Le stress chez les enfants avec convulsions fébriles : mécanismes et contribution au pronostic

Stress is a phenomenon frequently associated with epileptogenesis and increased seizure frequency and severity. Animal studies suggest the relationship between stress and seizures may begin early in life, maybe even prenatally. Evidence showing a link between early programming through stress and seizure disorders has yet to be found in humans. Hence, the general objective of this thesis was to examine the relationship between early-life stress, including the prenatal period, and seizures in humans. For this purpose, the prime focus of this research was on febrile seizures  (FS).  FS  are  common  and  benign  pediatric  seizures,  associated  only  with  mild neurological and cognitive peculiarities. Due to their frequent incidence in early childhood and lack of severe consequences, they allow for the investigation of the relationship between early-life stress and seizures through a relatively large sample, while reducing the impact of potential confounding variables.In this context, our general objective was investigated through five sub-objectives. First, we aimed toreview the current knowledge on the link between seizures and stress, as well as the impact stress could have on the cognitive prognosis of seizure disorders (1starticle).The second sub-objective was to study the relationship between self-reported maternal emotion  distress  during  both  the  pregnancy  and  postpartum  period,  on  FS.  Through  a longitudinal  cohort,  this  research  supports  increased  prenatal  pregnancy-specific  anxiety  and postpartum depressive symptoms are associated with a lowered FS threshold, as shown through a younger age at first FS occurrence (2ndarticle). Moreover,  the  third  sub-objective,  which  was  studied  through  the  same  longitudinal research,  was  to  evaluate  how  biological  changes  associated  with  prenatal  exposure  to  stress may  be  linked  to  FS.  This  study  showed  changes  in  the  placental  serotoninergic  system  are found in children with FS history. More precisely, these changes are associated with increased FS incidence, and lowered FS threshold (3rdarticle). On  the  other  hand,  the  fourth  sub-objective  of  this  thesis  was  to  study  the  biological stress response of children with past FS, compared to that of children without personal history of seizures. Our case-control study suggested only children with “simple” FS showed increased sensibility  to  stress  (4tharticle).  Hence,  these  results  do  not  show  systematic  changes  in  the  ivbiological stress reaction of all children with FS. Still, they do show changes in some children, which could be premorbid to the first FS episode.Incidentally, while studying the fourth sub-objective, we were unable to show changes in  the  developmental  skills  of  children  with  FS,  nor  did  we  show  an  interaction  with  stress reactivity.   Hence,   the   fifth   and   final   subjective   of   this   thesis   was   to   investigate   the electrophysiological prognosis of children with past FS, and its association with stress reactivity. Our results show differences in the electrophysiological profile of children with “complex” FS only, which could be linked to cognitive alterations in the long-term (5tharticle). Moreover, we showed these abnormalities differ depending on the type of complex FS. Still, we were unable to identify an additive or interactive link with stress reactivity (addendum). Taken together, these results highlight the existence of a link between stress, starting in the  prenatal  period,  and  FS.  Hence,  they  highlight  the  importance  of  investigating  prenatal, postnatal and current stress in the context of seizure disorders at large, including FS. Given the significant  impact  of  stress  on  the  quality  of  life  of  people  living  with  epilepsy,  increased knowledge on the link between early stress and seizures could lead to the development of early and non-invasive treatments targeting stress in the future. Moreover, although these results do not show stress to be associated with altered cognitive or electrophysiological prognosis in the context of FS, this link is nevertheless supported by animal research and should be the subject of future studies

Keyphrases: stress, febrile seizures, epilepsy, anxiety, early programming, depression