Caracterization of the Combined Alterations in Respiration and aROUSal in Patients With Drug-resistant EpiLepsy

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.

HCVR measures the increase in minute ventilation (VE) induced by an increase of PETCO2. The HCVR slope, expressed in L/min/mmHg, will be calculated from the linear regression of VE and PETCO2. Data from the two procedures per night described aboves will be averaged for each subject.

will be measured during hypercapnic sleep challenges during the night of hospitalization.

As detailed in section 6.1.3, a hypercapnic challenge will be performed awake after arrival of the patient/subject in the epilepsy monitoring unit. Calculation of the awake HCVR slope wil be performed as described for HCVR slope during sleep

VRT reflects the PCO2 value at which the central chemoreflex is initiated and corresponds to the onset of compensatory and progressive rise in VE during hypercapnic challenge. The determination of VRT requires a hyperventilation baseline period during which the measured VE is the one required to maintain hypopnea under resting metabolic conditions; termed basal ventilation or the "wakefulness drive" to drive. To determine VRT, it is therefore required that the subject breathes deeply for few minutes, raising her/his tidal volume such that she/he rapidly achieves and maintaines a PETCO2 of 20-25 mmHg. Then the hypercapnic challenge can be performed. In this context, VRT can not be determined during sleep.

Sleep apneas can classified as obstructive, central or both central sleep apnea, Apnea will be defined as a decrease in peak nasal pressure of >90% of baseline, lasting at least 10 s. Hypopnea was defined as a decrease of >30% of the baseline nasal pressure, lasting at least 10 s and associated with ≥4% drop in SpO2. Central apnea will be defined by cessation > 10 seconds of airflow with simultaneous cessation of respiratory effort. The respiratory events will be scored according to the 2007 American Academy of Sleep Medicine guidelines. Apnea index will correspond to total number of each apnea type divided by total sleep time over a 24-hour period.

The paradigm will be the one proposed by Martin et al. 1996 ; Philip et al. 1994 . The stimulation will be manually delivered using earphone inserts and will consist in pure sounds of 1000Hz, from 40dB to 110dB, duration 5s. Stimulation starts after 5 min of unequivocal NREM, as assessed with continuous EEG montoring. The stimulation will start with intensity I1=50dB. If complete behavioral arousal (=awakening): stop stimulation and wait until 2 min of stable sleep (defined by re-apparition of a spindle, a K complex or REM) and next trial with I1-10dB. If arousal but no awakening: wait until 2 min of stable sleep and next trial with sound +10dB. If no Arousal : wait 10s and deliver sound +10dB or longer sound (10s)

Current usual caffeine intake and the one over the last ten years will be assessed by a validated self-survey (Simonin et al., Neuroobiology of Disease 2013) filled-in at home by the patient and, if needed, the help of the caregiver filled between the inclusion visit and the polysomnography. Its reliability, assessed by retest (mean interval: 37.5 ± 5.5 days) in 31 patients, was excellent (intraclass correlation coefficient by Fleiss method: 0.97 [95% CI: 0.94-0.98]). The mean daily intake of caffeine containing items (coffee, tea, chocolate, sodas) will be reported, along with any changes of consumption over the 10 year period. All data will be then confirmed by interview perfomed during the stay in epilepsy monitoring unit.

Compare the subjective experience of awakenings induced by hypercapnic stimulations during sleep between healthy individuals and patients with drug-resistant epilepsy