Risk factors for subsequent febrile seizures in the FEBSTAT study

Abstract

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 five 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 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 HR=2.9, p<0.05). The risk for a second FS of any type or of subsequent FS lasting >10 minutes over the five-year follow-up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 of 21 children (23.8%) with subsequent FS lasting ≥10 minutes. 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 minutes 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.

Inflammation in epileptogenesis after traumatic brain injury

“…Many studies have now demonstrated that early exposure of the brain to immune responses can have varied and persistent consequences on adult physiology [99–102]. Febrile seizures (FS) and febrile status epilepticus in children is a risk factor for developing epilepsy later in life [103], which may be induced by fever often associated with inflammation and infection [47]. Although the mechanisms underlying FS remains unclear, it is thought that cytokines play a key role in its development [104].…”

Simple Febrile Seizures: A Benign Phenomena?

“…However, the FEBSTAT study revealed that some virus may be associated with the occurrence of febrile status epilepticus. 6 Specifically, the authors identified an association between the presence of human herpes virus type 6B (HHV-6B) DNA and RNA in serum of children with febrile status epilepticus. 7 Routine viral studies are still not recommended in the evaluation of SFS as the results do not modify the clinical impression and do not change the treatment or prognosis.…”

Febrile Status Epilepticus

“…They are classified as complex if they are prolonged (>10 minutes), focal, or multiple. 8,9 FSE (30 minutes) is considered the extreme end of the complex febrile seizure spectrum.…”

“…As mentioned before, having FSE is a risk factor for having subsequent FSE and febrile seizures in general. 9 It has also been associated with the development of epilepsy, specifically TLE. The time between FSE and the development of MTLE can be greater than 10 years and therefore this is hard to prove in prospective studies.…”