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Sudden Unexpected Death in Epilepsy (SUDEP), the commonest cause of death in epilepsy, is the most feared complication. SUDEP usually occurs following a seizure, most often in patients who are non-responsive to antiepileptic drugs. These patients are typically found dead in bed following respiratory apnea and cardiac arrest. Our group has shown that seizures in the brainstem are associated with cardiorespiratory failure and death. It is not known whether the fatal brainstem seizures impair the brainstem arousal system or if seizure directly impairs brainstem cardio-respiratory centres. It is also not clear what the underlying mechanisms are which could indicate rational treat strategies to prevent this frightening complication. In this project, we aim to understand (1) whether the brainstem pH- sensitive neurons for hypercapnia in SUDEP model are impaired, (2) the roles of chemotransmitters in the cardiorespiratory and central brainstem chemoreceptor regions in seizure spread into the brainstem and in cardio-respiratory arrest, (3) If pH correction or other modulations in the brainstem cardiorespiratory regions can inhibit brainstem seizure occurrence and prevent death.
Health care and social assistance
University of Toronto
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