Karl Sillay

Deep brain stimulator hardware-related infections: incidence and management in a large series.

OBJECTIVE Device-related infection is a common complication of deep brain stimulator (DBS) implantation. We reviewed the incidence and management of early hardware-related infections in a large series. METHODS All patients undergoing DBS implantation surgery between 1998 and 2006 at a single institution were entered into a prospectively designed database. After database verification by cross-referencing manufacturer implantation records, a query was performed to include all new Medtronic (Minneapolis, MN) implantations performed with standard operating room technique. Hardware-related infections requiring further surgery were identified, and charts were reviewed to assess the success of lead-sparing partial hardware removal in this group. RESULTS Four hundred twenty patients received 759 new DBS electrodes and 615 new internal pulse generators for the treatment of movement disorders or pain. Nineteen patients (4.5%) had an early (<6 mo) hardware-related infection requiring further surgery. There were no intracranial infections. Four patients presented with extensive cellulitis or wound dehiscence and were treated with total hardware removal. Fourteen patients presented with more localized infections and were treated by removal of the involved components only, followed by intravenously administered antibiotics. In nine of these patients, partial hardware removal successfully resolved the infection without requiring removal of the DBS electrodes. Wound washout alone was attempted in one patient and failed. CONCLUSION In a large series of new DBS hardware implantations, the incidence of postoperative hardware-related infection requiring further surgery was 4.5%. When only one device component was involved, partial hardware removal was often successful.

Deep Brain Stimulation for Medically Intractable Cluster Headache

Cluster headache is the most severe primary headache disorder known. Ten to 20% of cases are medically intractable. DBS of the posterior hypothalamic area has shown effectiveness for alleviation of cluster headache in many but not all of the 46 reported cases from European centers and the eight cases studied at the University of California, San Francisco. This surgical strategy was based on the finding of increased blood flow in the posterior hypothalamic area on H(2)(15)O PET scanning during spontaneous and nitroglycerin-induced cluster headache attacks. The target point used, 4-5 mm posterior to the mamillothalamic tract, is in the border zone between posterior hypothalamus, anterior periventricular gray matter, and inferior thalamus. Recently, occipital nerve stimulation has shown efficacy, calling in question the use of DBS as a first line surgical therapy. In this report, we review the indications, techniques, and outcomes of DBS for cluster headache.

A Micro-Electrocorticography Platform and Deployment Strategies for Chronic BCI Applications

Over the past decade, electrocorticography (ECoG) has been used for a wide set of clinical and experimental applications. Recently, there have been efforts in the clinic to adapt traditional ECoG arrays to include smaller recording contacts and spacing. These devices, which may be collectively called “micro-ECoG” arrays, are loosely defined as intercranial devices that record brain electrical activity on the submillimeter scale. An extensible 3D-platform of thin film flexible microscale ECoG arrays appropriate for Brain-Computer Interface (BCI) application, as well as monitoring epileptic activity, is presented. The designs utilize flexible film electrodes to keep the array in place without applying significant pressure to the brain and to enable radial subcranial deployment of multiple electrodes from a single craniotomy. Deployment techniques were tested in non-human primates, and stimulus-evoked activity and spontaneous epileptic activity were recorded. Further tests in BCI and epilepsy applications will make the electrode platform ready for initial human testing.

Long-Term Measurement of Impedance in Chronically Implanted Depth And Subdural Electrodes During Responsive Neurostimulation in Humans

Long-term stability of the electrode-tissue interface may be required to maintain optimal neural recording with subdural and deep brain implants and to permit appropriate delivery of neuromodulation therapy. Although short-term changes in impedance at the electrode-tissue interface are known to occur, long-term changes in impedance have not previously been examined in detail in humans. To provide further information about short- and long-term impedance changes in chronically implanted electrodes, a dataset from 191 persons with medically intractable epilepsy participating in a trial of an investigational responsive neurostimulation device (the RNS(®) System, NeuroPace, Inc.) was reviewed. Monopolar impedance measurements were available for 391 depth and subdural leads containing a total of 1564 electrodes; measurements were available for median 802 days post-implant (range 28-1634). Although there were statistically significant short-term impedance changes, long-term impedance was stable after one year. Impedances for depth electrodes transiently increased during the third week after lead implantation and impedances for subdural electrodes increased over 12 weeks post-implant, then were stable over the subsequent long-term follow-up. Both depth and subdural electrode impedances demonstrated long-term stability, suggesting that the quality of long-term electrographic recordings (the data used to control responsive brain stimulation) can be maintained over time.

Long-Term Measurement of Therapeutic Electrode Impedance in Deep Brain Stimulation

Objective:  Deep brain stimulation technology now allows a choice between constant current and constant voltage stimulation, yet clinical trials comparing the two are lacking. Impedance instability would theoretically favor constant current stimulation; however, few publications address this with long‐term follow‐up. In this report, we review our series for impedance change and discuss our findings and their implications for future study design.

