SAFETY AND EVIDENCE FOR EFFICACY OF AN IMPLANTABLE RESPONSIVE NEUROSTIMULATOR (RNS™) FOR THE TREATMENT OF MEDICALLY INTRACTABLE PARTIAL ONSET EPILEPSY IN ADULTS
1Gregory Worrell, 2Robert Wharen, 3Robert Goodman, 4Gregory Bergey,
5Anthony Murro, 6Donna Bergen, 6Michael Smith, 7David Vossler, and 8Martha Morrell.
1Department of Neurology, Mayo Clinic, Rochester, MN; 2Department of Neurosurgery, Mayo Clinic, Jacksonville, FL; 3Comprehensive Epilepsy Center, Columbia University, NYC, NY; 4Department of Neurology, Johns Hopkins University School of Medicine and Hospital, Baltimore, MD; 5Department of Neurology, Medical College of Georgia, Augusta, GA; 6Rush Epilepsy Center, Rush University Medical Center, Chicago, IL; 7Epilepsy Center, Swedish Neuroscience Inst., Seattle, WA; and 8NeuroPace, Inc., Mountain View, CA
Rationale: A multi-center clinical feasibility investigation was designed to assess the safety and explore evidence for efficacy of a cranially based implantable, programmable responsive neurostimulator (RNS system™) to treat adults with medically intractable partial onset seizures.
Methods: Adults with medically intractable partial onset seizures with an epileptogenic onset zone previously localized by standard diagnostic testing, were medically and psychiatrically stable, and did not have a history of nonepileptic seizures, primarily generalized seizures, or status epilepticus within the preceding year. Seizure frequency was recorded in daily diaries and seizure severity was evaluated by the Liverpool Seizure Severity Scale. Subjects with >4 disabling simple partial (SP) sensory or motor seizures, CPS or GTC seizures over 3 consecutive prospective 28-day periods were qualified to receive the RNS device, which was cranially implanted and connected to up to 2 leads containing 4 electrodes each (subdural or depth). Placement of the electrodes was determined by the investigational team. With 28 days post-op,
subjects received neurostimulation in response to investigator identified epileptogenic discharges (in an open design). Safety data was monitored continuously and efficacy data was analyzed for 3-28 day periods following the 28 days post-op.
Results: The responder rate ( > 50% reduction in seizures) was 43% for CPS and 35% for total disabling seizures (SP motor, CPS and GTC). The mean reduction in total disabling seizures, as analyzed by the generalized estimating equation (Poisson distribution), which controls for seizure variability, was significant at p=0.0006. Seizure severity was significantly reduced (p<0.0001). There were no serious device related adverse events and responsive neurostimulation was well tolerated.
Conclusion: A clinical feasibility investigation of the RNS system demonstrated a significant reduction in the frequency and severity of CPS and total disabling seizures. The safety experience was excellent. Responsive cortical stimulation utilizing an implantable programmable RNS may provide a safe and efficacious treatment for adults with medically intractable partial onset seizures.
Supported by NeuroPace, Inc.
 Return to Top
TOTAL CHARGE DELIVERED WITH RESPONSIVE NEUROSTIMUALTION CORRELATES WITH SEIZURE REDUCTION
1Joseph Drazkowski, 1Richard Zimmerman, 1Greg Worrell, 1David Chabolla, 1Joseph Sirven, 1Greg Cascino, 1Richard Marsh, 1Robert Wharen, 1Emily Mirro, and 1Brett Wingeier
1Neurology/Neurosurgery, Mayo Clinic; and 1NeuroPace, Inc.
Rationale: Adults with medically intractable partial onset seizures were implanted as part of a multi-center safety/feasibility study with a NeuroPace responsive neurostimulator system (RNSTM) to continuously monitor and record Electrocorticography (EcoG) from depth and/or subdural strip electrodes and deliver electrical stimulation upon detection of ictal activity. Delivery of responsive stimulation is controlled by selection of various stimulation parameters including: 1. pulse width, 2. frequency, 3. current and 4. burst duration. Stimulation may also be controlled by adjustment of detection sensitivity; detectors may be configured to respond to interictal and/or ictal onset activity. We sought to determine whether the amount of responsive stimulation correlates with a reduction in seizure frequency.
