The effect of increased intracranial EEG sampling rates in clinical practice.

OBJECTIVE: Recent research suggests that high frequency intracranial EEG (iEEG) may improve localization of epileptic networks. This study aims to determine whether recording macroelectrode iEEG with higher sampling rates improves seizure localization in clinical practice. METHODS: 14 iEEG seizures from 10 patients recorded with >2000 Hz sampling rate were downsampled to four sampling rates: 100, 200, 500, 1000 Hz. In the 56 seizures, seizure onset time and location was marked by 5 independent, blinded EEG experts. RESULTS: When reading iEEG under clinical conditions, there was no consistent difference in time or localization of seizure onset or number of electrodes involved in the seizure onset zone with sampling rates varying from 100 to 1000 Hz. Stratification of patients by outcome did not improve with higher sampling rate. CONCLUSION: When utilizing standard clinical protocols, there was no benefit to acquiring iEEGs with sampling rate >100 Hz. Significant variability was noted in EEG marking both within and between individual expert EEG readers. SIGNIFICANCE: Although commercial equipment is capable of sampling much faster than 100 Hz, tools allowing visualization of subtle high frequency activity such as HFOs will be required to improve patient care. Quantitative methods may decrease reader variability, and potentially improve patient outcomes.

Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The U.S. E-37 Trial.

OBJECTIVES: The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and long- term clinical outcomes of the device stimulating in all modes. MATERIALS AND METHODS: The E-37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR(®) in subjects with drug-resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events. RESULTS: Twenty implanted subjects (ages 21-69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3). CONCLUSIONS: The Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements.

Intraoperative monitoring for intracranial aneurysms: the Michigan experience.

Intraoperative neurophysiological monitoring is routinely used during the repair (endovascular or microsurgical) of intracranial aneurysms at major centers. There is a continued need of data sets from institutions with dedicated intraoperative neurophysiological monitoring services to further define the predictive factors of postoperative neurological deficits. We retrospectively reviewed and analyzed our database of all patients who underwent repair of intracranial aneurysms (endovascular or microsurgical). A total of 406 patients underwent 470 procedures. The changes were noted during monitoring in 3.83% of the cases. Most of the changes were first detected in somatosensory evoked potential (88.89%) followed by brainstem auditory evoked potential (16.67%). Changes were completely reversible in 44.44%, only partly reversible in 22.22%, and irreversible in 33.33% of cases. Intraoperative neurophysiological monitoring changes demonstrated high sensitivity, specificity, and negative predictive value for postoperative neurological deficits. The association between intraoperative neurophysiological monitoring changes and Glasgow outcome scale was significant for reversible changes compared against irreversible and partly reversible changes. Presence of any intraoperative neurophysiological monitoring modality change during repair of intracranial aneurysm may suggest a higher risk for postoperative neurological deficits. Reversibility of the changes is a favorable marker, whereas irreversible changes are predictive of postoperative neurological deficits with deterioration of Glasgow outcome scale on a longer follow-up.

Nonepileptic paroxysmal events in a pediatric population.

Nonepileptic paroxysmal events in children are common, and may be more diverse in etiology than those seen in adults. We determined the types of nonepileptic events that are most prominent in the pediatric population, and stratified those events by age group. Ninety-four of 416 pediatric patients monitored during a 3-year period (23%) were found to have had nonepileptic events. Thirty-eight percent of these children were diagnosed with psychogenic nonepileptic seizures, and 72% of those were adolescents. In children younger than 5 years of age, behavioral events and parasomnias were the most common mimickers of epilepsy. Other events, including stereotyped movements and myoclonus, were also diagnosed. We suggest that children with refractory paroxysmal events should be considered for early inpatient monitoring.

Formulation of current density weighted indices for correspondence between functional MRI and electrocortical stimulation maps.

OBJECTIVE: Accurate localization of functionally significant brain regions reduces risks of post-operative neurological deficits. The gold standard for presurgical brain mapping is subdural electrocortical stimulation (ECS), which is an open-cranium surgical procedure. Functional MRI (fMRI) may be a noninvasive alternative if it can be shown that fMRI and ECS maps are spatially consistent. We formulate new 3D current density weighted ECS-fMRI correspondence indices and illustrate their use on human data. METHODS: Current density maps were computed for simulated and human datasets by solving the electrostatic Laplace equation. The proposed indices were characterized and compared with fixed radii and Euclidean distance indices. RESULTS: Results from simulated datasets showed that the proposed indices quantify correspondence between fMRI and the ECS truth predictably, and provide conspicuous sensitivity increase from fixed radii indices, whereas Euclidean distances may not be suitable measures of the correspondence. CONCLUSIONS: The proposed indices reflect contextual information from surrounding electrodes and may be physiologically more meaningful in evaluating ECS-fMRI correspondence. SIGNIFICANCE: To identify safe limits of resection, an ECS map requires placement of electrodes on a patient's brain. Our proposed indices accurately quantify ECS-fMRI correspondence and may be used to evaluate fMRI as a noninvasive alternative for defining resection limits.

Oxcarbazepine in infants and young children with partial seizures.

