Fine, Anthony

Abstract Objective The objective of this study is to characterize contemporary surgical management practices and factors influencing surgical decision‐making in the management of Lennox–Gastaut Syndrome (LGS) across pediatric epilepsy centers in the United States. Methods A 45‐item cross‐sectional survey was developed and distributed to Pediatric Epilepsy Research Consortium centers. Domains included institutional demographics, surgical evaluation timing and goals, presurgical workup, procedural utilization and outcomes, and barriers to surgery. Descriptive statistics and thematic analysis were performed. Results Thirty‐two pediatric epilepsy centers participated (38% response), the majority comprising pediatric epileptologists at Level 4 National Association of Epilepsy Centers. Most centers (66%) considered surgery after failure of 3–4 antiseizure medications. Presurgical workup typically included brain magnetic resonance imaging (MRI), long‐term electroencephalography (EEG) monitoring, and neuropsychological assessment, while use of functional imaging, magnetoencephalography, and intracranial EEG varied considerably. All centers offered vagus nerve stimulation and corpus callosotomy; 80%–90% offered resection, hemispherectomy, responsive neurostimulation (RNS); 60%–65% offered deep brain stimulation (DBS) and laser ablation. Among centers offering RNS, half targeted thalamic structures exclusively, and the remainder targeted cortical or combined cortical‐thalamic structures; the centromedian nucleus was the preferred thalamic target for RNS and DBS. Surgical decision‐making was influenced by patient characteristics, procedural considerations, and systemic factors. Seizure frequency, family preference, and multidisciplinary input were highly rated across all interventions. Etiology was critical for resection and hemispherectomy, while financial constraints, insurance barriers, and the need for future neuroimaging impacted neuromodulation selection. Scenario‐specific trends included less frequent consideration of DBS and RNS in children under five years, less use of hemispherectomy in older children, preference for corpus callosotomy in children with predominantly drop seizures, and procedural selection based on MRI findings. Significance Substantial variability exists in the surgical management of LGS. These findings highlight critical opportunities to harmonize practices, reduce disparities, and guide comparative effectiveness research to optimize outcomes. Plain Language Summary Lennox–Gastaut Syndrome (LGS) is a severe form of epilepsy that may require surgery when medications are not effective. This study found that surgical care for LGS varies widely across pediatric epilepsy centers in the United States, including when surgery is recommended, how patients are evaluated, and which procedures are available. Newer approaches such as brain stimulation are being used more often, although access remains inconsistent. These findings highlight the need for clearer treatment pathways to ensure that children with LGS have equitable access to the best possible care.

Abstract Objective To assess the localization and lateralization values of ictal emotional features and ictal defensive behaviors in pediatric and young adult patients with frontal lobe epilepsy (FLE). Methods Children and young adults with FLE were identified from a single institution's epilepsy surgery database. Two epileptologists determined by consensus the presence of ictal emotional features (positive‐ smile, laughter, humming, singing; negative‐ fear, crying, anger, disgust, contempt, sadness) and ictal defensive behaviors (freezing with a fearful facial expression, shielding the face with hands, burying the face in a pillow, or exhibiting hyperkinetic motor behaviors like attempting to escape from bed or resisting restraint) in each patient's first video EEG (vEEG). Historic seizure semiology and vEEG reports were compared with the consensus vEEG analysis. Longitudinal changes in ictal emotional features were defined by the emergence or resolution of ictal emotional features between historic seizure semiology and re‐review of presurgical vEEG analysis. Subgroup analyses were conducted according to the seizure lateralization (left vs. right) and sublobar localization (precentral, medial, lateral, extensive) based on surgical extent. Results Twenty‐three FLE patients were included (female 39%; mean age at vEEG analysis: 11.28 years, range 1.75–20.17). The inter‐rater reliability was very good for both ictal emotional features ( κ = 0.81, 95% CI: 0.59–1) and ictal defensive behaviors ( κ = 0.91, 95% CI: 0.79–1). Ictal emotional features were observed in 10 patients (43.4%), with negative emotions present in 70% (7/10) of these cases. vEEG reports lacked documentation of ictal emotional features in two patients. Although ictal emotional features showed no statistical correlation by sublobar regions, ictal defensive behaviors were consistently seen in medial compared to lateral FLE (100% vs. 16.6%; p = 0.004). Longitudinal changes in ictal emotional features were observed in 8 (34.7%) patients. Significance Ictal emotional features were common in pediatric and young adult FLE patients and were mainly negative. Ictal defensive behaviors were more likely associated with medial FLE. Longitudinal changes in ictal emotional features occurred in about a third of pediatric and young adult patients with FLE. Plain Language Summary This study examined emotional features and defensive behaviors during seizures in children and young adults with FLE. Negative emotions were commonly seen during seizures. Ictal defensive behaviors were more frequently observed in patients with medial FLE, and recognizing these signs could help clinicians localize the seizures. Changes in emotional features were seen over time in about one‐third of children and young adult patients.