Methods: Subjects ages 18-65 with > 4 disabling seizures per month for 3 consecutive months were implanted with the RNS at 3 Mayo sites (Arizona, Rochester and Jacksonville). Clinical seizure counts (simple partial motor, complex partial and secondarily generalized) were collected for 3 months pre-implant and 4 months post-implant. Detection and responsive stimulation were enabled for a minimum of 3 months. The number of episodes treated with stimulation was recorded by each subject's implanted RNS device. Responsive stimulation settings (current, pulse width, frequency, and burst duration) and detection parameters were adjusted per clinical judgement during the study and varied among subjects. No burst durations > 3000 ms were delivered in response to a detection. The total amount of responsive stimulation delivered for each subject was quantified in terms of the total charge delivered over all electrodes in the leading phase of charge-balanced biphasic stimulation (the product of current, leading phase pulse width, pulses per stimulation burst, and number of stimulations delivered).
Results: As of May 3, 2005, data are presented for a three month analysis spanning days 28 through day 111 post-implant. Nine subjects were implanted and had responsive stimulation enabled for a minimum of 3 months. Monthly averages of episodes-treated-per-day ranged from 1.17 to 3750 per day (mean 1580). Monthly averages of charge-delivered-per-day (current x pulse width x number of pulses x stimulations per day) ranged from 0.114 millicoulombs to 224 millicoulombs (mean 74.8 millicoulombs). The total charge delivered over the analysis period was found to be related to a reduction in seizure frequency with a Pearson r correlation of -0.83 (significance p < 0.01).
Conclusion: An implanted RNS system delivered stimulation for at least 3 months in 9 patients. Increased delivery of responsive stimulation, as measured by total charge delivered, was found to be significantly correlated with reduction in clinical seizure frequency.
Supported by NeuroPace, Inc.
Return to Top
CRANIOPLASTIC TECHNIQUE FOR THE IMBEDDING OF THE RESPONSIVE NEUROSTIMULATOR SYSTEM
1Kost Elisevich, 1Gregory Barkley, 1Brien Smith, and 1David Greene
1Neurosurgery/Neurology, Henry Ford Hospital, Detroit, MI; and NeuroPace, Inc., Mountain View, CA
Rationale: The Responsive Neurostimulator System (RNS) is currently undergoing testing under an investigational device exemption from the FDA. The system consists of a cranially implanted pulse generator connected to strip and/or depth electrode arrays and an implantable ferrule for fixating the RNS to the cranium. The RNS is curved to allow for a contoured cranial placement. A cranial bed is required to implant the ferrule and generator unit. This bed is commonly produced by performing a full thickness craniectomy. We report an alternative method which affords certain advantages regarding the support and stability of the unit.
Methods: After placement of electrode arrays intracranially, a location and orientation for the RNS is determined and a template used to mark the cranium accordingly. Midas drills (M32, AM8) are used to mill the outer table and trabeculated bone to create a cranial bed within the defined site while preserving the inner table. This process requires 20 - 30 minutes and is performed in an iterative manner with the fit checked periodically. The ferrule is imbedded and secured to the cranium with 4 mm screws (Lorentz). The RNS is then attached to the ferrule with an integrated clamp. Any discontinuities between the ferrule, RNS and cranium are transitioned with methylmethacrylate cement to produce a smooth contour.
Results: Three patients were implanted using the described approach. All had previously undergone intracranial long term monitoring through craniotomies in the past. Following placement of the RNS, patients have been followed 2 - 3 months with good cosmetic results and no complaints of irregularities or auditory sensations resulting from isolated pockets of fluid in the construct.
