Information here always being updated
Hypothesized Pathophysiology of SUDEP
SUDEP likely occurs through multiple mechanisms. However, evidence suggests that a majority of patients have substantial respiratory dysfunction at the initial stages of the terminal event. The fact that many patients are found prone in bed suggests that this position plays a role in the pathophysiology. The prone position where the face may be covered by pillows or blankets likely predisposes to worsening ventilation and oxygenation during respiratory dysfunction. This position also suggests a loss of arousal by the patient, as they don’t sense the alarm of rising CO2 levels. Therefore, we suggest SUDEP may commonly occur by seizure induced hypoventilation and/or apnea with oxygen desaturation and loss of arousal, where being prone worsens oxygenation, resulting in secondary autonomic cardiac dysfunction and lethal bradyarrhthmias. Although yet to be found, genetic mutations may predispose epilepsy patients to worsening oxygen desaturation during seizures. Additionally, cardiac arrhythmias and dysfunction may be more likely to occur during periods of seizure induced oxygen desaturation in patients with congenital LQTS or other genetic mutations including ion channel mutations. Other causes of SUDEP may include primary cardiac arrhythmias from seizure activated autonomic pathways.
New Research out on SUDEP
Dlouhy et. al. Breathing inhibited when seizures spread to the amygdala and upon amygdala stimulation. The Journal of Neuroscience. Published July 15, 2015.
Summary of article: This study suggests that seizure spread to a normal functioning amygdala may result in the apnea/hypoventilation and O2 desaturation that is commonly observed in seizures (up to 33% of all seizures) and thought to play a role and may be the inciting factor in SUDEP. It also suggests that amygdala mediated apnea may not result in alarming or arousing the patient, even with very low oxygen levels. This loss of arousal and alarm may be the contributing factor in why SUDEP is "unexpected."
Hypothesized Pathway for SUDEP
We have proposed a hypothesized pathway for SUDEP based on multiple studies and reviews and our most recent research suggesting the amygdala is a site for inhibition of breathing during seizures:
Generalized tonic clonic seizure (GTCS) results in seizure spread to the amygdala. Inhibitory output pathways from the central nucleus inhibit the medullary respiratory centers and the midbrain ascending arousal system. This results in apnea and loss of arousal resulting in oxygen desaturation which could lead to lethal arrhythmias. Apnea and oxygen desaturation is common during seizures (from Nashef and Bateman). Therefore, multiple other factors are likely to play a role in the cardiorespiratory collapse in the post ictal period.
Sudden Unexpected Death in Epilepsy (SUDEP)
Copyright 2015 Brian J Dlouhy MD. All rights reserved.
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