Drug‐resistant epilepsy and mortality—Why and when do neuromodulation and epilepsy surgery reduce overall mortality

Abstract

Patients with drug‐resistant epilepsy have an increased mortality rate, with the majority of deaths being epilepsy related and 40% due to sudden unexpected death in epilepsy (SUDEP). The impact of epilepsy surgery on mortality has been investigated since the 1970s, with increased interest in this field during the past 15 years. We systematically reviewed studies investigating mortality rate in patients undergoing epilepsy surgery or neuromodulation therapies. The quality of available evidence proved heterogenous and often limited by significant methodological issues. Perioperative mortality following epilepsy surgery was found to be <1%. Meta‐analysis of studies that directly compared patients who underwent surgery to those not operated following presurgical evaluation showed that the former have a two‐fold lower risk of death and a three‐fold lower risk of SUDEP compared to the latter (odds ratio [OR] 0.40, 95% confidence interval [CI]: 0.29–0.56; p < .0001 for overall mortality and OR 0.32, 95% CI: 0.18–0.57; p < .001 for SUDEP). Limited data are available regarding the risk of death and SUDEP in patients undergoing neuromodulation therapies, although some evidence indicates that vagus nerve stimulation might be associated with a lower risk of SUDEP. Several key questions remain to be addressed in future studies, considering the need to better inform patients about the long‐term benefit–risk ratio of epilepsy surgery. Dedicated long‐term prospective studies will thus be required to provide more personalized information on the impact of surgery and/or neuromodulation on the risk of death and SUDEP.

Cenobamate in refractory epilepsy: Overview of treatment options and practical considerations

“…A recent meta-analysis demonstrated that patients who underwent epilepsy surgery have a two-fold lower risk of death and a three-fold lower risk of SUDEP, but limited data are available for patients undergoing neuromodulation. 34…”

“…All options have specific advantages and drawbacks with regard to outcome and side effects and are typically used alongside ongoing and optimized ASM regimens. A recent meta‐analysis demonstrated that patients who underwent epilepsy surgery have a two‐fold lower risk of death and a three‐fold lower risk of SUDEP, but limited data are available for patients undergoing neuromodulation 34 …”

SUDEP counseling: Where do we stand?

“…48 Furthermore, neuromodulation through deep brain stimulation has also been associated with decreased SUDEP risk. 49 In addition to reducing seizure frequency, nocturnal supervision may be similarly helpful in modifying SUDEP risk. In epilepsy care centers, the centers with the lowest grade of nocturnal supervision had the highest incidence of SUDEP.…”

“…Vagus nerve stimulation should be considered in patients who are not resective candidates as it may independently reduce the risk of SUDEP, possibly via brainstem mechanisms 48 . Furthermore, neuromodulation through deep brain stimulation has also been associated with decreased SUDEP risk 49 . In addition to reducing seizure frequency, nocturnal supervision may be similarly helpful in modifying SUDEP risk.…”

Epilepsy surgery is not palliative

“…These are resection, ablation, and neuromodulation procedures intended to reduce seizure frequency or severity, but unlikely to cure the epilepsy or result in post‐operative discontinuation of all anti‐seizure medications. However, in many children and adults, surgeries that reduce seizures may provide considerable benefit, improving quality of life and cognitive function, and reducing the risk of sudden death or injury 1–3 . Furthermore, some patients who continue to have seizures after epilepsy surgery may become seizure‐free in a delayed fashion, or have extended periods of several months without seizures, allowing discontinuation of some concomitant treatments while limiting polypharmacy and the associated adverse effects 4 .…”