In the early 2000s, a subcommittee of the American Clinical Neurophysiology Society (ACNS) set out to “standardize terminology of periodic and rhythmic EEG patterns in the critically ill to aid in future research involving such patterns.” The initial proposed terminology was published in 2005.1 This was presented at many meetings on several continents, subjected to multiple rounds of testing of interrater reliability, underwent many revisions, and was then published as an ACNS guideline in 2013.2 Interrater agreement of the 2012 version (published in early 2013) was very good, with almost perfect agreement for seizures, main terms 1 and 2, the +S modifier, sharpness, absolute amplitude, frequency, and number of phases.3 Agreement was substantial for the +F and +R modifiers (66% and 67%) but was only moderate for triphasic morphology (58%) and fair for evolution (21%, likely at least partly because of the short EEG samples provided).3 The authors concluded that interrater agreement for most terms in the ACNS critical care EEG terminology was high and that these terms were suitable for multicenter research on the clinical significance of these critical care EEG patterns.

With the help of infrastructure funding from the American Epilepsy Society and administrative and website support from the ACNS, a database that incorporated the ACNS terminology was developed for clinical and research purposes, tested during routine clinical care in multiple centers,4 and made available at no cost on the ACNS website (https://www.acns.org/research/critical-care-eeg-monitoring-research-consortium-ccemrc/ccemrc-public-database). This greatly enhanced the ability to complete multicenter investigations.

After the establishment of the standardized terminology and free access to a database incorporating these terms, there have been many investigations into the clinical significance of rhythmic and periodic patterns (RPPs) in critically ill patients. Patterns such as lateralized rhythmic delta activity (LRDA) were found to be highly associated with acute seizures,5,6 equivalent to the association found with lateralized periodic discharges (LPDs) in one study.5 The association of all the main patterns in the nomenclature with seizures was defined in a multicenter cohort of almost 5,000 patients, with seizure rates highest for LPDs, intermediate for LRDA and generalized periodic discharges (GPDs), and lowest for generalized rhythmic delta activity (GRDA).6 This and other studies have shown that several of the modifiers within the nomenclature do indeed have clinically relevant meaning. For example, studies have shown that higher frequency (especially >1.5 Hz), higher prevalence, longer duration, and having a “plus” modifier are all associated with a higher chance of acute seizures.6,7 On the other hand, whether a pattern was spontaneous or “stimulus-induced” did not seem to have a significant effect on its association with seizures.6 In other investigations, the “triphasic morphology” modifier was investigated blindly with multiple expert reviewers, calling into question its relationship with metabolic encephalopathy and its lack of a relationship with seizures.8,9 For patients with refractory status epilepticus treated with anesthetic-induced coma, the presence of “highly epileptiform” bursts suggested that an attempted wean off of anesthetics at that time was much more likely to lead to seizure recurrence than if the bursts were not highly epileptiform.10 Even long-term outcome seemed to be associated with some modifiers, with a higher risk of later epilepsy found if LPDs were more prevalent, had longer duration, or had a “plus” modifier.7

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American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2021 Version.

OBJECTIVE To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER NCT00572195. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

https://n.neurology.org/content/neurology/early/2020/07/20/WNL.0000000000010154.full.pdf

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Structural magnetic resonance imaging (MRI) is of fundamental importance to the diagnosis and treatment of epilepsy, particularly when surgery is being considered. Despite previous recommendations and guidelines, practices for the use of MRI are variable worldwide and may not harness the full potential of recent technological advances for the benefit of people with epilepsy. The International League Against Epilepsy Diagnostic Methods Commission has thus charged the 2013-2017 Neuroimaging Task Force to develop a set of recommendations addressing the following questions: (1) Who should have an MRI? (2) What are the minimum requirements for an MRI epilepsy protocol? (3) How should magnetic resonance (MR) images be evaluated? (4) How to optimize lesion detection? These recommendations target clinicians in established epilepsy centers and neurologists in general/district hospitals. They endorse routine structural imaging in new onset generalized and focal epilepsy alike and describe the range of situations when detailed assessment is indicated. The Neuroimaging Task Force identified a set of sequences, with three-dimensional acquisitions at its core, the harmonized neuroimaging of epilepsy structural sequences-HARNESS-MRI protocol. As these sequences are available on most MR scanners, the HARNESS-MRI protocol is generalizable, regardless of the clinical setting and country. The Neuroimaging Task Force also endorses the use of computer-aided image postprocessing methods to provide an objective account of an individual's brain anatomy and pathology. By discussing the breadth and depth of scope of MRI, this report emphasizes the unique role of this noninvasive investigation in the care of people with epilepsy.

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Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: A consensus report from the International League Against Epilepsy Neuroimaging Task Force.

