Acute and chronic cardiorespiratory consequences of focal intrahippocampal administration of seizure-inducing agents. Implications for SUDEP

Lovick, T.A.; Jefferys, John G. R.

doi:10.1016/j.autneu.2021.102864

Cited by 5 publications

(3 citation statements)

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“…GTC seizures in PWE and animal models can lead to central and/or peripheral causes of hypoxemia, including, most prominently, central apnea, as well as obstructive apnea, pulmonary edema, and laryngospasm, which are also reported in PWE and animal models of SUDEP. 11,36,[50][51][52][53][54][55][56][57][58][59][60] Drugs that depress respiration, such as alcohol, may also contribute to SUDEP. 61 Spreading depolarization in the brainstem leading to cardiorespiratory collapse is proposed as a critical postictal event in certain genetic models of SUDEP, 31,62,63 which would trigger hypoxia.…”

Section: Key Pointsmentioning

confidence: 99%

Section: Cardiac Versus Respiratory Mechanisms In Sudepmentioning

confidence: 99%

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A unified hypothesis of SUDEP: Seizure‐induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

Faingold

Feng

2023

Epilepsia

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Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Adenosine released during seizures is proposed to be an important seizure termination mechanism. However, adenosine also depresses respiration, and this effect is mediated, in part, by inhibition of neuronal activity in subcortical structures that modulate respiration, including the periaqueductal gray (PAG). Drugs that enhance the action of adenosine increase postictal death in SUDEP models. Serotonin is also released during seizures, but enhances respiration in response to an elevated carbon dioxide level, which often occurs postictally. This effect of serotonin can potentially compensate, in part, for the adenosine‐mediated respiratory depression, acting to facilitate autoresuscitation and other restorative respiratory response mechanisms. A number of drugs that enhance the action of serotonin prevent postictal death in several SUDEP models and reduce postictal respiratory depression in PWE. This effect of serotonergic drugs may be mediated, in part, by actions on brainstem sites that modulate respiration, including the PAG. Enhanced activity in the PAG increases respiration in response to hypoxia and other exigent conditions and can be activated by electrical stimulation. Thus, we propose the unifying hypothesis that seizure‐induced adenosine release leads to respiratory depression. This can be reversed by serotonergic action on autoresuscitation and other restorative respiratory responses acting, in part, via the PAG. Therefore, we hypothesize that serotonergic or direct activation of this brainstem site may be a useful approach for SUDEP prevention.

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Section: Key Pointsmentioning

confidence: 99%

Section: Cardiac Versus Respiratory Mechanisms In Sudepmentioning

confidence: 99%

A unified hypothesis of SUDEP: Seizure‐induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

Faingold

Feng

2023

Epilepsia

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“…There is general consensus that there is cardiorespiratory dysfunction triggered by a convulsive seizure that leads to death. Although breathing [45,46 ▪ ] and other cardiorespiratory function can be profoundly affected by focal seizures [47], SUDEP is thought to occur more commonly following GCS. It is becoming apparent that there are likely to be different primary mechanisms for SUDEP in different given patients depending on their seizure type and semiology.…”

Section: Mechanisms For Sudden Unexpected Death In Epilepsymentioning

confidence: 99%

Sudden unexpected death in epilepsy

Buchanan

Maciel

Summerfield

2023

Current Opinion in Neurology

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Purpose of reviewSudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with epilepsy. This review highlights the recent literature regarding epidemiology on a global scale, putative mechanisms and thoughts towards intervention and prevention.Recent findingsRecently, numerous population-based studies have examined the incidence of SUDEP in many countries. Remarkably, incidence is quite consistent across these studies, and is commensurate with the recent estimates of about 1.2 per 1000 patient years. These studies further continue to support that incidence is similar across the ages and that comparable factors portend heightened risk for SUDEP. Fervent research in patients and animal studies continues to hone the understanding of potential mechanisms for SUDEP, especially those regarding seizure-induced respiratory dysregulation. Many of these studies and others have begun to lay out a path towards identification of improved treatment and prevention means. However, continued efforts are needed to educate medical professionals about SUDEP risk and the need to disclose this to patients.SummarySUDEP is a devastating potential outcome of epilepsy. More is continually learned about risk and mechanisms from clinical and preclinical studies. This knowledge can hopefully be leveraged into preventive measures in the near future.

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The Role of Ion Channel in Epilepsy Including SUDEP Cases

Akyuz,

Aslan

2024

Handbook of Neurodegenerative Disorders

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Acute and chronic cardiorespiratory consequences of focal intrahippocampal administration of seizure-inducing agents. Implications for SUDEP

Cited by 5 publications

References 100 publications

A unified hypothesis of SUDEP: Seizure‐induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

A unified hypothesis of SUDEP: Seizure‐induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray

Sudden unexpected death in epilepsy

The Role of Ion Channel in Epilepsy Including SUDEP Cases

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