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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. [ABSTRACT FROM AUTHOR]

Objectives: To identify risk and risk factors for developing a subsequent febrile seizure (FS) in children with a first febrile status epilepticus (FSE) compared to a first simple febrile seizure (SFS). To identify home use of rescue medications for subsequent FS. Methods: Cases included a first FS that was FSE drawn from FEBSTAT and Columbia cohorts. Controls were a first SFS. Cases and controls were classified according to established FEBSTAT protocols. Cumulative risk for subsequent FS over a 5-year period was compared in FSE versus SFS, and Cox proportional hazards regression was conducted. Separate analysis examined subsequent FS within FSE. The use of rescue medications at home was assessed for subsequent FS. Results: Risk for a subsequent FSE was significantly increased in FSE versus SFS. Any magnetic resonance imaging (MRI) abnormality increased the risk 3.4-fold (p < 0.05), adjusting for age at first FS and FSE and in analyses restricted to children whose first FS was FSE (any MRI abnormality hazard ratio [HR] 2.9, p < 0.05). The risk for a second FS of any type or of subsequent FS lasting >10 min over the 5-year follow-up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 (23.8%) of 21 children with subsequent FS lasting =10 min. Significance: Compared to controls, FSE was associated with an increased risk for subsequent FSE, suggesting the propensity of children with an initial prolonged seizure to experience a prolonged recurrence. Any baseline MRI abnormality increased the recurrence risk when FSE was compared to SFS and when FSE was studied alone. A minority of children with a subsequent FS lasting 10 min or longer were treated with rectal diazepam at home, despite receiving prescriptions after the first FSE. This indicates the need to further improve the education of clinicians and parents in order to prevent subsequent FSE. [ABSTRACT FROM AUTHOR]

Objective Treatment of seizures varies by region, with no standard emergency treatment protocol. Febrile status epilepticus ( FSE) is often a child's first seizure; therefore, families are rarely educated about emergency treatment. Methods From 2002 to 2010, 199 subjects, age 1 month to 6 years, were recruited as part of a prospective, multicenter study of consequences of FSE, which was defined as a febrile seizure or series of seizures lasting >30 min. The patients' charts were reviewed. No standardized treatment protocol was implemented for this observational study. Results One hundred seventy-nine children received at least one antiepileptic drug ( AED) to terminate FSE, and more than one AED was required in 140 patients (70%). Median time from the seizure onset to first AED by emergency medical services (EMS) or emergency department (ED) was 30 min. Mean seizure duration was 81 min for subjects given medication prior to ED and 95 min for those who did not (p = 0.1). Median time from the first dose of AED to end of seizure was 38 min. Initial dose of lorazepam or diazepam was suboptimal in 32 (19%) of 166 patients. Ninety-five subjects (48%) received respiratory support by EMS or ED. Median seizure duration for the respiratory support group was 83 min; for the nonrespiratory support group the duration was 58 min (p-value < 0.001). Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration. Significance FSE rarely stops spontaneously, is fairly resistant to medications, and even with treatment persists for a significant period of time. The total seizure duration is composed of two separate factors, the time from seizure onset to AED initiation and the time from first AED to seizure termination. Earlier onset of treatment results in shorter total seizure duration. A standard prehospital treatment protocol should be used nationwide and education of EMS responders is necessary. [ABSTRACT FROM AUTHOR]

Purpose: In a prospective study, Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT), we determined the frequency of human herpesvirus (HHV)-6 and HHV-7 infection as a cause of febrile status epilepticus (FSE). Methods: Children ages 1 month to 5 years presenting with FSE were enrolled within 72 h and received a comprehensive assessment including specimens for HHV-6 and HHV-7. The presence of HHV-6A, HHV-6B, or HHV-7 DNA and RNA (amplified across a spliced junction) determined using quantitative polymerase chain reaction (qPCR) at baseline indicated viremia. Antibody titers to HHV-6 and HHV-7 were used in conjunction with the PCR results to distinguish primary infection from reactivated or prior infection Key Findings: Of 199 children evaluated, HHV-6 or HHV-7 status could be determined in 169 (84.9%). HHV-6B viremia at baseline was found in 54 children (32.0%), including 38 with primary infection and 16 with reactivated infection. No HHV-6A infections were identified. HHV-7 viremia at baseline was observed in 12 children (7.1%), including eight with primary infection and four with reactivated infection. Two subjects had HHV-6/HHV-7 primary coinfection at baseline. There were no differences in age, characteristics of illness or fever, seizure phenomenology or the proportion of acute EEG or imaging abnormalities in children presenting with FSE with or without HHV infection. Significance: HHV-6B infection is commonly associated with FSE. HHV-7 infection is less frequently associated with FSE. Together, they account for one third of FSE, a condition associated with an increased risk of both hippocampal injury and subsequent temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hippocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology. Methods: The 'Consequences of Prolonged Febrile Seizures in Childhood' (FEBSTAT) study is a prospective, multicenter study. Enrolled are children, aged 1 month to 6 years of age, presenting with a febrile seizure lasting 30 min or longer based on ambulance, emergency department, and hospital records, and parental interview. At baseline, procedures included a magnetic resonance imaging (MRI) study and electroencephalography (EEG) recording done within 72 h of FSE, and a detailed history and neurologic examination. Baseline development and behavior are assessed at 1 month. The baseline assessment is repeated, with age-appropriate developmental testing at 1 and 5 years after enrollment as well as at the development of epilepsy and 1 year after that. Telephone calls every 3 months document additional seizures. Two other groups of children are included: a 'control' group consisting of children with a first febrile seizure ascertained at Columbia University and with almost identical baseline and 1-year follow-up examinations and a pilot cohort of FSE from Duke University. Key Findings: The FEBSTAT cohort consists of 199 children with a median age at baseline of 16.0 months (interquartile range [IQR] 12.0-24.0) and a median duration of FSE of 70.0 min (IQR 47.0-110.0). Seizures were continuous in 57.3% and behaviorally intermittent (without recovery in between) in 31.2%; most were partial (2.0%) or secondary generalized (65.8%), and almost all (98.0%) culminated in a generalized tonic-clonic seizure. Of the 199 children, 86.4% had normal development and 20% had prior febrile seizures. In one third of cases, FSE was unrecognized in the emergency department. The Duke existing cohort consists of 23 children with a median age of FSE onset of 18.0 months (IQR 14.0-28.0) and median duration of FSE of 90.0 min (IQR 50.0-170.0). The Columbia control cohort consists of 159 children with a first febrile seizure who received almost the same workup as the FEBSTAT cohort at baseline and at 1 year. They were followed by telephone every 4 months for a median of 42 months. Among the control cohort, 64.2% had a first simple FS, 26.4% had a first complex FS that was not FSE, and 9.4% had FSE. Among the 15 with FSE, the median age at onset was 14.0 months (IQR 12.0-20.0) and the median duration of FSE was 43.0 min (IQR 35.0-75.0). Significance: The FEBSTAT study presents an opportunity to prospectively study the relationship between FSE and acute hippocampal damage, the development of mesial temporal sclerosis, epilepsy (particularly temporal lobe epilepsy), and impaired hippocampal function in a large cohort. It is hoped that this study may illuminate a major mystery in clinical epilepsy today, and permit the development of interventions designed to prevent the sequelae of FSE. [ABSTRACT FROM AUTHOR]

Febrile status epilepticus is a serious and frightening event in the life of the child and parent. It is regarded as a medical emergency with potential long lasting consequences. The purpose of this study was to look at the immediate and long term effects of such an event on parental stress and parents’ perception of their child’s physical and psychosocial wellbeing. Methods From 2003 to 2010, 199 subjects, age 1 month to 5 years, were recruited as part of a prospective, multicenter study (FEBSTAT) of consequences of febrile status epilepticus (FSE). At one month and one year after the episode of FSE, parents were asked to complete the Parenting Stress Index, short form (PSI/SF), the Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist (CBCL). In addition to PedsQL and CBCL in the FEBSTAT subjects only, a comparison was made between Columbia Study of First Febrile Seizures subjects with a first simple febrile seizure (SFS) and the FEBSTAT group, including 15 subjects with FSE from the Columbia group, in the area of parental stress which was administered at the same time intervals in both studies. Results At baseline, the PSI/SF was statistically significantly higher for SFS versus FSE on the parent-child dysfunctional score and the total raw score, however at one year this difference resolved. In the FSE group, significantly higher parental stress over one year was reported in children with abnormal versus normal prior development (p= 0.02). Prior abnormal development was a risk factor at 1 year for lower total PEDSQL (p=0.01) versus prior normal development. Mean scores on the CBCL at baseline and 1 year were within the normal range for both empirically based scales and major risk factors. Conclusions Parents of children experiencing a SFS experienced more stress at baseline than those with FSE. Families of children in the FEBSTAT cohort with identified development problems at baseline that continued, or progressed over the one year period, reported decreasing QOL. [ABSTRACT FROM AUTHOR]