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). Adenosine released during seizures is proposed to be an important seizure termination mechanism. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. 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. Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Significance: These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.įeaturing the work of former CURE grantee Dr. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% CI 0.84-2.0), which was not significantly different from the general population. The duration of exposure to cenobamate for patients with SUDEP ranged from 130-620 days. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. Five cases of definite or probable SUDEP were identified, for a rate of 0. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic-clonic seizures. Results: A total of 2132 patients (n=2018 focal epilepsy n=114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. All-cause mortality and SUDEP rates were expressed per 1000 person-years. All deaths were evaluated by two epileptologists. Total person-years included all days a patient received cenobamate during completed studies or up to Jfor ongoing studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Methods: We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic-clonic, focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ?1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. Objective: We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program. To find out what’s actually causing that scientists are studying the complication in mice. Some begin breathing normally, but not all. What they’ve hypothesized is SUDEP patients can experience a lack of oxygen because of their severe seizures. And still, not much is known about it,” she said. But before that, not much is known about it. “About 15 years ago, we started to really start to fully understand. Powered by a $1.5 million NIH grant and a team of undergraduates, graduate students, and medical students, the study aims to make strides in an area that’s long been understudied. “She really inspired me to try to figure out ways she could help keep her daughter alive.” Kristina Simeone, lead investigator of the lab. “I do this work because I have a friend who has a daughter who is at high risk for SUDEP, and ten years ago when I met her,” said Dr. It’s something that hits home for the couple. Those with severe, uncontrolled seizures have a one in 150 chance of dying from this complication. It’s called Sudden Unexpected Death in Epilepsy or SUDEP. Their project at the Creighton University School of Medicine is investigating a fatal complication of epilepsy. Timothy SimeoneĪ husband-wife science duo is putting their brains together to study other brains. Featuring the work of CURE Epilepsy grantees Dr.
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