Perturbed interneurons' activity leads to seizures in Dravet syndr.: biomarker for their prediction.

What is it about?

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by onset in the first year of life with seizures triggered by fever/hyperthermia, which persist also in adulthood, and later appearance of afebrile seizures, as well as of developmental plateauing with behavioral disorders. It is caused by mutations of the SCN1A/NaV1.1 sodium channel leading to hypoexcitability of GABAergic interneurons. We found that most of the seizures in both DS patients and mouse models have low-voltage-fast onset, which is instead thought to be generated by hyperactivity of GABAergic neurons. We disclosed a disorganization in the temporal pattern of the firing of single interneurons before the seizure (preictal period) and a rebound hyperactivity at seizure onset. Consistently, the electrographic signal showed a decrease of fast oscillations in the preictal period. Thus, perturbed interneurons’ preictal activity, consistent with the main mechanism of DS, leads to their hyperactivity at seizure onset and induces specific electrographic signatures, which can be exploited for reliable seizure prediction.

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Photo by Hal Gatewood on Unsplash

Photo by Hal Gatewood on Unsplash

Why is it important?

We disclosed the cellular/network mechanism of convulsive seizure generation in a severe epilepsy and we identified specific EEG biomarker (electrographic signatures), which can be exploited for seizure prediction. The identification of a potential EEG biomarker that is able to predict seizure several minutes before their onset could be clinically very useful, allowing families to organize themselves and possibly to use preventive therapeutic interventions that could inhibit seizures, possibly including closed-loop systems.

Perspectives