A pilot study has identified a potential link between obstructive sleep apnea and a higher risk of sudden unexpected death in epilepsy.
Erik St. Louis, MD
Findings of a small pilot study have identified a possible link between obstructive sleep apnea (OSA) and sudden unexpected death in epilepsy (SUDEP), suggesting that the identification and treatment of OSA in those with epilepsy could be a novel approach to risk prevention for SUDEP.
Ultimately, the study found a high frequency of probable OSA in those being monitored for epilepsy. These patients were found to be older and heavier, with higher screening symptoms for sleep apnea, more frequent focal seizures, and a longer epilepsy duration (P <.05 for all).
Conducted by a group of researchers including Erik K. St. Louis, MD, the chair of the Division of Sleep Neurology and an associate professor of neurology at Mayo Clinic in Rochester, Minnesota, the trial prospectively recruited 49 consecutive adult patients which were admitted to the Mayo Clinic Epilepsy Monitoring Unit. These patients all had either focal, generalized, or unclassified epilepsy syndromes. In total, 14 (28.6%) had treatment-resistant epilepsy.
"We are interested in the relationships between epilepsy and sleep, which seem to be reciprocal and bidirectional—the worse the sleep, the worse the seizures; the worse the seizures/epilepsy, the worse the sleep," St. Louis told NeurologyLive. "It has been known that OSA is a frequent comorbidity in adults and children with epilepsy, especially those with drug-resistant epilepsy, in comparison to other people of similar age and sex, and even those with other neurological conditions. OSA may worsen seizure control, sleep quality, and quality of life in epilepsy."
He added that OSA has been associated with sudden death in the general population, but the relationship between sudden unexpected death in epilepsy and OSA has not been previously explored, to his knowledge. "SUDEP is a tragic consequence of drug-resistant epilepsy in adults and children and has been known to be associated with central apnea, both during and following seizures," he said.
Of the 49 patients, 38% (n = 19) had probable OSA by either oximetry, SA‐SDQ, or STOP‐BAG (a slightly altered version of the STOP-BANG) sleep apnea questionnaire criteria. All told, 43 patients had analyzable oximetry, with a mean oxyhemoglobin desaturation index (ODI) of 4.65 ±5.7 (range, 0.1 to 22.8 ), and 35% (n = 15) having an ODI ≥5/h.
“Although all 19 subjects who screened positive were advised to pursue sleep medicine consultation and polysomnography, only 3 of 19 (15.8%) did so, and in these subjects, OSA was confirmed, with a mean apnea‐hypopnea index of 6.3/h,” St. Louis and his co-authors wrote.
Those with ODI ≥5/h had a higher Sleep Apnea—Sleep Disorders Questionnaire (SA‐SDQ) and STOP-BAG scores. As stated prior, they also tended to be older, and more likely to have focal epilepsy and at a longer duration. In particular, those with at ≥30 years of epilepsy had a significantly higher frequency of probable OSA, as identified by any measure compared with patients with epilepsy for <30 years (P <.05).
“Agreement between STOP ‐BAG and ODI for [probable OSA] diagnosis was fair (k = .39), whereas agreement between SA‐SDQ and ODI was moderate (k = .45). Agreement for probable OSA diagnosis was best between SA‐SDQ and STOP‐BAG measures (k = .66),” the authors noted.
The median Revised SUDEP Risk Inventory (rSUDEP-7) score was 3 ±1.4 (range, 0 to 6). A higher rSUDEP‐7 score was associated with a higher ODI value (Pearson’s r = .32; P = .036), and rSUDEP‐7 scores of >3 were also associated with a probable OSA diagnosis by ODI ≥5/h (univariate P = .036). Those with an rSUDEP‐7 score of ≥5 had a higher adjusted ODI compared with those with scores of <5 (P = .007), which endured as significantly associated with probable OSA when the authors adjusted for age, sex, calculated antiepileptic drug load, number of antiepileptic drugs at the time of the study, and body mass index (P = .03).
"We confirmed that: 1., OSA is a frequent comorbidity in those with drug-resistant epilepsy; 2., that the specific clinical characteristics of older age, heavier body weight, focal epilepsy syndrome diagnosis, and longer epilepsy duration may help identify those patients with epilepsy who also have comorbid OSA and may benefit from diagnosis and treatment; and 3., we learned that there appears to be an association between sleep apnea and possible SUDEP risk in drug-resistant epilepsy patients," St. Louis said.
Additionally, those with rSUDEP‐7 scores of ≥5 were more likely to have a diagnosis of OSA by all 3 measures combined (P = .006), as well as ODI (P = .01), STOP‐BAG (P = .04), and SA‐SDQ (P = .008), individually. St. Louis et. al. also found associations between rSUDEP‐7 scores ≥5 and patients having a probable OSA diagnosis by measures of oximetry, STOP‐BAG, and SA‐SDQ (P = .001).
Although there were no associations between rSUDE P‐7 score and age, sex, BMI, epilepsy type, nocturnal seizures, refractory epilepsy, or sleepiness, those who had a longer duration of epilepsy had higher rSUDEP‐7 scores (P = .008).
“Future larger confirmatory studies with combined video‐electroencephalography—polysomnography for more definitive identification of OSA, delineating its relationship to interictal and preictal hypoxia, hypercapnia, and autonomic function, are needed. Given the potential association between OSA, seizures, and SUDEP, patients with epilepsy should be screened and treated for OSA to reduce its impact on cardiorespiratory function and improve sleep consolidation,” St. Louis and colleagues concluded.
McCarter AR, Timm PC, Shepard PW, et al. Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy. Epilepsia. 2018;59(9):1-9. doi: 10.1111/epi.14548.