Long-Term Surface Electrode Impedance Recordings Associated with Gliosis for a Closed-Loop Neurostimulation Device.

BACKGROUND: Closed-loop neurostimulation is a novel alternative therapy for medically intractable focal epilepsy for patients who are not candidates for surgical resection of a seizure focus. Electrodes for this system can be implanted either within the brain parenchyma or in the subdural space. The electrodes then serve the dual role of detecting seizures and delivering an electrical signal aimed at aborting seizure activity. The Responsive Neurostimulation (RNS®) system (Neuropace, Mountain View, CA, USA) is an FDA-approved implantable device designed for this purpose. OBJECTIVE: One of the challenges of the brain machine interface devices is the potential for implanted neurostimulator devices to induce progressive gliosis, apart from that associated with the minimal trauma at implantation. Gliosis has the potential to alter impedances over time, thereby affecting the clinical efficacy of these devices, and also poses a challenge to the prospects of in vivo repositioning of depth electrodes. We present a clinical case with 3-year follow-up and pathology. METHODS: Single-case, retrospective review within a randomized trial with specific minimum follow-up and impedance measurements. RESULTS: Impedance changes in the surface electrode over time were observed. Surgical pathological findings revealed significant gliosis in the leptomeninges of the cortices. CONCLUSION: We report, for the first time, long-term impedance recordings from a surface electrode associated with pathologic findings of gliosis at the Neuropace device-tissue interface in a patient who was enrolled in the multicenter RNS System Pivotal Clinical Investigation. Further study is required to elucidate the temporal relationship of pathological findings over time. Impedance changes were more complex than can be explained by a progressive or transient pathological mechanism. Further effort is required to elucidate the relationship between impedance change and seizure event capture.

Ambulatory Seizure Monitoring: From Concept to Prototype Device.

BACKGROUND: The brain, made up of billions of neurons and synapses, is the marvelous core of human thought, action and memory. However, if neuronal activity manifests into abnormal electrical activity across the brain, neural behavior may exhibit synchronous neural firings known as seizures. If unprovoked seizures occur repeatedly, a patient may be diagnosed with epilepsy. PURPOSE: The scope of this project is to develop an ambulatory seizure monitoring system that can be used away from a hospital, making it possible for the user to stay at home, and primary care personnel to monitor a patient's seizure activity in order to provide deeper analysis of the patient's condition and apply personalized intervention techniques. METHODS: The ambulatory seizure monitoring device is a research device that has been developed with the objective of acquiring a portable, clean electroencephalography (EEG) signal and transmitting it wirelessly to a handheld device for processing and notification. RESULT: This device is comprised of 4 phases: acquisition, transmission, processing and notification. During the acquisition stage, the EEG signal is detected using EEG electrodes; these signals are filtered and amplified before being transmitted in the second stage. The processing stage encompasses the signal processing and seizure prediction. A notification is sent to the patient and designated contacts, given an impending seizure. Each of these phases is comprised of various design components, hardware and software. The experimental findings illustrate that there may be a triggering mechanism through the phase lock value method that enables seizure prediction. CONCLUSION: The device addresses the need for long-term monitoring of the patient's seizure condition in order to provide the clinician a better understanding of the seizure's duration and frequency and ultimately provide the best remedy for the patient.

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.

Awake Neurophysiologically Guided versus Asleep MRI-Guided STN DBS for Parkinson Disease: A Comparison of Outcomes Using Levodopa Equivalents.

BACKGROUND: Deep brain stimulation (DBS) for Parkinson's disease (PD) has traditionally been performed in awake patients. Some patients are unable to tolerate awake surgery or extensive time off their medication to allow for neurophysiological testing during traditional DBS implantation, which has previously limited surgical options for these patients. Recently, asleep image-guided lead placement using intraoperative MRI or CT for verification has been proposed as an alternative for patients unable or unwilling to undergo awake DBS surgery. METHODS: We conducted a retrospective chart review comparing PD patients who underwent asleep MRI-guided subthalamic nucleus (STN) DBS lead placement (n = 14) and awake neurophysiologically guided STN DBS lead placement (n = 23) at our institution. Both groups' levodopa equivalent daily doses (LEDDs) and complications at approximately 6 months of follow-up were compared, along with operative times. RESULTS: Both groups showed statistically similar reductions in LEDD at 6 months of therapy (38.27% for awake, 49.27% for asleep; p = 0.4447), and similar complications. Operative times were initially longer for MRI-guided DBS but improved with surgical experience. CONCLUSION: Asleep MRI-guided DBS is a viable option for PD patients unable or unwilling to undergo awake placement, with similar results in terms of LEDD reduction and complications.

Wide-bore 1.5 T MRI-guided deep brain stimulation surgery: initial experience and technique comparison.

