Patients With Drug-resistant Focal Epilepsy, SEEG as Part of Presurgical Evaluation
Conditions
Keywords
Epilepsy, Sleep, Dreams, Stereoelectroencephalography, Brain stimulation
Brief summary
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
Interventions
OTHERDirect 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.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of arousal or awakening following DES | The time window to detect arousal or awakenings will start at the onset of the DES and end within 10 seconds after the end of the DES or the after-discharge. | Rate of arousal (sudden change in the EEG pattern characterized by a shift to higher-frequency activity (e.g., alpha, beta, or theta excluding sleep spindles) lasting at least 3 seconds and preceded by at least 10 seconds of stable sleep associated with an increase in muscle tone \>1sec) or awakening (\>15sec) as detected on the scalp EEG or eloquent SEEG channels, following DES 1) when after-discharges or seizures were induced and 2) when no after-discharges nor seizure were induced (including all patients, all topography, seizure onset zone \[SOZ\] and no SOZ, triggered symptoms or not). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spectral power of the EEG following DES during sleep | baseline (pre-stimulation 10 seconds time-window) post-stimulation (the time window will start at the onset of the DES and end within 10 seconds after the end of the DES or the after-discharge) | Spectral power in usual frequency band of interest (delta 0.3-3.5Hz Hz, theta 4-7.5 Hz , alpha 8-11 Hz, sigma (11.5-15.5 Hz) beta (16-30 Hz), low gamma (30-40 Hz) and high gamma (50-80 Hz) during baseline and during post-stimulation recorded over all non-stimulated channels, for DES inducing after-discharges/seizures versus DES inducing no after-discharges/seizures. |
| Factors associated with arousal reactions | The time window to detect arousal or awakenings will start at the onset of the DES and end within 10 seconds after the end of the DES or the after-discharge | 1. Type or arousal reaction (no arousal/arousal/awakening) 2. Factors of modulation: i) presence and type of induced epileptic activity (after-discharge vs seizure) ii) topography of the stimulated channel (within the SOZ or not; temporal vs frontal lobe, medial vs lateral) iii) anatomic extension of the induced epileptic activity (involvement of the thalamus, involvement of the cingulate cortex) iv) ongoing sleep stage (NREM vs REM sleep) v) presence of triggered symptoms as assessed during baseline wakefulness DES, iv) the type of stimulation (1 Hz vs 50 Hz, intensity in mA) |
| Dream recall during sleep following stimulations | Within the 5 minutes after the end of the DES or the after-discharge | Dream recall (yes/no) following DES inducing after-discharges or seizures versus DES not inducing after-discharges or seizures |
| Mental content during sleep following stimulations | Within the 5 minutes after the end of the DES or the after-discharge | Mental content (some content/no content and if content: white dream, dream including seizure symptoms, dream of seizure, dream related to epilepsy, dream unrelated to epilepsy, feeling and if feeling: related or not to epilepsy) following DES inducing after-discharges or seizures versus DES not inducing after-discharges or seizures. |
| Subjective sleep depth following stimulations | Within the 5 minutes after the end of the DES or the after-discharge | Sleep depth (Likert scale ranging from 0: awake, 1: drowsiness, 2: light sleep, 3: moderately deep sleep; 4: deep sleep) following DES inducing after-discharges or seizures versus DES not inducing after-discharges or seizures. |
| Factors associated with dream recall sleep following stimulations | Within the 5 minutes after the end of the DES or the after-discharge | 1. Subjective experience : dream recall 2. factors of modulation: i) presence and type of induced epileptic activity (after-discharge vs seizure) ii) topography of the channel (within the SOZ or not; medial temporal vs medial frontal lobe) iii) anatomic extension of the induced epileptic activity (involvement of the thalamus, involvement of the cingulate cortex1) iv) ongoing sleep stage (NREM vs REM sleep) v) presence of triggered symptoms as assessed during baseline wakefulness DES, vi) type of stimulation (1 Hz vs 50 Hz, intensity in mA) |
| Factors associated with sleep depth sleep following stimulations | Within the 5 minutes after the end of the DES or the after-discharge | 1. Subjective experience : sleep depth 2. factors of modulation: i) presence and type of induced epileptic activity (after-discharge vs seizure) ii) topography of the channel (within the SOZ or not; medial temporal vs medial frontal lobe) iii) anatomic extension of the induced epileptic activity (involvement of the thalamus, involvement of the cingulate cortex1) iv) ongoing sleep stage (NREM vs REM sleep) v) presence of triggered symptoms as assessed during baseline wakefulness DES, vi) type of stimulation (1 Hz vs 50 Hz, intensity in mA) |
| Sensitivity of performing DES during sleep + wake versus during wake only for delineating the seizure onset zone | During wake and sleep DES sessions | In the seizure onset zone: 1. Frequency of induced after-discharges and/or seizures in sleep (NREM and/or REM) + wake \& Frequency of induced after-discharges and/or seizures in wake only 2. median stimulation intensity triggering an after-discharge during sleep (all sleep, and NREM and REM separately) and during wakefulness. |
Countries
France, United States
Contacts
CONTACTPETER-DEREX MD Laure, MD
Outcome results
None listed