TY  - JOUR
AU  - Pong, Amanda
AU  - Klein, Pavel
PY  - 2024
DA  - 2024/05/08
TI  - Prevention of Drug Resistant Epilepsy and Developmental Epileptic Encephalopathy: Preventative Vigabatrin Treatment in Tuberous Sclerosis Complex and the Case for Fenfluramine Treatment of Children with Newly Diagnosed Dravet Syndrome
JO  - OBM Genetics
SP  - 234
VL  - 08
IS  - 02
AB  - Tuberous sclerosis complex (TSC) is caused by mutations of hamartin (TSC1) or tuberin (TSC2) resulting in disinhibition of the mTOR pathway of cellular proliferation and differentiation and severe neurocognitive impairment, intractable epilepsy and tumors. Epilepsy develops in ~90% folllowed by drug-resistant epilepsy (DRE). Recently, prevention of DRE and developmental encephalopathy was shown to be possible in TSC using early administration of vigabatrin. For the first time, medical treatment successfully prevented epilepsy and reduced neurocognitive and behavioural co-morbidities. The crucial difference between the preventive and standard treatment groups was the timing of treatment initiation, not the type of the intervention. This paradigm can be extended to patients with other genetic or acquired conditions, including Dravet Syndrome (DS), a severe developmental epileptic encephalopathy (DEE) with DRE and high mortality, due to a de novo mutation of the gene SCN1A which codes for the sodium channel protein a subunit Nav1.1. Infants usually develop normally until their first seizure, commonly between 2-15 months. This is followed by DRE and developmental regression. Randomized controlled trials (RCTs) of adjunctive fenfluramine treatment in DS reduced median convulsive seizure frequency by 55.7% over placebo at 0.7 mg/kg/day. 50% of children had 75% seizure frequency reduction, 8% had convulsive seizure freedom versus 0% with placebo, and 18% had only one convulsive seizure versus 0% with placebo. Other pivotal studies showed similar results and efficacy was sustained in for 
SN  - 2577-5790
UR  - https://doi.org/10.21926/obm.genet.2402234
DO  - 10.21926/obm.genet.2402234
ID  - Pong2024
ER  -