Authors :
Presenting Author: Sanam Zarei, MD – Childrens National Medical Center
Thuy-anh Vu, MD – Childrens National Medical Center; Elizabeth Wells, MD – Childrens National Medical Center; Dana Harrar, MD – Childrens National Medical Center; Sara Preisendanz, RD, MS, LD – Childrens National Medical Center
Rationale:
Febrile infection-related epilepsy syndrome (FIRES) is a rare, presumed immune-mediated epileptic encephalopathy in which new-onset refractory status epilepticus is preceded by a febrile illness 24 hours to 2 weeks prior to the onset of seizures, requiring anesthetics to control seizures, and not accompanied by other cause. Seizure treatment of FIRES is difficult, typically unresponsive to anti-seizure medications and anesthetic agents and after the acute phase of status epilepticus, patients with FIRES often develop chronic pharmacoresistant epilepsy, neurologic and cognitive impairment, and functional disability. The ketogenic diet (KD) targets dysregulated adaptive and innate immunity that occurs in refractory status epilepticus and has been reported to reduce seizure burden and improves outcomes. Recent consensus guidelines offer treatment algorithms with anti-seizure medication, anesthetics, and early immunotherapy, as well as a recommendation to initiate the KD in FIRES. There are few recent reports about the utility of the diet in patients with early immunotherapy and management of adverse effects in these patients. We present five patients with early immunotherapy and ketogenic diet in the pediatric intensive care unit.
Methods:
We have performed a retrospective cohort study of five children with FIRES who were initiated on the KD from 2018 to 2022. We characterized seizure outcomes as well as adverse effects. The primary outcome was defined as the number of children having >50% reduction in seizure frequency compared to prior to KD initiation. Secondary outcomes include time on anesthetic drips and length of hospitalization.
Results:
Ketogenic diet was initiated within 10 days of presentation and four out of five children were ultimately weaned off of anesthetics, and one child died. One of five children met the primary outcome of >50% reduction in seizure frequency within one week and three of five met the primary outcome within two weeks. Five out of five children developed hyperlipidemia, four out of five developed acidosis, three out of five developed constipation, two out of five developed nephrolithiasis. Acidosis, hyperlipidemia, and constipation were expeditiously addressed with improvement in most. Three out of five children developed secondary hemophagocytic lymphohistiocytosis (sHLH), a known sequelae of FIRES.
Only one in five patients reached three months of treatment. KD was discontinued in one patient due to resolution of seizures. Three had premature discontinuation: All three had sHLH. Two of three had nephrolithiasis. One of three had significant hyperlipidemia, and one of three had significant hypertriglyceridemia, despite symptom management.
Conclusions:
The ketogenic diet can be a tolerable and effective treatment option for FIRES. Risk of nephrolithiasis and hyperlipidemia can be mitigated by surveillance with urinalysis to screen for nephrolithiasis and treatment with alkalinization and hydration, as well as surveillance of lipid profiles with adjustment of diet ratios, respectively. In FIRES, intractable hyperlipidemia, hypertriglyceridemia and acidosis with associated nephrolithiasis may be a manifestation of ketogenic diet adverse effects or secondary hemophagocytic lymphohistiocytosis or both, and may indicate a more severe ICU course.
Funding: none