OBJECT: We report results of the initial experience with magnetic resonance image (MRI)-guided implantation of subthalamic nucleus (STN) deep brain stimulating (DBS) electrodes at the University of Wisconsin after having employed frame-based stereotaxy with previously available MR imaging techniques and microelectrode recording for STN DBS surgeries. METHODS: Ten patients underwent MRI-guided DBS implantation of 20 electrodes between April 2011 and March 2013. The procedure was performed in a purpose-built intraoperative MRI suite configured specifically to allow MRI-guided DBS, using a wide-bore (70 cm) MRI system. Trajectory guidance was accomplished with commercially available system consisting of an MR-visible skull-mounted aiming device and a software guidance system processing intraoperatively acquired iterative MRI scans. RESULTS: A total of 10 patients (5 male, 5 female)-representative of the Parkinson Disease (PD) population-were operated on with standard technique and underwent 20 electrode placements under MRI-guided bilateral STN-targeted DBS placement. All patients completed the procedure with electrodes successfully placed in the STN. Procedure time improved with experience. CONCLUSION: Our initial experience confirms the safety of MRI-guided DBS, setting the stage for future investigations combining physiology and MRI guidance. Further follow-up is required to compare the efficacy of the MRI-guided surgery cohort to that of traditional frame-based stereotaxy.

Image-guided convection-enhanced delivery into agarose gel models of the brain.

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. Neuroinfusion catheter CED allows for positive pressure bulk flow to deliver greater quantities of therapeutics to an intracranial target than traditional drug delivery methods. The clinical utility of real time MRI guided CED (rCED) lies in the ability to accurately target, monitor therapy, and identify complications. With training, rCED is efficient and complications may be minimized. The agarose gel model of the brain provides an accessible tool for CED testing, research, and training. Simulated brain rCED allows practice of the mock surgery while also providing visual feedback of the infusion. Analysis of infusion allows for calculation of the distribution fraction (Vd/Vi) allowing the trainee to verify the similarity of the model as compared to human brain tissue. This article describes our agarose gel brain phantom and outlines important metrics during a CED infusion and analysis protocols while addressing common pitfalls faced during CED infusion for the treatment of neurological disease.

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.

Perioperative brain shift and deep brain stimulating electrode deformation analysis: implications for rigid and non-rigid devices.

UNLABELLED: Deep brain stimulation (DBS) efficacy is related to optimal electrode placement. Several authors have quantified brain shift related to surgical targeting; yet, few reports document and discuss the effects of brain shift after insertion. OBJECTIVE: To quantify brain shift and electrode displacement after device insertion. Twelve patients were retrospectively reviewed, and one post-operative MRI and one time-delayed CT were obtained for each patient and their implanted electrodes modeled in 3D. Two competing methods were employed to measure the electrode tip location and deviation from the prototypical linear implant after the resolution of acute surgical changes, such as brain shift and pneumocephalus. In the interim between surgery and a pneumocephalus free postoperative scan, electrode deviation was documented in all patients and all electrodes. Significant shift of the electrode tip was identified in rostral, anterior, and medial directions (p < 0.05). Shift was greatest in the rostral direction, measuring an average of 1.41 mm. Brain shift and subsequent electrode displacement occurs in patients after DBS surgery with the reversal of intraoperative brain shift. Rostral displacement is on the order of the height of one DBS contact. Further investigation into the time course of intraoperative brain shift and its potential effects on procedures performed with rigid and non-rigid devices in supine and semi-sitting surgical positions is needed.

Robustness of implantable algorithms to detect epileptiform activity in the presence of broad-spectrum background noise.

Detection of epileptiform activity is of interest for responsive stimulation and diagnostic or monitoring devices in epilepsy; some implantable systems use low-computational-complexity algorithms such as line length trending and half-wave detection. Broadband noise was added to recorded electrocorticographic signals in order to model the potential impact of factors such as electrode-tissue interface properties and distance from the epileptic focus on these detection tools. Simulation demonstrated that half-wave and line length tools can yield consistent results in the presence of moderate amounts of noise.

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.

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. MATERIALS AND METHODS: A retrospective chart review was performed of all consecutive patients seen in the outpatient clinic for deep brain stimulation adjustments at the University of Wisconsin-Madison from February 2006 to May 2007. The following data were extracted: Quadrapolar contact selection, frequency, voltage, pulse width, and measured impedance at the therapeutic parameters. Patients were selected if consecutive measurements of therapeutic impedances for the same patient were performed with the same frequency, pulse width, voltage, and configuration of active contacts. RESULTS: A total of 63 patients with 110 electrodes had 301 documented programming visits. From these, 16 patients had 20 consecutive measurements with unchanged parameters in 19 electrodes at a median interval of 68 days and median follow-up of 549 days after implantation. No significant intra-patient intra-electrode therapeutic impedance variability was observed in this study (SD = 105.3 Ω, paired t-test, p= 0.312). In contrast, marked inter-patient variability in impedance was noted. This variability could not be explained by stimulation target, measurement interval, time since implantation, monopolar vs. bipolar stimulation, stimulation voltage, or stimulation frequency. CONCLUSIONS: No significant change in the same electrode therapeutic impedance was identified. Given the assumption that stimulation current is the critical parameter influencing clinical outcomes, these findings would not disadvantage constant voltage stimulation. However, inter-patient variability suggests a possible advantage for constant current stimulation when generalizing experience and comparisons over multiple patients. Further study of the relationship of stimulation efficacy to stimulation mode and impedance change is warranted.

Flexible thin film electrode arrays for minimally-invasive neurological monitoring.

We present approaches for using thin film polymeric electrode arrays for use in applications of minimally invasive neurological monitoring. The flexibility and unique surface properties of the thin-film polyimide substrate in combination with a compact device platform make them amenable to a variety of surgical implantation procedures. Using a rapid-prototyping and fabrication technique, arrays of various geometries can be fabricated within a week. In this paper we test two different approaches for deploying electrode arrays through small cranial openings.

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.