Authors :
Presenting Author: Elena Gonzalez-Alguacil, MD – Hospital Universitario Niño Jesus
Nuria Lamagrande Casanova, MD – Hospital Universitario Niño Jesus
Anna Duat Rodríguez, PhD – Hospital Universitario Niño Jesus
Juan Jose García Peñas, MD – Hospital San Rafael, Madrid
Víctor Soto Insuga, PhD – Hospital Universitario Niño Jesus
Cristina Benitez Provedo, MD – Hospital Universitario Niño Jesus
Verónica Cantarín Extremera, PhD – Hospital Universitario Niño Jesus
Rationale: Rett Syndrome (RTT) is an X-linked dominant disorder caused by mutations in the MECP2 gene. It is common for patients with RTT to present with epilepsy. However, distinguishing between respiratory non-epileptic paroxysmal disorders and secondary epileptic seizures triggered by apnea can be challenging. Fenfluramine, a serotonin and sigma-1 agonist, could have a dual mechanism of action due to its antiepileptic effect and reduction of respiratory dysrhythmia.
Methods: A longitudinal observational study was conducted through a monocentric cohort of 75 patients with RTT. Patients were recruited between January 2024 and June 2024 and were treated with fenfluramine.
Results:
In our cohort, 47 patients had associated epilepsy (47/75 [63%]; refractory epilepsy 33/47 [70%]). 4/33 (12%) were treated with fenfluramine in combination with other antiseizures medicaments (ASM). The median dose at their last follow-up was 0.45 mg/kg/day, with a median treatment duration of 6 months.
In the 6 months prior to receiving fenfluramine, patients experienced multiple types of seizures, including generalized tonic-clonic, tonic, and focal seizures. All patients had non-epileptic paroxysmal disorders of the Valsalva auto-induced type, as well as focal motor seizures reflex to anoxia following apnea-hyperventilation.
Overall seizure reduction was 75-90% after 3 months of fenfluramine treatment, with one patient being seizure-free. Clinically meaningful improvement was observed significantly from baseline at 3 months on various clinical scales specific to Rett Syndrome:
- Rett Syndrome Behavior Questionnaire: -5.5
- Clinical Global Impression-Improvement: -0.5
- Clinical Severity Scale: -6
- Motor Behavior Assessment-9: (-1.5)
- Sleep Disturbance Scale for children, with subsequent normalization in all 4 patients.
No treatment-related adverse events were reported.
Conclusions:
Fenfluramine may be an effective drug for the treatment of epileptic seizures in RTT, especially those triggered by anoxia, with significant clinical improvement on various clinical scales specific to this syndrome. Fenfluramine may be a promising ASM for randomized clinical trials in RTT.
Funding: No funding