Serotoninergic Pathways in Sudden and Unexpted Death in Epilepsy (SUDEP)
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| diagnostic of SUDEP 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
Collected in patients died
Other: Skin samples
Collected in patients died
|
| Control 1 Subjects with a known epilepsy, whose death is linked to a specific cause. Brain samples and skin samples are collected. |
Other: Brain samples
Collected in patients died
Other: Skin samples
Collected in patients died
|
| Control 2 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
Collected in patients died
Other: Skin samples
Collected in patients died
|
Outcome Measures
Primary Outcome Measures
- Density of Medullary 5-HT Neurons [between 1 to 30 hours following death]
5-HT1A receptor binding density in within the medulla
Secondary Outcome Measures
- Other markers of 5HT within the medulla [between 1 to 30 hours following death]
Expression of 5HT-1A and 5HT-2 receptors, expression of 5HT transporter, Tryptophan Hydroxylase 2 (TPH2)
- Serotoninergic pathway in the pons, the hippocampus and the insula [between 1 to 30 hours following death]
5-HT1A receptor binding density, Expression of 5HT-1A and 5HT-2 receptors, expression of 5HT transporter, Tryptophan Hydroxylase 2 (TPH2)
- Catecholaminergic pathway [between 1 to 30 hours following death]
Number of neurons expressing the tyrosine hydroxylase, expression of alpha and beta adrenergic receptors, expression of dopamine-bêta-hydroxylase
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospices Civils de Lyon - Institut Médico-Légal | Lyon | France | 69008 |
Sponsors and Collaborators
- Hospices Civils de Lyon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D50830