most efficacious target, and optimal stimulation parameters.

Bilateral subthalamic nucleus deep brain stimulation in a patient with cervical dystonia and essential tremor.

The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well established in Parkinsons disease, but experience with STN DBS in other movement disorders is limited. We report on a patient with medically refractory cervical dystonia and essential tremor resulting in dystonic head tremor and action tremor of the hands who obtained complete tremor suppression and near resolution of her cervical dystonia with bilateral STN stimulation. The results in this case demonstrate that STN DBS can dramatically improve dystonia and tremor in nonparkinsonian movement disorders.

Cerebral blood flow, vascular resistance, and oxygen metabolism in acute brain trauma: Redefining the role of cerebral perfusion pressure?

OBJECTIVES To evaluate normal or high cerebral perfusion pressure in relation to cerebral blood flow and oxygen metabolism, as well as other multivariate cerebral hemodynamic and metabolic interrelationships, in acute brain trauma in humans. DESIGN Prospective, observational study. SETTING Neuroscience intensive care unit of a university hospital. PATIENTS Adults (n = 66) with severe acute brain trauma (Glasgow Coma Scale scores from 4 to 8), undergoing multivariate physiologic studies involving cerebral perfusion pressure, cerebral blood flow, cerebral metabolic rate of oxygen consumption, total hemoglobin content, arterio-jugular oxygen content difference, and cerebral vascular resistance, along with other routine procedures. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Statistical analysis did not demonstrate any correlation between cerebral perfusion pressure and cerebral blood flow, between cerebral perfusion pressure and arterio-jugular oxygen content difference, and between cerebral perfusion pressure and cerebral metabolic rate of oxygen consumption, over a broad spectrum of perfusion pressures ranging from 60 to 130 mm Hg. In contrast, a significant negative correlation was found between cerebral vascular resistance and cerebral blood flow, where higher values of cerebral vascular resistance were associated with lower blood flow levels, and vice versa. CONCLUSIONS In severe acute brain trauma, cerebral hemodynamic and oxygen metabolic variables are not necessarily correlated with normal or even high levels of cerebral perfusion pressure. Under these circumstances, cerebral vascular resistance (not perfusion pressure) is more closely correlated with different patterns of cerebral blood flow and metabolism.

Deep brain stimulation in the treatment of refractory epilepsy: update on current data and future directions.

Deep brain stimulation for epilepsy has garnered attention from epileptologists due to its well-documented success in treating movement disorders and the low morbidity associated with the implantation of electrodes. Given the large proportion of patients who fail medical therapy and are not candidates for surgical amelioration, as well as the suboptimal seizure control offered by vagus nerve stimulation, the search for appropriate brain structures to serve as targets for deep brain stimulation has generated a useful body of evidence to serve as the basis for larger investigations. Early results of the SANTE trial should lay the foundation for widespread implementation of DBS for epilepsy targeting the anterior thalamic nucleus. Other targets also offer promise, including the caudate nucleus, the subthalamic nucleus, the cerebellum, the centromedian nucleus of the thalamus, and the hippocampus. This paper reviews the logic which underlies these potential targets and recapitulates the current data from limited human trials supporting each one. It also provides a succinct overview of the surgical procedure used for electrode implantation.

Brain shift during deep brain stimulation surgery for Parkinson's disease.

Background: Brain shift may occur during deep brain stimulation (DBS) surgery, which may affect the position of subcortical structures, compromising target localization. Methods: We retrospectively evaluated pre- and postoperative magnetic resonance imaging in 50 Parkinson’s disease patients who underwent bilateral subthalamic nucleus (STN) DBS. Patients were separated into two groups: group A – those with <2 mm cortical displacement (66 leads) and group B – those with ≧2 mm cortical displacement (34 leads). Pre and post-op coordinates of anterior (AC) and posterior commissures (PC), as well as the boundaries of red nucleus (RN) were compared. Results: AC-PC shortening due to posterior displacement of AC correlated with cortical displacement (p < 0.02) and was significantly greater in group B (0.41 ± 0.68 mm) than A (0.04 ± 0.76 mm; p < 0.005). Posterior shift of AC and RN’s center positively correlated (p < 0.0001). Shift appeared to impact the number of microelectrode tracks made to optimize STN targeting. AC-PC shortening also correlated with age (p < 0.003) and duration of surgery (p < 0.04). Conclusions: Subcortical structures shift during DBS surgery. This shift appears to be gravity-dependent since structures only shifted posteriorly, and patients were primarily in the supine position. Posterior shift of RN may indicate STN displacement. Such positional change may compromise target localization, requiring multiple microelectrode adjustments. This may provide indirect justification for the necessity of microelectrode recordings during DBS surgery.

Neuronal Activity in the Human Subthalamic Nucleus Encodes Decision Conflict during Action Selection

The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes.