Prognostic value of early electrographic biomarkers of epileptogenesis in high-risk ischaemic stroke patients.

BACKGROUND AND PURPOSE: Post-stroke epilepsy (PSE) is frequent. Better prediction of PSE would enable individualized management and improve trial design for epilepsy prevention. The aim was to assess the complementary value of continuous electroencephalography (EEG) data during the acute phase compared with clinical risk factors currently used to predict PSE. METHODS: A prospective cohort of 81 patients with ischaemic stroke who received early continuous EEG monitoring was studied to assess the association of early EEG seizures, other highly epileptogenic rhythmic and periodic patterns, and regional attenuation without delta (RAWOD, an EEG pattern of stroke severity) with PSE. Clinical risk factors were investigated using the SeLECT (stroke severity; large-artery atherosclerosis; early clinical seizures; cortical involvement; territory of middle cerebral artery) scores. RESULTS: Twelve (15%) patients developed PSE. The presence of any of the investigated patterns was associated with a risk of epilepsy of 46%, with a sensitivity and specificity of 83% and 78%. The association remained significant after adjusting for the SeLECT score (odds ratio 18.8, interquartile range 3.8-72.7). CONCLUSIONS: It was found that highly epileptogenic rhythmic and periodic patterns and RAWOD were associated with the development of PSE and complemented clinical risk factors. These findings indicate that continuous EEG provides useful information to determine patients at higher risk of developing PSE and could help individualize care.

Combined depth and scalp electroencephalographic monitoring in acute brain injury: Yield and prognostic value.

BACKGROUND AND PURPOSE: Depth electroencephalography (dEEG) is an emerging neuromonitoring technology in acute brain injury (ABI). We aimed to explore the concordances between electrophysiological activities on dEEG and on scalp EEG (scEEG) in ABI patients. METHODS: Consecutive ABI patients who received dEEG monitoring between 2018 and 2022 were included. Background, sporadic epileptiform discharges, rhythmic and periodic patterns (RPPs), electrographic seizures, brief potentially ictal rhythmic discharges, ictal-interictal continuum (IIC) patterns, and hourly RPP burden on dEEG and scEEG were compared. RESULTS: Sixty-one ABI patients with a median dEEG monitoring duration of 114 h were included. dEEG significantly showed less continuous background (75% vs. 90%, p = 0.03), higher background amplitude (p < 0.001), more frequent rhythmic spike-and-waves (16% vs. 3%, p = 0.03), more IIC patterns (39% vs. 21%, p = 0.03), and greater hourly RPP burden (2430 vs. 1090 s/h, p = 0.01), when compared to scEEG. Among five patients with seizures on scEEG, one patient had concomitant seizures on dEEG, one had periodic discharges (not concomitant) on dEEG, and three had no RPPs on dEEG. Features and temporal occurrence of electrophysiological activities observed on dEEG and scEEG are not strongly associated. Patients with seizures and IIC patterns on dEEG seemed to have a higher rate of poor outcomes at discharge than patients without these patterns on dEEG (42% vs. 25%, p = 0.37). CONCLUSIONS: dEEG can detect abnormal electrophysiological activities that may not be seen on scEEG and can be used as a complement in the neuromonitoring of ABI patients.

Delayed Deterioration of Electroencephalogram in Patients with Cardiac Arrest: A Cohort Study.

BACKGROUND: The aim of this study was to assess the prevalence of delayed deterioration of electroencephalogram (EEG) in patients with cardiac arrest (CA) without early highly malignant patterns and to determine their associations with clinical findings. METHODS: This was a retrospective study of adult patients with CA admitted to the intensive care unit (ICU) of a university hospital. We included all patients with CA who had a normal voltage EEG, no more than 10% discontinuity, and absence of sporadic epileptic discharges, periodic discharges, or electrographic seizures. Delayed deterioration was classified as the following: (1) epileptic deterioration, defined as the appearance, at least 24 h after CA, of sporadic epileptic discharges, periodic discharges, and status epilepticus; or (2) background deterioration, defined as increasing discontinuity or progressive attenuation of the background at least 24 h after CA. The end points were the incidence of EEG deteriorations and their association with clinical features and ICU mortality. RESULTS: We enrolled 188 patients in the analysis. The ICU mortality was 46%. Overall, 30 (16%) patients presented with epileptic deterioration and 9 (5%) patients presented with background deterioration; of those, two patients presented both deteriorations. Patients with epileptic deterioration more frequently had an out-of-hospital CA, and higher time to return of spontaneous circulation and less frequently had bystander resuscitation than others. Patients with background deterioration showed a predominantly noncardiac cause, more frequently developed shock, and had multiple organ failure compared with others. Patients with epileptic deterioration presented with a higher ICU mortality (77% vs. 41%; p < 0.01) than others, whereas all patients with background deterioration died in the ICU. CONCLUSIONS: Delayed EEG deterioration was associated with high mortality rate. Epileptic deterioration was associated with worse characteristics of CA, whereas background deterioration was associated with shock and multiple organ failure.