Conclusions: In addition to providing additional structural support for the generator unit, preservation of the inner table allows for a foundation upon which a synthetic cranioplasty may be applied in the event of generator removal. A firm seating of the ferrule and generator unit with the additional application of methylmethacrylate creates a well-contoured surface that is mechanically noiseless.
Return to Top
CLOSED-LOOP STIMULATION IMPLANTABLE SYSTEM FOR THE MANAGEMENT OF FOCAL, MEDICALLY REFRACTORY EPILEPSY: IMPLANTATION TECHNIQUE AND PRELIMINARY RESULTS
1Kostas N Fountas, 1Joseph R Smith, 2Anthony M Murro, 2Jeffrey Politsky, 2Yong D Park, 1Patrick D Jenkins, and 3David Greene
1Neurosurgery, Medical College of Georgia, Augusta, GA; 2Neurology, Medical College of Georgia, Augusta, GA; and 3NeuroPace, Inc., Mountain View, CA
Study: A novel closed-loop stimulation system referred to as the Responsive Neurostimulator (RNSTM) system (NeuroPace, Inc., Mountain View, CA, USA) has been utilized in our institution for the treatment of patients with focal, drug-resistant epilepsy, who are not candidates for surgical resection. In our current communication, we present the surgical technique of implanted RNS, its complications and technical difficulties as well as the preliminary results in our prospective series.
Methods: The implantable RNS consists of a cranially, extradurally implanted pulse generator, one or two quadripolar strip or depth leads and a programmer. The RNS pulse generator continuously analyzes the patient's obtained electrocorticograms (ECoGs) and automatically triggers electrical stimulation when specific ECoG characteristics programmed by the clinician as indicative of electrographic seizures or precursor or epileptiform activities are detected. The pulse generator then stores diagnostic information detailing detections and stimulations, including multi-channel stored EcoGs.
The RNS programmer communicates transcutaneously with the implanted pulse generator when initiated by a clinician. The RNS programmer can download diagnostics and stored ECoGs for review. The RNS programmer can be used to analyze stored ECoGs to adjust the detection settings. The RNS programmer can then be used to program detection and stimulation parameters into the implanted pulse generator.
Six patients (2 males and 4 females, mean age 28.6y and age range between 17-42y) have been treated so far in our institution with the above mentioned device. All of these patients underwent phase I and phase II investigation for localization of their epileptogenic foci. Their workup included surface ictal and interictal EEG, brain MRI, video-EEG monitoring, neuropsychological evaluation and depth and strip electrode implantation for invasive EEG recording and ictal SPECT study.
Results: No complications related to the implantable system have occurred in our series. Our follow-up ranges between 4-16 months, mean follow-up time 9.2 months. Five of these patients (83.3%) had more than 45% decrease in their seizure frequency, with one patient (16.6%) demonstrating more than 75% decrease. The other patient (16.6%) had no change in his seizure frequency after implantation.
Conclusion: Our preliminary results support the ability of RNS in automatic detection and therapeutic abortion of seizures in patients with well-localized medically refractory epilepsy, not candidates for surgical resection. Further validation of our results is necessary.
Return to Top
RELATION BETWEEN SUBCLINICAL SEIZURES AND FOCUS LOCATION IN EPILEPTIC PATIENTS IMPLANTED WITH A RESPONSIVE NEUROSTIMULATOR
1Yong Park, 2Rosana Esteller, 1Anthony Murro, 1Jeffrey Politsky, 1Ki Lee, 1Patty Ray, 3 and Joseph Smith
1Neurology, Medical College of Georgia, Augusta, GA; 2NeuroPace, Inc., Mountain View, CA; and 3Neurosurgery, Medical College of Georgia, Augusta, GA
Rational: The Medical College of Georgia (MCG) is participating in a multicenter study approved by FDA and MCG IRB to evaluate feasibility, safety, and efficacy of a Responsive Neurostimulator System (RNS) in subjects with medically intractable seizures. Eight patients have been implanted with the RNS at MCG. Implanted patients are trained to upload data from their RNS to the Patient Data Management System (PDMS) by using a data transmitter (DTR) that downloads RNS' stored data to a portable computer and then uploads it through a telephone line into PDMS. Investigators can access PDMS through the Internet and review stored ECoGs and diagnostics. Using these resources, we are studying the relationship between clinical reported seizures and stored electrographic seizures (EGSz).
