Caracterization of the Combined Alterations in Respiration and aROUSal in Patients With Drug-resistant EpiLepsy
概览
- 阶段
- 不适用
- 干预措施
- Video-EEG monitoring
- 疾病 / 适应症
- Epilepsy
- 发起方
- Hospices Civils de Lyon
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- End tidal CO2 (PETCO2) value at arousal in patients with epilepsy and in healthly subjects
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
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.
研究者
入排标准
入选标准
- •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
排除标准
- •Ongoing or chronic respiratory and/or cardiac insufficiency
- •Obstructive sleep-apnea syndrome
- •Ongoing treatment with selective serotonin reuptake inhibitor
- •Patient treated with vagal nerve stimulation
- •Pregnant women or breastfeeding women, based on declarations at V0
- •Persons receiving psychiatric care
- •Persons deprived of their liberty by a judicial or administrative decision
- •Adults subject to a legal protection measure (guardianship, curatorship)
- •Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
- •Positive urine pregnancy test at V1, if applicable
研究组 & 干预措施
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
干预措施: Video-EEG monitoring
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
干预措施: Respiratory monitoring and polysomnography
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
干预措施: 1 Hypercapnic challenge while participant is awake
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
干预措施: 2 Hypercapnic challenges while participant is sleeping
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
干预措施: Auditory stimulus
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
干预措施: Questionnaires
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
干预措施: Video-EEG monitoring
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
干预措施: Respiratory monitoring and polysomnography
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
干预措施: 1 Hypercapnic challenge while participant is awake
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
干预措施: 2 Hypercapnic challenges while participant is sleeping
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
干预措施: Auditory stimulus
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
干预措施: Questionnaires
结局指标
主要结局
End tidal CO2 (PETCO2) value at arousal in patients with epilepsy and in healthly subjects
时间窗: the night of hospitalization
PETCO2 corresponds to the value taken at the end of a breath of the partial pressure of CO2. Two hypercapnic challenges will be performed the same night. The first will start once unequivocal N3 stage of NREM will be observed, as determined online by polysomnography data. After the termination of the first test, the patient/subject will go back to sleep and a second procedure will be performed once she/he will reach N3 stage of NREM again. Data from the two procedures will be averaged for each subject.
次要结局
- Value of the awake HCVR slope in patients with epilepsy and in healthly subjects(will be measured during hypercapnic challenges on awakening on the first day of hospitalization.)
- Value of the HCVR slope during sleep in patients with epilepsy and in healthy subjects(one night of hospitalization)
- Central apnea index and Obstructive Apnea Hypopnea Index(one night of hospitalization)
- Value of the ventilatory recruitment threshold (VRT) in patients with epilepsy and in healthly subjects(will be measured during hypercapnic challenges on awakening on the first day of hospitalization.)
- Number of focal to bilateral tonic-clonic seizures during the 3 months preceding the polysomnography in patients with epilepsy(Will be collected during the first day of hospitalization)
- Sound intensity (dB) required to induced awakening(one night of hospitalization)
- Current and past mean daily intake of caffeine (mg/day)(Will be collected between inclusion and the first day of hospitalization)