Trends in the use of automated algorithms for the detection of high-frequency oscillations associated with human epilepsy.

High-frequency oscillations (HFOs) in intracranial electroencephalography (EEG) are a promising biomarker of the epileptogenic zone and tool for surgical planning. Many studies have shown that a high rate of HFOs (number per minute) is correlated with the seizure-onset zone, and complete removal of HFO-generating brain regions has been associated with seizure-free outcome after surgery. In order to use HFOs as a biomarker, these transient events must first be detected in electrophysiological data. Because visual detection of HFOs is time-consuming and subject to low interrater reliability, many automated algorithms have been developed, and they are being used increasingly for such studies. However, there is little guidance on how to select an algorithm, implement it in a clinical setting, and validate the performance. Therefore, we aim to review automated HFO detection algorithms, focusing on conceptual similarities and differences between them. We summarize the standard steps for data pre-processing, as well as post-processing strategies for rejection of false-positive detections. We also detail four methods for algorithm testing and validation, and we describe the specific goal achieved by each one. We briefly review direct comparisons of automated algorithms applied to the same data set, emphasizing the importance of optimizing detection parameters. Then, to assess trends in the use of automated algorithms and their potential for use in clinical studies, we review evidence for the relationship between automatically detected HFOs and surgical outcome. We conclude with practical recommendations and propose standards for the selection, implementation, and validation of automated HFO-detection algorithms.

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome.

OBJECTIVE: High frequency oscillations (HFO) between 80-500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting. METHODS: Spikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed. RESULTS: 24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome. CONCLUSIONS: Scalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome. SIGNIFICANCE: Analysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.

Sudden unexpected death in epilepsy in patients treated with brain-responsive neurostimulation.

OBJECTIVE: To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System. METHODS: All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. RESULTS: There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036 patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant years. Stored electrocorticograms around the time of death were available for 4 patients with probable/definite SUDEP and revealed the following: frequent epileptiform activity ending abruptly (n = 2), no epileptiform activity or seizures (n = 1), and an electrographic and witnessed seizure with cessation of postictal electrocorticography (ECoG) activity associated with apnea and pulselessness (n = 1). SIGNIFICANCE: The SUDEP rate of 2.0/1000 patient stimulation years among patients treated with the RNS System is favorable relative to treatment-resistant epilepsy patients randomized to the placebo arm of add-on drug studies or with seizures after resective surgery. Our findings support that treatments that reduce seizures reduce SUDEP risk and that not all SUDEPs follow seizures.

Spatial-temporal patterns of electrocorticographic spectral changes during midazolam sedation.

OBJECTIVE: To better understand 'when' and 'where' wideband electrophysiological signals are altered by sedation. METHODS: We generated animation movies showing electrocorticography (ECoG) amplitudes at eight spectral frequency bands across 1.0-116 Hz, every 0.1s, on three-dimensional surface images of 10 children who underwent epilepsy surgery. We measured the onset, intensity, and variance of each band amplitude change at given nonepileptic regions separately from those at affected regions. We also determined the presence of differential ECoG changes depending on the brain anatomy. RESULTS: Within 20s following injection of midazolam, beta (16-31.5 Hz) and sigma (12-15.5 Hz) activities began to be multifocally augmented with increased variance in amplitude at each site. Beta-sigma augmentation was most prominent within the association neocortex. Augmentation of low-delta activity (1.0-1.5 Hz) was relatively modest and confined to the somatosensory-motor region. Conversely, injection of midazolam induced attenuation of theta (4.0-7.5 Hz) and high-gamma (64-116 Hz) activities. CONCLUSIONS: Our observations support the notion that augmentation beta-sigma and delta activities reflects cortical deactivation or inactivation, whereas theta and high-gamma activities contribute to maintenance of consciousness. The effects of midazolam on the dynamics of cortical oscillations differed across regions. SIGNIFICANCE: Sedation, at least partially, reflects a multi-local phenomenon at the cortical level rather than global brain alteration homogeneously driven by the common central control structure.

National trends and complication rates for invasive extraoperative electrocorticography in the USA.

Invasive electrocorticography (ECoG) is used in patients when it is difficult to localize epileptogenic foci for potential surgical resection. As MR neuroimaging has improved over the past decade, we hypothesized the utilization of ECoG diminishing over time. Using the USA Nationwide Inpatient Sample, we collected demographic and complication data on patients receiving ECoG over the years 1988-2008 and compared this to patients with medically refractory epilepsy during the same time period. A total of 695 cases using extraoperative ECoG were identified, corresponding to 3528 cases nationwide and accounting for 1.1% of patients with refractory epilepsy from 1988-2008. African Americans were less likely to receive ECoG than whites, as were patients with government insurance in comparison to those with private insurance. Large, urban, and academic hospitals were significantly more likely to perform ECoG than smaller, rural, and private practice institutions. The most frequent complication was cerebrospinal fluid leak (11.7%) and only one death was reported from the entire cohort, corresponding to an estimated six patients nationally. Invasive ECoG is a relatively safe procedure offered to a growing number of patients with refractory epilepsy each year. However, these data suggest the presence of demographic disparities in those patients receiving ECoG, possibly reflecting barriers due to race and socioeconomic status. Among patients with nonlocalized seizures, ECoG often represents their only hope for surgical treatment. We therefore must further examine the indications and efficacy of ECoG, and more work must be done to understand if and why ECoG is preferentially performed in select socioeconomic groups.