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ABSTRACT: Febrile seizures are the most common seizure disorder in childhood. Most febrile seizures have a benign course and children have a good prognosis. However, febrile seizures are traumatizing events for a child's family or caregiver to witness. Appropriate caregiver education is crucial to ease anxiety. This article reviews the risk factors, clinical presentation, diagnostics, treatment, and prevention of febrile seizures in addition to providing a guideline for effective caregiver education and support.

Asunto(s)

Cuidadores , Convulsiones Febriles , Humanos , Convulsiones Febriles/terapia , Convulsiones Febriles/diagnóstico , Convulsiones Febriles/etiología , Cuidadores/educación , Factores de Riesgo , Niño , Anticonvulsivantes/uso terapéutico , Lactante , Preescolar

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BACKGROUND: Febrile convulsion (FC) among children is a common emergency concern received in hospitals and clinics. However, in Ghana, FC is commonly perceived as a non-hospital disease and usually managed at home. There is limited research on the home management of FC. This study, therefore, explored the home management of FC. METHODS: The study design was a descriptive and interpretive phenomenology. Data sources were triangulated among 42 participants across 5 communities within 2 km distance from regional hospitals in the Cape Coast Metropolis. Participants were purposively selected and interviewed face to face in their homes and treatment centres using semistructured interview guides. Interviews were transcribed and thematically analysed with QSR NVivo V.14. RESULTS: Three themes were identified from the inductive analysis. These themes were treatment, prevention and case referral. Subthemes on treatment were tepid sponging with lukewarm water, the use of herbal medicine and spiritual approaches. FC was referred to as 'asram suro'. The 'asram' literally means the moon, and 'suro' connotes the skies, indicating possibly that the condition emanates from a god of the moon. Caregivers prevented FC through behavioural approaches, herbal medicine, and mystical approaches including making scarification and tying amulets and beads particularly on the child's face and wrists respectively. FC cases were referred for clinical attention after home care resulted in undesirable treatment outcomes. A conceptual framework depicting the decision-making and practices towards FC management is presented. CONCLUSION: FC is commonly managed at home independent of orthodox care availability. Caregivers employed herbal and ad hoc treatment regimens, usually unwarranted, visually frightening and spiritual approaches which were not the best home management approaches. These findings call for the need to educate caregivers about the best home management of FC.

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Cuidadores , Investigación Cualitativa , Convulsiones Febriles , Humanos , Ghana , Masculino , Femenino , Cuidadores/psicología , Convulsiones Febriles/terapia , Adulto , Preescolar , Lactante , Servicios de Atención de Salud a Domicilio , Entrevistas como Asunto , Niño , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud

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BACKGROUND: Febrile seizures are the most common type of convulsions affecting children aged six months to five years. However, febrile seizures can be difficult to identify due to the vague nature of the symptoms, which can lead to incorrect diagnosis and treatment. Thus, this study explores febrile seizure-related uncertainty, knowledge, and anxiety among mothers. DESIGN AND METHODS: A cross-sectional design included 190 Jordanian mothers, about half with children having febrile seizure history. Instruments included the State-Trait Anxiety Inventory (STAI), Parental Perception of Uncertainty Scale (PPUS), and Parental Knowledge, Attitudes, Concerns, and Practices (KACP). RESULTS: Mothers exhibited poor febrile seizure knowledge, with affected mothers significantly scoring higher than unaffected. Affected mothers had higher state and trait anxiety and uncertainty. Correlations showed uncertainty positively correlated with anxiety. Regression analysis showed that trait anxiety and knowledge predicted uncertainty in affected mothers, while only trait anxiety predicted uncertainty in unaffected mothers. CONCLUSION: Mothers, especially those with affected children, demonstrated low febrile seizure knowledge, high anxiety, and uncertainty. Lack of knowledge may contribute to ineffective febrile seizure management. The study identifies trait anxiety and knowledge as predictors of uncertainty, emphasizing the need for tailored interventions. PRACTICE IMPLICATIONS: Healthcare professionals can design interventions targeting febrile seizure education and anxiety reduction. Policymakers should focus on raising awareness and allocating resources for effective interventions, potentially improving children with febrile seizure outcomes. This study underscores the importance of addressing maternal knowledge gaps, anxiety, and uncertainty related to febrile seizures, suggesting the need for comprehensive educational programs and support strategies for mothers.

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Ansiedad , Conocimientos, Actitudes y Práctica en Salud , Madres , Convulsiones Febriles , Humanos , Convulsiones Febriles/diagnóstico , Convulsiones Febriles/psicología , Femenino , Madres/psicología , Estudios Transversales , Incertidumbre , Adulto , Masculino , Preescolar , Jordania , Lactante

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INTRODUCTION: Febrile seizures in children can be associated with various underlying conditions, including COVID-19. Differentiating COVID-19 and non-COVID-19 related febrile seizures is crucial for tailored patient management and for implementing appropriate infection control measures to prevent nosocomial transmission. This study aimed to describe the clinical features of children hospitalised for COVID-19 and non-COVID-19 febrile seizures and to identify factors that differentiate between the two groups. MATERIALS AND METHODS: This retrospective cross-sectional study involved children aged 6 months to 6 years who were hospitalised for febrile seizures in Hospital Tuanku Ja'afar Seremban (HTJS) from January 2021 to June 2022. Descriptive statistics were used to summarise the differences in demographics and clinical presentations. Logistic regression analyses were performed to identify factors associated with COVID-19 and non-COVID-19 febrile seizures. RESULTS: Of the 345 patients (median age 22 months, IQR 15- 32; 59.7% were males) included in the study, 130 (37.7%) tested positive for COVID-19, while 215 (62.3%) tested negative. There were no significant differences between both groups based on age, comorbidities, history of febrile seizures, seizure types, temperature on arrival, cough and rhinorrhoea. Multivariate analysis revealed that a family history of febrile seizures and leucocytosis were associated with increased odds of non-COVID-19 febrile seizures. In contrast, lymphopenia was associated with decreased odds. CONCLUSION: The clinical presentation of COVID-19 and non- COVID-19 febrile seizures are remarkably similar, highlighting the importance of including COVID-19 screening in febrile seizures workup. Full blood count readings may be potentially useful for differentiating between these conditions.

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COVID-19 , Convulsiones Febriles , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , Masculino , Convulsiones Febriles/diagnóstico , Femenino , Estudios Retrospectivos , Lactante , Preescolar , Estudios Transversales , Niño , SARS-CoV-2 , Hospitalización , Diagnóstico Diferencial

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Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait. Patients with GEFS+ may develop typical febrile seizures (FS), while generalized tonic-clonic seizures (GTCSs) with fever commonly occur between 3 months and 6 years of age, which is generally followed by febrile seizure plus (FS+), with or without absence seizures, focal seizures, or GTCSs. GEFS+ exhibits significant genetic heterogeneity, with polymerase chain reaction, exon sequencing, and single nucleotide polymorphism analyses all showing that the occurrence of GEFS+ is mainly related to mutations in the gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2) gene. The most common mutations in GABRG2 are separated in large autosomal dominant families, but their pathogenesis remains unclear. The predominant types of GABRG2 mutations include missense (c.983A → T, c.245G → A, p.Met199Val), nonsense (R136*, Q390*, W429*), frameshift (c.1329delC, p.Val462fs*33, p.Pro59fs*12), point (P83S), and splice site (IVS6+2T → G) mutations. All of these mutations types can reduce the function of ion channels on the cell membrane; however, the degree and mechanism underlying these dysfunctions are different and could be linked to the main mechanism of epilepsy. The γ2 subunit plays a special role in receptor trafficking and is closely related to its structural specificity. This review focused on investigating the relationship between GEFS+ and GABRG2 mutation types in recent years, discussing novel aspects deemed to be great significance for clinically accurate diagnosis, anti-epileptic treatment strategies, and new drug development.

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Mutación , Receptores de GABA-A , Convulsiones Febriles , Humanos , Receptores de GABA-A/genética , Convulsiones Febriles/genética , Mutación/genética , Epilepsia/genética , Animales

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BACKGROUND: IFIH1 variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether IFIH1 variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive. METHODS: Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations. RESULTS: Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. IFIH1 is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients. CONCLUSIONS: IFIH1 variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of IFIH1 variants.

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Epilepsia Generalizada , Secuenciación del Exoma , Estudios de Asociación Genética , Helicasa Inducida por Interferón IFIH1 , Mutación Missense , Convulsiones Febriles , Humanos , Convulsiones Febriles/genética , Epilepsia Generalizada/genética , Masculino , Femenino , Helicasa Inducida por Interferón IFIH1/genética , Mutación Missense/genética , Preescolar , Lactante , Niño , Predisposición Genética a la Enfermedad , Adulto , Fenotipo

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BACKGROUND: Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1-3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model. METHODS: This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence. RESULTS: Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P < 0.001), duration of the first episode (OR = 1.03, 95% CI: 1.00, 1.06, P = 0.040), and peak temperature (OR = 0.68, 95% CI: 0.47, 0.98, P = 0.036) were identified as independent risk factors for FS recurrence. Age had the highest relative importance in predicting FS recurrence, followed by the duration of the first episode, with an area under the ROC curve of 0.717. CONCLUSION: Young age and duration of the first seizure are important independent risk factors for FS recurrence and are key considerations for predicting recurrence. Further research is needed to confirm the potential use of Neutrophil-lymphocyte ratio (NLR) as a predictor of FS recurrence.

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Recurrencia , Convulsiones Febriles , Humanos , Convulsiones Febriles/epidemiología , Convulsiones Febriles/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Masculino , Femenino , China/epidemiología , Lactante , Preescolar , Factores de Edad , Estudios de Seguimiento , Niño , Pronóstico

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OBJECTIVE: The aim of this study was to evaluate the association between nutritional status, inflammation, and susceptibility to seizures in febrile children. METHODS: This observational single-center study was carried out from January 2020 to December 2023 with 324 children aged 6 months and 6 years; 106 were diagnosed with febrile seizure, 108 were febrile children, and 110 were healthy controls. The prognostic nutritional index and neutrophil-to-lymphocyte ratio were calculated, and the cutoff threshold was established through receiver operating characteristics. The study utilized correlation and univariate-multivariate logistic regression analysis. The comparison between simple and complex febrile seizure was conducted to analyze differences. RESULTS: The optimal cutoff values were identified as 61.25 for prognostic nutritional index and 1.04 for neutrophil-to-lymphocyte ratio. Our findings showed a significant negative association between febrile seizure and platelet count, high C-reactive protein, and high ferritin levels. Additionally, the febrile seizure group showed a significant positive correlation with high neutrophil-to-lymphocyte ratio values (≥1.04) and body temperature (≥38). Our findings revealed that high neutrophil-to-lymphocyte ratio, high C-reactive protein, and age less than 18 months were independently associated with seizure susceptibility in febrile children. CONCLUSION: High neutrophil-to-lymphocyte ratio values and low prognostic nutritional index scores may serve as novel surrogate independent factors for seizure susceptibility in febrile children. Febrile children who are less than 18 months old are more prone to experience seizures than older febrile children. Moreover, there was a correlation between febrile seizures and elevated C-reactive protein levels and neutrophil-to-lymphocyte ratio values.

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Neutrófilos , Evaluación Nutricional , Estado Nutricional , Convulsiones Febriles , Humanos , Convulsiones Febriles/sangre , Femenino , Masculino , Preescolar , Estado Nutricional/fisiología , Lactante , Niño , Pronóstico , Linfocitos , Proteína C-Reactiva/análisis , Recuento de Linfocitos , Estudios de Casos y Controles , Inflamación/sangre , Curva ROC

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Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

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Epilepsia , Genotipo , Canal de Sodio Activado por Voltaje NAV1.1 , Canal de Sodio Activado por Voltaje NAV1.2 , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Adulto Joven , China/epidemiología , Pueblos del Este de Asia/genética , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/epidemiología , Epilepsia/genética , Epilepsia/epidemiología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Canal de Sodio Activado por Voltaje NAV1.1/genética , Canal de Sodio Activado por Voltaje NAV1.2/genética , Fenotipo , Estudios Retrospectivos , Convulsiones Febriles/genética , Convulsiones Febriles/epidemiología

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This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric tertiary hospital between 1 March 2020 and 28 February 2023. This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a median age of 3.2 years (interquartile range: 1-11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases, reached a decreasing frequency over time (p < 0.001), and showed different frequencies among the age groups. Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves.

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COVID-19 , Enfermedades del Sistema Nervioso , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , COVID-19/virología , Preescolar , Niño , Masculino , Femenino , Lactante , Adolescente , Enfermedades del Sistema Nervioso/virología , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/etiología , Cefalea/epidemiología , Cefalea/etiología , Recién Nacido , Convulsiones Febriles/epidemiología , Convulsiones Febriles/virología , Convulsiones Febriles/etiología , Convulsiones/epidemiología , Convulsiones/virología , Convulsiones/etiología , Pandemias

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FIRES and NORSE are clinical presentations of disease processes that, to date, remain unexplained without an established etiology in many cases. Neuroinflammation is thought to have paramount importance in the genesis of these conditions. We hereby report the clinical, EEG, brain MRI, and genetic findings of a nuclear family with recurrent febrile-related encephalopathy with refractory de novo Status Epilepticus. Whole-exome sequencing (WES) revealed a homozygous p.C105W pathogenic variant of FADD gene (FAS-associated protein with death domain, FADD), known to cause ultrarare forms of autosomal recessive immunodeficiency that could be associated with variable degrees of lymphoproliferation, cerebral atrophy, and cardiac abnormalities. The FADD-related conditions disrupt FAS-mediated apoptosis and can cause a clinical picture with the characteristics of FIRES. This observation is important because, on one hand, it increases the number of reported patients with FADD deficiency, showing that this disorder may present variable expressivity, and on the other hand, it demonstrates a genetic cause of FIRES involving a cell-mediated inflammation regulatory pathway. This finding supports early treatment with immunomodulatory therapy and could represent a new avenue of research in the field of new onset refractory status epilepticus and related conditions.

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Proteína de Dominio de Muerte Asociada a Fas , Humanos , Proteína de Dominio de Muerte Asociada a Fas/genética , Femenino , Masculino , Convulsiones Febriles/genética , Estado Epiléptico/genética , Estado Epiléptico/etiología , Linaje , Secuenciación del Exoma , Fiebre/genética , Fiebre/complicaciones , Síndromes Epilépticos/genética , Electroencefalografía

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BACKGROUND: Febrile seizures (FS) are the most common seizure disorder in children and a common neurologic complication in children with coronavirus disease 2019 (COVID-19). This study aimed to identify differences in clinical characteristics and disease burden between FS with and without COVID-19. MATERIALS AND METHODS: We conducted a retrospective analysis of medical data at our hospital from December 2019 to July 2023, focusing on hospitalized patients under the age of 14 diagnosed with FS who underwent COVID-19 polymerase chain reaction (PCR) testing. Descriptive statistics and analysis of variance were employed to compare the COVID-19 and non-COVID-19 groups in terms of clinical characteristics and disease burden. RESULTS: A total of 514 patients were included, with 106 testing positive for COVID-19 and 408 testing negative. Patients with COVID-19 were older (34.87 ± 6.16 vs. 28.61 ± 11.35 months, P < 0.001) and had a higher proportion of males (79.2% vs. 62.3%, P = 0.001). The COVID-19 group had longer seizure durations (4.57 ± 4.38 vs. 3.22 ± 2.91 min, P = 0.006) and more complex FS (25.5% vs. 15.9%, P = 0.022). Laboratory tests showed lower lymphocyte counts in the COVID-19 group (1.87 ± 1.48 vs. 2.75 ± 1.51 × 103/µL, P < 0.001) and higher creatine kinase levels (158.49 ± 82.89 vs. 110.89 ± 56.11 U/L, P < 0.001). No significant differences were found in hospital costs, length of hospitalization, and intensive care unit admissions. CONCLUSION: Clinicians should be knowledgeable about the distinct clinical characteristics of FS in children with COVID-19. Despite distinct features, the prognosis remains favorable and does not require excessive intervention. Ongoing monitoring and research are needed to fully understand the impact of COVID-19 on FS and optimize management strategies.

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COVID-19 , Convulsiones Febriles , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Niño , Lactante , Costo de Enfermedad , SARS-CoV-2 , Hospitalización/estadística & datos numéricos , Adolescente , Tiempo de Internación/estadística & datos numéricos

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A significant number of patients with genetic epilepsy do not obtain seizure freedom, despite developments in new antiseizure drugs, suggesting a need for novel therapeutic approaches. Many genetic epilepsies are associated with misfolded mutant proteins, including GABRG2(Q390X)-associated Dravet syndrome, which we have previously shown to result in intracellular accumulation of mutant GABAA receptor γ2(Q390X) subunit protein. Thus, a potentially promising therapeutic approach is modulation of proteostasis, such as increasing endoplasmic reticulum (ER)-associated degradation (ERAD). To that end, we have here identified an ERAD-associated E3 ubiquitin ligase, HRD1, among other ubiquitin ligases, as a strong modulator of wildtype and mutant γ2 subunit expression. Overexpressing HRD1 or knockdown of HRD1 dose-dependently reduced the γ2(Q390X) subunit. Additionally, we show that zonisamide (ZNS)-an antiseizure drug reported to upregulate HRD1-reduces seizures in the Gabrg2+/Q390X mouse. We propose that a possible mechanism for this effect is a partial rescue of surface trafficking of GABAA receptors, which are otherwise sequestered in the ER due to the dominant-negative effect of the γ2(Q390X) subunit. Furthermore, this partial rescue was not due to changes in ER chaperones BiP and calnexin, as total expression of these chaperones was unchanged in γ2(Q390X) models. Our results here suggest that leveraging the endogenous ERAD pathway may present a potential method to degrade neurotoxic mutant proteins like the γ2(Q390X) subunit. We also demonstrate a pharmacological means of regulating proteostasis, as ZNS alters protein trafficking, providing further support for the use of proteostasis regulators for the treatment of genetic epilepsies.

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Retículo Endoplásmico , Epilepsias Mioclónicas , Proteolisis , Receptores de GABA-A , Epilepsias Mioclónicas/metabolismo , Epilepsias Mioclónicas/genética , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética , Animales , Retículo Endoplásmico/metabolismo , Ratones , Humanos , Convulsiones Febriles/metabolismo , Convulsiones Febriles/genética , Degradación Asociada con el Retículo Endoplásmico , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Mutación , Células HEK293 , Chaperón BiP del Retículo Endoplásmico/metabolismo

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The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12 µg/L (0.14-2.95) vs 1.79 µg/L (0.33-47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.

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Proteína HMGB1 , Convulsiones Febriles , Humanos , Proteína HMGB1/sangre , Convulsiones Febriles/sangre , Masculino , Femenino , Lactante , Preescolar , Estudios de Seguimiento , Niño , Recurrencia

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Introduction: SARS-CoV-2 infection in children is usually asymptomatic or only mild symptoms are typical. The aim of our study was to assess the incidence of febrile convulsions in our own patients with COVID-19. Patients and Methods: In our retrospective study, we reviewed the data of children who presented at our University Hospital from March 2020 to March 2022 with febrile convulsion. The control group were children admitted to the hospital because of febrile convulsions from January 2018 to January 2020. Results: During the coronavirus pandemic, 51 patients were examined with febrile convulsions. The majority (86.3%) of children had their first febrile convulsion during this period. We diagnosed simple febrile convulsions in 40 cases and complicated ones in 11 cases. The family history of febrile convulsion or epilepsy was present in 12 (23.5%) patients. In addition to febrile convulsion, SARS-CoV-2 infection was confirmed by laboratory testing in 4 cases (7.8%). Three of them had febrile convulsion during the Omicron variant period. Conclusions: During the coronavirus pandemic, the number of children examined because of having febrile convulsions was not higher than in the control period. The coronavirus is unlikely to increase the risk of febrile convulsions.

Asunto(s)

COVID-19 , Convulsiones Febriles , Humanos , Convulsiones Febriles/epidemiología , COVID-19/epidemiología , COVID-19/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Incidencia , Preescolar , Niño , Lactante , SARS-CoV-2 , Adolescente , Pandemias

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Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally 'benign' nature. Nonetheless, they frequently lead to pediatric consultations, and their management can vary depending on the clinical context. For parents and caregivers, witnessing a seizure can be a distressing experience, significantly impacting their quality of life. In this review, we offer an in-depth exploration of FS management, therapeutic interventions, and prognostic factors, with the aim of providing support for physicians and enhancing communication with families. We conducted a comprehensive literature search using the PubMed and Web of Science databases, spanning the past 50 years. The search terms utilized included "febrile seizure," "complex febrile seizure," "simple febrile seizure," in conjunction with "children" or "infant." Only studies published in English or those presenting evidence-based data were included in our assessment. Additionally, we conducted a cross-reference search to identify any additional relevant data sources. Our thorough literature search resulted in a compilation of references, with carefully selected papers thoughtfully integrated into this review.

Asunto(s)

Convulsiones Febriles , Humanos , Convulsiones Febriles/terapia , Convulsiones Febriles/diagnóstico , Niño , Lactante , Guías de Práctica Clínica como Asunto , Anticonvulsivantes/uso terapéutico , Pronóstico

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BACKGROUND: Paediatric 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. METHODS: A 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. DISCUSSION: If 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 REGISTRATION: EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

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Dióxido de Carbono , Estado Epiléptico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Equilibrio Ácido-Base/efectos de los fármacos , Acidosis Respiratoria/etiología , Administración por Inhalación , Dióxido de Carbono/administración & dosificación , Dióxido de Carbono/efectos adversos , Método Doble Ciego , Concentración de Iones de Hidrógeno , Oxígeno , Convulsiones Febriles/tratamiento farmacológico , Estado Epiléptico/tratamiento farmacológico , Resultado del Tratamiento

Asunto(s)

Inflamación , Convulsiones Febriles , Canales Catiónicos TRPV , Convulsiones Febriles/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Humanos , Inflamación/metabolismo , Alcalosis Respiratoria/metabolismo , Ratones

RESUMEN

OBJECTIVE: Sex determines cognitive outcome in animal models of early life seizure, where males exhibit impaired hippocampal-dependent learning and memory compared with females. The physiological underpinnings of this sex effect are unclear. Cholinergic signaling is essential for the generation of hippocampal oscillations, and supplementation of cholinergic precursors prior to status epilepticus in immature male rats prevents subsequent memory deficits. We hypothesized that there are sex differences in acetylcholine circuits and their response to experimental febrile status epilepticus (eFSE). METHODS: eFSE was induced in male and female rat pups. We transversed the hippocampus of postnatal day >60 control (CTL) and eFSE rats with a 64-channel laminar silicon probe to assay cholinergic-dependent theta oscillations under urethane anesthesia. Local field potential properties were compared during (1) baseline sensory stimulation, (2) pharmacological stimulation via acetylcholine reuptake blockade, and (3) sensory stimulation after muscarinic acetylcholine receptor block (atropine). RESULTS: In all groups, a baseline tail pinch could elicit theta oscillations via corticohippocampal synaptic input. Following atropine, a tail pinch response could no longer be elicited in CTL male, CTL female, or eFSE female rats. In contrast, induced slow theta power in eFSE males after atropine was not decreased to spontaneous levels. Analysis of oscillation bandwidths revealed sex differences in acetylcholine modulation of theta frequency and slow gamma frequency and power. This study also identified significant effects of both sex and eFSE on baseline theta-gamma comodulation, indicating a loss of coupling in eFSE males and a potential gain of function in eFSE females. SIGNIFICANCE: There are differences in cholinergic modulation of theta and gamma signal coordination between male and female rats. These differences may underlie worse cognitive outcomes in males following eFSE. Promoting the efficacy of muscarinic acetylcholine signaling prior to or following early life seizures could elucidate a mechanism for the temporal discoordination of neural signals within and between hippocampus and neocortex and provide a novel therapeutic approach for improving cognitive outcomes.

Asunto(s)

Ritmo Gamma , Hipocampo , Caracteres Sexuales , Estado Epiléptico , Ritmo Teta , Animales , Femenino , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Ratas , Ritmo Teta/efectos de los fármacos , Ritmo Teta/fisiología , Ritmo Gamma/efectos de los fármacos , Ritmo Gamma/fisiología , Estado Epiléptico/fisiopatología , Estado Epiléptico/tratamiento farmacológico , Ratas Sprague-Dawley , Convulsiones Febriles/fisiopatología , Acetilcolina/metabolismo , Atropina/farmacología

RESUMEN

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

Asunto(s)

Epilepsia del Lóbulo Temporal , Hipocampo , Imagen por Resonancia Magnética , Esclerosis , Convulsiones Febriles , Estado Epiléptico , Humanos , Hipocampo/patología , Hipocampo/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/patología , Masculino , Femenino , Esclerosis/patología , Estado Epiléptico/diagnóstico por imagen , Estado Epiléptico/patología , Estado Epiléptico/etiología , Convulsiones Febriles/patología , Convulsiones Febriles/diagnóstico por imagen , Lactante , Preescolar , Niño , Estudios de Seguimiento , Atrofia/patología , Esclerosis del Hipocampo