Methods: All data from six randomly chosen patients was reviewed marking all electrographic seizures date/times. This information was correlated with the clinical seizures reported in the patients' diaries. The RNS has a limited storage capability; therefore, in some instances stored ECoG(s) were overwritten by most recent ones.
Results: All patients except one with bilateral foci, have their focus on the left hemisphere. In the six patients analyzed a total of 170 seizures were stored until the moment of this analysis. From these EGSzs stored 28% (range:11%-75%) were clinical seizures. The patients with neocortical focus (2/6), hippocampal focus (2/6), and hippocampal/anterior subtemporal focus (2/6) reported 61%, 25%, and 12% of their EGSzs as clinical seizures, respectively. These observations suggest that neocortical patients have less subclinical seizures (39%) than hippocampal patients (75%), and the patients with diffuse ictal zone (hippocampal/anterior subtemporal) exhibited the highest rate of subclinical seizures (88%).
Conclusions: The RNS feasibility study has made possible for the first time, monitoring these patients intracranial EEG activity and storing their electrographic seizures on a daily basis, for an unlimited period of time, currently reaching up to 11 months in our first implanted patient. It is not surprising to find out that these patients experience many EGSz that either go unnoticed or have no clinical manifestations. The observations obtained in this initial phase of our on-going study are preliminary, and as time progresses with more patients added to the study results with statistical significance are expected.
Supported by NeuroPace, Inc.
Return to Top
EFFECTS OF ELECTRICAL STIMULATION PARADIGM ON SEIZURE FREQUENCY IN MEDICALLY INTRACTABLE PARTIAL SEIZURE PATIENTS WITH A CRANIALLY IMPLANTED RESPONSIVE CORTICAL NEUROSTIMULATOR
1Jeffrey M Politsky, 2Rosana Estellar, 1Anthony M Murro, 1Joseph R Smith, 1Patty Ray, 1Yong D Park, and 2Martha J Morrell
1Neurosciences, Medical College of Georgia, Augusta, GA; and 2NeuroPace, Inc., Mountain View, CA
Rationale: Eight adults with intractable partial seizures have received a cranially implanted responsive cortical neurostimulator (NeuroPace RNS? at the Medical College of Georgia (MCG) as part of an FDA approved trial to evaluate safety and to assess effects on seizures. Electrical stimulation configurations are broadly divided into mono-polar and bipolar paradigms. Debate exists regarding whether the most effective stimulation paradigm includes monopolar or bipolar configurations, since several variables such as etiology, location of seizure focus or foci, size of epileptogenic zone, and rate and pathway of spread of electrical activity may impact therapeutic response. We analyzed the various electrical stimulation paradigms according to the effect on seizure frequency in six patients participating in an open-label period of the trial.
Methods: All electrode configurations implemented in the six open label patients at MCG and their respective seizure outcomes were reviewed. Etiology, seizure focus or foci, relative size of epileptogenic zone, and rate and pathway of spread of epileptic activity were noted in all patients.
Results: The mean time since device implantation was 8 months (range 6-10). Three patients had multiple seizure foci (involving both hemispheres). All patients underwent lead implantation into one (5/6; 4 left, 1 right) or both (1/6) temporal regions. Only one patient (with bilateral hippocampal sclerosis) received one lead. Cathodal monopolar stimulation was used in 5 of 6 patients and bipolar stimulation was used in 3 of 6 patients; 2/3 with depth electrodes only and 1/3 with two 4-contact subdural strips. Five of six patients have experienced a reduction in seizure frequency of 45% or greater since device implantation (four patients have experienced a reduction in seizure frequency of 75% or greater); one patient is seizure-free. Seizures have increased in one patient with multiple seizure foci.
