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One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non‐invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre‐surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non‐redundant information and improve the pre‐surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field. [ABSTRACT FROM AUTHOR]

Objective: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM‐induced seizures (EISs) between the two electrode types. Methods: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. Results: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. Significance: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM. [ABSTRACT FROM AUTHOR]

Summary: Objective: The understanding of childhood absence epilepsy (CAE) has been revolutionized over the past decade, but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose in this prospective observational study was to determine how pretreatment ictal network pathways, defined using a combined electroencephalography (EEG)–functional magnetic resonance imaging (EEG‐fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response. Methods: Sixteen children with newly diagnosed and drug‐naive CAE had 31 typical absence seizures during EEG‐fMRI and 74 during MEG. The spatial extent of the pretreatment ictal network was defined using fMRI hemodynamic response with an event‐related independent component analysis (eICA). This spatially defined pretreatment ictal network supplied prior information for MEG‐effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX)–treatment responders (N = 11) or nonresponders (N = 5). Effective connectivity of the pretreatment ictal network was compared to the treatment response. Results: Patterns of pretreatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (P < .05). ETX treatment nonresponders had pretreatment connectivity, which was decreased in the precuneus region and increased in the frontal cortex compared to ETX responders (P < .05). Significance: Pretreatment ictal connectivity differences in children with CAE were associated with response to antiepileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome. [ABSTRACT FROM AUTHOR]

Despite a positive prognosis for seizure remission, children with benign epilepsy with centrotemporal spikes ( BECTS) have been reported to exhibit subtle neuropsychological difficulties. We examined the relationship between patterns of centrotemporal spikes (the typical electroencephalography [ EEG] finding in BECTS) and neuropsychological and motor outcomes in children with new-onset BECTS. Thirty-four patients with new-onset BECTS (not taking antiepileptic medication) and 48 typically developing children participated in the study. In BECTS patients, centrotemporal spikes ( CTS) were evaluated in the first hour awake and first 2 h of sleep in a 24-h EEG recording and left or right-sided origin was noted. General intellectual function, language, visuospatial skill, processing speed, and fine motor skill were assessed in all participants. We found no significant difference between BECTS patients and controls on measures of general intellectual function, or visuospatial or language testing. There were significant differences in processing speed index and nondominant hand fine motor scores between groups. Significant negative relationships were observed between rates of left-sided CTS and right hand fine motor scores. This suggests that psychomotor and fine motor speed are affected in BECTS, but the extent of affected domains may be more limited than previously suggested, especially in untreated patients early in the course of their epilepsy. [ABSTRACT FROM AUTHOR]

Objective To describe the natural history of electroencephalography ( EEG) changes in patients with benign epilepsy with centrotemporal spikes ( BECTS) over 1 year. Methods Centrotemporal spikes were visually evaluated based on 24-h ambulatory EEG studies to determine the total, left, right, and bilateral centrotemporal spikes patients were awake and asleep. These spike rates were then used to compare the entire night of sleep to the first 2 h of sleep, the repeatability of spike frequency over two recordings (done within days to weeks), and longitudinal changes in spike rate over 6 and 12 months. Results Nineteen children with newly diagnosed and untreated BECTS were included in this analysis. An excellent correlation was found between the centrotemporal spike rate during the entire duration of sleep and the first 2 h of sleep (intraclass correlation [ ICC] 0.87, 95% confidence interval [ CI] 0.67-0.95). In addition, an excellent correlation was found between two recordings completed an average of 23 days apart while patients were asleep ( ICC 0.92, 95% CI 0.80-0.97) and good correlation while patients were awake ( ICC 0.70, 95% CI 0.39-0.87). The average change in spike rate between recordings at baseline and at 6 months was a decrease of 64.7% (range −100% to +51.5%, p = 0.01) and the average change in rate between recordings at baseline and at 12 months was a decrease of 57.7% (range −100% to +29.1%, p = 0.01). In addition, within 6 months, most children had decreased centrotemporal rates, with 30% of children being spike-free. This absence of spikes did not continue in all children, since the majority (60%) had some spikes at 1 year following diagnosis. Significance Centrotemporal spike rates during sleep are stable when compared over days to weeks; however, when comparing spike rates over months there is a larger degree of variability. [ABSTRACT FROM AUTHOR]

Objective The predictive value of intraoperative electrocorticography ( ECoG) in pediatric epilepsy surgery is unknown. In a population of children undergoing ECoG followed typically by invasive extraoperative monitoring ( IEM) and resection, we aimed to determine the relationship between frequent ECoG abnormalities and the seizure onset zone and outcome after resection. Methods We retrospectively identified 103 children with preresection ECoG of sufficient technical quality. ECoG records were scored based on electrode location and frequency, blinded to the seizure-onset zone and outcome. Electrographic seizure and spike locations were identified. Locations of seizures and spike populations were then compared to the location of seizure-onset zone defined by IEM using subdural electrodes and resection margin. Results Electrographic seizures were identified in 11 (11%) of 103 patients. A spike population of one or more was noted in 79 (77%) of 103 patients. In 50 (63%) of 79 patients, spike populations correlated with seizure-onset zone location. The overall surgical outcome was good ( ILAE 1 to 3) in 53 (52%) of 101 patients. Outcome was good in seven (78%) of nine patients when electrographic seizure location was resected. The best outcomes were obtained with resection of both the seizure-onset zone and ECoG abnormalities to include seizures and spike locations (22/33 good outcome, 67%, p = 0.008). There was a significantly better outcome in children with complete resection of ECoG-identified spike populations (14/26, 62% good outcome) compared to when none were resected (4/14, 29%, p = 0.043). Significance Electrographic seizures and frequent spikes are frequently seen on pre-resection ECoG in children. The brain locations corresponding to these discharges are highly concordant with the seizure-onset zone; resection of these regions is correlated with good seizure outcome. Further research is needed to design interventions that increase the reliability of ECoG prediction of the epileptogenic zone and obviate the need for IEM. [ABSTRACT FROM AUTHOR]

Objectives Magnetoencephalography ( MEG) is used to guide intracranial electroencephalography ( ICEEG) monitoring and determine areas for resection. The purpose of this retrospective cross-sectional study was to report our experience using dipole modeling/dipole scanning, current density reconstructions, and beam-forming methods in a large cohort of pediatric patients with intractable epilepsy. Methods Source localization results for each algorithm and seizure-onset zone, defined by ICEEG, were described by three blinded reviewers according to five location criteria. The accuracy of each algorithm was then compared to ICEEG. The relationships between the accuracy of these algorithms (discordant, lobar concordant, sublobar concordant) and long-term seizure outcome was calculated using positive and negative predictive values. Results Thirty-two patients (mean age ± SD, 10.8 ± 5 years) were included in this retrospective review. No algorithms had sublobar concordance with ICEEG in all patients, including when algorithms were grouped by type (dipole modeling/dipole scanning, current density reconstruction, beam forming). Synthetic aperture magnetometry ( SAM) with excess kurtosis tended to be the most accurate, but there were no significant differences between algorithms. When comparing the source modeling with ICEEG findings, significantly more patients with a seizure-free outcome were found to have lobar or sublobar concordance of multiple signal classification ( MUSIC) (61.1%) and standardized low resolution brain electromagnetic tomography (s LORETA) (52.9%). Positive predictive values were highest for MUSIC (61.9%) and equivalent current dipole ( ECD) (57.1%). Negative predictive values were highest for SAM( g2)- VS (83%), minimum norm estimate ( MNE) (75%), MUSIC (73.7%), and ECD (73.5%). Significance This study describes the use of multiple MEG source estimation techniques and demonstrates that all algorithms have similar rates of concordance with ICEEG. Also, the concordance or discordance of MUSIC with ICEEG was the best predictor of long-term seizure outcome. [ABSTRACT FROM AUTHOR]

Objectives Metabolic imaging studies, such as positron emission tomography ( PET), allow for an assessment of physiologic functioning of the brain, and [18 F]fluoro-2-deoxyglucose ( FDG)- PET is now a commonly used technique in presurgical epilepsy evaluations. Focal interictal decreases in glucose consumption are often but inconsistently concordant with the ictal onset area, and the underlying mechanisms are poorly understood. The current study tests the hypothesis that areas of glucose hypometabolism, determined by FDG- PET, are associated with mitochondrial dysfunction in patients with medically intractable epilepsy associated with isolated focal cortical dysplasia ( FCD). Methods Measures of electron transport chain ( ETC) functioning and mitochondrial abnormalities ( ETC complex biochemistry, protein kinase B subtype 1 (Akt1), glial fibrillary acidic protein (GFAP)) were assessed in surgical resection specimens that had hypometabolic abnormalities and those that were normal on FDG- PET. Determination of FDG- PET abnormalities was based on coregistration of statistical parametric mapping ( SPM) results with postsurgical images. Results Twenty-two patients (11 male, 11 female; mean age at the time of surgery 10.5 ± 4.4 years), with pathologically confirmed FCD, were included in this retrospective review. Complex IV function was found to be significantly reduced in areas of hypometabolism (p = 0.014), whereas there was a trend toward a significant reduction in complex II and III function in areas of hypometabolism (p = 0.08, p = 0.059, respectively). These decreases were independent of cortical dysplasia severity (p = 0.321) and other clinical epilepsy measures. Significance This study suggests an association between glucose hypometabolism and reduced mitochondrial complex IV functioning, which is independent of the degree of cortical dysplasia. This supports the role of cellular energy failure as a potential mechanism for intractable epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level–dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level–dependent (BOLD) fMRI in the brain was measured by using T[sub 2] *-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using γ-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike–wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [ABSTRACT FROM AUTHOR]