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Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the interictal suppression hypothesis posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-13 Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analysed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the interictal suppression hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the interictal suppression hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.
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Conectoma , Epilepsia Resistente a Medicamentos , Eletroencefalografia , Epilepsias Parciais , Convulsões , Humanos , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Masculino , Feminino , Adulto , Eletroencefalografia/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/cirurgia , Convulsões/fisiopatologia , Conectoma/métodos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Encéfalo/fisiopatologia , Aprendizado de Máquina não SupervisionadoRESUMO
OBJECTIVE: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal-to-bilateral tonic-clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally. METHODS: We obtained electrographic data from 74 patients with stereoelectroencephalography (SEEG). Sliding window band power, functional connectivity, and segregation were computed on preictal, ictal, and postictal data. Five-minute epochs of wake, rapid eye movement sleep, and deep sleep were also extracted. Connectivity of subcortical arousal structures was analyzed in a cohort of patients with both SEEG and functional magnetic resonance imaging (fMRI). Given that custom neuromodulation of seizures is predicated on detection of seizure type, a convolutional neural network was used to classify seizure types. RESULTS: We found that in the frontoparietal association cortex, an area associated with consciousness, both consciousness-impairing seizures (FIASs and FBTCSs) and deep sleep had increases in slow wave delta (1-4 Hz) band power. However, when network measures were employed, we found that only FIASs and deep sleep exhibited an increase in delta segregation and a decrease in gamma segregation. Furthermore, we found that only patients with FIASs had reduced subcortical-to-neocortical functional connectivity with fMRI versus controls. Finally, our deep learning network demonstrated an area under the curve of .75 for detecting consciousness-impairing seizures. SIGNIFICANCE: This study provides novel insights into ictal network measures in FASs, FIASs, and FBTCSs. Importantly, although both FIASs and FBTCSs result in loss of consciousness, our results suggest that ictal network changes in FIASs uniquely resemble those that occur during deep sleep. Our results may inform novel neuromodulation strategies for preservation of consciousness in epilepsy.
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OBJECTIVES: Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug-resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi-institutional epilepsy surgery database to characterize the use of CC across participating centers. METHODS: Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0-18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically. RESULTS: Eighty-three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0-9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1-20) and 10.46 (.2-20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini-craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow-up was 12.8 months (range 1-39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant. SIGNIFICANCE: CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less-invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.
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Epilepsia Resistente a Medicamentos , Epilepsia , Terapia a Laser , Psicocirurgia , Humanos , Criança , Pré-Escolar , Resultado do Tratamento , Epilepsia Resistente a Medicamentos/cirurgia , Convulsões/cirurgia , Epilepsia/cirurgia , Terapia a Laser/métodos , Corpo Caloso/cirurgia , Estudos RetrospectivosRESUMO
Why are people with focal epilepsy not continuously having seizures? Previous neuronal signalling work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is a high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure-onset zones have increased inward connectivity that could be associated with interictal suppression of seizure activity. Accordingly, we hypothesize that seizure-onset zones are actively suppressed by the rest of the brain network during interictal states. Full testing of this hypothesis would require collaboration across multiple domains of neuroscience. We focused on partially testing this hypothesis at the electrographic network level within 81 individuals with drug-resistant focal epilepsy undergoing presurgical evaluation. We used intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, early propagation and non-involved zones. We then used diffusion imaging to acquire estimates of white-matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, we generated a resting-state classification model to assist clinicians in detecting seizure-onset and propagation zones without the need for multiple ictal recordings. Our findings indicate that seizure onset and early propagation zones demonstrate markedly increased inwards connectivity and decreased outwards connectivity using both resting-state (one-way ANOVA, P-value = 3.13 × 10-13) and neurostimulation analyses to evaluate evoked responses (one-way ANOVA, P-value = 2.5 × 10-3). When controlling for the distance between regions, the difference between inwards and outwards connectivity remained stable up to 80 mm between brain connections (two-way repeated measures ANOVA, group effect P-value of 2.6 × 10-12). Structure-function coupling analyses revealed that seizure-onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue (two-way repeated measures ANOVA, interaction effect P-value of 9.76 × 10-21). Using these observations, our support vector classification models achieved a maximum held-out testing set accuracy of 92.0 ± 2.2% to classify early propagation and seizure-onset zones. These results suggest that seizure-onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure-onset zones. These findings have implications for the identification of seizure-onset zones using only brief electrographic recordings to reduce patient morbidity and augment the presurgical evaluation of drug-resistant epilepsy. Further testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative and neuromodulation approaches to improve surgical success rates in those suffering from drug-resistant focal epilepsy.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Humanos , Eletroencefalografia/métodos , Convulsões , EncéfaloRESUMO
BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) milestones state that neurology residents should be able to "interpret common EEG abnormalities, recognize normal EEG variants, and create a report." Yet, recent studies have shown that only 43% of neurology residents express confidence in interpreting EEG without supervision and can recognize less than half of normal and abnormal EEG patterns. Our objective was to create a curriculum to improve both confidence and competence in reading EEGs. METHODS: At Vanderbilt University Medical Center (VUMC), adult and pediatric neurology residents have required EEG rotations in their first and second years of neurology residency and can choose an EEG elective in their third year. A curriculum consisting of specific learning objectives, self-directed modules, EEG lectures, epilepsy-related conferences, supplemental educational material, and tests was created for each of the three years of training. RESULTS: Since the implementation of an EEG curriculum at VUMC from September 2019 until November 2022, 12 adult and 21 pediatric neurology residents completed pre- and post-rotation tests. Among the 33 residents, there was a statistically significant improvement in post-rotation test scores, with a mean score improvement of 17% (60.0 ± 12.9 to 77.9 ± 11.8, n = 33, p < 0.0001). When differentiated by training, the mean improvement of 18.8% in the adult cohort was slightly higher than in the pediatric cohort, 17.3%, though it was not significantly different. Overall improvement was significantly increased in the junior resident cohort with a 22.6% improvement in contrast to 11.5% in the senior resident cohort (p = 0.0097 by Student's t-test, n = 14 junior residents and 15 senior residents). DISCUSSION: With the creation of an EEG curriculum specific to each year of neurology residency, adult and pediatric neurology residents demonstrated a statistically significant mean improvement between pre- and post-rotation test scores. The improvement was significantly higher in junior residents in contrast to senior residents. Our structured and comprehensive EEG curriculum objectively improved EEG knowledge in all neurology residents at our institution. The findings may suggest a model which other neurology training programs may consider for the implementation of a similar curriculum to both standardize and address gaps in resident EEG education.
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Internato e Residência , Neurologia , Humanos , Adulto , Criança , Currículo , Educação de Pós-Graduação em Medicina , Neurologia/educação , Eletroencefalografia , Competência ClínicaRESUMO
OBJECTIVE: Drug-resistant epilepsy (DRE) occurs at higher rates in children <3 years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3 years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery Database, a multicentered, cross-sectional collaboration of 21 US pediatric epilepsy centers, collects prospective data on children <18 years of age referred for epilepsy surgery evaluation. We compared patient characteristics, diagnostic utilization, and surgical treatment between children <3 years old and those older undergoing initial presurgical evaluation. We evaluated patient characteristics leading to delayed referral (>1 year) after DRE diagnosis in the very young. RESULTS: The cohort included 437 children, of whom 71 (16%) were <3 years of age at referral. Children evaluated before the age of 3 years more commonly had abnormal neurological examinations (p = .002) and daily seizures (p = .001). At least one ancillary test was used in 44% of evaluations. Fifty-nine percent were seizure-free following surgery (n = 34), with 35% undergoing limited focal resections. Children with delayed referrals more often had focal aware (p < .001) seizures and recommendation for palliative surgeries (p < .001). SIGNIFICANCE: There are relatively few studies of epilepsy surgery in the very young. Surgery is effective, but may be disproportionally offered to those with severe presentations. Relatively low utilization of ancillary testing may contribute to reduced surgical therapy for those without evident lesions on magnetic resonance imaging. Despite this, a sizeable portion of patients have favorable outcome after focal epilepsy surgery resections.
