Nonfebrile Seizures Research Articles

Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT))

BackgroundPaediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid–base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment.MethodsA double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as ‘carbogen’.Due to the urgent need to treat the seizure, deferred consent is used.The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality.DiscussionIf safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff.Trial registrationEudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

ASSESSING IRON DEFICIENCY AS RISK FACTOR FOR FEBRILE SEIZURES IN CHILDREN BETWEEN SIX MONTHS AND FIVE YEARS OF AGE

This case-control study was conducted from September 2023 to December 2023 at the Department of Pediatrics in Pak Emirates Military Hospital, Rawalpindi. The study aimed to determine the relationship between iron deficiency and the development of febrile seizures in children. A total of 150 patients aged between 1 and 6 years, with a history of febrile seizures and currently suffering from pyrexia, were included in the study. Children with a history of recent febrile seizures, structural/organic brain lesions, congenital metabolic/chromosomal anomalies, non-febrile seizures, delayed milestones, or those who were on medications that altered serum iron levels within the past six months were excluded. All participants were assessed for serum iron, ferritin, total iron binding capacity, magnesium, zinc, and calcium at enrollment. Patients were observed for the development of febrile seizures until they were afebrile for twenty-four continuous hours. Of the total sample, the mean age was 3.41 ± 1.51 years, and 83 (55.3%) were male. Patients with a transferrin saturation below 6.5% had a higher adjusted odds ratio (aOR) of 3.96 (CI 95% 1.29 – 12.18, p=0.016) for developing febrile seizures during a pyrexial illness. Similarly, patients with hypozincaemia, defined as a serum zinc level <65 μg/dL, had an aOR of 2.54 (CI 95% 1.13 – 5.67, p=0.023). The study concluded that low serum levels of iron were associated with a higher risk of developing febrile seizures in pyrexial children with a history of the disorder.

A Systematic Review and Clinical Presentation of Central Nervous System Complications of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Pediatric Patients During the Coronavirus Disease 2019 Pandemic in Israel

BackgroundCoronavirus disease-associated central nervous system complications (CNS-C) in hospitalized children, especially during the Omicron wave, and in comparison with influenza associated CNS-C, are not well understood. MethodsThe study population included 755 children aged <18 years hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Sheba Medical Center, during March 2020 to July 2022. A comparative cohort consisted of 314 pediatric patients with influenza during the 2018-2019 and 2019-2020 influenza seasons. ResultsOverall, 5.8% (n = 44) of patients exhibited CNS-C. Seizures at presentation occurred in 33 patients with COVID-19 (4.4%), with 2.6% (n = 20) experiencing nonfebrile seizures, 1.1% (n = 8) febrile seizures, and 0.7% (n = 5) status epilepticus. More patients with CNS-C experienced seizures during the Omicron wave versus the pre-Omicron period (77.8% vs 41.2%, P = 0.03). Fewer patients were admitted to the intensive care unit in the Omicron wave (7.4%) versus prior waves (7.4% vs 41.2%, P = 0.02). Fewer patients with SARS-CoV-2 experienced CNS-C (5.8%) versus patients with influenza (9.9%), P = 0.03. More patients with SARS-CoV-2 experienced nonfebrile seizures (2.6% vs 0.6%, P = 0.06), whereas more patients with influenza experienced febrile seizures (7.3% vs 1.1%, P < 0.01). ConclusionsThe Omicron wave was characterized by more seizures and fewer intensive-care-unit admissions than previous waves. Pediatric patients with SARS-CoV-2 experienced fewer CNS-C and more nonfebrile seizures compared with patients with influenza.

