New insights into the early mechanisms of epileptogenesis in a zebrafish model of Dravet syndrome

By |2020-03-10T10:43:51-05:00March 8th, 2020|Categories: DSF Research Review|Tags: , , |

This study used zebrafish to try to gain insights into the very earliest neurodevelopmental effects occurring in Dravet syndrome. In previous posts we have explained that appropriately mutated zebrafish are now an established and useful model for Dravet syndrome. The authors performed behavioral analysis, measured convulsions, and did extensive examination of the functional and [...]

SCN8A Antisense Oligonucleotide is Protective in Mouse Models of SCN8A Encephalopathy and Dravet Syndrome

By |2020-04-07T10:49:03-05:00February 6th, 2020|Categories: DSF Research Review|Tags: , , |

Dravet Syndrome is caused by loss-of-function mutations affecting the NaV1.1 sodium channel.  In a July 2019 research summary, we pointed out that gain-of-function mutations in another sodium channel, called NaV1.6, can lead to severe epileptic conditions - suggesting that NaV1.1 and NaV1.6 exist in a balance that maintains proper nerve conduction.   This raised the possibility [...]

Early EEG and behavioral alterations in Dravet mice

By |2020-04-07T10:52:04-05:00February 6th, 2020|Categories: DSF Research Review|Tags: , , |

This study explored EEG characteristics over the life cycle of Dravet mice; that is, through the febrile, worsening, and stabilization stages. One common way to analyze EEG spectra is to compute the "power spectral density" (PSD) profile. The authors found that normal EEG patterns were observed at the febrile stage, however a marked reduction in [...]

Dravet syndrome: Treatment options and management of prolonged seizures

By |2020-04-07T10:58:38-05:00February 6th, 2020|Categories: DSF Research Review|Tags: , , |

The journal Epilepsia has devoted a Special Issue to "Dravet Syndrome and other Sodium Channel Related Encephalopathies".  It is Volume 60, Issue S3, and can be accessed online - it contains many good articles, all of which are Open Access. I will point out one here - a review by an international panel of distinguished [...]

Sexually Divergent Mortality and Partial Phenotypic Rescue after Gene Therapy in a Mouse Model of Dravet Syndrome

By |2020-04-07T10:58:11-05:00January 8th, 2020|Categories: DSF Research Review|Tags: , , |

Dravet syndrome is caused by a mutation in the SCN1A gene, which codes for the NaV1.1 sodium channel a subunit. As described in previous summaries, gene therapy is becoming a very promising approach for fixing genetic disorders, with the use of adeno-associated virus ("AAV") as the preferred delivery system - but the coding region of [...]

Profound Reduction in Seizure Frequency (≥75%) Leads to Improved Everyday Executive Function: Analysis From a Phase 3 Study of ZX008 (Fenfluramine HCl) in Children/Young Adults With Dravet Syndrome

By |2020-04-07T10:57:49-05:00January 8th, 2020|Categories: DSF Research Review|Tags: , , |

This month my literature survey returned a poster that was presented at the recent American Epilepsy Society meeting. Although this is not a peer-reviewed journal article, I include it because it is interesting, and I have no concerns about its legitimacy. In previous summaries, the story of fenfluramine has been presented; along with some results [...]

SCN1A variants in vaccine-related febrile seizures: a prospective study

By |2019-12-17T12:41:21-05:00December 17th, 2019|Categories: DSF Research Review|Tags: , , |

Prolonged febrile seizures (that is, seizures triggered by a fever) are a manifestation of Dravet syndrome. Vaccination is a highly effective public health approach that has led to reduced childhood morbidity and mortality from many infectious diseases, and has an excellent safety profile, but in rare cases can be followed by febrile seizures. Given [...]

SCN1A variants from bench to bedside – improved clinical prediction from functional characterization

By |2019-12-17T12:46:54-05:00December 17th, 2019|Categories: DSF Research Review|Tags: , , |

Dravet syndrome is caused by mutations in the SCN1A gene, which encodes for the voltage-gated sodium channel Nav1.1 - a protein that participates in conduction of nerve signals. Thousands of different SCN1A mutations have been reported, but only a small number of these have been characterized functionally. This is unfortunate, because some SCN1A mutations [...]

Stiripentol: A Review in Dravet Syndrome

By |2019-11-12T12:55:08-05:00November 12th, 2019|Categories: DSF Research Review|Tags: , , |

This article is a summary of the efficacy and safety of stiripentol (Diacomit), a drug indicated for use in patients with Dravet syndrome as an adjunctive therapy in conjunction with clobazam (Onfi) and valproate (Depakote). Stiripentol was first reported to be helpful in Dravet syndrome in 2000, and was approved in the EU in [...]

Early hippocampal hyperexcitability followed by disinhibition in a mouse model of Dravet syndrome

By |2019-11-12T13:54:07-05:00November 12th, 2019|Categories: DSF Research Review|Tags: , , |

Dravet syndrome can be conceptualized as a three-stage disease - the first stage (febrile; up to age 1) is typically characterized by prolonged complex febrile seizures and status epilepticus; followed by a second stage (worsening; up to age 5) which is characterized by the appearance of additional seizure types (e.g. generalized motor, atypical, myoclonic, [...]

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