Brief Summary

30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. 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 5. Apnea was the primary cause of death in several epilepsy models. 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. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown.

Trial Health

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Trial Health Score

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Enrollment

participants targeted

Target at below P25 for not_applicable

Timeline

25mo left

Started Sep 2026

Typical duration for not_applicable

Geographic Reach

1 country

1 active site

Status

not yet recruiting

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Trial Relationships

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Study Timeline

Key milestones and dates

2.1 years study duration

First Submitted

Initial submission to the registry

May 6, 2026

Completed

14 days until next milestone

First Posted

Study publicly available on registry

May 20, 2026

Completed

3 months until next milestone

Study Start

First participant enrolled

September 1, 2026

Expected

2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2028

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2028

Last Updated

May 20, 2026

Status Verified

May 1, 2026

Enrollment Period

2.1 years

First QC Date

May 6, 2026

Last Update Submit

May 13, 2026

Conditions

Epilepsy SUDEP

Keywords

EpilepsySUDEPrespiratory challengesevoked potentials

Outcome Measures

Primary Outcomes (1)

Cortical localization of pre-expiratory potentials (via SEEG) during HETL (20 cmH₂O) in drug-resistant epilepsy
Localization of SEEG contacts will use the anatomical MRI images performed in clinical routine. Pre-expiratory potentials are defined as a slow negative shift from the baseline signal starting between 2 and 0.5 s before the onset of expiration. Both visual and statistical analyses will be used to conclude on the presence of significant pre-expiratory potentials over each recording contact, using the same approach as the one our group used in the past in another physiological paradigm.
Through study completion, an average of 1 year

Secondary Outcomes (8)

dentification of cortical SEEG contacts showing pre-expiratory potentials under 10 cmH₂O low expiratory threshold load (LETL) in drug-resistant epilepsy
Through study completion, an average of 1 year
Cortical localization of SEEG contacts exhibiting pre-expiratory potentials during a hypercapnic challenge (HyperCO₂) in patients with drug-resistant epilepsy.
Through study completion, an average of 1 year
Latency (ms) of the pre-expiratory potentials in each condition (HETL, LETL, HyperCO2)
Through study completion, an average of 1 year
Value of hypercapnic ventilatory response (HCVR)* in each condition (HETL, LETL, HyperCO2)
Through study completion, an average of 1 year
Number of focal to bilateral tonic-clonic seizures during the 18 months preceding the SEEG
Inclusion visit
+3 more secondary outcomes

Study Arms (1)

Patients with drug-resistant epilepsy

EXPERIMENTAL

Patients with drug-resistant focal epilepsy, as defined by the International League Against Epilepsy, who undergo SEEG as part of presurgical evaluation of epilepsy. In addition to SEEG monitoring, the following procedures will be carried out as part of the research: * Comprehensive respiratory monitoring * Cardio-respiratory monitoring * Expiratory load compensation * Hypercapnic challenge * Questionnaires completion.

Procedure: SEEG monitoringProcedure: Comprehensive respiratory monitoringProcedure: Cardio-respiratory monitoringProcedure: Expiratory load compensationProcedure: Hypercapnic challengeOther: Questionnaires

Interventions

SEEG monitoringPROCEDURE

Patients will be recruited among adult patients suffering from drug-resistant focal epilepsy who undergo SEEG monitoring at the Epilepsy Department of the Neurological Hospital. The study will be offered to patients during the hospitalization.