Diagnostic and therapeutic approaches in refractory insular epilepsy.

Due to heterogenous seizure semiology and poor contribution of scalp electroencephalography (EEG) signals, insular epilepsy requires use of the appropriate diagnostic tools for its diagnosis and characterization. The deep location of the insula also presents surgical challenges. The aim of this article is to review the current diagnostic and therapeutic tools and their contribution to the management of insular epilepsy. Magnetic resonance imaging (MRI), isotopic imaging, neurophysiological imaging, and genetic testing should be used and interpretated with caution. Isotopic imaging and scalp EEG have demonstrated a lower value in epilepsy from insular compared to temporal origin, which increases the interest of functional MRI and magnetoencephalography. Intracranial recording with stereo-electroencephalography (SEEG) is often required. The insular cortex, being highly connected and deeply located under highly functional areas, is difficult to reach, and its ablative surgery raises functional issues. Tailored resection based on SEEG or alternative curative treatments, such as radiofrequency thermocoagulation, laser interstitial thermal therapy, or stereotactic radiosurgery, have produced encouraging results. The management of insular epilepsy has benefited from major advances in the last years. Perspectives for diagnostic and therapeutic procedures will contribute to better management of this complex form of epilepsy.

Duration of nonconvulsive seizures in critically ill patients.

INTRODUCTION: Non-convulsive seizures (NCSz) and non-convulsive status epilepticus (NCSE) are frequent in critically ill patients. Specific temporal thresholds to define both are lacking and may be needed to guide appropriate treatment. METHOD: Retrospective review of 995 NCSz captured during continuous EEG monitoring of 111 consecutive critically ill patients. Seizures were classified according to their type and underlying etiology (acute or progressive brain injury, seizure-related disorders and acute medical illness). Median and interquartile ranges [IQR] were calculated. Suggested temporal threshold for NCSE was defined as the 95 percentile of seizure duration. RESULTS: Most (69%) patients had an underlying acute or progressive brain injury. The 95 percentile of seizure duration was 518 s, overall, with variation according to underlying etiology (median 86 [47-137] s for brain injury, 73 [45-115] s for seizure-related disorders, and 92 [58-223] s for acute medical illness, respectively; p = 0.0025; 95 percentile 424, 304, and 1725 s, respectively). Forty-one (37%) patients were comatose and had significantly longer seizures than non-comatose patients (median 99 [49-167] vs. 73 [46-123] s; p < 0.001; 95 percentile: 600 vs 444 s). CONCLUSION: To define NCSE, a temporal threshold of 10 min in critically ill patients with a primary neurological diagnosis can be applied, while a temporal threshold of 30 min might be suitable for patients with an underlying acute medical illness.

Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation.

BACKGROUND: Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome. METHODS: Retrospective analysis of all patients undergoing venous-venous (V-V) or venous-arterial (V-A) ECMO with a concomitant EEG recording (April 2009-December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge. RESULTS: A total of 139 patients (54 [41-62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno-arterial (V-A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25-16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24-82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories. CONCLUSIONS: In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.

The Epilepsy Surgery Grading Scale: Validation in an independent population with drug-resistant focal epilepsy.

The Epilepsy Surgery Grading Scale (ESGS) is a simple tool that predicts a patient's likelihood of progressing to resective surgery and becoming seizure-free. The aim of our study was to validate the ESGS in an independent patient cohort. We retrospectively calculated the ESGS score for adult patients with drug-resistant focal epilepsy undergoing presurgical evaluation at two reference centers for drug-resistant epilepsy in Belgium. We classified patients into ESGS grade 1 (most favorable), grade 2 (intermediate), and grade 3 (least favorable). We assessed progression to surgery and postsurgical seizure freedom. A total of 238 patients underwent presurgical evaluation (presurgical cohort), of whom 140 progressed to surgery (surgical cohort). In the presurgical cohort, we observed significant differences in rates of surgery and in rates of seizure freedom between grades 1, 2, and 3. In the surgical cohort, we observed significant differences in rates of seizure freedom between grades 1 and 2 and between grades 1 and 3. We confirm the usefulness of the ESGS for the prognostic stratification of patients with drug-resistant focal epilepsy undergoing presurgical evaluation. Our results support the use of the ESGS in the decision process of presurgical evaluation in clinical practice.

Dynamics underlying interictal to ictal transition in temporal lobe epilepsy: insights from a neural mass model.

We propose an approach that combines a neural mass model and clinical intracranial electroencephalographic (iEEG) recordings to explore the potential pathophysiological mechanisms (at the neuronal population level) of ictogenesis. Thirty iEEG recordings from 10 temporal lobe epilepsy (TLE) patients around seizure onset were investigated. Physiologically meaningful parameters [average excitatory (Ae ), slow (B), and fast (G) inhibitory synaptic gain] were identified during interictal to ictal transition. Four ratios (Ae /G, Ae /B, Ae /(B + G), and B/G) were derived from these parameters, and their evolution over time was analyzed. The excitation/inhibition ratio increased around seizure onset and decreased before seizure offset, indicating the impairment and re-emergence of excitation/inhibition balance around seizure onset and before seizure offset, respectively. Moreover, the slow inhibition may have an earlier effect on excitation/inhibition imbalance. We confirm the decrease in excitation/inhibition ratio upon seizure termination in human temporal lobe epilepsy, as revealed by optogenetic approaches both in vivo in animal models and in vitro. The increase in excitation/inhibition ratio around seizure occurrence could be an indicator to detect seizures.

Seizure evolution can be characterized as path through synaptic gain space of a neural mass model.

Physiologically based models could facilitate better understanding of mechanisms underlying epileptic seizures. In this paper, we attempt to reveal the dynamic evolution of intracranial EEG activity during epileptic seizures based on synaptic gain identification procedure of a neural mass model. The distribution of average excitatory, slow and fast inhibitory synaptic gain in the parameter space and their temporal evolution, i.e., the path through the model parameter space, were analyzed in thirty seizures from ten temporal lobe epileptic patients. Results showed that the synaptic gain values located roughly on a plane before seizure onset, dispersed during seizure and returned to the plane when seizure terminated. Cluster analysis was performed on seizure paths and demonstrated consistency in synaptic gain evolution across different seizures from the individual patient. Furthermore, two patient groups were identified, each one corresponding to a specific synaptic gain evolution in the parameter space during a seizure. Results were validated by a bootstrapping approach based on comparison with random paths. The differences in the path revealed variations in EEG dynamics for patients despite showing identical seizure onset pattern. Our approach may have the potential to classify the epileptic patients into subgroups based on different mechanisms revealed by subtle changes in synaptic gains and further enable more robust decisions regarding treatment strategy.

Time-dependent risk of seizures in critically ill patients on continuous electroencephalogram.

OBJECTIVE: Find the optimal continuous electroencephalographic (CEEG) monitoring duration for seizure detection in critically ill patients. METHODS: We analyzed prospective data from 665 consecutive CEEGs, including clinical factors and time-to-event emergence of electroencephalographic (EEG) findings over 72 hours. Clinical factors were selected using logistic regression. EEG risk factors were selected a priori. Clinical factors were used for baseline (pre-EEG) risk. EEG findings were used for the creation of a multistate survival model with 3 states (entry, EEG risk, and seizure). EEG risk state is defined by emergence of epileptiform patterns. RESULTS: The clinical variables of greatest predictive value were coma (31% had seizures; odds ratio [OR] = 1.8, p < 0.01) and history of seizures, either remotely or related to acute illness (34% had seizures; OR = 3.0, p < 0.001). If there were no epileptiform findings on EEG, the risk of seizures within 72 hours was between 9% (no clinical risk factors) and 36% (coma and history of seizures). If epileptiform findings developed, the seizure incidence was between 18% (no clinical risk factors) and 64% (coma and history of seizures). In the absence of epileptiform EEG abnormalities, the duration of monitoring needed for seizure risk of <5% was between 0.4 hours (for patients who are not comatose and had no prior seizure) and 16.4 hours (comatose and prior seizure). INTERPRETATION: The initial risk of seizures on CEEG is dependent on history of prior seizures and presence of coma. The risk of developing seizures on CEEG decays to <5% by 24 hours if no epileptiform EEG abnormalities emerge, independent of initial clinical risk factors. Ann Neurol 2017;82:177-185.

