Authors :
Presenting Author: Virginia Liu, MD PhD – UCI/Children's Hospital of Orange County
Michael Kung, MD – Children's Hospital of Orange County
Janetta Arellano, MD – UCI/Children's Hospital of Orange County
Divya Gupta, MD – Children's Hospital of Orange County
Pilar Pichon, MD – Children's Hospital of Orange County
Rationale:
FIRES (febrile infection related epilepsy syndrome) is neurologically devastating condition with poor outcomes; morbidity reportedly as high as 9-18% in the acute phase, 90% develop refractory epilepsy and cognitive issues are common in surviving patients. Given presumed autoimmune etiology of FIRES, there is compelling rationale to trial anti-seizure medication with both immunosuppressive properties and mechanism that has efficacy despite internalization of synaptic GABA(A) receptors during super refractory status.
Methods:
Patients who met criteria for clinical diagnosis of FIRES were identified and treated with standard immunotherapies per new-onset refractory status epilepticus (NORSE)/FIRES international consensus guidelines and novel anti-seizure regimens less commonly described in literature. FIRES subjects were identified from the last three years at a tertiary children’s hospital. Felbamate and Ganaxalone, which is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, were trialed while clinical outcomes and potential effect on ketosis and beta-hydroxybutyrate levels were monitored for those treated with ketogenic diet as adjunct. Ganaxolone oral suspension was administered with 4 week dose uptitration inpatient and one patient was continued on Ganaxalone maintenance (35mkd) outpatient. Results:
Pediatric patients (n=6), gender (4 males, 2 female) presented with refractory focal/multifocal seizures in the setting of elevated serum or CSF Interleukin-2 or Interleukin-6. MRI brain findings ranged from normal to T2 hyperintensities in the temporal operculum, basal ganglia/deep grey, thalamic, and bilateral cortical abnormalities. There was no mortality in the patients that received ganaxalone (0%) vs those that did not (66%), furthermore seizure freedom > 20 months has been achieved for one patient that received ganaxalone maintenance course outpatient. Ganaxalone did not adversely affect the maintenance of beta-hydroxybutyrate levels in those also on ketogenic diet. Patients on Felbamate who survived acute inpatient hospitalization with FIRES (3/5) had decreased duration of ICU hospitalization, mean 36 days (SD= 10.4).
Conclusions:
1) Felbamate was trialed during acute phase of illness and continued as maintenance regimen 2) Ganaxalone was trialed off label for two severe cases of FIRES. Both medication trials correlated with lower mortality, decreased ICU duration compared to data described in prior NORSE/FIRES literature, and exhibit no recurrence of seizures to date. This institutional experience suggests that utilizing Ganaxalone and Felbamate during acute hospitalization and continuing outpatient may facilitate improved outcomes as defined by seizure control, mortality, and relatively shorter ICU duration. Funding: None