Dataset Information

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

ABSTRACT: Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk. Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05. Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2-137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up. Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold.

SUBMITTER: Ochoa-Urrea M

PROVIDER: S-EPMC7907515 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

Ochoa-Urrea Manuela M Lacuey Nuria N Vilella Laura L Zhu Liang L Jamal-Omidi Shirin S Rani M R Sandhya MRS Hampson Johnson P JP Dayyani Mojtaba M Hampson Jaison J Hupp Norma J NJ Tao Shiqiang S Sainju Rup K RK Friedman Daniel D Nei Maromi M Scott Catherine C Allen Luke L Gehlbach Brian K BK Reick-Mitrisin Victoria V Schuele Stephan S Ogren Jennifer J Harper Ronald M RM Diehl Beate B Bateman Lisa M LM Devinsky Orrin O Richerson George B GB Zhang Guo-Qiang GQ Lhatoo Samden D SD

Frontiers in neurology 20210212

<b>Rationale:</b> Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations ...[more]

PMID: 33643216

Similar Datasets

Project description:ObjectiveSudden unexpected death in epilepsy (SUDEP) is the cause of premature death of 50% patients with chronic refractory epilepsy. Respiratory failure during seizures is regarded as an important mechanism of SUDEP. Previous studies have shown that abnormal serotonergic neurotransmission is involved in the pathogenesis of seizure-induced respiratory failure, while enhancing serotonergic neurotransmission in the brainstem suppresses it. Because peripheral inflammation is known to enhance serotonergic neuron activation and 5-HT synthesis and release, we investigated the effect of intraperitoneal lipopolysaccharide (LPS)-induced inflammation on the S-IRA susceptibility during audiogenic seizures in DBA/1 mice.MethodsAfter DBA/1 mice were primed by exposing to sound stimulation for three consecutive days, they were tested for seizure severity and seizure-induced respiratory arrest (S-IRA) induced by sound stimulation under different conditions. We determined the dose and time course of the effects of intraperitoneal administration of LPS on audiogenic seizures and S-IRA. The effects of blocking TLR4 or RAGE receptors and blocking 5-HT receptors on the LPS-induced effect on S-IRA were investigated. Statistical significance was evaluated using the Kruskal-Wallis test.ResultsIntraperitoneal injection of LPS significantly had dose-dependent effects in reducing the incidence of S-IRA as well as seizure severity in DBA/1 mice. The protective effect of LPS on S-IRA peaked at 8-12 hours after LPS injection and was related to both reducing seizure severity and enhancing autoresuscitation. Blocking TLR4 or RAGE receptor with TAK-242 or FPS-ZM1, respectively, prior to LPS injection attenuated its effects on S-IRA and seizure severity. Injection of a nonselective 5-HT receptor antagonist, cyproheptadine, or a 5-HT3 receptor antagonist, ondansetron, was effective in blocking LPS-induced effect on S-IRA. Immunostaining results showed a significant increase in c-Fos-positive serotonergic neurons in the dorsal raphe.SignificanceThis is the first study that demonstrates the effect of intraperitoneal LPS injection-induced inflammation on reducing S-IRA susceptibility and provides additional evidence supporting the serotonin hypothesis on SUDEP. Our study suggests that inflammation may enhance brainstem 5-HT neurotransmission to promote autoresuscitation during seizure and prevent SUDEP.

Project description:This study was designed to evaluate cardiac and respiratory dysfunction in a mouse model of sudden unexpected death in epilepsy i.e., SUDEP. We simultaneously monitored respiration via plethysmography and the electrocardiogram via telemetry before, during, and after an audiogenic seizure. DBA/1 mice responded to an acoustic stimulus with one or two cycles of circling and jumping before entering a clonic/tonic seizure. This was followed by death unless the mice were resuscitated by mechanical ventilation using room air. During the initial clonic phase, respiration declined and cardiac rhythm is slowed. By the tonic phase, respiration had ceased, atrial P-waves were absent or dissociated from the QRS complex, and heart rate had decreased from 771±11 to 252±16 bpm. Heart rate further deteriorated terminating in asystole unless the mice were resuscitated at the end of the tonic phase which resulted in abrupt recovery of P-waves and a return to normal sinus rhythm, associated with gasping. Interestingly, P-waves were preserved in the mice treated with methylatropine during the pre-ictal period (to block parasympathetic stimulation) and heart rate remained unchanged through the end of the tonic phase (765±8 vs. 748±21 bpm), but as in control, methylatropine treated mice died from respiratory arrest. These results demonstrate that a clonic/tonic seizure in the DBA/1 mouse results in abrupt and simultaneous respiratory and cardiac depression. Although death clearly results from respiratory arrest, our results suggest that seizure activates two central nervous system pathways in this model-one inhibits respiratory drive, whereas the other inhibits cardiac function via vagal efferents. The abrupt and simultaneous recovery of both respiration and cardiac function with mechanical ventilation within an early post-ictal timeframe shows that the vagal discharge can be rapidly terminated. Understanding the central mechanism associated with the abrupt cardiorespiratory dysfunction and equally abrupt recovery may provide clues for therapeutic targets for SUDEP.

Project description:BACKGROUND:Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in those with drug-resistant epilepsy (DRE). There is a need for inventories and biomarkers associated with the risk for SUDEP. OBJECTIVE:To explore the revised SUDEP Risk Inventory (SUDEP-7) in a cohort with DRE and determine the association with Heart Rate and other covariates. METHODS:Twenty-five subjects with severe DRE were enrolled in a clinical trial for epilepsy. Baseline demographics, duration of epilepsy, seizure types, seizure frequency, seizure severity, AEDs, and vital signs were collected. Heart rate variability (HRV) was calculated from 1-h recordings of ECG. A SUDEP Risk Inventory (SUDEP-7) was administered, which included seven validated and weighted risk factors initially identified by Walczak et al. as factors associated with SUDEP risk. RESULTS:The total score on the revised SUDEP-7 ranged from 1 to 7, mean?=?3.4 (SD 1.8). The SUDEP Risk Inventory score was inversely correlated with RMSSD (Pearson r?=?-0.45, p?=?0.027). The following variables were significantly associated with RMSSD: epilepsy duration (p?=?0.02), age (p?=?0.03), and developmental intellectual disability (p?<?0.001). The correlation between RMSSD and SUDEP-7 tended to persist also after the adjustment for patient age (r?=?-0.40, p?=?0.05). Two subjects died of SUDEP: their SUDEP-7 scores were above average and in the upper twenty-fifth and fiftieth percentiles, respectively (6 and 4, mean?=?3.4). CONCLUSION:RMSSD, a measure of low frequency HRV, was significantly associated with SUDEP Risk Inventory (SUDEP-7) scores. Using a multivariate model, the covariates of developmental intellectual disability, age, and duration of epilepsy were also significantly associated with decreased HRV. The correlation between decreased HRV and a higher SUDEP-7 score remained unchanged even after the adjustment for patient age. The results suggest that older age, greater duration of epilepsy, and the presence of developmental intellectual disability may increase the risk of SUDEP through their direct influence on decreasing the vagus nerve-mediated HRV. Further validation of the SUDEP-7 inventory is indicated. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00871377.

Dataset Information

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

Publications

Seizure Clusters, Seizure Severity Markers, and SUDEP Risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets