David C. Spencer

Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

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.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Psychogenic nonepileptic seizures in US veterans

Objectives: Psychogenic nonepileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) and can result in significant long-term disability. We reviewed our experience with veterans undergoing seizure evaluation in the EMU to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug (AED) treatment. We compared veterans with PNES to civilians with PNES studied in the same EMU. Methods: We reviewed records of all patients admitted to one Veterans Affairs Medical Center (VAMC) EMU over a 10-year interval. These patients included 203 veterans and 726 civilians from the university affiliate. The percentage of patients with PNES was calculated for the veteran and civilian groups. Fifty veterans with only PNES were identified. Each veteran with PNES was matched to the next civilian patient with PNES. The 2 groups were compared for interval from onset of the habitual spells to EMU diagnosis, cumulative AED treatment, and other measures. Results: PNES were identified in 25% of veterans and 26% of civilians admitted to the EMU. The delay from onset of spells to EMU diagnosis averaged 60.5 months for veterans and 12.5 months for civilians (p < 0.001). Cumulative AED treatment was 4 times greater for veterans with PNES as compared to civilians (p < 0.01). Fifty-eight percent of veterans with PNES were thought to have seizures related to traumatic brain injury. Conclusions: The results indicate a substantial delay in the diagnosis of PNES in veterans as compared to civilians. The delay is associated with greater cumulative AED treatment.

Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers

We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs.

The Role of the Intracarotid Amobarbital Procedure in Evaluation of Patients for Epilepsy Surgery

Purpose: To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization‐related epilepsy.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography

Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video–electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology

Objective: To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. Methods: An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. Results and recommendations: The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case.

Laterality and temporal distribution of seizures in patients with bitemporal independent seizures during a trial of responsive neurostimulation

We describe seizure laterality and temporal seizure patterns in six subjects with bilateral temporal lobe epilepsy (bTLE) implanted with bilateral hippocampal depth electrodes and the NeuroPace RNS™ system over 84 consecutive days. Seizures were disproportionate in laterality in three subjects and disproportionate in time for two subjects. Clustering of seizures did not clearly affect laterality. Some but not all subjects with bTLE displayed nonrandom temporal or lateral clustering of seizures.

Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring.

Previous studies reporting circadian patterns of epileptiform activity and seizures are limited by (1) short‐term recording in an epilepsy monitoring unit (EMU) with altered antiepileptic drugs (AEDs) and sleep, or (2) subjective seizure diary reports. We studied circadian patterns using long‐term ambulatory intracranial recordings captured by the NeuroPace RNS System.

Topiramate effects on the EEG and alertness in healthy volunteers: A different profile of antiepileptic drug neurotoxicity☆

OBJECTIVE Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness. METHODS Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400mg/day for TPM or 3600 mg/day for GBP, over a 10-week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test-retest changes for all measures were scored against similar test-retest distributions previously obtained from untreated healthy volunteers. RESULTS TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT. CONCLUSIONS TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP.