Authors :
Presenting Author: Stephanie Burkhalter, APRN, FNP-C – Nemours Children's Health, Jacksonville
Presenting Author: Douglas Nordli, – University of Chicago
Stephanie Burkhalter, APRN, FNP-C – Nemours Childrens Health Jacksonville; Fernando Galan, MD – Nemours Childrens Health Jacksonville
Rationale:
We report a remarkable response observed on the EEG of a pediatric patient with intractable epilepsy and associated epileptic encephalopathy (EE) with developmental regression. Studies on seizure control with fenfluramine in patients with Dravet Syndrome (DS) and Lennox Gastaut Syndrome (LGS) exist. However, no reports on other EE's exist at this stage. The dramatic response seen in the EEG with fenfluramine initiation is not described in DS or LGS. Our report highlights these novel findings with the hope of encouraging more research into fenfluramine's use in patients with difficult-to-treat epilepsies and EE.
Methods:
A 3-year-old, right-handed boy with intractable focal epilepsy and associated EE with developmental regression was admitted to the EMU for EEG characterization. Seizures began at the age of two years and initially occurred weekly during sleep. The semiology of the predominant seizure type was described as tonic body stiffening with upward eye deviation, followed by full-body convulsive activity. Other seizure types included hypermobile seizures with flailing limbs out of sleep, facial clonic spasms, and frequent full-body myoclonic seizures. The initial EEG had revealed a disorganized and slow background with superimposed multifocal epileptiform discharges. A more recent EEG revealed an EE with associated developmental regression. MRI scans were normal. An epilepsy gene panel and whole-exome sequence were non-diagnostic. Previously trialed medications included levetiracetam, ethosuximide, and valproic acid. Current medications consisted of FDA-approved cannabidiol, lacosamide, and clobazam at therapeutic doses. The patient's examination was remarkable for developmental delay and was otherwise non-focal.
During EMU admission the patient was started on fenfluramine (0.2 mg/kg/day).
Results:
During hospital EMU admission, baseline EEG recording was obtained on the first day of admission. Following, fenfluramine (0.2 mg/kg/day divided twice daily) was started with a robust response noted on EEG within 24-48 hours of starting fenfluramine.
Figure 1: Baseline longitudinal bipolar EEG during wakefulness (A) and sleep (B). Note the diffusely slowed background with multifocal discharges during wakefulness. During sleep there is diffuse delta slowing with loss of normal sleep architecture.
Figure 2: Day 3 longitudinal bipolar EEG after starting fenfluramine with dramatic clearance of previously appreciated background slowing during wakefulness (A). There is now a discernible posterior dominant rhythm and anterior to posterior gradient during also seen while awake. In sleep (B) there is clearance of previously seen diffuse delta slowing and emergence of normal sleep architecture.
Conclusions:
This report showcases a dramatic response seen on EEG with initiation of fenfluramine (0.2 mg/kg/day) in a pediatric patient with refractory epilepsy and EE with developmental regression. This novel report indicates the need for further investigation in both fenfluramine’s ability to impact EE's and potentially other types of epilepsies with deleterious patterns outside of DS and LGS.
The patient described is still under active investigation and follow up.
Funding: No funding