Original Article Citation Mithani K, Niazi F, Suresh H, Alrumayyan Y, Rayco ER, Ochi A, Otsubo H, Kerr E, Breitbart S, LeBlanc-Millar A, Gadgil N, Raskin JS, Weil AG, Hadjinicolaou A, Iorio-Morin C, Weiss S, Jain P, Sham L, Donner E, Fasano A, Gorodetsky C, Ibrahim GM. Deep brain stimulation of the centromedian nucleus for drug-resistant epilepsy in children: Quality-of-life and functional outcomes from the CHILD-DBS registry. Epilepsia. 2025 Apr 1. doi: 10.1111/epi.18393. Epub ahead of print. PMID: 40167366. Objective: Deep brain stimulation of the centromedian nucleus of the thalamus (CM-DBS) is an investigational, off-label treatment for drug-resistant epilepsy (DRE) in children. Although emerging evidence supports its safety and efficacy for select indications, the effect of CM-DBS on quality of life and functional outcomes such as school attendance has not been studied. Here, we analyzed data from the prospective CHILD-DBS (Child and Youth Comprehensive Longitudinal Database for Deep Brain Stimulation) to examine the impact of CM-DBS on patient- and caregiver-reported outcomes. Methods: Twenty-two children and youth underwent bilateral CM-DBS. Caregiver–child dyads completed surveys related to seizure frequency, seizure severity, quality of life, and school attendance at baseline, 6 months, and 1 year postsurgery. Simulated volumes of tissue activation were analyzed to identify optimal stimulation targets associated with treatment outcome. Results: Of 22 children, 10 experienced ≥50% reduction in seizure frequency (mean reduction = 66.7 ± 17.3%), one exhibited a modest benefit (37.5% reduction), and the remaining 11 experienced no change. The majority (73% of patients) exhibited a clinically important reduction in seizure severity, including six children who did not demonstrate any change in seizure frequency. Only those who experienced a reduction in seizure frequency demonstrated significant improvements in general health and overall quality of life. Furthermore, we observed an increase in school attendance across participants 1 year after CM-DBS. Significance: CM-DBS can lead to reduction in seizure burden concurrent with improvements in quality of life and relevant functional outcomes in children with DRE. These findings further our understanding of the impact of CM-DBS on meaningful outcomes for children and caregivers.

Developmental/epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS) is newly proposed nomenclature put forth by the International League Against Epilepsy (ILAE) to replace the problematic electrographic and/or clinical phenotypes of electrical status epilepticus of sleep (ESES) and continuous spike-wave in sleep (CSWS). The nomenclature update represents a noble effort to minimize the confusion of how to define and appropriately utilize this alphabet soup of acronyms, thereby aiding in future clinical and research efforts. The name change fails to capture greater challenges within the field, which still plague diagnosis and treatment and stagnates substantive research advancements. Through a directed literature review of DEE-SWAS with emphasis on the new ILAE nomenclature and the RESCUE-ESES trial, we will highlight major persistent quandaries in the field. These include inadequate or insufficient diagnostic biomarkers (ie, the spike wave index), the highly variable clinical manifestations, ranging from dubious associations to profound developmental regression, presumptively caused by spike-wave activation in sleep, and variable and often ineffective treatment paradigms. We will also review the broader diagnostic evaluation of DEE-SWAS. By doing so, we aim to shed light on crucial research and clinical questions that could advance our understanding of diagnosing and treating children with DEE-SWAS, as well as addressing the uncertainty surrounding the neurological effects of sleep-activated epileptiform discharges.