Clinical Correlates of Periodic Discharges and Nonconvulsive Seizures in Posterior Reversible Encephalopathy Syndrome (PRES).

IMPORTANCE: The pathophysiological mechanisms of Posterior Reversible Encephalopathy Syndrome (PRES) and related seizures remain poorly understood. The prevalence and clinical significance of nonconvulsive seizures (NCSz) and related epileptiform patterns during continuous electroencephalography monitoring (CEEG) in PRES have not been well described. OBJECTIVE: To report the prevalence, characteristics and risk factors for NCSz and related highly epileptiform patterns in patients with PRES, and to determine their relation to imaging abnormalities and outcome. DESIGN, SETTING AND PARTICIPANTS: From a prospective CEEG database, we retrospectively identified patients with PRES and reviewed their medical charts. Based on CEEG findings, we designed a retrospective cohort study comparing two groups defined based on the presence or the absence of NCSz and/or periodic discharges (PDs). MAIN OUTCOMES AND MEASURES: The prevalence and risk factors for PDs and NCSz, description of EEG and magnetic resonance imaging (MRI) abnormalities and functional outcome as measured by the Glasgow Outcome Scale (GOS) at hospital discharge. RESULTS: Among 37 eligible patients, 23 (62%) had PDs or NCSz. The presence of NCSz was associated with the presence of PDs (15/22 vs. 1/15; p = 0.0002). NCSz and PDs were usually either lateralized or bilateral independent and predominated in the posterior regions. No clinical features were associated with the occurrence of PDs or NCSz. Cortical restricted diffusion on MRI was more frequent in the PDs/NCSz group (17/23 vs. 1/14; p < 0.001). PDs/NCSz were associated with worse outcome, with 3 deaths vs. 0 in the no PDs/NCSz group and fewer cases with low disability (4 vs. 9 cases with GOS = 5, p < 0.04). CONCLUSIONS AND RELEVANCE: Our results reveal a high prevalence of NCSz and PDs in critically ill patients with PRES and an association with restricted diffusion and worse outcome, whether treating or preventing these EEG findings can improve outcome requires further research.

The Prognostic Value of 48-h Continuous EEG During Therapeutic Hypothermia After Cardiac Arrest.

BACKGROUND: The aim of this study was to evaluate the prognostic value of continuous electroencephalogram (cEEG) during the first 48 h following cardiac arrest (CA) in patients treated with targeted temperature management (TTM). METHODS: We reviewed data from 92 comatose post-CA patients over a 6 year-period; cEEG recordings were performed during TTM and restoration of normothermia. EEG findings were divided into four time-periods: 0-8, 8-16, 16-24, and 24-48 h after CA. Background EEG findings were defined as moderate encephalopathy (diffuse slowing with reactivity/variability), severe encephalopathy (diffuse slowing without reactivity/variability), burst suppression or suppression, and dichotomized as malignant (suppression/burst suppression/severe encephalopathy) or benign (moderate encephalopathy). Epileptiform activity was defined as the presence of seizures, sporadic epileptiform discharges, or periodic discharges. Neurological outcome was assessed at 3 months using the cerebral performance categories (CPC) score (good outcome: CPC 1-2). RESULTS: 26/92 (28%) patients had a good outcome. Malignant patterns were associated with a poor outcome at all time-points, with a high positive predictive value (94-97%) but a poor negative predictive value (44-56%). Epileptiform activity did not influence the prognostic value of EEG patterns. All patients with moderate encephalopathy and seizures or generalized periodic discharges had a poor outcome. CONCLUSIONS: cEEG can identify patients with poor outcome from the first hours following CA, with limited predictive value for good outcome. Epileptiform activity did not improve the prognostic accuracy of EEG, but seizures and generalized periodic discharges were associated with poor outcome even when developing on a benign EEG pattern.

Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy.

We identified a small family with autosomal recessive, infantile onset epilepsy and intellectual disability. Exome sequencing identified a homozygous missense variant in the gene TNK2, encoding a brain-expressed tyrosine kinase. Sequencing of the coding region of TNK2 in 110 patients with a similar phenotype failed to detect further homozygote or compound heterozygote mutations. Pathogenicity of the variant is supported by the results of our functional studies, which demonstrated that the variant abolishes NEDD4 binding to TNK2, preventing its degradation after epidermal growth factor stimulation. Definitive proof of pathogenicity will require confirmation in unrelated patients.

