Potentially high‐risk cardiac arrhythmias with focal to bilateral tonic–clonic seizures and generalized tonic–clonic seizures are associated with the duration of periictal hypoxemia

Park, Katherine J.; Sharma, Gaurav; Kennedy, Jeffrey D.; Seyal, Masud

doi:10.1111/epi.13934

Cited by 47 publications

(34 citation statements)

References 24 publications

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“…14 A similar study exploring the effect of potential high-risk cardiac arrhythmias on duration of ictal hypoxemia only included EMU data for a single primary GTCS case; the rest were focal onset GTCS. 16 Despite multiple studies showing that focal-onset GTCS exhibit prolonged nocturnal PGES, respiratory distress, ictal hypoxemia, and subsequent prolonged postictal immobility, and the concept that people with GGE are at a lower risk of SUDEP, our data suggest that people with GGE also bear significant SUDEP risk. Population-based studies are needed to ascertain the true relative frequencies of SUDEP among GGE and FE.…”

Section: Discussioncontrasting

confidence: 75%

“…[14][15][16] Patients with focal epilepsy (FE) are considered higher risk for SUDEP than those with GGE, based on studies of post-focal onset GTCS hypoxemia and respiratory distress (highest in temporal lobe epilepsies), and due to high relative rates of seizure intractability. 7,15,16 Other series focus on patients at high SUDEP risk with developmental encephalopathic epilepsies (DEEs), such as Dravet syndrome 17 or dup15q syndrome. 18 We assessed the frequency of GGE in a consecutive series of 262 SUDEP cases enrolled in the North American SUDEP Registry (NASR).…”

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confidence: 99%

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Genetic generalized and focal epilepsy prevalence in the North American SUDEP Registry

et al. 2020

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ObjectiveTo assess relative rates and clinical features of patients with genetic generalized epilepsy (GGE), focal epilepsy (FE), and developmental encephalopathic epilepsy (DEE) in the North American SUDEP Registry (NASR).MethodsWe identified all adjudicated definite, definite plus, and probable sudden unexpected death in epilepsy (SUDEP) cases (n = 262) and determined epilepsy type (GGE, FE, or DEE) from medical record review including history, imaging and EEG results, genetics, and next-of-kin interviews.ResultsOf the 262 SUDEP cases, 41 occurred in GGE, 95 in FE, 24 in DEE, and 102 were unclassifiable. GGE cases comprised 26% of NASR cases with an epilepsy syndrome diagnosis. The relative frequency of FE:GGE was slightly lower (2.3:1) than in population cohorts (2.1–6:1). Compared to patients with FE, patients with GGE had similar (1) ages at death and epilepsy onset and rates of (2) terminal and historical antiseizure medication adherence; (3) abnormal cardiac pathology; (4) illicit drug/alcohol use histories; and (5) sleep state when SUDEP occurred.ConclusionsGGE cases were relatively overrepresented in NASR. Because GGEs are less often treatment-resistant than FE or DEE, seizure type rather than frequency may be critical. Many people with GGE predominantly have generalized tonic-clonic seizures (GTCS) when they have uncontrolled or breakthrough seizures, whereas patients with FE more commonly experience milder seizures. Future mechanistic SUDEP studies should assess primary and focal-to-bilateral GTCS to identify potential differences in postictal autonomic and arousal disorders and to determine the differential role that lifestyle factors have on breakthrough seizures and seizure types in GGE vs FE to effectively target SUDEP mechanisms and prevention.

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Section: Discussioncontrasting

confidence: 75%

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confidence: 99%

Genetic generalized and focal epilepsy prevalence in the North American SUDEP Registry

et al. 2020

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“…Seizure-related occurrence of cardiac arrhythmias was recently reported to be linked to periictal oxygen desaturation. 26 In our patient group, however, SpO 2 monitoring was unreliable and did not allow further subgroup analyses, which may have provided additional insight into the relationship between seizure-related hypoxemia and cardiac arrhythmias or release of circulating markers of cardiac injury. twofold increase at 6 hours.…”

