PROJECT: JTC2021: AUTONOMIC

Neurodevelopmental impact of epilepsy on autonomic functions in Dravet Syndrome

Abstract

Dravet syndrome (DS) is a genetically caused severe neurodevelopmental disease with drug-resistant epilepsy, cognitive impairment and a strongly increased risk of premature death already at young ages. The occurrence of sudden death is most probably facilitated by sustained susceptibility to cardiorespiratory dysfunction. Our primary hypothesis is that the alterations of autonomic functions observed in DS result from the interplay between the genetically-based neurodevelopmental disorder and effects of recurrent seizures. Epilepsy might thus progressively aggravate the autonomic abnormalities and risk of sudden death related to the underlying genetic disease, through an effect on central control of vegetative functions, a direct effect on cardiac functioning or both. Here, we will: (i) analyze in a DS animal model and in DS patients the temporal relationship between evolution of epilepsy and alteration of autonomic, cardiorespiratory functions; (ii) distinguish in rodents the relation between these evolutions of the alterations of the central regulation, the cardiac functioning, and the risk of sudden death; and (iii) evaluate in rodents and in DS patients if the evolution of autonomic dysfunction can be monitored with or functional imaging targeting the serotonin pathway. The anticipated findings will be used to stratify DS patients at very high risk of sudden death and may allow novel approaches for pharmacological modulation of the risk of sudden death in DS.

Keywords

Imaging techniques, Epilepsy, Molecular modelling techniques, Electrophisiological approaches, Patient cohorts, Animal studies, SUDEP

Call topic

Neurodevelopmental Disorders

Proposed runtime

n/a - n/a

Project team

Sylvain Rheims (Coordinator)
France (ANR)
Massimo Mantegazza
France (ANR)
Rainer Surges
Germany (BMBF)
Stijn Verhulst
Belgium (FWO)