Febrile‐infection related epilepsy syndrome (FIRES) is a devastating neurological condition characterized by a febrile illness preceding new onset refractory status epilepticus (NORSE). Increasing evidence suggests innate immune dysfunction as a potential pathological mechanism. We report an international retrospective cohort of 25 children treated with anakinra, a recombinant interleukin‐1 receptor antagonist, as an immunomodulator for FIRES. Anakinra was potentially safe with only one child discontinuing therapy due to infection. Earlier anakinra initiation was associated with shorter duration of mechanical ventilation, ICU and hospital length of stay. Our retrospective data lay the groundwork for prospective consensus‐driven cohort studies of anakinra in FIRES.

Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended.

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Abstract:Objective:To examine if telemedicine remains safe and of high quality despite rapid expansion of services by comparing telemedicine encounters prior to and during COVID 19 pandemic.Methods:Pre-post study investigating 2999 telemedicine encounters: 2/1/2020 - 5/15/2020. 2919 completed visits before and after strict social distancing implementation were analyzed for patient and provider characteristics, encounter characteristics (history, physical exam, etc) and quality and safety metrics (phone calls <=7 days post visit, visit- cause specific hospital admission or mortality <=30 days after visit). Stratified analysis of 3 groups for outcomes (young age, neuromuscular diagnosis and new encounters) was performed.Results:Patients ranging from 1 month old to 33 years were seen. Rural patients were less likely to be seen during pandemic compared to urban patients(8 % vs 90% p< 0.0001); teaching clinic and specialty clinic encounters increased significantly during pandemic ( 8% vs 3% ; p=0.005), documentation of at least two systems on exam was noted significantly more frequently during pandemic ( 13% vs 7%; p=0.009). No deaths were reported. There were no differences pre/ during pandemic for safety or telemedicine failure metrics within entire group and high-risk subgroupsConclusions:Despite a markedly and rapidly expanded scope of ambulatory telemedicine care during the COVID19 pandemic, telemedicine remained a safe and high-quality option for pediatric neurology patients. Additionally, populations perceived as high risk for telemedicine (the very young, new patients and those with neuromuscular diagnoses) can benefit from telemedicine visits, particularly when access to in-person care is limited.

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.

Comorbidities in children with Dravet syndrome may involve more systems than previously reported. We report a cohort of children with Dravet syndrome with reduced height and weight growth trend, as well as a subset with endocrine dysfunction evidenced by low IGF-1 and testosterone levels. Additional prospective research is needed to further define the significance of this relationship.

ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.ObjectiveTo evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.ExposuresGenetic test results.Main Outcomes and MeasuresClinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms.ResultsAmong 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%).Conclusions and RelevanceResults of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

ObjectiveEpilepsy with myoclonic‐atonic seizures (EMAS) is a rare childhood onset epileptic encephalopathy. There is no clear consensus for recommended treatments, and pharmacoresistance is common. To better assess the clinical phenotype, most effective treatment, and determinants of cognitive and seizure outcomes, three major pediatric epilepsy centers combined data, creating the largest cohort of patients with EMAS ever studied to date.MethodsAuthors performed a retrospective chart review of patients with EMAS who received care at the authors’ institutions.ResultsA total of 166 children were identified. Global developmental delay (>1 domain) was present in 2% of children at onset and 49% during the course of the disease. Afebrile seizures occurred after the age of 2 years in 88%, generalized tonic‐clonic seizures in 60%, and drop attack or myoclonic seizures in 30%. At onset, electroencephalography (EEG) found 28% normal, background slowing in 20%, and epileptiform discharges or seizures in 69%. Subsequent EEG found slowing in 62% and discharges or seizures in 90%. Response (>50% seizure reduction) to the first three antiseizure drugs (ASDs) was 26% (levetiracetam, 17%; valproic acid, 31%; other ASDs combined, 26%). Diet therapy was used as a second or third therapy in 19% and ultimately used in 57%; response was 79%, significantly greater than the first three ASDs (P = .005, χ2). Seizure freedom occurred in 57% and was less likely in the case of persistent global developmental delays (P < .001), seizure recorded on subsequent EEGs (P = .027), and failure to respond to diet therapy (P = .005). Development was normal in 47%, and 12% had delays in one domain, which was less likely in the case of global developmental delay after epilepsy onset (P < .001) and failure to achieve seizure freedom (P < .001).SignificanceThis large cohort of children with EMAS clarifies areas of variability in practice. Diet therapy is by far the most effective treatment; failure to respond was associated with failure to attain seizure freedom. This therapy should be used early in the treatment in EMAS. This study also identified a bidirectional link between cognitive and seizure outcomes.