Section: Limitationsmentioning

confidence: 83%

Blood markers of cardiac stress after generalized convulsive seizures

et al. 2019

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Summary Objective Generalized convulsive seizures (GCS) are associated with high demands on the cardiovascular system, thereby facilitating cardiac complications. To investigate occurrence, influencing factors, and extent of cardiac stress or injury, the alterations and time course of the latest generation of cardiac blood markers were investigated after documented GCS. Methods Adult patients with refractory epilepsy who underwent video–electroencephalography (EEG) monitoring along with simultaneous one‐lead electrocardiography (ECG) recordings were included. Cardiac biomarkers (cardiac troponin I [cTNI]; high‐sensitive troponin T [hsTNT]; N‐terminal prohormone of brain natriuretic peptide [NT‐proBNP]; copeptin; suppression of tumorigenicity‐2 [SST‐2]; growth differentiation factor 15, [GDF‐15]; soluble urokinase plasminogen activator receptor [suPAR]; and heart‐type fatty acid binding protein [HFABP]) and catecholamines were measured at inclusion and at different time points after GCS. Periictal cardiac properties were assessed by analyzing heart rate (HR), HR variability (HRV), and corrected QT intervals(QTc). Results Thirty‐six GCS (6 generalized‐onset tonic–clonic seizures and 30 focal to bilateral tonic–clonic seizures) were recorded in 30 patients without a history of cardiac or renal disease. Postictal catecholamine levels were elevated more than twofold. A concomitant increase in HR and QTc, as well as a decrease in HRV, was observed. Elevations of cTNI and hsTNT were found in 3 of 30 patients (10%) and 6 of 23 patients (26%), respectively, which were associated with higher dopamine levels. Copeptin was increased considerably after most GCS, whereas SST‐2, HFABP, and GDF‐15 displayed only subtle variations, and suPAR was unaltered in the postictal period. Cardiac symptoms did not occur in any patient. Significance The use of more sensitive biomarkers such as hsTNT suggests that signs of cardiac stress occur in about 25% of the patients with GCS without apparent clinical symptoms. SuPAR may indicate clinically relevant troponin elevations. Copeptin could help to diagnose GCS, but specificity needs to be tested.

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“…[5][6][7][8] Although seizure-related cardiac dysregulation has also been strongly implicated and surely plays an important role, in recorded cases of SUDEP occurring in epilepsy monitoring units, terminal respiratory arrest precedes terminal asystole. [10][11][12] Due to its role in modulation of breathing, arousal, and seizures, serotonin (5-hydroxytrypamine; 5-HT) has been implicated in the etiology of SUDEP. [10][11][12] Due to its role in modulation of breathing, arousal, and seizures, serotonin (5-hydroxytrypamine; 5-HT) has been implicated in the etiology of SUDEP.…”

Section: Introductionmentioning

confidence: 99%

“…9 Furthermore, cardiac effects have been shown to occur secondary to hypoxemia, or hypoxia. [10][11][12] Due to its role in modulation of breathing, arousal, and seizures, serotonin (5-hydroxytrypamine; 5-HT) has been implicated in the etiology of SUDEP. Patients with refractory epilepsy have a decreased risk for ictal hypoxemia if treated with selective serotonin reuptake inhibitors (SSRIs).…”

Section: Introductionmentioning

confidence: 99%

Effect of monoamine reuptake inhibition and α₁ blockade on respiratory arrest and death following electroshock‐induced seizures in mice

et al. 2019

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Summary Objective Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Although the mechanisms for SUDEP are incompletely understood, seizure‐induced respiratory arrest (S‐IRA) has been strongly and consistently implicated. A body of evidence indicates that serotonin (5‐HT), a modulator of breathing, plays a critical role in SUDEP. Because the 5‐HT and norepinephrine (NE) systems interact in many biologic processes and NE is known to modulate breathing and seizures, we hypothesized that NE may play a role in S‐IRA and SUDEP. Methods We examined the effects of pharmacologic manipulation of 5‐HT and NE on S‐IRA and death following maximal electroshock (MES)–induced seizures in adult wild‐type (WT) mice, genetically 5‐HT neuron–deficient (Lmx1bf/f/p) mice, and chemically NE neuron–deficient mice. Mice were treated with pharmacologic agents targeting the serotonergic and noradrenergic systems and subjected to seizure induction via MES while breathing was measured via whole‐body plethysmography. Results S‐IRA and death was reduced in WT mice with NE reuptake inhibitors (NRIs), reboxetine and atomoxetine, selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram, and the dual 5‐HT/NE reuptake inhibitor (SNRI), duloxetine. S‐IRA and death was also reduced in Lmx1bf/f/p mice with reboxetine and fluoxetine. The protective effects of the reuptake inhibitors were prevented by the α1 antagonist, prazosin. Citalopram did not reduce S‐IRA and death in NE neuron–deficient mice. Significance These data suggest that 5‐HT and NE critically interact in the modulation of breathing following a seizure and potentially inform preventive strategies for SUDEP.

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Potentially high‐risk cardiac arrhythmias with focal to bilateral tonic–clonic seizures and generalized tonic–clonic seizures are associated with the duration of periictal hypoxemia

Cited by 47 publications

References 24 publications

Genetic generalized and focal epilepsy prevalence in the North American SUDEP Registry

Genetic generalized and focal epilepsy prevalence in the North American SUDEP Registry

Blood markers of cardiac stress after generalized convulsive seizures

Effect of monoamine reuptake inhibition and α₁ blockade on respiratory arrest and death following electroshock‐induced seizures in mice

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Potentially high‐risk cardiac arrhythmias with focal to bilateral tonic–clonic seizures and generalized tonic–clonic seizures are associated with the duration of periictal hypoxemia

Cited by 47 publications

References 24 publications

Genetic generalized and focal epilepsy prevalence in the North American SUDEP Registry

Genetic generalized and focal epilepsy prevalence in the North American SUDEP Registry

Blood markers of cardiac stress after generalized convulsive seizures

Effect of monoamine reuptake inhibition and α1 blockade on respiratory arrest and death following electroshock‐induced seizures in mice

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Effect of monoamine reuptake inhibition and α₁ blockade on respiratory arrest and death following electroshock‐induced seizures in mice