Nocturnal Hypoxia and Sleep Apnea Associated With Late-Onset Epilepsy

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A recent study showed a significant association between sleep apnea, additional sleep characteristics, and late-onset epilepsy in older adults, even after adjusting for comorbidities.

Rebecca Gottesman, MD, PhD

(Credit: NINDS)

Rebecca Gottesman, MD, PhD

(Credit: NINDS)

A new study funded by the National Institutes of Health (NIH) demonstrated that sleep apnea and low oxygen levels during sleep were associated with late-onset epilepsy, independent of hypertension and other comorbidities. Published in Sleep, these findings may help clinicians to better understand the relationship between sleep disorders and late-onset epilepsy as well as assist them with identifying potential treatment targets for this patient population.1

In over 1300 participants, findings showed that those who had late-midlife oxygen desaturation that was less than 80% during sleep, also known nocturnal hypoxia, were associated with subsequent development of late-onset epilepsy, with an adjusted subhazard ratio of 3.28 (1.18-9.08). Overall, apnea-hypopnea index was not related. Notably, investigators observed that participant report of diagnosis of sleep apnea between 2011 and 2013 was also associated with subsequent late-onset epilepsy, demonstrated by adjusted subhazard ratio of 2.59 (1.24-5.39).

“There’s increasing evidence that late-onset epilepsy may be indicative of underlying vascular disease, or neurodegenerative disease, even potentially as a preclinical marker of neurodegenerative disease,” coauthor Rebecca Gottesman, MD, PhD, chief of the Stroke Branch at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), said in a statement.2 “Compared to other age groups, older adults have the highest incidence of new cases of epilepsy – up to half of which have no clear cause. Sleep apnea is common among people with epilepsy, but the association is not well understood.”

In this study, lead author Christopher Carosella, MD, assistant professor of neurology at Johns Hopkins University, and colleagues determined the relationship between sleep apnea and additional sleep characteristics and late-onset epilepsy, adjusting for comorbidities, using data from the large, prospective Atherosclerosis Risk in Communities (ARIC) Study cohort. Researchers used Medicare claims to identify cases of late-onset epilepsy among the participants from the ARIC study. Authors also used polysomnography data from 1309 of the ARIC participants who also participated in the Sleep Heart Health Study (NCT00005275) between 1995 and 1998, as well as demographic and comorbidity data from ARIC.

READ MORE: Mixed Topline Data Reported in Phase 3 RAISE Trial of Ganaxolone for Refractory Status Epilepticus

Top Clinical Takeaways

  • Late-midlife oxygen desaturation during sleep, rather than the apnea-hypopnea index, was associated with the subsequent development of late-onset epilepsy.
  • Self-reported diagnosis of sleep apnea in 2011-2013 was linked to an increased risk of developing late-onset epilepsy.
  • The findings suggest that sleep apnea and oxygen saturation levels during sleep are associated with late-onset epilepsy.

Investigators assessed later risk of late-onset epilepsy using survival analysis with a competing risk of death. In addition, researchers utilized a survival analysis of 2672 participants from ARIC to identify the association between self-reported obstructive sleep apnea between 2011 and 2013, and the risk of subsequent late-onset epilepsy.

Further findings revealed that the degree of hypoxia while patients were sleeping was associated with late-onset epilepsy. This link was noted as independent of other cooccurring medical issues and demographic factors by the investigators. This finding suggests that repeated chronic exposure to low oxygen levels overnight may lead to brain changes that can ultimately lead to the risk of epilepsy. Moreover, authors noted that they did not observe an association between the apnea-hypopnea index, which is known as a traditional measure for sleep apnea severity.

All told, the study couldn’t determine whether treating or preventing sleep apnea would reduce the risk of epilepsy, but the findings suggest that it may be an important potential target for reducing risk of late-onset epilepsy. Additionally, the results may also help clinicians identify patients at risk for other conditions since sleep apnea can have cardiovascular brain health-related effects, providing them a potential outlet for treatment and prevention. According to the authors, studies in the future need to assess whether treating sleep apnea in patients at risk for late-onset epilepsy can help prevent the onset of the disease.

“Discovering a reversible cause for the development of any type of idiopathic epilepsy is an aspirational goal for epilepsy researchers or clinician,” Carosella commented in a statement.2 “We hope this study might be a small first step in that direction and also an encouragement to evaluate and treat sleep disorders in patients with epilepsy.”

REFERENCES
1. Carosella CM, Gottesman RF, Kucharska-Newton A, et al. Sleep apnea, hypoxia, and late-onset epilepsy: the Atherosclerosis Risk in Communities study. Sleep. 2024;47(6):zsad233. doi:10.1093/sleep/zsad233
2. Low oxygen during sleep and sleep apnea linked to epilepsy in older adults. News Release. Published April 30, 2024. Accessed June 17, 2024. https://nih.gov/news-events/news-releases/low-oxygen-during-sleep-sleep-apnea-linked-epilepsy-older-adults
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