Transient CNS deficits and migrainous auras in individuals without a history of headache.

OBJECTIVE: To demonstrate that benign transient focal neurological symptoms represent equivalents of migraine auras without headache. BACKGROUND: Benign focal neurological symptoms suggesting cerebral dysfunction are common and usually prompt an extensive diagnostic workup, but their etiology is often not elucidated. We hypothesized that benign transient focal neurological symptoms represent equivalents of migraine auras without headache, even in subjects who have never experienced migraine headaches. METHODS: We led a cross-sectional study and identified individuals who presented at least 1 episode of unexplained transient focal neurological symptoms suggestive of cerebral dysfunction, but no history of migraine headache, among physicians and inpatients of an academic hospital. Cortical hyperexcitability, assessed by occipital transcranial magnetic stimulation (oTMS), was used as a marker of possible migraine auras without headache. RESULTS: Frequency of transient focal neurological symptoms suggestive of cerebral dysfunction among the physicians who responded was 9% (21/233), vs 0.09% (6/690) of inpatients. Most episodes resembled typical visual migrainous auras. Motor, sensory, and language dysfunction were more common among inpatients than among physicians. oTMS induced phosphenes in 12/16 (75%) subjects and in none of 10 controls. CONCLUSION: Benign focal neurological symptoms were common in our population and likely represent migraine aura without headache. Non-visual symptoms are less common and lead to medical consultation. oTMS is abnormal in most cases, supporting the diagnosis of migraine aura without headache and helping separate this benign condition from transient ischemic attacks.

EEG patterns compatible with nonconvulsive status epilepticus are common in elderly patients with delirium: a prospective study with continuous EEG monitoring.

INTRODUCTION: Delirium is a leading cause of hospitalization and morbidity in elderly persons. Nonconvulsive status epilepticus (NCSE) and delirium share many risk factors. We tested the hypothesis that NCSE plays an important role in delirium by performing continuous EEG (cEEG) monitoring in elderly patients with delirium of any cause. MATERIAL AND METHODS: Patients over 65 years old presenting with delirium in the emergency room were prospectively included and underwent either routine 20-minute EEG or cEEG within 24h after admission. Clinical, biological, and imaging characteristics, length of hospitalization, and outcome were compared between patients with possible NCSE and patients without epileptic discharges. RESULTS: There were 32 patients in each group. Continuous EEG detected patterns compatible with NCSE in 28% and focal interictal epileptiform discharges (IEDs) in 16% of the patients. Routine EEG detected patterns compatible with NCSE in 6% and focal IEDs in 16% of the patients. History of cognitive impairment and use of antibiotics and hypernatremia were significantly associated with the presence of possible NCSE. Delirium in patients with possible NCSE was initially attributed to another cause in over 80% of the cases. Patterns compatible with NCSE were associated with a longer hospitalization stay and a higher mortality rate. CONCLUSION: Electroencephalographic patterns compatible with NCSE are found in 28% of elderly with delirium when cEEG monitoring is performed. No clinical or paraclinical parameter can reliably distinguish elderly patients with delirium with or without patterns compatible with NCSE in the absence of cEEG monitoring. Elderly patients with delirium and patterns compatible with NCSE have significantly higher mortality rates and longer hospital stays.

Intravenous lacosamide in refractory seizure clusters and status epilepticus: comparison of 200 and 400 mg loading doses.

BACKGROUND: The treatment of refractory status epilepticus (RSE) remains largely empirical. Lacosamide (LCM) is a new anticonvulsant available in intravenous (IV) form, but its optimal dosing regimen for the treatment of RSE is unknown. We compared safety and efficacy of two loading doses: 200 and 400 mg. METHODS: Prospective observational study of all patients who received IV LCM for RSE or seizure clusters between October 2010 and December 2012. A first group received an IV load of 200 mg of LCM. After the initial part of the study, and due to poor results with this dosage, a second group received a loading dose of 400 mg. Outcome measures included response rate, time to response, and adverse events. RESULTS: There was a trend in favor of a higher response rate to LCM in the 400 mg group [7/14 (50 %) vs. 2/11 (18 %), respectively; p = 0.2]. Early responses (occurring within 3 h of initiation of LCM) were significantly more frequent in the 400 mg group [4/14 (28 %) vs. 0/11 (0 %); p = 0.026]. Overall, 9/25 patients (36 %) responded to LCM and seizures were terminated in eight more patients (32 %), by adding other anticonvulsants. The following adverse events were attributed to LCM: myoclonus and confusion, increase in seizure frequency, vertigo, ataxia, and an asymptomatic increase in liver enzymes level. All occurred in the 200 mg group. No skin rash, renal, cardiac, or hemodynamic side effects were observed in any group. CONCLUSIONS: In this small prospective observational study, an initial dose of 400 mg of IV LCM was associated with a higher proportion of early termination of RSE and with a trend toward a higher response rate.