Defining a bio-electrical marker for the brain area responsible for initiating a seizure remains an unsolved problem. Fast gamma activity has been identified as the most specific marker for seizure onset, but conflicting results have been reported. In this study, we describe an alternative marker, based on an objective description of interictal to ictal transition, with the aim of identifying a time-frequency pattern or 'fingerprint' that can differentiate the epileptogenic zone from areas of propagation. Seventeen patients who underwent stereoelectroencephalography were included in the study. Each had seizure onset characterized by sustained gamma activity and were seizure-free after tailored resection or laser ablation. We postulated that the epileptogenic zone was always located inside the resection region based on seizure freedom following surgery. To characterize the ictal frequency pattern, we applied the Morlet wavelet transform to data from each pair of adjacent intracerebral electrode contacts. Based on a visual assessment of the time-frequency plots, we hypothesized that a specific time-frequency pattern in the epileptogenic zone should include a combination of (i) sharp transients or spikes; preceding (ii) multiband fast activity concurrent; with (iii) suppression of lower frequencies. To test this hypothesis, we developed software that automatically extracted each of these features from the time-frequency data. We then used a support vector machine to classify each contact-pair as being within epileptogenic zone or not, based on these features. Our machine learning system identified this pattern in 15 of 17 patients. The total number of identified contacts across all patients was 64, with 58 localized inside the resected area. Subsequent quantitative analysis showed strong correlation between maximum frequency of fast activity and suppression inside the resection but not outside. We did not observe significant discrimination power using only the maximum frequency or the timing of fast activity to differentiate contacts either between resected and non-resected regions or between contacts identified as epileptogenic versus non-epileptogenic. Instead of identifying a single frequency or a single timing trait, we observed the more complex pattern described above that distinguishes the epileptogenic zone. This pattern encompasses interictal to ictal transition and may extend until seizure end. Its time-frequency characteristics can be explained in light of recent models emphasizing the role of fast inhibitory interneurons acting on pyramidal cells as a prominent mechanism in seizure triggering. The pattern clearly differentiates the epileptogenic zone from areas of propagation and, as such, represents an epileptogenic zone 'fingerprint'.awx306media15687076823001.

A fingerprint of the epileptogenic zone in human epilepsies

Importance A major change has occurred in the evaluation of epilepsy with the availability of robotic stereoelectroencephalography (SEEG) for seizure localization. However, the comparative morbidity and outcomes of this minimally invasive procedure relative to traditional subdural electrode (SDE) implantation are unknown. Objective To perform a comparative analysis of the relative efficacy, procedural morbidity, and epilepsy outcomes consequent to SEEG and SDE in similar patient populations and performed by a single surgeon at 1 center. Design, Setting and Participants Overall, 239 patients with medically intractable epilepsy underwent 260 consecutive intracranial electroencephalographic procedures to localize their epilepsy. Procedures were performed from November 1, 2004, through June 30, 2017, and data were analyzed in June 2017 and August 2018. Interventions Implantation of SDE using standard techniques vs SEEG using a stereotactic robot, followed by resection or laser ablation of the seizure focus. Main Outcomes and Measures Length of surgical procedure, surgical complications, opiate use, and seizure outcomes using the Engel Epilepsy Surgery Outcome Scale. Results Of the 260 cases included in the study (54.6% female; mean [SD] age at evaluation, 30.3 [13.1] years), the SEEG (n = 121) and SDE (n = 139) groups were similar in age (mean [SD], 30.1 [12.2] vs 30.6 [13.8] years), sex (47.1% vs 43.9% male), numbers of failed anticonvulsants (mean [SD], 5.7 [2.5] vs 5.6 [2.5]), and duration of epilepsy (mean [SD], 16.4 [12.0] vs17.2 [12.1] years). A much greater proportion of SDE vs SEEG cases were lesional (99 [71.2%] vs 53 [43.8%];P  Conclusions and Relevance This direct comparison of large matched cohorts undergoing SEEG and SDE implantation reveals distinctly better procedural morbidity favoring SEEG. These modalities intrinsically evaluate somewhat different populations, with SEEG being more versatile and applicable to a range of scenarios, including nonlesional and bilateral cases, than SDE. The significantly favorable adverse effect profile of SEEG should factor into decision making when patients with pharmacoresistant epilepsy are considered for intracranial evaluations.

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Analysis of Morbidity and Outcomes Associated With Use of Subdural Grids vs Stereoelectroencephalography in Patients With Intractable Epilepsy.

OBJECTIVE
Stereoelectroencephalography (SEEG) is designed to target distributed cortical networks responsible for electroclinical seizure syndrome and to enable localization of the site of seizure onset in patients with intractable epilepsy. When the preimplantation hypothesis invokes the bilateral mesial frontal lobes, sampling of several deep-seated cortical sites in both hemispheres is required. In this study, the authors have demonstrated the feasibility of sampling bihemispheric areas with intentional implantation of an SEEG electrode crossing the midline (SECM) for sampling the cortex on both sides of the interhemispheric fissure.


METHODS
An analysis of 231 consecutive SEEG procedures over 8 years was used to identify instances of bihemispheric sampling by using the transmidline SEEG technique.


RESULTS
The authors identified 53 SEEG cases, with a total of 126 electrodes that crossed the interhemispheric fissure; all were in the frontal lobes. Eighty-three electrodes targeted the cingulate gyrus (18 rostral, 43 anterior, and 22 middle), 31 targeted the posterior orbitofrontal region, 8 sampled the medial prefrontal cortex, and 4 targeted nodular heterotopia around the frontal horns. The ictal onset zone was localized to the frontal lobe in 16 cases. SECM isolated interictal and ictal activity in the contralateral hemisphere in 6 cases and independent bihemispheric seizure activity in 2 cases. No hemorrhagic or infectious complications were noted in any of these cases.


CONCLUSIONS
Based on this extensive experience of bihemispheric sampling, the authors concluded that this technique is safe and effective. In this series, SECM showed contralateral interictal and/or ictal epileptiform activity in 8 (15%) cases, and 9 (16%) cases (with unilateral implantation) had sufficient data to discard contralateral involvement, contributing to support of the epileptogenic network. SECM may reduce the number of electrodes used to sample bilateral mesial frontal or orbitofrontal cortices, and such an approach may lower the risk of hemorrhage and costs.

Stephen A. Thompson

Papers

Safety and efficacy of bihemispheric sampling via transmidline stereoelectroencephalography.