Balancing Safety and Independence for People With Epilepsy Under Threat of SUDEP

Abstract

Clinical Risk Factors in SUDEP: A Nationwide Population-Based Case-Control Study

Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T. Neurology. 2020;94(4):e419-e429. doi:10.1212/WNL.0000000000008741 [published correction appears in Neurology. 2020;94(10):459].

Objective:

We conducted a nationwide case–control study in Sweden to test the hypothesis that specific clinical characteristics are associated with an increased risk of sudden unexpected death in epilepsy (SUDEP).

Methods:

The study included 255 SUDEP cases (definite and probable) and 1148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% CIs and interaction assessed by attributable proportion due to interaction (AP).

Results:

Experiencing generalized tonic–clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR: 26.81, 95% CI: 14.86-48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR: 1.15, 95% CI: 0.54-48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR: 15.31, 95% CI: 9.57-24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR: 5.01, 95% CI: 2.93-8.57), and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI: 29.66-151.88), with AP estimated at 0.69 (95% CI: 0.53-0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with an excess risk of SUDEP.

Conclusions:

Individuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

Commentary

People with epilepsy face the threat of seizure-related morbidity and mortality. Death directly resulting from seizures can occur by drowning, motor vehicle crashes, and by other means, but the most common cause is sudden unexpected death in epilepsy (SUDEP).¹ Sudden unexpected death in epilepsy is estimated to occur in a given year in 1:4500 children and 1:1000 adults living with epilepsy.² Physicians caring for people with epilepsy will almost certainly encounter at least one case of SUDEP in their career, an event that is heartbreaking for all involved. While SUDEP is not predictable on an individual basis, the primary risk factor is the presence of generalized tonic–clonic seizures (GTC), with risk increasing with rising GTC frequency.² Both SUDEP and near SUDEP have occurred under supervised circumstances, including in-group homes and epilepsy monitoring units, but most cases occur when the affected individual is unsupervised particularly at night.²

A new population-based study by Sveinsson et al of SUDEP in Sweden reinforces our current understanding of SUDEP risk factors.³ A total of 255 cases of definite or probable SUDEP from 2006 to 2011 were retrospectively identified from national patient registry data, with further diagnostic confirmation from review of death certificates, medical records, police records, and available documented interviews with family and eyewitnesses. The sample size, population-based design, and rigor of determination of SUDEP are strengths of this investigation. Age at death ranged from 4 to 92 years. Each case was balanced by 5 living sex-matched controls with epilepsy diagnosis confirmed by chart review. Cases and controls were overall similar in age, duration of epilepsy (mean of 24 years in SUDEP cases vs 20 years in controls), and epilepsy type (focal onset in 73% of cases and 69% of controls). The authors found SUDEP risk was strongly influenced by the presence of GTC seizures, but that this risk was significantly modified by living situation. A history of any GTC increased SUDEP risk 10 times, while a GTC in the prior year increased risk 27 times, and 4 to 10 GTC in the prior year increased it 32-fold. A history of 1 to 3 GTC in the prior year combined with living alone increased the risk 66 times, while sharing a bed lowered this risk to 16-fold elevation. The combination of 4 to 10 GTC in the last year and living alone increased the risk of SUDEP 82 times. However, those with frequent GTC who shared a bedroom were less likely to have SUDEP, with a 20-fold risk elevation. Nocturnal seizures that were not GTC were not associated with increased SUDEP risk. Furthermore, in the absence of a GTC in the prior year, having your own bedroom did not increase risk, while living alone increased it 4-fold. Treatment with both monotherapy and polytherapy antiseizure drugs or with vagus nerve stimulation reduced SUDEP risk by about 50% compared to no treatment.

Despite growing understanding of SUDEP risk, this is still a potential outcome of epilepsy that is often left unspoken. Physicians generally do not provide counseling about SUDEP, yet families who have lost a loved one to SUDEP express wishing this information had been shared.^4,5 Why are these conversations avoided? Many physicians report reluctance to cause unnecessary stress and anxiety given the relatively low frequency of SUDEP.⁵ Others may cite the challenge of limited time in clinic, with competing priorities that also need to be addressed. Let us acknowledge, however, the unspoken barrier that these conversations are simply hard. As physicians we have an obligation to educate our patients about epilepsy-associated health hazards and to recommend reasonable precautions to improve safety. However, efforts to minimize risk may run counter to the physician role of patient advocate in goals of independence and living well. Adults with epilepsy surveyed about their primary concerns impacting quality of life ranked driving and independence most important.⁶ The prioritization of independence reflects historical American values, values borne out in our housing, and sleeping practices. While in many cultures co-sleeping and multigenerational households are the norms, in the majority of US society, there is a common expectation for babies to sleep in their own cribs and children to have their own rooms. Entering adulthood is often marked by achieving independent housing and finances; those who fail to meet this expectation are pejoratively labeled as “boomerangs” with “failure to launch.” Compared to other safety issues reviewed in the epilepsy clinic, discussions about living and sleeping arrangements can be emotionally charged and uncomfortable, as they may directly touch on individual and family relationships as well as cultural, religious, and societal beliefs and taboos. Certainly, physicians caring for people with epilepsy can improve safety, including lowering SUDEP risk, by optimizing therapies for seizures with a goal of seizure freedom. Seizure monitoring devices may provide additional avenues for families and caregivers to be alerted to GTC without staying in the bedroom.² However, given the high stakes, providers need to have these difficult discussions on risks of GTC and SUDEP, so people with epilepsy can make informed decisions about their own life and living arrangements. Let’s keep the conversation going.

By Katherine Noe