Conclusion: Seizure frequency was reduced in a small number of adults with medically intractable partial seizures using either cathodal monopolar or bipolar stimulation paradigms. Though bipolar stimulation was used more exclusively in patients with depth electrodes, bipolar (intra-lead) stimulation appeared to have a favorable effect in patients with small seizure foci (e.g. hippocampal sclerosis), whereas cathodal monopolar stimulation may be effective in patients with larger epileptogenic zones or multiple epileptic foci.
Supported by NeuroPace, Inc.
Return to Top
COMPLEMENTING THE RESPONSIVE NEUROSTIMULATOR SYSTEM WITH A PATIENT OPERATED DATA TRANSMITTER - ON DEMAND MONITORING IN THE OUTPATIENT ENVIRONMENT
1Eva Katharina Ritzl, 1Eric Kossoff, 1Gregory Bergey, 1Pam Coe, and 2Deepak Gupta
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; and NeuroPace, Inc., Mountain View, CA
Rationale: The Responsive Neurostimulator System (RNS ) is an investigational device currently undergoing study for the treatment of intractable epilepsy. The RNS continuously monitors cortical activity and delivers stimulation in response to detected epileptiform activity. The RNS is capable of storing detailed diagnostics and electrocorticograms (ECOGs), but has limited internal memory capabilities. As a result, patients being seen on a typical follow-up schedule will have much of the collected diagnostic data overwritten prior to their infrequent office visits. To provide better follow-up and a more continuous diagnostic record, a patient operable Data Transmitter (DTR) has been developed.
Methods: IRB approval was obtained for the investigational use of the RNS and DTR as part of a multicenter trial. Five patients have been implanted with RNS's at our center. All have been given DTR's. Interrogation of the RNS is accomplished by simply placing the DTR wand over the RNS. Data transfer occurs via transcutaneous telemetry. On an intermittent basis, the DTR is connected to a phone line and data is transmitted to the secure server where it can be viewed by the treating physician over any Internet connected computer.
Results: All patients were able to use the DTR without difficulty. Each patient established a flexible interrogation schedule in keeping with his or her treatment requirements and lifestyle. Immediate interrogation after the occurrence of a break through seizure provided valuable information in individual cases.
The time required to download data from the RNS to the DTR ranged from 20 seconds to 3 minutes for an RNS with a full memory buffer. The phone line transmission time was dependent on the amount of data collected since the last transmission, but was usually less than 10 minutes.
An example of an ECOG downloaded and transmitted by the DTR is shown in figure 1. The upper panel is the entire ECOG (90 seconds) and the lower panel is a scrollable 10-second view. Detailed reports are also available on the secure server and provide summary statistics since the last interrogation.
Conclusion: The DTR allows remote assessment of RNS data regarding detections and stimulations, as well as ECOG captured according to a schedule or in response to a clinical event. Patients were able to use the device with ease. The clinician can then make treatment decisions based on objective, quantitative real-time clinical data.
Supported by NeuroPace, Inc.
Return to Top
CHRONIC MEASUREMENT OF INCREASED EPILEPTIFORM ACTIVITY DURING MENSES USING THE RESPONSIVE NEUROSTIMULATOR SYSTEM (RNS) IN A PATIENT WITH CATAMENIAL SEIZURES
1Mariana Spanaki, 1,2Brien Smith, 1David Burdette, 3David Greene, 3Martha Morrell, and 1,2Gregory Barkley
1Neurology Dept, Henry Ford Hospital, Detroit, MI; 2Neurology Dept, Wayne State University, Detroit, MI; and 3NeuroPace, Inc., Mountain View, CA
Rationale: Seizure frequency is known to increase during the perimenstrual period in some patients. Thus far, no electrophysiological studies have documented alterations in human brain excitability in related to menses. In patients implanted with the NeuroPace Inc responsive neurostimulator (RNS ), epileptiform activity can be quantified over the menstrual cycle.