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Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Pré-Escolar , Estudos Transversais , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia/cirurgia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Convulsões/cirurgia , Tempo para o Tratamento , Resultado do TratamentoRESUMO
PURPOSE: To ascertain the rates of 30-day readmissions and emergency department presentations among pediatric patients with an index admission for functional seizures. METHOD: A retrospective chart review of pediatric patients with an index discharge from the pediatric epilepsy monitoring unit (EMU) or general neurology service for functional seizures. Data collected included demographics, comorbidities, risk factors, and treatment during the index admission. RESULTS: A total of one hundred and two patients were included, of which nearly one in five had a 30-day readmission or emergency department presentation. Index admission to the general neurology service was independently associated with more re-presentations to the hospital (t = 3.26, p < 0.0015). The univariate analysis indicated that cognitive impairment and autism were associated with a lower likelihood of readmission, while a neurology referral and being started on an anti-seizure medication were associated with a greater likelihood of readmission. CONCLUSION: A substantial proportion of pediatric patients with FS return to the hospital within 30 days of discharge. Our data suggest that patients admitted to the EMU service have a lower likelihood of readmission. We speculate that this may be due to differences in patient clinical characteristics as well as the comprehensiveness of the diagnostic evaluation and management in the EMU compared to the general neurology service.
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Alta do Paciente , Readmissão do Paciente , Criança , Humanos , Estudos Retrospectivos , Hospitalização , Fatores de Risco , EletroencefalografiaRESUMO
The benefits of continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU) are increasingly appreciated, though expanding indications for cEEG may strain resources. The current standard of care in babies with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) includes cEEG monitoring throughout the entire TH and rewarming process (at least 72â¯h). Recent cEEG data demonstrate that most seizures occur within the first 24â¯h of monitoring. We hypothesized that abnormal head imaging and EEG background could stratify seizure risk in babies with HIE undergoing TH to identify candidates for early cEEG discontinuation. In this retrospective review of 126 neonates undergoing TH and cEEG, we identified seizures in 38 (30%) neonates, 33 (87%) of whom seized within the first 24â¯h of cEEG monitoring. EEG background was graded and demonstrated that 90% of neonates with seizures had a moderately/markedly abnormal background versus 33% of neonates who did not seize (pâ¯<â¯0.0001). Additionally, while head ultrasound (HUS) obtained before EEG did not stratify seizure risk alone, no neonates with both a normal/mildly abnormal EEG background and a normal HUS (0/25) experienced seizures in contrast to 60% (24/40) neonates with both an abnormal EEG background and an abnormal HUS (pâ¯<â¯0.0001). Our data suggest that neonates with abnormal EEG backgrounds and abnormal HUS should be monitored for seizures throughout TH and rewarming, while neonates with normal/mildly abnormal EEG backgrounds and normal HUS are at low risk of seizures after 24â¯h of monitoring, and thus would be candidates for early cEEG discontinuation.
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Hipotermia Induzida , Hipotermia , Hipóxia-Isquemia Encefálica , Eletroencefalografia/métodos , Humanos , Hipotermia/terapia , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Lactente , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/etiologia , Convulsões/terapiaRESUMO
Mutations in GABAA receptor subunit genes (GABRs) are a major etiology for developmental and epileptic encephalopathies (DEEs). This article reports a case of a genetic abnormality in GABRG2 and updates the pathophysiology and treatment development for mutations in DEEs based on recent advances. Mutations in GABRs, especially in GABRA1, GABRB2, GABRB3, and GABRG2, impair GABAergic signaling and are frequently associated with DEEs such as Dravet syndrome and Lennox-Gastaut syndrome, as GABAergic signaling is critical for early brain development. We here present a novel association of a microdeletion of GABRG2 with a diagnosed DEE phenotype. We characterized the clinical phenotype and underlying mechanisms, including molecular genetics, EEGs, and MRI. We then compiled an update of molecular mechanisms of GABR mutations, especially the mutations in GABRB3 and GABRG2 attributed to DEEs. Genetic therapy is also discussed as a new avenue for treatment of DEEs through employing antisense oligonucleotide techniques. There is an urgent need to define treatment targets and explore new treatment paradigms for the DEEs, as early deployment could alleviate long-term disabilities and improve quality of life for patients. This study highlights biomolecular targets for future therapeutic interventions, including via both pharmacological and genetic approaches.