Complications during and after ICU stay are associated with increased mortality after status epilepticus.

BACKGROUND: Status Epilepticus (SE) is a neurological emergency with high mortality rate that often requires admission in Intensive Care Units (ICU). Several factors of worse outcome have been identified in prior studies. The aim of our study was to determine the mortality in ICU and in the ward in patients with SE admitted to an ICU and to identify risk factors of mortality. METHODS: Retrospective cohort study of patients admitted with SE treated in the ICU of a tertiary medical center between 2015 and 2020. The primary outcome measure was mortality in the ICU (ICU death) or in the ward after ICU discharge (post-ICU death). RESULTS: 252 patients were included, with a mean age of 63 (±16) years and 127 males (50 %). 58 died in the ICU, 27 died in the ward. Overall mortality was associated with a higher burden of comorbidities (OR:1.28, p < 0.001), the use of vasopressors (OR: 5.65, p < 0.001) and a higher burden of ICU complications (OR: 1.32, p = 0.002). Mortality rate was higher in more severe SE episodes (nonconvulsive, acute symptomatic and refractoriness. In-ICU mortality was associated with the use of vasopressors (OR: 7.92, p<0.001) and mechanical ventilation (OR: 3.13, p = 0.031), the length of in-ICU stay (OR: 0.91, p = 0.005) and a higher burden of ICU complications (OR: 1.37, p = 0.001). Compared to post-ICU deaths, ICU deaths also had higher Sequential Organ Failure Assessment (SOFA) score on ICU admission (p<0.001). Post-ICU mortality was associated with a higher burden of comorbidities (OR: 1.34, p<0.001), a higher burden of complications after ICU-discharge (OR: 1.33, p = 0.01), and more often refractory SE episode (OR: 2.63, p = 0.01). Compared to survivors, post-ICU deaths experienced mostly infectious and respiratory complications, after ICU-discharge. CONCLUSION: Death was more frequent in more severe SE episodes: non convulsive semiology, acute etiology, and refractoriness. In-ICU, post-ICU and all-cause mortality in patients with SE admitted to an ICU are all associated with a higher burden of comorbidities, which are non-modifiable prognostic factors, but also with a higher burden of complications, some of which are preventable, such as respiratory infections.

Variability of cortico-cortical evoked potentials in the epileptogenic zone is related to seizure occurrence.

INTRODUCTION: Cortico-cortical evoked potentials (CCEPs) were described as reproducible during trains of single-pulse electrical stimulations (SPES). Still, few studies described a variability of CCEPs that was higher within the epileptogenic zone (EZ). This study aimed at characterizing the relationship of CCEP variability with the occurrence of interictal/ictal epileptiform discharges at the temporal vicinity of the stimulation, but not during the stimulation, by effective connectivity modifications. METHODS: We retrospectively included 20 patients who underwent SPES during their stereo-electroencephalography (SEEG). We analyzed the variability of CCEPs by using the post-stimulation time course of intertrial standard deviation (amplitude) and the timing of peak amplitude signal of CCEP epochs (latency). Values were corrected for the Euclidian distance between stimulating/recording electrodes. Receiver operating characteristics curves were used to assess the relationship with the EZ. The link between CCEP variability and interictal discharges occurrence, seizure frequency prior to the SEEG recording, and number of seizures during SEEG recording was assessed with Spearman's correlations. RESULTS: A relationship was demonstrated between the EZ and both the distance-corrected latency variation (area under the curve (AUC): 0.73-0.74) and the distance-corrected amplitude variation (AUC: 0.71-0.72) and both were related with the occurrence of seizures. CONCLUSION: Seizures before/during SEEG impact the dynamics of effective connectivity within the epileptogenic network by reducing the variability of CCEP latency/amplitude when the seizure frequency increases. It suggests a strengthening of the epileptogenic network with the occurrence of many seizures. These findings stress the importance of early epilepsy surgery at a time when the network organization has not yet been complete.