Serotoninergic Pathways in Sudden and Unexpted Death in Epilepsy (SUDEP)

Study Overview
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Brief Summary
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The mortality rate is increased in patients with epilepsy, and especially among patients with drug-resistant epilepsy. This increased mortality is mainly related to the risk of SUDEP whose incidence is between 3.5 and 9 per 1,000 for patients with drug-resistant epilepsy. The term SUDEP refers to a sudden death occurring in a patient with epilepsy in whom anamnestic and post-mortem evidence does not identify a particular cause. Experimental and clinical data strongly suggest that most of SUDEP result from a postictal respiratory dysfunction progressing to terminal apnea. Due to the major role of serotonin in regulating breathing rhythms and data in animal models of epilepsy, it is envisaged that an alteration of serotonergic systems of the brainstem and limbic regions may play a central role in the occurrence of SUDEP. The objective of this work is to look for abnormalities of the serotonergic transmission within regulatory regions of respiratory and autonomic functions in brain samples prospectively collected in patients died from SUDEP.

Official Title
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Serotoninergic Pathways in Sudden and Unexpted Death in Epilepsy (SUDEP)

Conditions
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Sudden Unexpected Death in Epilepsy (SUDEP)

Intervention / Treatment
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* Other: Brain samples
* Other: Skin samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Postmortem time before autopsy <30 hours Exclusion Criteria: Age <18 years postmortem time before autopsy > 30 hours Any subject whose brain would be of forensic interest Any patient who expressed an opposition to organ donation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| diagnostic of SUDEP<br>patient with epilepsy in whom anamnestic and post-mortem evidence does not identify a particular cause (diagnosis of SUDEP). Brain samples and skin samples are collected. | Other: Brain samples<br>* Collected in patients died<br>Other: Skin samples<br>* Collected in patients died<br>|
| Control 1<br>Subjects with a known epilepsy, whose death is linked to a specific cause. Brain samples and skin samples are collected. | Other: Brain samples<br>* Collected in patients died<br>Other: Skin samples<br>* Collected in patients died<br>|
| Control 2<br>Subjects without known pathological history, remained victims of unexplained sudden unexpected death (SUDEP) after all investigations and for which a heart rhythm disorder is suspected in first intention. Brain samples and skin samples are collected. | Other: Brain samples<br>* Collected in patients died<br>Other: Skin samples<br>* Collected in patients died<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Density of Medullary 5-HT Neurons | 5-HT1A receptor binding density in within the medulla | between 1 to 30 hours following death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other markers of 5HT within the medulla | Expression of 5HT-1A and 5HT-2 receptors, expression of 5HT transporter, Tryptophan Hydroxylase 2 (TPH2) | between 1 to 30 hours following death | 
| Serotoninergic pathway in the pons, the hippocampus and the insula | 5-HT1A receptor binding density, Expression of 5HT-1A and 5HT-2 receptors, expression of 5HT transporter, Tryptophan Hydroxylase 2 (TPH2) | between 1 to 30 hours following death | 
| Catecholaminergic pathway | Number of neurons expressing the tyrosine hydroxylase, expression of alpha and beta adrenergic receptors, expression of dopamine-bêta-hydroxylase | between 1 to 30 hours following death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, SUDEP, Serotonin