Authors :
Presenting Author: Victor Soto-Insuga, PhD – Hospital Niño Jesus (Madrid)
Marta Marin Gracia, MD – University Clinic of Navarra
Elena González-Alguacil, MD – Hospital Niño Jesus (Madrid)
Nuria Lamagrande, MD – Hospital Niño Jesus (Madrid)
Francisca Romero, MD – Hospital Niño Jesus (Madrid)
Marta Bascuas, MD – Hospital Niño Jesus (Madrid)
Ángel Aledo-Serrano, MD – Epilepsy Unit, Clinical Neuroscience Institute, Vithas Madrid University Hospitals
Rationale:
Fenfluramine, a recently approved antiseizure medication, has demonstrated efficacy in developmental and epileptic encephalopathies. Beyond its antiepileptic properties, fenfluramine acts as a serotoninergic agonist and sigma-1 receptor modulator, suggesting potential involvement in brainstem-mediated respiratory regulation. Due to the bidirectional relationship between epilepsy and sleep-disordered breathing, the potential benefit of fenfluramine on respiratory function warrants investigation.Methods:
A retrospective case series was conducted involving four pediatric patients from three Spanish hospitals. All had Lennox-Gastaut Syndrome spectrum and comorbid obstructive and/or central sleep apnea. Baseline polysomnography or respiratory polygraphy was performed prior to fenfluramine initiation and repeated three months after treatment. Only apneas that were not secondary to a seizure during sleep were considered. Clinical variables, including seizure frequency and polysomnographics parameters, were analyzed.
Results:
Four patients, with median age at fenfluramine initiation: 15 years (range: 11–23) were included. Three had cryptogenic Lennox-Gastaut syndrome and one had a Lennox-Gastaut-like phenotype secondary to Rett syndrome (MECP2 mutation). All were pharmacoresistant, with a median of 13 previous antiseizure drugs (range: 8–13). All of them presented tonic seizures and atypical absences; two of them also had myoclonic seizures, and one had atonic seizures. The median fenfluramine dose achieved at three months was 0.32 mg/kg/day (range: 0.21–0.62). After three months, one patient achieved complete seizure control, while the remaining three showed partial control in all types of seizures (60–70% reduction in seizure frequency). Sleep studies revealed an improvement in respiratory parameters: the median apnea-hypopnea index (AHI) decreased from 17.9/hour to 7.3/hour. Most significantly, the proportion of median central apneas declined from 16.3% to 3.3% of total events.
Conclusions:
In this small series, fenfluramine was associated not only with improved seizure control but also with marked improvement in central sleep apnea. These findings suggest a potential dual benefit of fenfluramine in epilepsy management and respiratory regulation, possibly mediated through its serotonergic and sigma-1 receptor activity in the brainstem. Further prospective studies are warranted to explore this novel therapeutic mechanism of actionFunding: This work has been carried out without funding