AbstractObjectiveStereoelectroencephalography‐guided radiofrequency thermocoagulation (SEEG‐guided RFTC) has been increasingly used as diagnostic and therapeutic approach for drug‐resistant focal epilepsies (DREs). We aimed to describe seizure outcomes of RFTC before and after further neurosurgical intervention.MethodsRetrospective single‐institution case series of patients who underwent SEEG‐RFTC. The primary outcome was Engel class I–IV classification ([responders Engel I–III and non‐responders Engel IV]) at last follow‐up after RFTC and prior to further neurosurgical intervention (open surgical resection, laser ablation, and neuromodulation).ResultsTwenty‐five patients (median age 18.9 years) with DRE were included. The median follow‐up time after RFTC was 7.2 months, including 20 patients who underwent further intervention (median follow‐up time of 7.3 months) and 5 without intervention (median of 3.5 months). From the patients who had further intervention, 17 (85%) underwent surgical procedure (laser ablation 53%, open surgical resection 47%) (median 4.4 months) and 3 (15%) had responsive neurostimulators placed (median 6.9 months). Prior to further intervention (median follow‐up 3.5 months after RFTC), 12 (48%) patients were classified as responders (12% Engel class I, 16% class II, and 20% class III) and 13 (52%) as non‐responders. Following neurosurgical intervention, 17 (68%) patients were followed for a median time of 2.7 months and 3 were lost to follow‐up. Of eight initial RFTC responders, 87.5% and 12.5% had Engel classes I and III, respectively. Of nine who were non‐responders, 33% had Engel class I, 22% II and III, and 44% IV outcomes following further intervention. No neurologic complications were reported.SignificanceSEEG‐guided RFTC is a well‐tolerated procedure and a beneficial diagnostic approach prior to further neurosurgical interventions in patients with DRE.Plain Language SummarySEEG‐guided RFTC is a well‐tolerated procedure and in the patients who experienced initial seizure reduction (n = 8), subsequent neurosurgical intervention (surgery or neuromodulation) led to favorable seizure outcomes (87.5% seizure freedom and 12.5% worthwhile seizure improvement).

AbstractDevelopmental and epileptic encephalopathies (DEEs) are a group of rare, severe, early-onset epilepsies characterized by pharmacoresistance, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. DEEs are associated with poor long-term outcomes and increased mortality; however, early recognition and targeted treatment can impact neurodevelopmental outcomes and overall quality of life. Treatment with antiseizure medication is often challenging given drug resistance, chronic polypharmacy, and medication interactions. With advances in genetic testing and increased understanding of the neurobiological mechanisms of DEEs, the treatment approach is evolving and includes repurposed antiseizure medications and targeted therapies, as well as early surgical intervention in select patients. In addition to high seizure burden and neurodevelopmental delay, DEEs are associated with comorbidities affecting a range of body systems; these can include intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems. Over time, these comorbidities increase the complexity of management and have important implications on the disease burden and quality of life for both patients and their caregivers. Multidisciplinary care in DEEs is paramount. We summarize the current evidence on the management of specific DEEs, focusing on targeted therapies and optimizing outcomes.