Risk of seizure recurrence in children with new-onset afebrile seizure

BACKGROUND A seizure is a brief change in the normal neuronal electrical activity of the brain that causes changes in consciousness, perception, behavior, or movement. This study aimed to evaluate clinical findings, initial electroencephalography (EEG), and brain imaging findings as predictors of seizure recurrence after the first nonfebrile seizure.&#x0D; METHODS This prospective follow-up study was conducted at Azadi Teaching Hospital, Kirkuk from July 2019 to January 2022 and enrolled 150 patients, ranging from 1 month to 15 years of age, who presented with their first afebrile seizure. The seizure types were classified based on the International League Against Epilepsy in 2017. A brain imaging with EEG was performed within 72 hours after admission.&#x0D; RESULTS The median age of the patients was 5 years. A higher risk of seizure recurrence occurred in patients with focal seizure (relative risk [RR] = 6.604) (95% confidence interval [CI] 3.975–10.971), seizure occurrence at sleep (RR = 3.815) (95% CI 2.410–6.039), an abnormal neurological presentation such as Todd’s paralysis (RR = 1.739) (95% CI 1.252–2.415), a positive family history of seizures (RR = 2.333) (95% CI 1.598–3.408), abnormal EEG (RR = 0.171) (95% CI 0.092–0.318), and abnormal brain image findings (RR = 0.681) (95% CI 0.492–0.941) within 72 hours. Seizure recurrence was not correlated with sex.&#x0D; CONCLUSIONS Early and late childhood new-onset afebrile seizures with a positive family history, focal epilepsy, seizure during sleep, prolonged attack duration with frequent attacks within 24 hours, and abnormal initial EEG and brain image had a high risk of seizure recurrence.

Meta-analysis of HMGB1 levels in the cerebrospinal fluid and serum of patients with epilepsy.

Epilepsy pathogenesis and progression are strongly influenced by inflammation. High-mobility group box-1 (HMGB1) is a key proinflammatory factor. The purpose of this study was to quantify and assess the relationship between HMGB1 level and epilepsy. We searched Embase, Web of Science, PubMed, and the Cochrane Library for studies examining the relationship between HMGB1 and epilepsy. Two independent researchers extracted data and assessed quality using the Cochrane Collaboration tool. Data extracted were analyzed using Stata 15 and Review Manager 5.3. The study protocol was registered prospectively at INPLASY, ID: INPLASY2021120029. A total of 12 studies were eligible for inclusion. After exclusion of one study with reduced robustness, 11 studies were included, with a total of 443 patients and 333 matched controls. Two of the articles included cerebrospinal fluid and serum HMGB1 data, which were distinguished by "a" and "b," respectively. The meta-analysis indicated that in comparison with the control group, the HMGB1 level was higher in epilepsy patients (SMD = 0.56, 95% CI = 0.27-0.85, P = 0.0002). Subgroup analysis of specimen types indicated that both serum HMGB1 and cerebrospinal fluid HMGB1 were higher in epilepsy patients than in the control group, with the increase in cerebrospinal fluid HMGB1 being more obvious. Subgroup analysis of disease types demonstrated that the serum HMGB1 level of epileptic seizure patients (including febrile and nonfebrile seizures) was significantly higher than that of matched controls. However, serum HMGB1 levels did not differ significantly between mild epilepsy patients and severe epilepsy patients. Patient age subgroup analysis showed higher HMGB1 in adolescents with epilepsy. Begg's test did not indicate publication bias. This is the first meta-analysis to summarize the association between HMGB1 level and epilepsy. The results of this meta-analysis indicate that epilepsy patients have elevated HMGB1. Large-scale studies with a high level of evidence are needed to reveal the exact relationship between HMGB1 level and epilepsy.

COVID-19 and Acute Neurologic Complications in Children.

Little is known about the epidemiology and outcomes of neurologic complications associated with coronavirus disease 2019 (COVID-19) in children. We performed a cross-sectional study of children 2 months to &lt;18 years of age with COVID-19 discharged from 52 children's hospitals from March 2020 to March 2022. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye's syndrome, and cerebral infarction. We assessed length of stay (LOS), ICU admission, 30 day readmissions, deaths, and hospital costs. We used multivariable logistic regression to identify factors associated with neurologic complications. Of 15 137 children hospitalized with COVID-19, 1060 (7.0%) had a concurrent diagnosis of a neurologic complication. The most frequent neurologic complications were febrile seizures (3.9%), nonfebrile seizures (2.3%), and encephalopathy (2.2%). Hospital LOS, ICU admission, ICU LOS, 30 day readmissions, deaths, and hospital costs were higher in children with neurologic complications compared with those without complications. Factors associated with lower odds of neurologic complications included: younger age (adjusted odds ratio [aOR]: 0.97; 95% confidence interval [CI]: 0.96-0.98), occurrence during delta variant predominant time period (aOR: 0.71; 95% CI: 0.57-0.87), presence of a nonneurologic complex chronic condition (aOR: 0.80; 95% CI: 0.69-0.94). The presence of a neurologic complex chronic condition was associated with higher odds of neurologic complication (aOR 4.14, 95% CI 3.48-4.92). Neurologic complications are common in children hospitalized with COVID-19 and are associated with worse hospital outcomes. Our findings emphasize the importance of COVID-19 immunization in children, especially in high-risk populations, such as those with neurologic comorbidity.

The evaluation of accesses for febrile and afebrile seizures in the pediatric emergency department during COVID-19 lockdown

We aimed to evaluate the admissions to the Pediatric Emergency Department (PED) due to seizures one year before and one year after the first COVID-19 case in Turkey. We divided the admission time into two: The prelockdown period (March 2019-February 2020) and the lockdown period (March 2020 – February 2021). We divided the seizures into six parts: First simple febrile convulsion (FK), first complex FK, recurrent simple FK, recurrent complex FK, first non-febrile seizure, and recurrent non-febrile seizure. We compared the prelockdown and lockdown periods in terms of demographic and clinical characteristics and monthly admission of patients. The total number of patients admitted to PED was 37.323 and 10.191 during the prelockdown and lockdown period, respectively. While seizure-related PED accesses were 918 during the prelockdown period, 508 patients were admitted to PED during the lockdown period. Monthly average admissions decreased in all seizure types during the lockdown period. The ratio of first simple febrile seizures to total seizures decreased from 22.4% (206/918) to 16.3% (83/508), while the ratio of first afebrile seizures to total seizures increased from 29.6% (272/918) to 36.8% (186/508). While the rate of first febrile seizures decreased, we observed a significant increase in the rate of first afebrile seizures. The findings suggested that risk factors such as depression/anxiety or screen exposure may have caused seizures in patients with a predisposition to seizures.

Symptomatic care of late-onset Alexander disease presenting with area postrema-like syndrome with prednisolone; a case report

BackgroundAlexander disease (AxD) is classified into AxD type I (infantile) and AxD type II (juvenile and adult form). We aimed to determine the potential genetic cause(s) contributing to the AxD type II manifestations in a 9-year-old male who presented area postrema-like syndrome and his vomiting and weight loss improved after taking prednisolone.Case presentationA normal cognitive 9-year-old boy with persistent nausea, vomiting, and a significant weight loss at the age of 6 years was noticed. He also experienced an episode of status epilepticus with generalized atonic seizures. He showed non-febrile infrequent multifocal motor seizures at the age of 40 days which were treated with phenobarbital. He exhibited normal physical growth and neurologic developmental milestones by the age of six. Occasionally vomiting unrelated to feeding was reported. Upon examination at 9 years, a weak gag reflex, prominent drooling, exaggerated knee-deep tendon reflexes (3+), and nasal tone speech was detected. All gastroenterological, biochemical, and metabolic assessments were normal. Brain magnetic resonance imaging (MRI) revealed bifrontal confluent deep and periventricular white matter signal changes, fine symmetric frontal white matter and bilateral caudate nucleus involvements with garland changes, and a hyperintense tumefactive-like lesion in the brain stem around the floor of the fourth ventricle and area postrema with contrast uptake in post-contrast T1-W images. Latter MRI at the age of 8 years showed enlarged area postrema lesion and bilateral middle cerebellar peduncles and dentate nuclei involvements. Due to clinical and genetic heterogeneities, whole-exome sequencing was performed and the candidate variant was confirmed by Sanger sequencing. A de novo heterozygous mutation, NM_001242376.1:c.262 C > T;R88C in exon 1 of the GFAP (OMIM: 137,780) was verified. Because of persistent vomiting and weight loss of 6.0 kg, prednisolone was prescribed which brought about ceasing vomiting and led to weight gaining of 3.0 kg over the next 3 months after treatment. Occasional attempts to discontinue prednisolone had been resulting in the reappearance of vomiting.ConclusionsThis study broadens the spectrum of symptomatic treatment in leukodystrophies and also shows that R88C mutation may lead to a broad range of phenotypes in AxD type II patients.

A de novo YY1 missense variant expanding the Gabriele-de Vries syndrome phenotype and affecting X-chromosome inactivation.

Yin and Yang 1 gene (YY1; MIM#600,013) is recognized as a dual transcriptional activating and repressing factor, RNA-binding protein, and 3D chromatin regulator, with multi roles in neurodevelopmental and maintenance pathways. YY1 haploinsufficiency caused either by heterozygous sequence variants or deletions involving the whole gene has been recently associated with Gabriele-de Vries syndrome (GADEVS), a rare congenital autosomal dominant condition, leading to intellectual disability (ID) and multiple physical/behavioural abnormalities. Herein, we describe clinical and molecular findings from a Brazilian female harbouring a de novo missense pathogenic variant in YY1 gene (NM_003403.5:c.1106A > G; p.Asn369Ser) found by whole exome sequencing with potential implications for protein structure and function. Undescribed or uncommon clinical features in this patient included non-febrile seizures, severe scoliosis, hearing impairment, and chorioretinitis. Further bioinformatics analyses using YY1-other protein interaction networks reinforced the involvement of YY1 interactors in such phenotypes, in exception of chorioretinitis. Moreover, X-chromosome inactivation (XCI) skewing was evidenced in the patient and attributed to the haploinsufficiency of YY1, which direct and indirectly interacts with numerous XCI key regulators. Besides expanding the mutational and phenotype spectrum of GADEVS, our results highlight the role of YY1 as an essential autosomal regulator of XCI epigenetic process.

Electroencephalographic localization of pathological activity areas in dynamics in patients with benign age-dependent focal epilepsy

Genetic focal age-dependent epilepsy accounts for 25% of epilepsy in children with non-febrile seizures and is a genetically determined focal pathology. The main pattern of interictal pathological activity include benign epileptiform discharges of childhood from the centrotemporal leads in patients with rolandic epilepsy and discharges from the posterior parietooccipital leads in patients with occipital epilepsy. We followed-up 72 patients with benign agedependent focal epilepsy aged 6 months to 10 years for a year to assess the electroencephalographic location of pathological activity areas in dynamics. Electroencephalography demonstrated a variety of locations of pathological activity both at disease onset and after one year of follow-up, as well as migration of this activity, regardless of age, gender, and therapy.

Neurologic complications of common respiratory tract virus infections

Three studies published in this volume of The Journal remind us that although common and familiar to parents and healthcare providers, respiratory tract viruses can lead to neurologic complications. Antoon et al used the Pediatric Health Information system (PHIS) of administrative data to capture 29 676 hospitalizations of children 2 months to <18 years of age with a discharge diagnosis of influenza during influenza seasons of 2015 through 2020 from 49 children's hospitals. Searching for coded concurrent neurologic complications, they found 2246 cases, with febrile seizures occurring in 5% of hospitalizations for influenza, encephalopathy in 1.7%, and non-febrile seizures in 1.2%.

Influenza-Associated Neurologic Complications in Children

Research Article| October 01 2021 Influenza-Associated Neurologic Complications in Children AAP Grand Rounds (2021) 46 (4): 39. https://doi.org/10.1542/gr.46-4-39 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Influenza-Associated Neurologic Complications in Children. AAP Grand Rounds October 2021; 46 (4): 39. https://doi.org/10.1542/gr.46-4-39 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: influenza, neurologic complications Source: Antoon JW, Hall M, Herndon A, et al Prevalence, risk factors, and outcomes of influenza-associated neurologic complications in children [published online ahead of print June 30, 2021]. J Pediatr. doi:10.1016/j.jpeds.2021.06.075 Investigators from multiple institutions conducted a retrospective study to estimate the prevalence of neurologic complications in children hospitalized with influenza, identify risk factors associated with these complications, and assess hospital-related outcomes. For the study, they abstracted data from the Pediatric Health Information System (PHIS) database, which includes information on admissions to 49 tertiary care children’s hospitals across the US. Participants for the current study were children 2 months through 17 years old hospitalized at a PHIS hospital during the influenza seasons from 2015 through 2020 with an ICD-10 diagnostic code for influenza. Information abstracted from the PHIS database on these patients included demographic data, geographic region, hospital length of stay (LOS), ICU admission, other ICD-10 diagnoses, presence of chronic neurologic conditions (defined using the pediatric complex chronic conditions classification system version 2), and hospital charges. The primary study outcome was an ICD-10 code for a neurologic complication, including febrile seizure, non-febrile seizure, encephalopathy, encephalitis, aseptic meningitis, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. Multivariate regression analyses to identify risk factors for a neurologic complication, with controlling for confounders, were conducted. Predominant influenza type was included in the regression model and estimated from CDC influenza surveillance data in each patient’s census division during the week that they were hospitalized. Bivariate analyses were used to compare hospital-related outcomes including LOS, ICU admission, costs (estimated from charge data), and in-hospital death rates among patients with and without neurologic complications. Data were analyzed on 29,676 children hospitalized with influenza. The median age of the included patients was 4 years, and 56% were male. A total of 2,246 (7.6%) had a neurologic complication. The most common neurologic complications were febrile seizure (N = 1,447, 5.0% of influenza admissions), encephalopathy (514, 1.7%), and non-febrile seizure (364, 1.2%). Risk factors identified in the multivariate analyses included male sex (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0, 1.2), Asian race (OR, 1.7; 95% CI, 1.4, 2.1), other race (includes Pacific Islander, American Indian, multiracial, and other; OR, 1.2; 95% CI, 1.03, 1.4), and presence of a chronic neurologic condition (OR, 3.7; 95% CI, 3.1, 4.2). There was no statistical association between predominant influenza type and neurologic complication. Patients with neurologic complications had longer ICU LOS than those without (mean values 2.7 and 2.2 days, respectively; P <0.05), a higher rate of ICU admissions (24.5% vs 15.3%; P <0.001), a higher rate of in-hospital death (0.7% vs 0.2%; P <0.001), and higher costs (mean costs $6,013 vs $5,282; P <0.001). The authors conclude that neurologic complications were common among children hospitalized with influenza, particularly in those with chronic neurologic conditions. Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. For... You do not currently have access to this content.

Recurrence rate of the first nonfebrile seizure in children with autism spectrum disorder

ObjectiveEpilepsy prevalence is higher in children with Autism Spectrum Disorder (ASD) and is a contributor to morbidity and mortality. Little is known about the recurrence rate after the first nonfebrile seizure in this population, specifically in regard to seizure type and electroencephalogram (EEG) findings. MethodsWe reviewed pediatric medical records at our institution between 2006 and 2016 for subjects with ASD who had a first seizure. We then looked for risk of a recurrent non-provoked seizure within the next two years. ResultsOverall, the recurrence rate in this study was 70.9%. This is much higher than the general population. The recurrence rate was higher in patients who had a generalized convulsion compared to those who had a behavioral arrest. When the first seizure was a generalized convulsion, there was an 84% chance of developing a second convulsion, whereas the recurrence rate was 59% for behavioral arrest type seizures (p = 0.002). The odds of having recurrence when the first seizure is a generalized convulsion was 5.36 higher than when it was a behavioral arrest (95% CI 2.14–13.42, p < 0.001). An abnormal EEG was a strong predictor of seizure recurrence in both seizure types. However, even with a normal EEG, generalized convulsions were more likely to recur within 2 years compared to behavioral arrest (OR 6.3, 95% CI 2.1–19). SignificanceThe recurrence rate for nonfebrile seizures in children with ASD is much higher than the general population, especially for generalized convulsions. An abnormal EEG has a strong predictive value for seizure recurrence. However, even when the EEG is normal, the recurrence rate for generalized convulsions is quite high. This is an important finding as epilepsy contributes to morbidity and mortality in this group and may impact clinical decisions about when to start anti-seizure medications.

Prevalence, Risk Factors, and Outcomes of Influenza-Associated Neurologic Complications in Children

To determine the frequency of neurologic complications associated with influenza in hospitalized children. We performed a cross-sectional study of children (2months through 17years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.

Aetiology of febrile seizures – a problem not fully understood

Febrile seizures are seizures that occur during febrile illnesses in the absence of central nervous system infection or other identifiable aetiology in children who have never had any non-febrile seizures before. Although the condition is quite common, affecting 2–5% of children between 3 months and 5 years of age, the underlying pathomechanism is not fully explained. Immaturity of the nervous system, as well as environmental, genetic and immune factors are contemplated. Viruses are the main aetiological factor of febrile infections accompanied by seizures. The risk of febrile seizures after vaccination is low and may be associated with the child’s genetic predisposition. Deficiency of trace elements, including zinc and iron, may also promote seizures. The association between febrile seizures and vitamin D levels was reported in only few studies. It seems that genetic background plays an important role, at least in some cases. In recent years, particular attention has been paid to the possible involvement of immune factors, including pro- and anti-inflammatory cytokines. Previous studies on the aetiology of febrile seizures confirmed their multifactorial nature and indicated their heterogeneity within this group of patients. Further research may not only contribute to a better understanding of the mechanisms underlying the pathogenesis of febrile seizures, but also determine the direction of actions that may reduce the risk of their occurrence and/or recurrence.

Seizure-related deaths in children: The expanding spectrum.

Although seizures are common in children, they are often overlooked as a potential cause of death. Febrile and nonfebrile seizures can be fatal in children with or without an epilepsy diagnosis and may go unrecognized by parents or physicians. Sudden unexpected infant deaths, sudden unexplained death in childhood, and sudden unexpected death in epilepsy share clinical, neuropathological, and genetic features, including male predominance, unwitnessed deaths, death during sleep, discovery in the prone position, hippocampal abnormalities, and variants in genes regulating cardiac and neuronal excitability. Additionally, epidemiological studies reveal that miscarriages are more common among individuals with a personal or family history of epilepsy, suggesting that some fetal losses may result from epileptic factors. The spectrum of seizure‐related deaths in pediatrics is wide and underappreciated; accurately estimating this mortality and understanding its mechanism in children is critical to developing effective education and interventions to prevent these tragedies.

Ictal EEG in patients with autistic spectrum disorder and epilepsy

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental disorder frequently associated with epilepsy and epilepsy is a leading cause of death in ASD patients. Despite growing interest in genetic, neurophysiological and clinical overlaps, data on ictal electroencephalographic (EEG) recordings in ASD are lacking since behavioral disorders often make it difficult to obtain EEG recordings. We examined ictal EEG features in a consecutive series of patients with ASD and epilepsy. MethodsWe retrospectively identified 400 consecutive patients with ASD and epilepsy at our Level 4 Epilepsy center between 2015 and 2019; 45 had at least one EEG-recorded seizure captured. Demographics, age of nonfebrile seizure onset, age of ASD diagnosis, language, magnetic resonance imagining findings, genetic testing and EEG studies were reviewed. Seizures were classified by semiologic and electrographic features. Ictal findings were analyzed. ResultsA total of 497 seizures were captured in 45 patients: 20 patients with focal onset epilepsy had 126 seizures (median: 1, range: 1-30), 17 patients with generalized onset epilepsy had 88 seizures (median: 2, range: 1-15), 7 patients with Lennox-Gastaut syndrome had 270 seizures (median: 12, range: 1-74) and one patient had both right hemisphere focal and generalized onsets (12 focal, 1 generalized). SignificanceOur study is the first to analyze a large set of ictal data in patients with autism spectrum disorder, a population traditionally difficult to obtain ictal recordings. Our results confirm the diverse spectrum of seizure types and provide clinical-EEG correlates of seizures in ASD patients. Both focal-onset and generalized-onset seizures were recorded, confirming that ASD patients have higher rates of both focal and generalized epilepsy syndromes. Among patients with focal epilepsy, temporal and frontal onsets were frequent, suggesting the possibility of epilepsy surgery or brain stimulation. EEG to classify seizures and epilepsies is critical to determine therapeutic options and effort should be made to obtain EEGs in this heterogenous population.

Child neurology services for children with epilepsy in Finland.

