Citations

Summary Objective To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Methods Randomized multicenter double‐blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period ( OLP ) to complete 2 years of postimplant follow‐up. Results All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Significance Responsive stimulation to the seizure focus reduced the frequency of partial‐onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial‐onset seizures.

SummaryObjectiveSeizures are currently defined by their electrographic features. However, neuronal networks are intrinsically dependent on neurotransmitters of which little is known regarding their periictal dynamics. Evidence supports adenosine as having a prominent role in seizure termination, as its administration can terminate and reduce seizures in animal models. Furthermore, microdialysis studies in humans suggest that adenosine is elevated periictally, but the relationship to the seizure is obscured by its temporal measurement limitations. Because electrochemical techniques can provide vastly superior temporal resolution, we test the hypothesis that extracellular adenosine concentrations rise during seizure termination in an animal model and humans using electrochemistry.MethodsWhite farm swine (n = 45) were used in an acute cortical model of epilepsy, and 10 human epilepsy patients were studied during intraoperative electrocorticography (ECoG). Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS)–based fast scan cyclic voltammetry (FSCV) and fixed potential amperometry were obtained utilizing an adenosine‐specific triangular waveform or biosensors, respectively.ResultsSimultaneousECoG and electrochemistry demonstrated an average adenosine increase of 260% compared to baseline, at 7.5 ± 16.9 s with amperometry (n = 75 events) and 2.6 ± 11.2 s withFSCV(n = 15 events) prior to electrographic seizure termination. In agreement with these animal data, adenosine elevation prior to seizure termination in a human patient utilizingFSCVwas also seen.SignificanceSimultaneousECoG and electrochemical recording supports the hypothesis that adenosine rises prior to seizure termination, suggesting that adenosine itself may be responsible for seizure termination. Future work using intraoperativeWINCS–basedFSCVrecording may help to elucidate the precise relationship between adenosine and seizure termination.

Background: The expertise required for proper electroencephalography (EEG) setup can make the 10-20 array unwieldy in the hospital setting. There may be a role for an EEG array with reduced leads to improve the efficiency of inpatient practice. Methods: Clips from 100 EEG records, 50 ictal and 50 non-ictal, in adult inpatients from January 1, 2007, to January 1, 2012, were retrospectively reviewed and selected for digital lead reduction and blind review. Two epileptologists reviewed these tracings and documented the presence of seizures and severe disturbance of background. The reduced array included 7 leads spanning the scalp. Three different montages were available. Sensitivity and specificity of the reduced array were calculated using the formal EEG report as the comparison standard. Results: For the detection of any seizure, the reduced array EEG had a sensitivity of 70% and specificity of 96%. Sensitivity for identifying encephalopathic patterns was 62% and specificity was 86%. Focal seizures were more readily identified by the reduced array (20 of 25) than were generalized ictal patterns (13 of 25). Conclusion: The reduced electrode array was insufficiently sensitive to seizure detection. Reducing EEG leads might not be a preferred means of optimizing hospital EEG efficiency.

High-frequency oscillations (HFO; gamma: 40–100 Hz, ripples: 100–200 Hz, and fast ripples: 250–500 Hz) have been widely studied in health and disease. These phenomena may serve as biomarkers for epileptic brain; however, a means of differentiating between pathological and normal physiological HFO is essential. We categorized task-induced physiological HFO during periods of HFO induced by a visual or motor task by measuring frequency, duration, and spectral amplitude of each event in single trial time-frequency spectra and compared them to pathological HFO similarly measured. Pathological HFO had higher mean spectral amplitude, longer mean duration, and lower mean frequency than physiological-induced HFO. In individual patients, support vector machine analysis correctly classified pathological HFO with sensitivities ranging from 70–98% and specificities >90% in all but one patient. In this patient, infrequent high-amplitude HFO were observed in the motor cortex just before movement onset in the motor task. This finding raises the possibility that in epileptic brain physiological-induced gamma can assume higher spectral amplitudes similar to those seen in pathologic HFO. This method if automated and validated could provide a step towards differentiating physiological HFO from pathological HFO and improving localization of epileptogenic brain.

Purpose. To investigate EEG and SPECT in the surgical outcome of patients with normal MRI (nonlesional) and extratemporal lobe epilepsy. Methods. We retrospectively identified 41 consecutive patients with nonlesional extratemporal epilepsy who underwent epilepsy surgery between 1997 and 2007. The history, noninvasive diagnostic studies (scalp EEG, MRI, and SPECT) and intracranial EEG (iEEG) monitoring was reviewed. Scalp and iEEG ictal onset patterns were defined. The association of preoperative studies and postoperative seizure freedom was analyzed using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard. Results. Thirty-six of 41 patients had adequate information with a minimum of 1-year followup. Favorable surgical outcome was identified in 49% of patients at 1 year, and 35% at 4-year. On scalp EEG, an ictal onset pattern consisting of focal beta-frequency discharge (>13–125 Hz) was associated with favorable surgical outcome (P=0.02). Similarly, a focal fast-frequency oscillation (>13–125 Hz) on iEEG at ictal onset was associated with favorable outcome (P=0.03). Discussion. A focal fast-frequency discharge at ictal onset identifies nonlesional MRI, extratemporal epilepsy patients likely to have a favorable outcome after resective epilepsy surgery.