Automated detection of tonic seizures using wearable movement sensor and artificial neural network Larsen SA, Johansen DH, Beniczky S. Epilepsia . 2024 Jul 30. doi: 10.1111/epi.18077 . Epub ahead of print. PMID: 39076045. Although several validated wearable devices are available for the detection of generalized tonic-clonic seizures, automated detection of tonic seizures is still a challenge. In this phase 1 study, we report the development and validation of an artificial neural network (ANN) model for automated detection of tonic seizures with visible clinical manifestation using a wearable wristband movement sensor (accelerometer and gyroscope). The dataset prospectively recorded for this study included 70 tonic seizures from 15 patients (7 males, age 3-46 years, median = 19 years). We trained an ANN model to detect tonic seizures. The independent test dataset comprised nocturnal recordings, including 10 tonic seizures from 3 patients and additional (distractor) data from 3 subjects without seizures. The ANN model detected nocturnal tonic seizures with visible clinical manifestation with a sensitivity of 100% (95% confidence interval = 69%-100%) and with an average false alarm rate of 0.16/night. The mean detection latency was 14.1 s (median = 10 s), with a maximum of 47 s. These data suggest that nocturnal tonic seizures can be reliably detected with movement sensors using ANN. Large-scale, multicenter prospective (phase 3) trials are needed to provide compelling evidence for the clinical utility of this device and detection algorithm.

AbstractThe aim of this study is to report three cases of epilepsy with eyelid myoclonia (EEM) with CHD2 pathogenic variants. A database of 134 patients with EEM evaluated at Mayo Clinic sites was searched to identify patients with CHD2 variants. The medical records of those identified were reviewed to describe their presentation, treatment, and clinical course. Three patients (2 males, 1 female) with EEM were found to harbor de novo CHD2 pathogenic variants (c.2636C>T p.(Ala879Val), c.3734delA p. (Lys1245Asnfs*4), and c.3896delTinsCG p. (Val1299Alafs*5)). All three patients had comorbid autism spectrum disorder (ASD), intellectual disability (ID), and attention deficit disorder (ADHD). Eyelid myoclonia was a prominent seizure type that persisted in the three patients despite trials of multiple antiseizure medications. Generalized tonic–clonic seizures occurred in two of the patients but were controlled with antiseizure medications. Genetic testing should be considered in patients presenting with EEM, especially when ADHD, ID, ASD, and drug‐resistant seizures are present. Further understanding of the relationship between CHD2 variants and epileptogenesis may provide important insights into the pathogenesis of EEM.

Severe Communication Delays are Independent of Seizure Burden and Persist Despite Contemporary Treatments in SCN1A+ Dravet Syndrome: Insights From the ENVISION Natural History Study Perry MS, Scheffer IE, Sullivan J, Brunklaus A, Boronat S, Wheless JW, Laux L, Patel AD, Roberts CM, Dlugos D, Holder D, Knupp KG, Lallas M, Phillips S, Segal E, Smeyers P, Lal D, Wirrell E, Zuberi S, Brünger T, Wojnaroski M, Maru B, O'Donnell P, Morton M, James E, Vila MC, Huang N, Gofshteyn JS, Rico S. Epilepsia . 2024 Feb;65(2):322–337. Epub 2023 Dec 22. PMID: 38049202. doi: 10.1111/epi.17850 Objective: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. Methods: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest). Results: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = 0.0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [0.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, P = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. Significance: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age.

OBJECTIVE Stereoelectroencephalography (SEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG findings are not in full agreement or definitively localizing, implanted SEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation. If an SOZ is eloquent, resection and ablation are both contraindicated, so identifying functional representation is crucial for therapeutic decision-making. The authors present a novel functional brain mapping technique that utilizes task-based electrophysiological changes in SEEG during behavioral tasks and test this in pediatric and adult patients. METHODS SEEG was recorded in 20 patients with epilepsy who ranged in age from 6 to 39 years (12 female, 18 of 20 patients < 21 years of age) and underwent implanted monitoring to identify seizure onset. Each performed 1) visually cued simple repetitive movements of the hand, foot, or tongue while electromyography was recorded; and 2) simple picture-naming or verb-generation speech tasks while audio was recorded. Broadband changes in the power spectrum of the SEEG recording were compared between behavior and rest. RESULTS Electrophysiological functional mapping of movement and/or speech areas was completed in all 20 patients. Eloquent representation was identified in both cortex and white matter and generally corresponded to classically described functional anatomical organization as well as other clinical mapping results. Robust maps of brain activity were identified in healthy brain, regions of developmental or acquired structural abnormality, and SOZs. CONCLUSIONS Task-based electrophysiological mapping using broadband changes in the SEEG signal reliably identifies movement and speech representation in pediatric and adult epilepsy patients.