Pathways of Infusate Loss During Convection Enhanced Delivery into the Putamen Nucleus

Background: New strategies aiming to treat Parkinson’s disease, such as delivery of trophic factors via protein infusion or gene transfer, depend upon localized intracerebral infusion, mainly into the putamen nucleus. Convection-enhanced delivery (CED) has been proposed as a method to improve intracerebral distribution of therapies. Yet analysis of controversial results during the clinical translation of these strategies suggests that intracerebral misdistribution of infusate may have affected the outcomes by limiting the amount of treatment into the target region. Objectives: This study aimed to identify possible pathways of infusate loss and their relative impact in the success of targeted CED into the postcommissural ventral putamen nucleus. Methods: Thirteen adult macaque monkeys received intraputaminal CED infusions of 100 µl of 2.0 mM gadoteridol and bromophenol blue (0.16 mg/ml) solution at a rate of 1.0 µl/min under intraoperative magnetic resonance imaging (MRI) guidance. Quantitative maps of infusate concentration were computed at 10-min intervals throughout the procedure in a 3-Tesla MRI scanner. The fraction of tracer lost from the putamen as well as the path of loss were evaluated and quantified for each infusion. Results: All injections (total 22) were successfully placed in the ventral postcommissural putamen nucleus. Four major paths of infusate loss from the putamen were observed: overflow across putamen boundaries, perivascular flow along large blood vessels, backflow along the inserted catheter and catheter tract leakage into the vacated catheter tract upon catheter removal. Overflow loss was observed within the first 30 µl of infusion in all cases. Measurable tracer loss following the path of an artery out of the putamen was observed in 15 cases, and in 8 of these cases, the loss was greater than 10% of infusate. Backflow that exited the putamen was observed in 4 cases and led to large loss of infusate (80% in 1 case) into the corona radiata. Loss into the vacated catheter tract amounted only to a few microliters. Conclusions: Our analysis demonstrates that after controlling for targeting, catheter type, infusion rate and infusate, the main issues during surgical planning are the identification of appropriate infusate volume that matches the target area, as well as mapping the regional vasculature as it may become a pathway for infusate loss. Most importantly, these results underscore the significance of presurgical planning for catheter placement and infusion, and the value of imaging guidance to ensure targeting accuracy.

The Substitute Brain and the Potential of the Gel Model

This purpose of this paper is to review the recent history of the use of agarose gels. Although originally confined to electrophoresis work, agarose gels have proven themselves useful to a number of disciplines in the modern world, which includes brain infusion studies for research involving the treatment of various neurological conditions, such as Parkinson’s Disease. In reviewing the relevant research leading up to the modern day, this paper attempts to track agarose gels through their stages of accuracy verification, highlighting why they are useful to the neurosurgery discipline and characterizing the nature of their use. Agarose gels do have significant limitations, which are also discussed, but they have substantial potential as a modifiable medium or as a basis of comparison for even more accurate models in the future.

Obesity and deep brain stimulation: an overview.

Deep brain stimulation (DBS) has been employed to treat a variety of disorders such as Parkinson disease, dystonia, and essential tremor. Newer indications such as epilepsy and obsessive-compulsive disorder have been added to the armamentarium. In this review, we present an initial summary of current methods in the management of obesity and then explore efforts in neuromodulation and DBS as a novel modality in the treatment of obesity disorders.

Strategies for the Delivery of Multiple Collinear Infusion Clouds in Convection-Enhanced Delivery in the Treatment of Parkinson's Disease

Background: Delivery of multiple collinear payloads utilizing convection-enhanced delivery (CED) has historically been performed by retraction of a needle or catheter from the most distal delivery site. Few studies have addressed end-infusion morphology and associated payload reflux in stacked and collinear infusions, and studies comparing the advancement with the retraction mode are lacking. Objective: To compare advancement versus retraction mode infusion results. Methods: Infusion cloud pairs were created with the advancement and retraction technique in agarose gel using both open end-port SmartFlow™ (SF) and valve tip (VT) catheter infusion systems. Backflow, radius of infusion, and morphology were assessed. Results: Infusions with the SF catheter, in contrast to the VT catheter, exhibited significantly more backflow in retraction mode at the shallow infusion site. Infusion morphology differed with the second infusion after retraction: the infusate at the proximal site first filling the channel left by the retraction and then being convected into gel in a pronouncedly non-spherical shape during the second infusion. Conclusions: Significant differences in cloud morphology were noted with respect to external catheter geometry with retraction versus penetration between infusions in an agarose gel model of the brain. Further study is warranted to determine optimal protocols for human clinical trials employing CED with multiple collinear payloads.

Convection enhanced delivery to the Brain: preparing for gene therapy and protein delivery to the Brain for functional and restorative Neurosurgery by understanding low-flow neurocatheter infusions using the Alaris® system infusion pump

Background Convection enhanced delivery (CED) is an emerging form of direct brain infusion therapy employed in human functional and restorative neurosurgery clinical trials delivering protein, viral vectors for gene therapy, and siRNA. Purpose Pressure monitoring has become a vital tool in ensuring infusion safety and success. We report details of this benchmark first trial of the use of a leading syringe infusion pump system capable of low-flow infusions. Methods Low-flow infusion performance of the FDA approved Alaris® System syringe pump, commonly used at our institution, was assessed during in vitro and ex vivo CED infusions. In vitro infusion cloud morphology and line pressure were analyzed utilizing a neuroinfusion catheter and delivering volumes and flow rates proposed for a human gene therapy protocol for Parkinson’s disease. Results Pressure monitoring results correlated with previously published in-line pressure monitoring results however the time to peak with catheter occlusion was extended due to the method of pressure monitoring with this device. Conclusion MRI compatible infusion pumps used for brain delivery injectables, pressure monitoring is set to be a guiding instrument for the health care professional employing this emerging form of infusion-to-brain delivery. Further development of infusion pump technology is warranted to allow for infuse/withdraw mode, infusion pressure graphical and numerical display, and pressure monitoring without the need for an inflatable reservoir pressure device. MRI safe infusion systems will need to be available and nursing staff educated to prepare infusions within the high-field environment.