Abstracts

Rationale: Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy of undetermined etiology characterized by refractory status epilepticus, refractory epilepsy, and poor neurocognitive outcomes occurring in previously healthy children. Outcomes include refractory seizures in 88%, significant intellectual disability in 66%, and diffuse cerebral atrophy.  There is no effective treatment. An autoinflammatory etiology has been proposed and there are reports of improved seizure control with anakinra, a recombinant interleukin-1 receptor antagonist. Long-term outcomes with this treatment are unknown. We report one patient’s outcomes through 2 years after diagnosis and treatment with anakinra. Methods: Chart review of a patient with FIRES treated with anakinra. Results: This is an 11-year-old previously healthy child that presented with a febrile illness and altered mental status quickly progressing to encephalopathy and super refractory status epilepticus. She failed treatment with multiple anti-seizure medications including versed, ketamine, and pentobarbital infusions. Treatment also included ketogenic diet, intravenous immune-globulin (IVIG), and anakinra (3.2 mg/kg/day). During the acute phase, seizures improved after initiation of anakinra and worsened with treatment interruption. Hospitalization lasted 10 weeks, including inpatient rehabilitation. She was discharged on phenobarbital, felbamate, ketogenic diet, and anakinra. Seizure frequency ranged from daily to once every few weeks. After discharge, phenobarbital was weaned and cannabidiol (CBD) and tetrahydrocannabinol (THC) were trialed without benefit. Clobazam was added due to cycles of multiple seizures (up to 20 per day) with a 75% decrease in seizures, though still with several seizures per week. MRI at 16 months demonstrated significant cerebral and cerebellar volume loss. Pre-morbid neuropsychological testing at 11.5 years-old showed a Full-scale IQ 126 (WISC-IV). Scores from neuropsychological testing at two, nine, and 13 months follow-up are in Table 1. Her Full-scale IQ = 61 (WASI-II) at 13-months follow-up. Intellectual functioning scores have been variable, while academic achievement for reading skills remained average. Repeat testing is planned at 20-month follow-up.  Conclusions: This is the first description of long-term outcomes in FIRES after treatment with anakinra. Despite significant improvement in seizure frequency in the acute phase, our patient’s long-term outcomes appear like previously reported cases. Her MRI revealed cerebral atrophy and her IQ remains well below pre-morbid levels. Her overall pattern of functioning is consistent with severe brain insult with preservation of literacy based skills. She requires three anti-seizure medications, as well as anakinra, with ongoing seizures. Though there was a positive response in the acute phase (as has been reported in other patients), the long-term prognosis still remains guarded and additional prospective data is needed to better understand the use of anakinra in children with FIRES.  Funding: There are no funding sources to report.