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Encefalopatias , Receptores de GABA-A , Humanos , Mutação , Núcleo Familiar , Fenótipo , Qualidade de Vida , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismoRESUMO
OBJECTIVES: The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. METHODS: We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices. RESULTS: Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002). SIGNIFICANCE: There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection. PLAIN LANGUAGE SUMMARY: In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.
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Epilepsia Resistente a Medicamentos , Eletroencefalografia , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Feminino , Masculino , Criança , Adolescente , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Bases de Dados Factuais , Pré-Escolar , Cuidados Pré-Operatórios , Lactente , Gravação em VídeoRESUMO
Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant <5 annually. The youngest RNS patient was 3 years old. Most centers (11/12) utilize MP2RAGE and/or FGATIR sequences for planning. Centromedian thalamic nuclei were the unanimous target for Lennox-Gastaut syndrome. Surgeon exposure to neuromodulation occurred mostly in clinical practice (14/17). Clinically significant hemorrhage (n = 2) or infection (n = 3) were rare. Meaningful seizure reduction (>50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.
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Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsia , Núcleos Intralaminares do Tálamo , Humanos , Criança , Pré-Escolar , Estimulação Encefálica Profunda/métodos , Epilepsia/terapia , Epilepsia Resistente a Medicamentos/terapia , Convulsões/terapiaRESUMO
BACKGROUND: Responsive neurostimulation (RNS), a closed-loop intracranial electrical stimulation system, is a palliative surgical option for patients with drug-resistant epilepsy (DRE). RNS is approved by the US Food and Drug Administration for patients aged ≥18 years with pharmacoresistant partial seizures. The published experience of RNS in children is limited. METHODS: This is a combined prospective and retrospective study of patients aged ≤18 years undergoing RNS placement. Patients were identified from the multicenter Pediatric Epilepsy Research Consortium Surgery Registry from January 2018 to December 2021, and additional data relevant to this study were retrospectively collected and analyzed. RESULTS: Fifty-six patients received RNS during the study period. The mean age at implantation was 14.9 years; the mean duration of epilepsy, 8.1 years; and the mean number of previously trialed antiseizure medications, 4.2. Five patients (9%) previously trialed dietary therapy, and 19 patients (34%) underwent prior surgery. Most patients (70%) underwent invasive electroencephalography evaluation before RNS implantation. Complications occurred in three patients (5.3%) including malpositioned leads or transient weakness. Follow-up (mean 11.7 months) was available for 55 patients (one lost), and four were seizure-free with RNS off. Outcome analysis of stimulation efficacy was available for 51 patients: 33 patients (65%) were responders (≥50% reduction in seizure frequency), including five patients (10%) who were seizure free at follow-up. CONCLUSIONS: For young patients with focal DRE who are not candidates for surgical resection, neuromodulation should be considered. Although RNS is off-label for patients aged <18 years, this multicenter study suggests that it is a safe and effective palliative option for children with focal DRE.
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Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Criança , Adolescente , Adulto , Estudos Retrospectivos , Estudos Prospectivos , Epilepsia Resistente a Medicamentos/cirurgia , ConvulsõesRESUMO
OBJECTIVE: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders. METHODS: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score. RESULTS: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02). SIGNIFICANCE: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative.
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Epilepsia , Criança , Humanos , Epilepsia/genética , Epilepsia/cirurgia , Convulsões , Bases de Dados Factuais , Neuroimagem , ProbabilidadeRESUMO
OBJECTIVE: Epilepsy with myoclonic absences is a rare epilepsy syndrome with distinct features and high rates of drug resistance. Identifying this syndrome may help guide treatment decisions. We highlight clinical heterogeneity in this case series and two cases in which corpus callosotomy was performed. METHODS: Medical records were reviewed between 2017 and 2021 to identify demographics, comorbidities, age at onset, EEG findings, diagnostic evaluations, seizure semiologies, seizure frequency, anti-seizure medications, diet therapy and surgical treatments in patients with myoclonic absences. RESULTS: Ten patients were identified including twins with myoclonic absence status epilepticus. Forty percent had an atonic component, 20% presented with myoclonic absence status epilepticus and 60% had incomplete control of seizures at last follow-up visit. Two patients with epilepsy with myoclonic absences with atonia underwent corpus callosotomy; one patient was seizurefree eight months after surgery and the other had greater than 50% seizure reduction over a five-month period. SIGNIFICANCE: Phenotypic heterogeneity was evident based on seizure semiologies, comorbidities, seizure frequency and response to anti-seizure medications and non-medication treatments. Of patients with an atonic component, 75% did not achieve seizure freedom with medication alone. Corpus callosotomy was performed in two of these patients with encouraging seizure response thus far, however, the efficacy of this treatment should be further evaluated in a larger study.
