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Sudden unexpected death in epilepsy: Impact, mechanisms, and prevention

March 15, 2008|Cleveland Clinic Journal of Medicine
Lara Jehi, MD;Imad M. Najm, MD
Author and Disclosure Information

Lara Jehi, MD
Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH

Imad M. Najm, MD
Director, Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH

Correspondence: Imad Najm, MD, Director, Epilepsy Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, S51, Cleveland, OH 44195; najmi@ccf.org

Both authors reported that they have no financial relationships that pose a potential conflict of interest with this article.

ABSTRACT

Patients with refractory epilepsy face an elevated risk of sudden death, with rates as high as 1% per year. This phenomenon, known as sudden unexpected death in epilepsy (SUDEP), is believed to be a seizure-related occurrence, but the exact underlying mechanisms are uncertain. Both pulmonary and cardiac pathophysiologies have been proposed. The cardiac mechanism of greatest interest is the precipitation of arrhythmias by seizure discharges via the autonomic nervous system. SUDEP prevention has centered on effective seizure control, and epilepsy surgery has reduced SUDEP incidence in a number of studies. Additional prophylaxis methods are needed, however, for the large number of patients with treatment-refractory epilepsy. Future research should aim to clarify whether the association between seizures and autonomic dysfunction and cardiac arrhythmias extends to a demonstrable cardiac mechanism for SUDEP.

SUDEP PREVENTION

Epilepsy control is first line of defense

A careful consideration of the incidence of SUDEP in various patient populations suggests that controlling patients’ epilepsy might just be the best method of preventing SUDEP. While estimated SUDEP incidence ranges from 0.7 to 1.3 cases per 1,000 patient-years in population-based studies of patients with epilepsy,1,2 this rate escalates by nearly tenfold (3.5 to 9.3 cases per 1,000 patient-years) in cohorts with severe epilepsy, such as those derived from anticonvulsant drug registries, medical device registries, and referral centers.3–5 Therefore, medical control of seizures might reduce the incidence of SUDEP.

Epilepsy surgery cuts SUDEP risk for many patients

Studies involving epilepsy surgery programs also suggest that successful epilepsy surgery reduces the impending risks of SUDEP. In cohorts in which the estimated risk of SUDEP is almost 1% per year without surgery, SUDEP incidence was significantly lower following epilepsy surgery. In a study of 305 patients who underwent temporal lobe epilepsy surgery in the United Kingdom, the incidence of SUDEP following surgery was 2.2 cases per 1,000 person-years, and only one-third of SUDEP cases were among seizure-free patients.31 A similar incidence of 2.4 cases per 1,000 person-years was seen following epilepsy surgery in 596 Swedish patients; none of the 6 SUDEP patients in that study was seizure free.32 In a US study, no SUDEP cases occurred among 256 seizure-free patients with a follow-up of about 5 years after epilepsy surgery.33

In our own experience at the Cleveland Clinic, we have reported on outcomes among 70 patients who underwent frontal lobectomy34 and among 371 patients who underwent temporal lobectomy.35 In the frontal lobectomy study,34 2 of the 39 patients who had persistent seizures following surgery died of SUDEP during follow-up, whereas none of the 31 patients who remained seizure free were dead up to 10 years after surgery. In the temporal lobectomy report,35 2 of the 141 patients with ongoing postoperative seizures died of SUDEP, as compared with none of the 230 patients who were seizure free after a mean follow-up of 5.5 years.

Additional means of prophylaxis needed

Unfortunately, as many as 30% to 40% of patients with epilepsy continue to suffer intractable epilepsy despite all the available treatment modalities, including epilepsy surgery. For these patients, controlling seizures to reduce the risk of SUDEP is neither a possible nor a realistic means of avoiding this devastating condition, and alternative methods of prophylaxis must be sought.

CONCLUSIONS AND FUTURE RESEARCH

Patients with refractory epilepsy currently face a life­long risk of sudden death as high as 1% per year.3 Elucidating the mechanisms of SUDEP might lead to preventive measures, which could have significant implications in reducing mortality in this patient population. Abundant evidence exists that autonomic dysfunction and cardiac arrhythmias are associated with seizures. The missing links in establishing a cardiac mechanism for SUDEP now include the following: (1) evidence of cardiac arrhythmias generally observed in seizures as a risk factor for SUDEP, (2) determination of clear electrophysiologic characteristics—from EEG and ECG standpoints—of patients at risk for SUDEP, and (3) clarification of the role of cardiac mechanisms in SUDEP and the role that cerebral influences on autonomic function might play. Early identification of patients at risk of SUDEP would offer a unique opportunity for early intervention to prevent this devastating condition.

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