Febrile Infection-Related Epilepsy Syndrome: Refractory Status Epilepticus and Management Strategies

Abstract

Febrile infection-related epilepsy syndrome (FIRES) is a rare, catastrophic epileptic syndrome that strikes previously healthy children. Its pathogenesis is unknown, it has few treatments, and it is typically refractory. In FIRES, refractory status epilepticus or a cluster of seizures starts a few days after the onset of an acute febrile illness, and it may continue as drug-resistant epilepsy, with neuropsychological impairments occurring without latency. Clinical knowledge and guidelines on FIRES are limited because it is sporadic and extremely rare. To date, the absence of specific biomarkers poses a significant diagnostic challenge; nevertheless, early diagnosis is very important for optimal management. Despite treatment with multiple immunotherapies and anti-seizure medications, the majority of patients with FIRES are left with significant cognitive disabilities and refractory epilepsy. This review aims to highlight the most recent insights into the clinical features, terminology, epidemiology, pathogenesis, diagnostic challenges, and therapeutic options associated with FIRES.

Enteral lorazepam is a promising weaning strategy for midazolam‐responsive febrile infection‐related epilepsy syndrome (FIRES): a case series

“…Similarly, in 29 patients with FIRES reported by Sakuma et al ., a mean duration of 52.3 days of barbiturate coma was required [21]. Lee et al ., more recently, in their cohort of 29 patients, also reported a median hospitalization duration of 89 days (range: 24–220 days) [17]. Thus, despite the availability of better care and treatment modalities over the last decades, strategies to reduce ICU and hospital stay in children with FIRES remains a challenge.…”

“…Usually, gamma-aminobutyric acid (GABA) mimetic agents, such as midazolam, thiopentone and high-dose phenobarbitone, have been the more effective agents [17][18][19][20]. Among these, midazolam is usually the first • 673 used anti-seizure medication for pharmacological coma, though with variable efficacy [17][18][19]21]. Lorazepam remains the mainstay for initial acute seizure management of all forms of status epilepticus (including FIRES) due to its favourable pharmacokinetics and longer duration of action, as compared to midazolam [22][23][24].…”

“…Usually, gamma‐aminobutyric acid (GABA) mimetic agents, such as midazolam, thiopentone and high‐dose phenobarbitone, have been the more effective agents [17-20]. Among these, midazolam is usually the first used anti‐seizure medication for pharmacological coma, though with variable efficacy [17-19, 21].…”

“…In these patients, prolonged periods of pharmacological coma to control electrographic and electroclinical seizures are often required [8]. Usually, gamma-aminobutyric acid (GABA) mimetic agents, such as midazolam, thiopentone and high-dose phenobarbitone, have been the more effective agents [17][18][19][20]. Among these, midazolam is usually the first • 673 used anti-seizure medication for pharmacological coma, though with variable efficacy [17][18][19]21].…”

Interleukin-1 in Febrile Infection-Related Epilepsy Syndrome

“…The historical mortality rate for FIRES during the acute phase is 9% to 18%. Additionally, only 18% of children maintain normal cognitive function in the acute phase, while more than 90% develop refractory epilepsy that requires lifelong treatment [1][2][3].…”