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Epilepsias Mioclônicas , Epilepsia , Estado Epiléptico , Idade de Início , Eletroencefalografia , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/cirurgia , Epilepsia/cirurgia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Functional connectivity (FC) measures can be used to differentiate epileptogenic zones (EZs) from non-EZs in patients with medically refractory epilepsy. Little work has been done to evaluate the stability of stereo-EEG (SEEG) FC measures over time and their relationship with antiseizure medication (ASM) use, a critical confounder in epilepsy FC studies. We aimed to answer the following questions: Are SEEG FC measures stable over time? Are they influenced by ASMs? Are they affected by patient data collection state? METHODS: In 32 patients with medically refractory focal epilepsy, we collected a single 2-minute prospective SEEG resting-state (awake, eyes closed) data set and consecutive 2-minute retrospective pseudo-rest (awake, eyes open) data sets for days 1-7 postimplantation. ASM dosages were recorded for days 1-7 postimplantation and drug load score (DLS) per day was calculated to standardize and compare across patients. FC was evaluated using directed and nondirected measures. Standard clinical interpretation of ictal SEEG was used to classify brain regions as EZs and non-EZs. RESULTS: Over 7 days, presumed EZs consistently had higher FC than non-EZs when using between imaginary coherence (ImCoh) and partial directed coherence (PDC) inward strength, without accounting for DLS. These measures were demonstrated to be stable over a short-term period of 3 consecutive days with the same DLS. Between ImCoh FC differences between EZs and non-EZs were reduced with DLS decreases, whereas other measures were not affected by DLS. FC differences between EZs and non-EZs were seen during both resting-state and pseudo-rest conditions; ImCoh values were strongly correlated between the 2 conditions, whereas PDC values were not. DISCUSSION: Inward and nondirected SEEG FC is higher in presumed EZs vs non-EZs and measures are stable over time. However, certain measures may be affected by ASM dose, as between ImCoh differences between EZs and non-EZs are less pronounced with lower doses, and other measures such as PDC are poorly correlated across recording conditions. These findings allow novel insight into how SEEG FC measures may aid surgical localization and how they are influenced by ASMs and other factors.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/tratamento farmacológico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Técnicas EstereotáxicasRESUMO
As awareness of pediatric epilepsy increases, accompanied by advancements in technology and research, it is important to identify certain types of patients that are overlooked for surgical management of epilepsy. Identifying these populations will allow us to study and elucidate the factors contributing to the underutilization and/or delayed application of surgical interventions. Demographically, African-American and Hispanic patients, as well as patients of certain Asian ethnicities, have relatively lower rates of undergoing epilepsy surgery than non-Hispanic and white patients. Among patients with epilepsy, those with higher odds of seizure-freedom following surgery are more likely to be referred for surgical evaluation by their neurologists, with the most common diagnosis being lesional focal epilepsy. However, patients with multifocal or generalized epilepsy, genetic etiologies, or normal (non-lesional) brain magnetic resonance imaging (MRI) are less likely be to referred for evaluation for resective surgery. With an increasing number of high-quality imaging modalities to help localize the epileptogenic zone as well as new techniques for both curative and palliative epilepsy surgery, there are very few populations of patients and/or types of epilepsy that should be precluded from evaluation to determine the suitability of epilepsy surgery. Ultimately, a clearer understanding of the populations who are underrepresented among those considered for epilepsy surgery, coupled with further study of the underlying reasons for this trend, will lead to less disparity in access to this critical treatment among patients with epilepsy.