The role of convulsive seizures in SUDEP

Nei, Maromi; Pickard, Allyson

doi:10.1016/j.autneu.2021.102856

Cited by 3 publications

(5 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…130 Physiological elevation of adenosine levels, which trigger non-rapid eye movement (NREM) sleep, 131,132 may also contribute to SUDEP by exerting an additive effect with seizure-induced release of adenosine, as SUDEP in PWE occurs most commonly during NREM sleep. 9,11,111,133,134 If the respiratory depression is too severe, it is proposed to induce apnea (see Purnell et al 108 for review), the terminal event in most observed human SUDEP cases. 9,10 In certain SUDEP models, sleep deprivation, which would tend to increase adenosine levels, also increases seizureinduced mortality.…”

Section: Adenosine Hypothesis Of Sudepmentioning

confidence: 99%

Section: Cardiac Versus Respiratory Mechanisms In Sudepmentioning

confidence: 99%

“…2,7,8 The landmark international MORTEMUS study 9 (Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units) documented the temporal sequence of cardiac and respiratory events of the witnessed SUDEP cases that occurred in epilepsy monitoring units and published a compilation of the terminal events that led to death in these cases. In most cases SUDEP occurred following generalized tonic-clonic (GTC) seizures, [9][10][11] although SUDEP has also been observed interictally. 12 Postictal generalized electroencephalographic suppression (PGES), observed in several SUDEP cases, is also proposed to be a contributing factor, but there is a lack of consensus on this.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A unified hypothesis ofSUDEP: Seizure‐induced respiratory depression induced by adenosine may lead toSUDEPbut 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

View full text Add to dashboard Cite

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.

show abstract

Section: Key Pointsmentioning

confidence: 99%

Section: Adenosine Hypothesis Of Sudepmentioning

confidence: 99%

Section: Cardiac Versus Respiratory Mechanisms In Sudepmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A unified hypothesis ofSUDEP: Seizure‐induced respiratory depression induced by adenosine may lead toSUDEPbut 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

View full text Add to dashboard Cite

show abstract

“…Generalized seizures, particularly uncontrolled ones, are important risk factors for SUDEP because they propagate trans-synaptically or by spreading depression and interrupt the brainstem functions that control cardiorespiratory activity and its connections to cortical, diencephalic, and spinal cord areas. This causes RA with subsequent cardiac failure, mechanisms that are proposed as the main cause of human SUDEP ( 122 , 124 ).…”

Section: Dba/2 Mice As Relevant Models Of Human Sudepmentioning

confidence: 99%

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

Bosco,

Guarnieri,

Leo

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic–clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic–clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed.

show abstract

Assessment of an under-mattress sensor as a seizure detection tool in an adult epilepsy monitoring unit

Nouboue¹,

Selfi²,

Diab³

et al. 2023

Seizure: European Journal of Epilepsy

View full text Add to dashboard Cite

The role of convulsive seizures in SUDEP

Cited by 3 publications

References 138 publications

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

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

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

Assessment of an under-mattress sensor as a seizure detection tool in an adult epilepsy monitoring unit

Contact Info

Product

Resources

About