Alyssa Ailion

Background and Purpose: Drug resistant epilepsy (DRE) affects approximately 15 million people worldwide, and surgery remains the only curative option. A key challenge in predicting outcomes is the lack of standardized, quantitative tools to help distinguish seizure driver regions from responder regions during stereoelectroencephalography (sEEG) recordings. We validated the CN Suite, a computational platform that uses causal network mapping and machine learning to assign criticality scores to sEEG contacts, testing whether higher scores correspond to surgically treated tissue in patients with favorable outcomes. Methods: We analyzed deidentified clinical data from 60 patients (aged 2 years and older) with focal or multifocal DRE who underwent sEEG monitoring and proceed to surgery at four U.S. Level 4 epilepsy centers. The algorithm was trained on an independent cohort (N=37) and locked prior to validation. The primary outcome was the standardized effect size (Cohens d) of the patient level surgical zone enrichment ratio between more favorable (Engel I or II) and less favorable (Engel III or IV) outcome groups. Contact level sensitivity, specificity, PPV, and NPV were evaluated at a prelocked threshold. Results: The findings support our hypothesis: the algorithm results showed significantly higher criticality values for surgically treated tissue in favorable outcome patients (d=0.74, 95% CI: 0.39 to 1.06, p=0.003). Three potentially clinically actionable findings emerged. First, high-criticality contacts formed spatially compact clusters (~9 mm nearest-neighbor distance vs. 17mm expected by chance), consistent with focal targets amenable to minimally invasive ablation. Second, sensitivity was highest in small focal procedures (80% at 10 or fewer treated contacts) and decreased with resection size. Third, in patients whose surgery failed, high-critical tissue remained outside the resection boundary, suggesting incomplete treatment coverage of the epileptogenic zone rather than mislocalization. Prediction specificity was 84% at the contact level. For adult and pediatric cases (n=28), 88% of contacts that were identified as seizure free were in fact seizure free. Conclusions: Causal network mapping of sEEG identifies compact epileptogenic targets that correspond to surgically treated tissue in patients with more favorable outcomes. CN-Suite performed best in focal procedures and may be best suited for LITT and other minimally invasive approaches. In addition, low-criticality regions were infrequently associated with seizure-generating tissue, particularly in the pediatric cohort although our sample size was small. When surgery failed, residual high-critical tissue outside the resection boundary offered both a mechanistic explanation for less favorable surgical outcome as well as a potential target for reoperation.

Background/Objectives: Children with single-sided deafness (SSD) have normal hearing in one ear and are deaf in the other. Navigating complex auditory environments with SSD may cause reallocation of cognitive resources necessary for executive functioning (EF), adding potential cognitive burden to listening, though this is not well understood. To characterize EF in children with SSD, we compared their test performance and everyday functioning on performance-based and caregiver-rated EF measures to normative values and to a group of children with temporal lobe epilepsy (TLE). Methods: A retrospective review compared children with unaided SSD (n = 45) to a clinically referred TLE group (n = 39), all aged 6–16 years old, on performance-based measures including verbal fluency (letter, category), digit span, coding, and the BRIEF general executive composite. In the SSD group, those with congenital and acquired onset were compared across the same performance-based measures and BASC-3 executive functioning composite, and BRIEF2 indexes (cognitive, emotional, and behavioral regulation). Within this SSD group, performance-based and caregiver-rated measures were correlated. Results: In the SSD group, caregiver-reported EF and test performance were within age expectations. However, SSD participants with congenital onset had poorer caregiver-reported everyday EF. Children with SSD and elevated caregiver-reported EF had greater challenges on performance measures of auditory working memory. EF profiles were similar in the SSD and TLE groups, except the TLE group showed significantly worse performance on semantic fluency. Conclusions: Caregiver-rated EF measures may serve as an important tool for detecting neuropsychological deficits in children with SSD. SSD children with congenital onset may benefit from closer EF monitoring. There was lower performance on digit span backward tasks that require auditory working memory in children with elevated daily EF. More research is needed to determine what factors, such as hearing technology use, contribute to EF in children with SSD. *The term SSD is used throughout this article as a neutral placeholder with respect to the variation of terms used with this population (e.g., deaf, hard of hearing, hearing loss, hearing differences, etc.). SSD is used to be inclusive of all cultural/medical perspectives and identities.

Objective: Despite being safe and effective, surgery for pediatric epilepsy is underutilized. Social determinants of health (SDoH) are important to consider when examining this treatment gap. This study examined the potential systemic inequities at three different stages in the journey toward epilepsy surgery across the Pediatric Epilepsy Research Consortium (PERC). Methods: Any youth in the PERC prospective surgery database (≤18 years) was eligible and included if sociodemographic factors were also available. We examined if there were differences in disparity factors in: (1) referral to Phase I evaluation, (2) offering of surgery, and (3) completion of surgery. Results: Of 1309 patients, the majority were male (53%, p = .04), White (82.2%, p < .001), not Hispanic or Latino (84.3%, p < .001), and privately insured (56.3%, p < .001). Of the youth who were offered surgical treatment ( n = 1103, 84.3%), there were no significant differences in race/ethnicity or sex. Those with a structural lesion were more likely to be offered surgery, and historically marginalized youth were more likely to have a lesion. Of patients who completed surgery ( n = 927, 84.0%), White patients were 1.88 times (95% confidence interval [CI]: 1.14–3.04) more likely than Black patients to complete surgery ( p = .01). Significance: Youth who began surgery evaluation are not representative of the demographics of those with epilepsy in the United States, with greater representation of White, non‐Hispanic male individuals. In addition, youth who began surgery evaluation disproportionally have private insurance. At the next stage of offering surgery, there were no differences based on SDoH. However, there is evidence that underrepresented youth that were magnetic resonance negative were less likely to be referred for surgical workup and that Black youth were less likely to undergo surgery. Therefore, efforts to provide equitable opportunity for all youth with refractory epilepsy should be concentrated at the referral for surgery evaluation point of care; however, additional efforts are also needed at later stages.

The persistence of common, heritable conditions, like epilepsy, that are associated with reduced reproductive fitness is an evolutionary paradox. Endogenous analgesic, anti‐depressant, and inflammatory mechanisms able to repair compromised functions can offer advantages in unexpected crises. Here, we challenge current thinking about the detrimental effects of seizures and epilepsy and suggest that (1) seizure‐driven neuroplasticity might provide a protective mechanism, (2) seizure‐induced neurotransmitter release not only helps to stop seizures but also increases resilience to pain, and (3) innate immune mechanisms triggered by recurrent seizures might neutralize novel viruses, like SARS‐CoV‐2, more rapidly, and so provided protection during the recent pandemic. Plain Language Summary: We explore the idea that epilepsy may activate the brain's natural repair systems, despite its risks. These include brain processes that help people recover from injury, infections, and reduce pain. Understanding these less frequently discussed aspects of seizures may help researchers develop novel questions and improve treatment.