Treating Sleep Disorders Can Improve Neurologic Outcomes

By Nancy Foldvary-Schaefer, DO, MS

Obstructive sleep apnea (OSA) is highly prevalent, affecting a reported 24 percent of U.S. men and 9 percent of U.S. women.1 As those rates are based on studies from the 1990s, when obesity rates were lower than current estimates, OSA prevalence today may be even higher.

The potential impact of OSA and other sleep disorders on patients with neurological disorders is becoming increasingly apparent. OSA has been observed to be highly prevalent in those with pharmacoresistant focal epilepsy, which suggests that ongoing untreated OSA may contribute to epilepsy pathophysiology.2 In a recent study of 130 adults with epilepsy unselected for sleep complaints, we found a 30 percent prevalence of OSA and a 16 percent prevalence of moderate to severe OSA.3

OSA therapy and seizures: What do we know?

Although several studies show that treatment of OSA with positive airway pressure (PAP) therapy or upper airway surgery improves seizure control in some cases, these studies are limited by small sample sizes.4,5 While not directly confirmed, sleep deprivation and fragmentation are proposed mechanisms for the seizure-promoting effects of OSA in epilepsy and the reduction in seizures observed with PAP therapy. Whether exposure to intermittent hypoxia, autonomic dysregulation and upregulation of systemic inflammation ‒ mechanisms by which OSA contributes to cardiovascular and metabolic disorders ‒ impacts epilepsy outcomes is unknown.

To shed light on this and related questions, our group recently sought to examine the effect of PAP therapy on seizure frequency in a large cohort of adults with epilepsy and suspected OSA referred for polysomnography.6

Our analysis at a glance

We undertook a retrospective review of adults with epilepsy who underwent polysomnography at Cleveland Clinic from 1997 to 2010.6 Patients were divided into three groups for comparison of seizure outcomes based on the presence/absence of OSA (apnea-hypopnea index [AHI] ≥ 5) and whether it was treated, as follows:

› Those without OSA (AHI < 5)

› Those with PAP-treated OSA

› Those with untreated OSA (intolerant of PAP or declined treatment)

Adherence to PAP therapy was defined as complete (≥ 4 hours/night for ≥ 70 percent of nights) or partial (lesser amounts of use). The following seizure measures were calculated for all groups:

› Percentage change in monthly seizure frequency from baseline to one-year follow-up (for all subjects)

› Percentage of subjects with ≥ 50 percent seizure reduction (“responder rate,” for subjects not seizure-free at baseline)

› Percentage of subjects with successful outcomes (≥ 50 percent total seizure reduction in patients not seizure-free at baseline, or continued seizure freedom in those seizure-free at baseline)

Results: Promising effects from PAP therapy

The analysis included 132 subjects (65 percent female) with a mean age of 40.2 ± 13 years. Among the overall sample, 76 patients (57.6 percent) had OSA; of these, 43 (56.6 percent) were on PAP therapy and 33 (43.4 percent) were untreated. Within the PAP-treated group, 83.7 percent of patients were fully adherent.

Subjects without OSA were significantly younger, were significantly more likely to be female and had significantly lower body mass index (BMI) compared with the two OSA groups. Age, gender and BMI did not differ between the PAP-treated OSA and untreated OSA groups.

Mean monthly baseline seizure frequency was 3.9 and did not differ significantly among the groups. The standardized antiepileptic drug dose change from baseline to follow-up, a measure of drug burden, was minimal and not significantly different among groups.

Key seizure outcomes6 were as follows:

-Seizure reductions at follow-up were significantly greater in the PAP-treated OSA group compared with the other groups.

-Among subjects not seizure-free at baseline, the responder rate was highest in the PAP-treated OSA group (73.9 percent), although the difference vs. the other groups reached statistical significance only compared with the untreated OSA group (14.3 percent; P < .001), not the group without OSA (40.5 percent) (Figure).

-In contrast, the successful outcomes rate (defined in above bullet list) was significantly higher in the PAP-treated group (83.7 percent) relative to both the untreated OSA group (39.4 percent; P < .001) and the group without OSA (53.6 percent; P= .003) (Figure).

Figure. Graph showing responder rate (i.e., percentage of subjects achieving ≥ 50 percent seizure reduction) and successful outcomes rate (i.e., percentage of subjects achieving ≥ 50 percent seizure reduction or maintaining seizure freedom if seizure-free at baseline) among the three patient groups (N = 132). The significance threshold for between-group comparisons was P < .017.

Seizure outcomes were not significantly different between subjects with mild vs. moderate to severe OSA, or between those with focal vs. generalized epilepsy.

Bolstered support for seizure control as an OSA treatment benefit

OSA is characterized by recurrent sleep-related respiratory events associated with arousal or oxygen desaturation. The result is typically a state of chronic sleep deprivation and a host of medical and psychosocial comorbidities. Although weight loss and lifestyle modification are central to OSA treatment, PAP therapy is first-line treatment for moderate to severe disease. PAP therapy eliminates respiratory events, arousals and oxygen desaturations, thereby reducing daytime sleepiness, cognitive impairment and blood pressure while also improving mood and metabolic and cardiovascular outcomes.7

Given that seizures are incompletely controlled in 30 to 40 percent of individuals with epilepsy, the need for a better understanding of the impact of sleep comorbidities in epilepsy is compelling.8 Taken together with prior investigations, our work supports adding seizure control to the list of beneficial effects of treating OSA and underscores the importance of routine OSA screening in epilepsy populations regardless of epilepsy type or seizure status.

Acknowledgments

The author thanks Darakul Pornsriniyom, MD; Hu won Kim, MD; James Bena, MS; Noah D. Andrews, RPSGT; and Douglas Moul, MD, MPH, for their contributions to this work.

Dr. Foldvary-Schaefer is Director of the Sleep Disorders Center and a staff physician in the Epilepsy Center in Cleveland Clinic’s Neurological Institute.

References

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5. Malow BA, Foldvary-Schaefer N, Vaughn BV, et al. Treating obstructive sleep apnea in adults with epilepsy: a randomized pilot trial. Neurology. 2008;71:572-577.
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