SUDEP Risk in Pediatric Epilepsy Syndromes

Parents Seeking Answers Lead the Charge

One of the great fears of parents of young children with severe forms of epilepsy is the constant specter of premature death. Support and family groups for severe childhood onset epilepsies, such as those due to Dravet syndrome, dup15q syndrome, and others, have been instrumental in helping to bring sudden unexpected death in epilepsy (SUDEP) out into the open and have spearheaded calls for more research and disclosure of SUDEP risk by physicians.

Parents and caregivers who witness dozens of seizures a day in a child with intractable epilepsy may wonder if the next seizure may take her life and many literally lose sleep to keep her safe. However, despite this great concern, we do not have adequate information to help the families of children with severe genetic epilepsies understand their child’s risk for SUDEP and other causes of premature epilepsy-related mortality.

What We Know About SUDEP Risk in Children

Population-based estimates of SUDEP risk in children less than 18 years of age have suggested that the rate of SUDEP is between 2-4 per 10,000 patients per year. However, it appears that the greatest burden of premature death are in children with treatment-resistant epilepsy, often with co-existing neurocognitive deficits.

While a large proportion of that risk is likely due to the frequent seizures these people experience, there is also a concern that the specific cause of epilepsy, such a genetic defect, may increase the SUDEP risk beyond what is predicted by the severity and frequency of seizures.

For instance, animal models of Dravet syndrome with mutations in the SCN1A gene have demonstrated autonomic and cardiac dysfunction that are associated with lethal seizure related arrhythmias. However, demonstrating that these mechanisms add to SUDEP risk in people with these mutations is difficult. Because the rate of SUDEP in Dravet syndrome is not known, making comparisons to other severe childhood epilepsies without this genetic lesion impossible.

Recently, Cooper and colleagues performed a prospective cohort study of 100 consecutive people with Dravet syndrome enrolled in an epilepsy genetics study to obtain estimates of the SUDEP rate in this pediatric epilepsy syndrome. The authors found that:

• 87% had a SCN1A mutation and 17% died over the course 10 years of follow up
• 59% of the deaths were due to definite or probable SUDEP
• The estimated a SUDEP rate was 9.3 per 1000 patient-years (with a 95% confidence interval of 4.5-19.5)
• Half of the SUDEP deaths occurred before age 10

The study was limited by its relatively small size so the precision of the estimate is low. Also, it is unknown if this SUDEP rate is different than what has been reported in other people with severe refractory epilepsy where estimated SUDEP rates range from 3-9 per 1000 patient-years.

Larger studies will be need to determine if this particular syndrome or if specific genetic mutations are independent contributors to SUDEP risk through unique mechanisms. However, this study will help provide families and clinicians caring for people with Dravet syndrome with a better understanding of prognosis.