Caracterization of the Combined Alterations in Respiration and AROUSal in Patients with Drug-resistant EpiLepsy

Status: Recruiting
Location: See location...
Intervention Type: Procedure, Other
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, from cognitive dysfunctions to premature mortality. Both seizures and their complications are modulated by patients' vigilance states, with a tight and bi-directional interplay between sleep and epilepsy. Several epilepsy complications are associated with sleep, such as sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP is a non-traumatic death, unrelated to a documented status epilepticus, which accounts for up 50% of premature deaths in epilepsy, with a cumulative risk of ≈ 10% at 40 years in patients with childhood-onset epilepsy. SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia, especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Finally, post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. The complex network that regulates arousal and sleep and the respiratory network are strongly interconnected. Impairment of the interaction between central respiratory control and arousal systems has been reported in several clinical situations, including sleep apnea syndrome, sudden infant death syndrome or Prader-Willi Syndrome. In epilepsy, preclinical data in rodents indirectly support a role for 5HT in the impairment of the interactions between the arousal and respiratory systems in the cascade of events leading to SUDEP. However, no direct evidence is available, and the link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 55
Healthy Volunteers: t
View:

∙ Patients :

• Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study

• Aged 18 to 55 years old

• Diagnosis of focal epilepsy

• Epilepsy is refractory to treatment, as defined by the International League Against Epilepsy

• Patients with ≥3 focal to bilateral tonic-clonic seizure (FBTCS) during the past 18 months

• Patients who had undergone long-term video-EEG (VEEG) monitoring for presurgical evaluation in the past ten years within the Department of Functional Neurology and Epileptology at Hospices Civils de Lyon, ensuring access to detailed information about:

‣ occurrence of transient respiratory dysfunction during the focal seizures, transient hypoxemia during strictly focal seizures being observed in 40% of patients(39) and in 87% of patients with at least one FBTCS during the VEEG monitoring(46)

⁃ localization of the epileptogenic zone, the risk of peri-ictal respiratory dysfunction being greater in seizures of temporal lobe origin than in extra-temporal seizures, even after FBTCS

∙ Healthy subjects

• Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study

• Aged 18 to 55 years old

Locations
Other Locations
France
Hôpital Pierre Wertheimer
RECRUITING
Bron
Contact Information
Primary
Sylvain Pr Rheims
sylvain.rheims@chu-lyon.fr
0472357106
Backup
Mathilde LECLERCQ
Mathilde.leclercq@chu-lyon.fr
0472355838
Time Frame
Start Date: 2024-11-04
Estimated Completion Date: 2027-01-04
Participants
Target number of participants: 60
Treatments
Other: Patients with drug-resistant focal epilepsy
Patients with \>3 focal to bilateral tonic-clonic seizure per year and who had undergone long-term video-EEG (VEEG) monitoring for presurgical evaluation.~After a prospective baseline, which will allow to ensure prospective seizure count for patients with epilepsy, all participants will undergo a 24-hours hospitalization. The following procedures will be carried out as part of the research:~* Video-EEG recordings~* Respiratory monitoring~* Full-night polysomnography~* 1 Hypercapnic challenge while participant is awake~* 2 Hypercapnic challenges while participant is sleeping~* Auditory stimulus All the medical devices used in this study are already in routine use at Hospices Civils de Lyon
Other: Healthy subjects
Selection of healthy subjects will be performed to ensure age-matching.~After a prospective baseline, which will allow to ensure prospective seizure count for patients with epilepsy, all participants will undergo a 24-hours hospitalization. The following procedures will be carried out as part of the research:~* Video-EEG recordings~* Respiratory monitoring~* Full-night polysomnography~* 1 Hypercapnic challenge while participant is awake~* 2 Hypercapnic challenges while participant is sleeping~* Auditory stimulus All the medical devices used in this study are already in routine use at Hospices Civils de Lyon
Sponsors
Leads: Hospices Civils de Lyon

This content was sourced from clinicaltrials.gov