Dravet Syndrome

Dravet syndrome, previously known as severe myoclonic epilepsy of infancy (SMEI), is a type of epilepsy with seizures that are often triggered by hot temperatures or fever.

Dravet and Bureau in 1981 described “benign myoclonic epilepsy in infancy” in 7 normal children with onset of myoclonic seizures in the first 3 years of life 1). The syndrome was defined as including myoclonic seizures only, except rare simple febrile seizures, with good prognosis regarding response to therapy and cognitive functions.

Dravet Syndrome (DS) is a severe epileptic encephalopathy of childhood involving intractable seizures, recurrent status epilepticus and cognitive decline. Because DS is a rare disease, available data is limited and evidence-based treatment guidelines are lacking.

Both VNS and corpus callosotomy (CC) can be effective at reducing seizure frequency. Patients with DS may benefit from earlier and more aggressive surgical intervention. Studies using larger patient cohorts will help clarify the role that surgery may play in the multidisciplinary approach to controlling seizures in DS. Further studies will help determine the appropriate timing of and type of surgical intervention 2).

Loss of function in the Scn1a gene leads to Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures.

Ritter-Makinson et al., showed enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS. In a mouse model of DS with a loss of function in Scn1a, reticular thalamic cells exhibited abnormally long bursts of firing caused by the downregulation of calcium-activated potassium SK channels. The study supports a mechanism in which loss of SK activity causes the reticular thalamic neurons to become hyperexcitable and promote non-convulsive seizures in DS. They propose that reduced excitability of inhibitory neurons is not global in DS and that non-GABAergic mechanisms such as SK channels may be important targets for treatment 3).


Vagus nerve stimulation (VNS) is an established neurostimulation treatment for intractable epilepsy, however little evidence is published on its efficacy in patients with DS.

Dibué-Adjei et al., performed a meta-analysis of all peer-reviewed English language studies reporting seizure outcomes of patients with DS treated with adjunctive vagus nerve stimulation. The primary and secondary outcome measures were ≥50% reduction of seizures or of the most-debilitating seizure type and seizure reduction per patient.

13 studies comprising 68 patients met the inclusion criteria of which 11 were single-center retrospective case series, one was a multi-center retrospective analysis and one was a case report. 52.9% of patients experienced a ≥50% reduction of seizures and the average seizure reduction, which could only be assessed in n=28 patients was 50.8%. 7 out of 13 studies reported additional benefits of VNS, however this could not be assessed systematically.

Vagus nerve stimulation appears to reduce seizure frequency in patients with DS. Based on this preliminary analysis, controlled trials of VNS in this rare condition using patient-centric outcome measures are indicated 4).

1)

Dravet C, Bureau M. [The benign myoclonic epilepsy of infancy (author’s transl)]. Rev Electroencephalogr Neurophysiol Clin. 1981 Dec;11(3-4):438-44. French. PubMed PMID: 6808601.
2)

Dlouhy BJ, Miller B, Jeong A, Bertrand ME, Limbrick DD Jr, Smyth MD. Palliative epilepsy surgery in Dravet syndrome-case series and review of the literature. Childs Nerv Syst. 2016 Sep;32(9):1703-8. doi: 10.1007/s00381-016-3201-4. Epub 2016 Jul 27. Review. PubMed PMID: 27465677.
3)

Ritter-Makinson S, Clemente-Perez A, Higashikubo B, Cho FS, Holden SS, Bennett E, Chkaidze A, Eelkman Rooda OHJ, Cornet MC, Hoebeek FE, Yamakawa K, Cilio MR, Delord B, Paz JT. Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome. Cell Rep. 2019 Jan 2;26(1):54-64.e6. doi: 10.1016/j.celrep.2018.12.018. PubMed PMID: 30605686.
4)

Dibué-Adjei M, Fischer I, Steiger HJ, Kamp MA. Efficacy of adjunctive vagus nerve stimulation in patients with Dravet syndrome: A meta-analysis of 68 patients. Seizure. 2017 Aug;50:147-152. doi: 10.1016/j.seizure.2017.06.007. Epub 2017 Jun 17. Review. PubMed PMID: 28666193.

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