Abstract
Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is
a severe developmental and epileptic encephalopathy caused by loss-of-function mutations
in one copy of SCN1A (haploinsufficiency), located on chromosome 2q24, with decreased function of Nav1.1
sodium channels in GABAergic inhibitory interneurons. Pharmacoresistant seizures in
DS start in the infancy in the form of hemiclonic febrile status epilepticus. Later,
other intractable seizure types develop including myoclonic seizures. Early normal
development in infancy evolves into moderate to severe intellectual impairment, motor
impairment, behavioral abnormalities, and later a characteristic crouching gait. Clobazam,
valproate, levetiracetam, topiramate, zonisamide, ketogenic diet, and vagus nerve
stimulation had been shown to be effective, but even with polytherapy, only 10% of
patients get adequate seizure control. The author provides a narrative review of the
current treatment paradigm as well as recent advances in the management of DS based
on a comprehensive literature review (MEDLINE using PubMed and OvidSP vendors with
appropriate keywords to incorporate recent evidence), personal practice, and experience.
In recent years, the treatment paradigm of DS is changing with the approval of pharmaceutical-grade
cannabidiol oil and stiripentol. Another novel antiepileptic drug (AED), fenfluramine,
had also shown excellent efficacy in phase 3 studies of DS. However, these AEDs primarily
control seizures without addressing the underlying pathogenesis and other important
common comorbidities such as cognitive impairment, autistic behavior, neuropsychiatric
abnormalities, and motor impairment including crouching gait. Several agents targeted
for DS are in the developmental stage: TAK935, lorcaserin, clemizole, huperzine analog,
ataluren, selective sodium channel modulators and activators, antisense oligonucleotide
therapy, and adenoviral vector therapy. As DS is associated with a high risk of sudden
unexpected death in epilepsy, seizure detection devices can be used in this population
for testing and clinical validation of these devices.
Keywords
Dravet syndrome - CBD - stiripentol - fenfluramine - antisense oligonucleotide therapy
- gene therapy - drug - treatment
