Sudden unexpected death in epilepsy in patients treated with brain-responsive neurostimulation.

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brain stimulation; closed-loop; neuromodulation; partial seizures; sudden unexpected death in epilepsy; Adolescent; Adult; Aged; Brain/physiopathology; Death, Sudden/epidemiology; Death, Sudden/prevention & control; Electric Stimulation Therapy/methods; Electric Stimulation Therapy/mortality; Electric Stimulation Therapy/trends; Electrocorticography/trends; Epilepsy/mortality; Epilepsy/physiopathology; Female; Humans; Implantable Neurostimulators/trends; Male; Middle Aged; Young Adult


OBJECTIVE: To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System.

METHODS: All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP.

RESULTS: There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036 patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant years. Stored electrocorticograms around the time of death were available for 4 patients with probable/definite SUDEP and revealed the following: frequent epileptiform activity ending abruptly (n = 2), no epileptiform activity or seizures (n = 1), and an electrographic and witnessed seizure with cessation of postictal electrocorticography (ECoG) activity associated with apnea and pulselessness (n = 1).

SIGNIFICANCE: The SUDEP rate of 2.0/1000 patient stimulation years among patients treated with the RNS System is favorable relative to treatment-resistant epilepsy patients randomized to the placebo arm of add-on drug studies or with seizures after resective surgery. Our findings support that treatments that reduce seizures reduce SUDEP risk and that not all SUDEPs follow seizures.

Clinical Institute

Neurosciences (Brain & Spine)