The European patient with Dravet syndrome: Results from a parent-reported survey on antiepileptic drug use in the European population with Dravet syndrome

Aras, Luis Miguel; Isla, Julián; Mingorance, Ana

doi:10.1016/j.yebeh.2014.12.028

Cited by 70 publications

(101 citation statements)

References 28 publications

(38 reference statements)

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“…Due to the rare nature of Dravet syndrome, there have been few randomized controlled trials of new or existing antiepileptic drugs 24 . Only stiripentol is specifically approved as an add-on treatment for Dravet syndrome, although there is widespread use of other drugs including valproic acid, clobazam and topiramate 25, 26 . Thus, there is a pressing need for additional therapeutic options.…”

Section: Discussionmentioning

confidence: 99%

Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome

Anderson

Hawkins

Thompson

et al. 2017

Sci Rep

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Dravet syndrome, an epileptic encephalopathy affecting children, largely results from heterozygous loss-of-function mutations in the brain voltage-gated sodium channel gene SCN1A. Heterozygous Scn1a knockout (Scn1a +/−) mice recapitulate the severe epilepsy phenotype of Dravet syndrome and are an accepted animal model. Because clinical observations suggest conventional sodium channel blocking antiepileptic drugs may worsen the disease, we predicted the phenotype of Scn1a +/− mice would be exacerbated by GS967, a potent, unconventional sodium channel blocker. Unexpectedly, GS967 significantly improved survival of Scn1a +/− mice and suppressed spontaneous seizures. By contrast, lamotrigine exacerbated the seizure phenotype. Electrophysiological recordings of acutely dissociated neurons revealed that chronic GS967-treatment had no impact on evoked action potential firing frequency of interneurons, but did suppress aberrant spontaneous firing of pyramidal neurons and was associated with significantly lower sodium current density. Lamotrigine had no effects on neuronal excitability of either neuron subtype. Additionally, chronically GS967-treated Scn1a +/− mice exhibited normalized pyramidal neuron sodium current density and reduced hippocampal NaV1.6 protein levels, whereas lamotrigine treatment had no effect on either pyramidal neuron sodium current or hippocampal NaV1.6 levels. Our findings demonstrate unexpected efficacy of a novel sodium channel blocker in Dravet syndrome and suggest a potential mechanism involving a secondary change in NaV1.6.

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Section: Discussionmentioning

confidence: 99%

Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome

Anderson

Hawkins

Thompson

et al. 2017

Sci Rep

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“…Recommendations already exist for West syndrome/infantile spasms; the most appropriate treatments are adrenocorticotropic hormone (ACTH), prednisolone, or vigabatrin. 2,3 For the other excluded syndromes, especially Dravet syndrome, there are opinion pieces 12,13 and some evidence from either observational or randomized trials to support certain treatment preferences. 14 …”

Section: Methodsmentioning

confidence: 99%

Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus

Shellhaas

Berg

Grinspan

et al. 2017

Pediatric Neurology

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OBJECTIVE There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years). METHODS Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records. RESULTS About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P < 0.0001). Although the first treatment varied across study centers (P < 0.0001), levetiracetam was the most commonly prescribed medication regardless of epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis. CONCLUSIONS Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies.

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“…The findings from both of these studies are in line with the DS study from Germany. Importantly, both studies also found markedly higher direct costs for patients with uncontrolled or more refractory epilepsy and for patients with comorbidities; both of which are aspects of DS [8,10,13]. Thus, we can expect that the costs associated with caring for a child with DS would be significantly higher than the costs associated with caring for a child with a less severe form of epilepsy or many other medical conditions; research is needed to evaluate this possibility.…”

Section: Direct Costs Of Dsmentioning

confidence: 99%

“…Epilepsy/seizure severity, presence of myoclonic seizures, and age at onset of seizures were among the strongest independent predictors of poor HRQOL, further underscoring the urgency and need for more effective antiepileptic treatment options for this patient population [3]. Other studies have found that DS is associated with significant financial costs to the family and to society [8,12], significant behavioral and medical comorbidities (such as autism spectrum characteristics, communication impairments, cardiovascular conditions, dysautonomia, cognitive dysfunction, disturbed sleep, and motor impairment, among many others) [4,8,10,13], and negative impact on the quality of life of caregivers [4,8].…”

Section: Introductionmentioning

confidence: 97%

The humanistic and economic burden of Dravet syndrome on caregivers and families: Implications for future research

Jensen

Brunklaus

Dorris

et al. 2017

Epilepsy & Behavior

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We reviewed the current literature with respect to the humanistic and financial burdens of Dravet Syndrome (DS) on the caregivers of children with DS, in order to (1) identify key unanswered questions or gaps in knowledge that need to be addressed and then, based on these knowledge gaps, (2) propose a research agenda for the scientific community to address in the coming decade. The findings support the conclusion that caring for a child with DS is associated with significant humanistic burden and direct costs. However, due in part to the paucity of studies, as well as the lack of measures of specific burden domains, there remains much that is not known regarding the burden of caregiving for children with DS. To address the significant knowledge gaps in this area, research is needed that will: (1) identify the specific domains of caregivers' lives that are impacted by caring for a child with DS; (2) identify or, if needed, develop measures of caregiving impact in this area; (3) identify the factors that influence DS caregiving burden; (4) develop and evaluate the efficacy of treatments for reducing the negative impact of DS and its comorbidities on DS caregivers; (5) quantify the direct medical costs associated with DS and DS comorbidities and identify the factors that influence these costs; and (6) quantify and fully explore the indirect costs of DS. Research that addresses these goals will provide the empirical foundation needed for improving the quality of life of children with DS and their families.

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The European patient with Dravet syndrome: Results from a parent-reported survey on antiepileptic drug use in the European population with Dravet syndrome

Cited by 70 publications

References 28 publications

Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome

Unexpected Efficacy of a Novel Sodium Channel Modulator in Dravet Syndrome

Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus

The humanistic and economic burden of Dravet syndrome on caregivers and families: Implications for future research

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