In this open-label study, the safety, tolerability, and pharmacokinetics of oxcarbazepine as monotherapy or adjunctive therapy were studied in infants and young children with partial seizures. In a 30-day treatment phase, oxcarbazepine was titrated from 10 mg/kg/day to 60 mg/kg/day. Blood samples for analysis of the oxcarbazepine metabolite, the 10-monohydroxy derivative (MHD), were obtained at regular intervals. Patients completing the treatment phase entered a 6-month extension phase. Safety and tolerability were assessed throughout the study. Twenty-four patients (mean [range] age, 20.4 [2-45] months) were enrolled. Nineteen (79%) patients completed the treatment phase and, together with one patient who discontinued prematurely during the treatment phase, entered the extension phase. Thirteen of 20 (65%) patients completed the extension phase. The most common adverse events were pyrexia, ear infection, and irritability. Whether patients (n = 23) received enzyme-inducing antiepileptic drugs or not, MHD concentrations were consistent with those predicted from a linear, one-compartment, population-pharmacokinetic model based on a model previously fitted for 3- to 17-year-old children. Oxcarbazepine was safe and well tolerated in infants and young children. The pharmacokinetic profile of MHD was predicted by extension of a model based on older children.

Diagnostic and localizing value of ictal SPECT in patients with nonconvulsive status epilepticus.

In this study, we evaluate the diagnostic and localizing value of SPECT in three patients with nonconvulsive status epilepticus (NCSE). Our results indicate that ictal/subtraction ictal SPECT is a useful complementary noninvasive diagnostic test in patients with focal NCSE. This is especially the case when the EEG findings are inconclusive and for patients in whom surgical treatment is being considered.

Efficacy of topiramate in children with refractory status epilepticus.

PURPOSE: Status epilepticus (SE) is a life-threatening medical condition associated with significant morbidity and mortality that requires urgent medical intervention. Although several agents are available to treat SE, they occasionally fail to abort seizure activity. Topiramate (TPM) was anecdotally reported to be effective in adult patients with refractory SE. In this study, we evaluated the efficacy of TPM administered to children with this condition. METHODS: We retrospectively reviewed the pediatric SE database at the University of Michigan Medical Center and identified three children with refractory SE who were treated with TPM. Those children failed to respond to treatment with benzodiazepines, phenytoin, phenobarbital, midazolam, or pentobarbital. Additional treatment with TPM was administered by nasogastric tube. All patients were continuously monitored by 21-channel digital EEG machines, and the diagnosis of SE was made by a board-certified neurophysiologist. RESULTS: The ages of the three children were 4.5 months, 34 months, and 11 years. TPM was initiated at 2 mg/kg/day in two children and at 3 mg/kg/day in the third. The status was terminated in all three children within 24 h of maintenance therapy with TPM at 5-6 mg/kg/day. CONCLUSIONS: These results support the potential efficacy of TPM for children with refractory SE. Larger prospective series are needed to confirm those results.

Relationship of epileptic seizures to sleep stage and sleep depth.

STUDY OBJECTIVES: Interictal epileptiform discharges (IEDs) are facilitated by NREM stages 3 and 4 sleep and as sleep is deepening. To determine whether sleep influences seizures in a similar way to IEDs, we examined seizure rates in various stages of sleep in epilepsy patients undergoing overnight video-EEG-polysomnography (VPSG). DESIGN: Cross-sectional study. SETTING: Neurology Department. PATIENTS, MEASUREMENTS, AND INTERVENTIONS: We reviewed VPSGs from our Sleep and Epilepsy Laboratories to identify patients with recorded seizures during sleep. A total of 55 patients having 117 seizures were identified. RESULTS: Ninety-five percent of seizures occurred in NREM sleep (61% in stage 2, 20% in stage 1, 14% in stages 3 and 4 combined), and 5% in REM sleep. Adjusting for time spent in each stage of sleep, patients had 0.34 seizures per hour in stage 1, 0.38 seizures per hour in stage 2, 0.29 seizures/hr in stage 3 and 4 combined, and 0.09 seizures per hour in REM sleep. Seizures/hour was higher in NREM sleep (0.35 for NREM and 0.09 for REM; p=0.0001). For single seizures occurring in 1 night, seizure rate was significantly higher in NREM stages 1 and 2 as compared to NREM stages 3 and 4 sleep. A significant increase in log delta power, an automated measure of sleep depth, was observed in the 10 minutes prior to seizures. CONCLUSIONS: Both seizures and IEDs are facilitated by NREM sleep. While deeper stages of NREM sleep activate IEDs, lighter stages of NREM sleep promote seizures, at least for single seizures occurring in 1 night.

Interictal epileptiform discharges do not change before seizures during sleep.

PURPOSE: Whether interictal epileptiform discharges (IEDs) increase, decrease, or are unchanged before epileptic seizures has implications for the pathophysiology of epilepsy. Prior studies relating IEDs and seizures have not demonstrated a change in IEDs before seizures. However, they have not controlled for changes in the depth of sleep. Our objective was to test the hypothesis that IEDs are related to seizures during sleep while adjusting for log delta power (LDP), a continuous measure of sleep depth. METHODS: Twenty-two seizures during sleep were identified in 16 subjects with epilepsy admitted for presurgical monitoring. The IEDs that occurred in the hour of sleep before each seizure were used to test the relation between IEDs and seizure occurrence. Sleep depth was measured by LDP (quantity of 1- to 4-Hz activity in 30-s epochs), and records were scored visually for sleep staging and for IEDs. Multivariate logistic regression analyses were applied. RESULTS: Adjusting for LDP, number of seizures before the current seizure, quartile of the night, and total number of IEDs that occurred during the night, IED did not increase or decrease before seizures (p > 0.1). The rate of IEDs increased directly with LDP (p=0.0001), as shown in prior work. CONCLUSIONS: IEDs are not activated or suppressed before seizures during sleep, suggesting that different pathophysiologic processes underlie these two phenomena. These results corroborate prior studies, while providing a more advanced analysis by adjusting for sleep depth and applying multivariate logistic regression analyses.