Methods: FDA and IRB approval were obtained for the investigational use of the RNS. A 22 year-old female with intractable seizures who was not a resective surgery candidate was implanted with the RNS. The RNS detection parameters were optimized during the first month with a line length tool utilized to detect a spike train pattern and a half wave tool for a gamma burst pattern. The RNS provides a detailed record of event detections and records electrocorticograms (ECoGs) that can be viewed by the clinician. The patient received a Data Transmitter (DTR) that could download ECoGs and detailed diagnostic data from their RNS and transmit the data over a telephone line to a secure server for review and analysis via the Internet. These downloads were typically performed by the patient twice per day. During the second month post-implant, the patient's detection rate per hour was calculated based on these diagnostic data.
 Results: Detections were graphed according to the patient's menstrual cycle. Detections were compared during menses as opposed to all other times of the cycle (non-menses). The daily detection rates during menses were 27.3+5.5 compared to 16.6+5.4 at other times of her cycle. The results were
significantly different at alpha = 0.05 level (95% confidence).
Conclusion: The RNS device provides objective quantification of epileptiform activity which can be correlated with the phases of the menstrual cycle. This preliminary data demonstrates that epileptiform activity in this patient increases in the premenstrual period and remains increased during menses. Ongoing data collection in this and other patients in the RNS Feasibility Clinical Investigation is permitting the first large scale chronic objective evaluation of the nature of epileptiform activity over multiple menstrual cycles in women with catamenial epilepsy.
Supported by NeuroPace, Inc.
Return to Top
AMBULATORY INTRACRANIAL ICTAL ELECTROCORTICOGRAM PATTERNS RECORDED CHRONICALLY USING THE FIRST IMPLANTED, SELF-CONTAINED ECOG RECORDING AND ANALYSIS INSTRUMENT
1David G Vossler, and 2Thomas Tcheng
1Epilepsy Center, Seattle Neuroscience Institute at Swedish Medical Center, Seattle, WA; and NeuroPace, Inc., Mountain View, CA
Rationale: The NeuroPace Responsive Neurostimulator System (RNS) is a fully implanted device currently being tested in a clinical trial. The RNS records electrocorticograms (ECoG) from subdural strip and depth electrodes implanted in or near the seizure focus when epileptiform discharges are detected. These ECoGs can later be retrieved and analyzed. This trial provides the first opportunity to analyze ambulatory ictal ECoG. The goal of this study is to analyze the range of intracranial ictal discharge patterns observed in an ambulatory patient population.
Methods: ECoG records, each containing 30 seconds to 4 minutes of ECoG from up to 8 electrodes, were recorded by RNS devices implanted in study patients. ECoG storage was triggered manually or by pattern detection, responsive stimulation or amplifier saturation. Thus, the sampling of ECoGs is heavily biased towards ECoGs that contain ictal discharge patterns. Artifacts from telemetry dropouts and stimulation were removed. The RNS detection algorithm was configured to detect specific ictal discharge patterns including: 1) increasing amplitude, 2) amplitude attenuation, 3) 1-4 Hz sinusoidal waves or spikes, 4) 4-30 Hz theta, alpha or beta frequency patterns, and 5) 13-125 Hz gamma frequency activity. The RNS detection algorithm was applied to all of the ECoG records and ECoG classifications were visually corroborated. Descriptive statistics were calculated for each ictal pattern. Within each patient, the number of ECoGs containing each pattern was calculated and the patterns were categorized by electrode location.
Results: A preliminary analysis using a computerized "increasing amplitude" detector tuned to a 150% area under-the-curve increase comparing a 4-second short-term window with a 2-minute long-term window produced the following results. From 47 patients, 35,838 ECoG records totaling 634.4 hours were analyzed. Of these, 7,637 (21%) of the ECoGs contained the "increasing amplitude" pattern. ECoGs containing this pattern were recorded from temporal (61%), frontal (22%), parietal (11%) and other (6%) areas. For each patient, the percentage of ECoGs containing the pattern was calculated. Across all patients, the average rate of occurrence of pattern-containing ECoGs was 20.5% 16.6% SD, ranging from 0.3% to 67.7%. Additional analysis will compare the rate of occurrence of the various ictal discharge patterns with respect to brain area and etiology.