ObjectiveThe aim of the study was to describe healthcare organization, training of and needs for child neurologists, patient accessibility to services, and treatment paths of children with epilepsy in Finland.MethodsData were collected from all geographic healthcare areas over Finland on training capacity in child neurology, number and density of child neurologists, and availability and accessibility of child neurological services. Data sources included the National Physician Register, Central Register of Healthcare Professionals of National Supervisory Authority for Welfare and Health, and phone and email inquiries to the heads of public healthcare units.ResultsThe overall density of child neurologists in Finland was 11.9/100 000 children aged 0‐15 years or 8402 children per child neurologist (in 2018). There is a remarkable geographic variation, from 7.1 in northern Finland to 15.6 in the metropolitan area. However, waiting times for the treatment are virtually the same all over the country. According to the Finnish current practice recommendation from the year 2013 and again 2020, children with any first nonfebrile or complicated febrile epileptic seizure are invariably admitted to hospital for evaluation. Children with simple febrile seizures are recommended to be treated as outpatients by general practitioners or by experienced pediatricians.SignificanceChild neurology services are today well provided and organized in Finland. While there is geographic variation in the number of child neurologists, the accessibility is virtually the same all over the country. A gap between the numbers of specialists at near‐to‐retire age and those in training is a challenge.

Neurologic Complications in Children Hospitalized With Influenza Infections: Prevalence, Risk Factors and Impact on Disease Severity.

Influenza infection is a common cause of respiratory disease and hospitalization in children. Neurologic manifestations of the infection have been increasingly reported and may have an impact on the severity of the disease. The aim of this study is to describe neurologic events in pediatric patients hospitalized with influenza and identify associated risk factors. Retrospective cohort study which included all hospitalized patients with microbiologic confirmation of influenza disease over 4 epidemic seasons, focusing on neurologic complications. Demographic, laboratory and clinical data, as well as past history, were recorded. Descriptive and analytic statistical study was performed using SPSS and R statistical software. Two hundred forty-five patients were included. Median age was 21 months (interquartile range, 6-57) and 47.8% had a previous underlying condition. Oseltamivir was administered to 86% of patients, median hospitalization was 4 days (interquartile range, 3-6), and pediatric intensive care unit admission rate 8.9%. Twenty-nine patients (11.8%) developed neurologic events, febrile seizures being the most frequent, followed by nonfebrile seizures and encephalopathy. Status epilepticus occurred in 4 children, and 69.6% of seizures recurred. Patients with a previous underlying condition were at greater risk of developing a neurologic complication [odds ratio (OR), 4.55; confidence interval (CI), 95% 1.23-16.81). Male sex (OR, 3.21; CI 95%, 1.22-8.33), influenza B virus (OR, 2.82; CI 95%, 1.14-7.14) and neurologic events (OR, 3.34; CI 95%, 1.10-10.19) were found to be risk factors for pediatric intensive care unit admission. A significant proportion of influenza-related hospitalized patients develop neurologic complications, especially seizures which may be prolonged or recurrent. Previous underlying conditions pose the greatest risk to neurologic events, which increase disease severity.

Characterization of Pediatric Seizures in the Commonwealth of the Northern Mariana Islands

Saipan is a United States (US) territory Western Pacific island where little recent data exists regarding epidemiology, clinical presentation, and standard of care for pediatric seizures. This paper characterizes these features in Saipan’s pediatric population with comparisons to mainland US. This is a retrospective chart review of all pediatric patients with a history of seizures at the island’s only hospital and major private neurology clinic over a 10-year period. Variables regarding demographics, presentation, diagnosis, and treatment were collected. A total of 144 patients were included, with 101 patients diagnosed with febrile seizures and 31 patients diagnosed with non-febrile seizures. Age at first presentation peaked at 1 year old overall. The most common identified etiology of epilepsy was found to be hypoxic injury (39%), hemorrhagic injury (10%), cerebral malformation (6%), and brain mass (6%). Simple versus complex classification of febrile seizures, etiologies, and first-line treatment for non-febrile seizures were comparable to the mainland US. Electroencephalogram (EEG) was not used consistently in diagnosis. The findings from this study demonstrate that clinical presentations of pediatric seizures in Saipan are comparable to those in the mainland US.