Links Between Epileptic Activity, Sleep Disruption and Mental Content During Sleep

Purpose

Interactions between epilepsy and sleep are numerous and bidirectional. Sleep can facilitate epileptic activity and seizures in several syndromes, while sleep deprivation increases cortical excitability and seizure susceptibility. Conversely, sleep disturbances are highly prevalent in patients with epilepsy (PWE). Using simultaneous stereoelectroencephalography (SEEG)-polysomnography, the investigators previously showed that sleep fragmentation in focal drug-resistant epilepsy is associated with both ictal and interictal epileptic activity, with increased interictal epileptiform discharges (IED) immediately before and during arousals. However, causality remains unclear, as sleep instability itself may promote epileptic discharges. Determining whether nocturnal seizures and IED directly induce awakenings is clinically important. Nocturnal epileptic activity is often considered less disabling than daytime seizures and rarely guides treatment decisions, yet demonstrating a direct impact on sleep continuity could support therapeutic strategies specifically targeting nocturnal epileptic activity to improve sleep quality. Beyond sleep continuity, epilepsy may also influence cognitive processes during sleep, including subjective sleep depth and dreaming. While the cognitive consequences of epilepsy during wakefulness are well established, relationships between epileptic activity, sleep architecture and subjective sleep experiences remain poorly understood. In a survey of 300 PWE, the investigators observed altered dream recall frequency and dream content, with seizure-related dreams associated with nocturnal seizures. However, retrospective morning reports cannot establish temporal relationships between epileptic discharges and dream phenomena, nor determine the influence of discharge localization or sleep stage. SEEG combined with direct electrical stimulation (DES) provides a unique framework to address these questions. DES is routinely used during presurgical evaluation to identify epileptogenic and eloquent cortex, but is mainly performed during wakefulness. Yet sleep modifies functional connectivity and facilitates epileptic activity, suggesting that DES during sleep may increase the sensitivity of stimulation-based localization of the seizure-onset zone. The EPIDREAM 3 study will investigate whether DES-induced epileptic activity during sleep provokes arousals, alters dream recall or content, and modifies perceived sleep depth. It will also assess whether sleep-related DES improves delineation of epileptogenic networks, particularly in sleep-related epilepsies. Detailed description: Patients with frontal or temporal drug-resistant focal epilepsy investigated with SEEG as part of presurgical evaluation will be included in the Department of Functional Neurology and Epileptology of the HCL, Lyon. The investigators will use intra-cranial DES performed during the SEEG investigation to explore the impact of focal induced epileptic activity on arousal and dreams. 1. DES will be first performed during wake as part of routine SEEG evaluation with the double purpose of localizing the seizure onset zone and providing a functional mapping. This step identifies channels: (i) in the assumed SOZ, where DES induces after-discharges with/without seizure symptoms; (ii) in the assumed SOZ, where DES induces no after-discharge/seizure but may induce clinical symptoms; (iii) in non-epileptic areas, where stimulation induces neither. For temporal lobe epilepsy, control channels will be selected in the frontal lobe; for frontal lobe epilepsy, in the temporal lobe 2. Stimulations will be repeated in REM and NREM sleep (N2/N3) during the first two sleep cycles of a single night with simultaneous PSG. The investigators will assess for each stimulation: (1) the precise location of the channel (2) the presence and characteristics of an induced after-discharge or seizure (3) presence of a spontaneous arousal (3-15 sec) or awakening (> 15 sec) (4) presence of objective symptoms (5) in case of awakening: presence of subjective reported symptoms, sleep depth and mind content

Conditions

  • Patients With Drug-resistant Focal Epilepsy
  • SEEG as Part of Presurgical Evaluation

Eligibility

Eligible Ages
Between 18 Years and 55 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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 temporal or frontal lobe epilepsy based on non-invasive work-up - Epilepsy is refractory to treatment, as defined by the International League Against Epilepsy 31 - Patients undergoing SEEG investigation - At least 1 frontal and 1 temporal electrode in the SEEG procedure - Patient affiliated to the French health care system

Exclusion Criteria

  • Multifocal epilepsy - Untreated severe obstructive sleep-apnea syndrome - Too abnormal SEEG recording interfering with sleep stage identification during the DES procedure - Severe cognitive impairment preventing full understanding and completion of the protocol - Unstable psychiatric condition - Subject participating in other interventional research with an exclusion period still in progress at pre-inclusion - 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

Study Design

Phase
Study Type
Observational
Observational Model
Other
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Patients Patients investigated with SEEG as part of presurgical evaluation in the Department of Functional Neurology and Epileptology of the HCL, Lyon, France and in the Epilepsy Department, Duke University Hospital, Durham, USA. Patients recruited will be: 1. Aged 18 to 55 years old 2. Diagnosis of focal temporal or frontal lobe epilepsy based on non-invasive work-up 3. Epilepsy is refractory to treatment, as defined by the International League Against Epilepsy 4. Patients undergoing SEEG investigation 5. At least 1 temporal and 1 frontal electrode in the SEEG procedure 6. Patient affiliated to the French health care system
  • Other: Direct Electric Stimulation (DES)
    1. DES will be first performed during wake as part of routine SEEG evaluation. Bipolar stimulations of adjacent contacts will be applied using biphasic square wave pulses at low frequency and at high frequency. Intensity will be increased stepwise by increments of 0.5mA until the appearance of an objective or a subjective symptom or after-discharges or seizure. 2. Stimulations will be repeated in rapid eye movement (REM) and non REM sleep during the first two cycles of a single night with simultaneous polysomnography (PSG) recording. Stimulation will involve channels from the seizure onset zone and channels outside de seizure onset zone. If the patient wakes up following stimulations, they will be asked what was going through their mind and how deep was their sleep before awakening. If no awakening occurs but an after-discharge or a seizure is provoked, the patient will be awoken (with a maximum of 6 awakenings in REM and 6 in NREM) and also asked about sleep depth and dream content.

More Details

Status
Recruiting
Sponsor
Hospices Civils de Lyon

Study Contact

PETER-DEREX MD Laure, MD
+33 (0) 4 72 35 70 44
laure.peter-derex@chu-lyon.fr