Conclusions: The results of this analysis suggest that chronic ambulatory electrocortigraphy patterns and frequencies are identical to those observed in acute electrocortography. Differences in ictal discharge patterns between brain areas and epilepsy etiologies are likely to be observed.
Funding Supported By: NIST Advanced Technology Program Cooperative Agreement No. 70NANB3H3044
Return to Top
RESPONSIVE NEUROSTIMULATION FOR EPILEPSY - AN ASSESSMENT OF SAFETY
1Richard S Zimmerman, 2W Richard Marsh, 3Robert E Wharen, 4Joseph F Drazkowski, 5Gregory A Worrell, 6David R Chabolla, 4Joseph R Sirven, and 5Gregory D Cascino
1Neurosurgery, Mayo Clinic, Phoenix, AZ; 2Neurosurgery, Mayo Clinic, Rochester, MN; 3Neurosurgery, Mayo Clinic, Jacksonville, FL; 4Neurology, Mayo Clinic, Phoenix, AZ; 5Neurology, Mayo Clinic, Rochester, MN; and 6Neurology, Mayo Clinic, Rochester, MN
Rationale: As part of a multicenter feasibility study with the primary endpoint of patient safety, patients with intractable partial onset seizures were implanted with a responsive neurostimulator system (NeuroPace RNSTM). This continuously monitors and records ECoGs from depth/subdural electrodes and delivers electrical stimulation when ictal discharges are detected. A significant aspect of safety relates to the tolerability of multiple stimulations at or near an epileptogenic focus.
Methods: Subjects ages 18-65 with > 4 disabling, partial seizures/month for 3 consecutive months were implanted with the RNS system. Responsive stimulation (therapy) was enabled after surgery according to the IRB approved protocol. Each subject underwent test stimulation when therapy was enabled to ensure that acute stimulation was well tolerated. Although some received less, the maximum responsive stimulation current delivered to any patient was 12 mA. Adverse events (AEs) were assessed throughout the study. The number of stimulations delivered per day was recorded for each subject.
Results: Data is current as of 5/3/2005. 13 subjects were enrolled at 3 Mayo Clinic sites (Phoenix AZ, Rochester MN, and Jacksonville FL). 80 AEs of any nature were reported for these 13 subjects, with no definite device related adverse events. 10 events were recorded as uncertain to be related to the device. One subject experienced eye blinking associated with stimulation but this habituated within minutes. Therapy was enabled in 11 subjects with a range of 48 to 260 days (mean 142.8). Therapies per day ranged from 136.8 to 592 (mean 345.6). The maximum total duration of stimulation received over 24 hours was 1.7 minutes.
| Location of Stimulation |
# of Subjects |
# of Stimulations/Day |
| Dominant lateral frontal |
3 |
353.7 |
| Nondominant lateral frontal |
3 (2 enabled) |
295.8 |
| Dominant lateral temporal |
4 |
330.2 |
| Occipital |
1 |
not enabled |
| Dominant hippocampus |
1 |
241.2 |
| Nondominant hippocampus |
1 |
323.6 |
|
Conclusion: The RNS system has been implanted in 13 subjects with no definite device related adverse events. Responsive stimulation was activated in 11 subjects at both cortical and subcortical locations near seizure foci, and was well tolerated in all. Despite delivery of multiple stimulations per day, total daily stimulation duration ranged from seconds to 2 minutes. In this small sample, there were no differences in numbers of stimulations delivered according to anatomic location of treatment. This feasibility data suggests that responsive stimulation is well tolerated, even when delivered hundreds of times each day at or near an epileptogenic focus.
Supported by NeuroPace, Inc.
Return to Top
|
