Dravet syndrome: Treatment options and management of prolonged seizures

Cross, J. Helen; Caraballo, Roberto; Nabbout, Rima; Vigevano, Federico; Guerrini, Renzo; Lagae, Lieven

doi:10.1111/epi.16334

Cited by 78 publications

(97 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…First line treatment of DS includes either CLB or VPA 30 . When either fails as independent treatment, CLB and VPA are administered together 11 . Stand-alone treatment of either 5 mg/kg CLB or 300 mg/kg VPA did not offer significant protection against hyperthermia-induced seizures in Scn1a A1783V/WT mice ( Table 2).…”

Section: Evaluation Of Add-on Treatment Against Hyperthermia-induced mentioning

confidence: 99%

“…5 mg/kg CLB and 150 mg/kg VPA significantly raised the temperature threshold compared to vehicle treated mice ( Figure 4A). If this combination fails in the clinic, a relevant second-line drug regimen combines CLB and VPA with STP as an add-on drug 11 . We tested a combination of 5 mg/kg CLB and 75 mg/kg which did not offer significant protection ( Figure 4B).…”

Section: Evaluation Of Add-on Treatment Against Hyperthermia-induced mentioning

confidence: 99%

See 1 more Smart Citation

Development of an Antiseizure Drug Screening Platform for Dravet Syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program

Pernici

Mensah

Dahle

et al. 2020

Preprint

View full text Add to dashboard Cite

Dravet syndrome is a rare, but catastrophic genetic epilepsy that is diagnosed in the first year of life. Approximately 80% of patients with DS carry a mutation in the SCN1A gene, which encodes for the voltage-gated sodium channel, Nav1.1. Currently, no anti-seizure drug (ASD) exists that adequately controls seizures. Patients with DS often present clinically with a febrile seizure and generalized tonic-clonic seizures that continue throughout life. To facilitate the development of ASDs for DS, the contract site of the NINDS Epilepsy Therapy Screening Program (ETSP) has evaluated a mouse model of DS, the conditional Scn1a*A1783V mouse. The heterozygous offspring have a 50% survival rate and all have hyperthermia-induced seizures, which mimic clinical afebrile seizures. Several prototype ASDs were administered via intraperitoneal injections at the time-to-peak effect, which was previously determined before the induction of a hyperthermia-induced seizure. The results suggest that hyperthermia-induced seizures in this model of DS are highly refractory to a battery of ASDs. Exceptions were clobazam and the combination of clobazam and valproic acid with add-on stiripentol, which elevated seizure thresholds. In addition, clobazam and carbamazepine were administered once a week over 4 weeks to demonstrate their effect on hyperthermia-induced seizures was consistent. Clobazam and carbamazepine consistently increased and lowered temperature thresholds, respectively. Overall, the data demonstrate the proposed model for DS is suitable for screening novel compounds for the ability to block hyperthermia-induced seizures and heterozygous mice can be evaluated repeatedly over the course of several weeks, allowing for higher throughput screening.

show abstract

Section: Evaluation Of Add-on Treatment Against Hyperthermia-induced mentioning

confidence: 99%

Section: Evaluation Of Add-on Treatment Against Hyperthermia-induced mentioning

confidence: 99%

Development of an Antiseizure Drug Screening Platform for Dravet Syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program

Pernici

Mensah

Dahle

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Dravet Syndrome is an epileptic encephalopathy with a significant seizure burden, often refractory to anticonvulsant treatment. In recent years, Stiripentol and Cannabidiol have been approved for the treatment of seizures in Dravet Syndrome, both having encouraging clinical trial and post-approval data [4]. In this study 49% of patients were previously on Stiripentol and 26% were previously on Cannabidiol, indicating an ongoing need for additional treatment options.…”

mentioning

confidence: 64%

Fenfluramine: New treatment for seizures in Dravet Syndrome.

Pierce

Mithal

2020

Pediatr Neurol Briefs

View full text Add to dashboard Cite

“…However, number of studies about the influence of KD on disabilities related to epilepsy itself is limited and should be increased. Even in patients in whom seizure reduction is not dramatic, the improvement of quality of life is frequently observed together with the reduction of the number of ASMs [115].…”

Section: Efficacy Of the Kdmentioning

confidence: 99%

Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned

Żarnowska

2020

Nutrients

View full text Add to dashboard Cite

Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic changes occurring during starvation. Except for classic KD, its modified counterparts, including modified Atkins diet and low-glycemic-index treatment, have gained grounds to increase palatability and adherence. Strong evidence exists that the KD offers protection against seizures in difficult-to-treat epilepsy and possesses long-lasting anti-epileptic activity, improving long-term disease outcome. The KD can also provide symptomatic and disease-modifying activity in a wide range of neurodegenerative diseases. In an era of highly available new anti-seizure medications (ASMs), the challenge of refractory epilepsy has still not been solved. This metabolic therapy is increasingly considered due to unique mechanisms and turns out to be a powerful tool in the hands of a skillful team. Despite decades of extensive research to explain the mechanism of its efficacy, the precise mechanism of action is to date still largely unknown. The key feature of this successful diet is the fact that energy is derived largely from fat but not from carbohydrates. Consequently, fundamental change occurs regarding the method of energy production that causes alterations in numerous biochemical pathways, thus restoring energetic and metabolic homeostasis of the brain. There are barriers during the use of this special and individualized therapy in many clinical settings worldwide. The aim of this review is to revisit the current state of the art of therapeutic application of KD in refractory epilepsy.

show abstract

Dravet syndrome: Treatment options and management of prolonged seizures

Cited by 78 publications

References 61 publications

Development of an Antiseizure Drug Screening Platform for Dravet Syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program

Development of an Antiseizure Drug Screening Platform for Dravet Syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program

Fenfluramine: New treatment for seizures in Dravet Syndrome.

Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned

Contact Info

Product

Resources

About