The Significance of Normal Mean Sleep Latency in Diagnosing Narcolepsy

Sleep onset is a complex, often ill-defined process that is often characterized by progressive modifications at the subjective, behavioral, cognitive, and physiological levels. Recent research shows that the neurophysiologic landscape of sleep onset has a complex pattern associated with a multitude of behavioral and physiological markers that are still largely understood.¹ A better understanding of the definition of sleep onset is needed for a greater conceptualization of the mechanisms underlying this process to influence the efficacy of current treatments for sleep disorders.

A recent systematic review and meta-analysis, published in Sleep Medicine, showed a longer average of mean sleep latency among healthy adults using a more updated later definition of sleep onset compared with a previous definition.² Among 110 cohorts, the average mean sleep latency was 11.7 min (95% CI, 10.8–12.6; 95% PI, 5.2–18.2) for the studies that used an earlier definition of sleep onset and 11.8 min (95% CI, 10.7–12.8; 95% PI, 7.2–16.3) for those evaluated using the later definition. Despite no significant associations between mean sleep latency and demographic or methodological variables, a negative association of −0.29 per one unit increase (95% CI, −0.55 to −0.04) was observed between mean sleep latency and apnea-hypopnea index on prior night polysomnography.

Recently, senior author Mark I. Boulos, MD, BSc, FRCP, CSCN, MSc, associate professor of medicine, division of neurology, Institute of Medical Science, University of Toronto, and staff neurologist for sleep and stroke disorders at Sunnybrook Health Sciences Center, sat down in an interview with NeurologyLive® to discuss the importance of understanding mean sleep latency when diagnosing sleep disorders like narcolepsy. He also talked about the role of the multiple sleep latency test (MSLT) plays in diagnosing narcolepsy, and the key criteria for this diagnosis. In addition, Boulos explained how the comprehensive meta-analysis contributes to the definition of normal mean sleep latency, and why the information is valuable for clinicians.

NeurologyLive: What were the main goals of the study and how did you go about achieving them?

Mark I. Boulos, MD, BSc, FRCP, CSCN, MSc: Normal values for sleep studies are very important to know about because as sleep specialists, when we send a patient to the sleep laboratory, we need to know what's normal and abnormal. We can then differentiate different disease states, and therefore make good treatment decisions for them. For the MSLT, only past smaller studies have looked at normal values for the mean sleep latency, which was the most important thing for the test.

The MSLT is for evaluating someone for narcolepsy or similar disorders. The test is a daytime sleep test where patients are asked to sleep at around 2-hour intervals. In the test, we find out how quickly they can fall asleep. They might be asked to fall asleep at like 9 AM, 11 AM, or at 1 PM, 3 PM, and so forth across 4 or 5 nap attempts to find out if they can fall asleep. We have them all wired up with the usual sleep study instruments to tell whether they've fallen asleep from a physiological point of view. Just as important, we also want to know if they do hit REM sleep.

The definition of narcolepsy is if you hit REM sleep on 2 or more of those naps or nap attempts, so this is very important for diagnosing narcolepsy. It's really one of the tried, tested, and true methods for diagnosing narcolepsy. How quickly someone falls asleep is also very important to know and can differentiate in pathological states. What's important to keep in mind is that before we do the MSLTs, we have the patients also do an overnight sleep study. They'll do an overnight sleep study and then the next day, they will do the MSLT.

The purpose of this study was to perform a larger and comprehensive meta-analysis on the mean sleep latency derived from the multiple sleep latency test involving more than 4000 people. We also wanted to look at the impact of things like age, sex, body mass index, other sleep metrics collected the night before. [We also wanted to look at] different methodological variables, such as sleep onset definitions, and sleep study features, as well as other markers the preceding overnight sleep study and see whether that affected performance on the mean sleep latency. We tried to be comprehensive to be able to elucidate and able to determine what would be a normal mean sleep latency.

What were the findings from the paper and the implications for patients?

We found, depending on the definition of sleep onset to use, that the normal sleep latency was about 11.7 or 11.8 minutes. How you define what sleep was, believe it or not, is still a debate in the literature. What is the onset of sleep? How do you define the onset of sleep, but that's more of a nitty gritty thing. This finding is pretty comparable with previous research. We're basically saying about 12 minutes would be the time while previous work showed maybe about 10:30plus or minus a few minutes, or 11:30, plus or minus a few minutes, depending on previous literature. I think our results are comparable within a minute or two with previous literature. It's good that all the literature is directed or extrapolated in the same direction. This will help clinicians down the line to tell what could potentially be pathological versus not pathological results on the sleep test.

Do you think there'll be more research about the definition and what should be used for studies going forward?

It's hard. I know the American Academy of Sleep Medicine provides guidelines for what they recommend for sleep onset and what the definition of sleep isn't. Frankly, our work shows that there isn't a major difference depending on the definition you use but it is good to have an international standard for how you define the onset of sleep.

What do you think are the next steps of research and what should be further investigated?

Yeah, there's a lot of exciting lines of avenues. We've published a norms paper in The Lancet Respiratory Medicine a few years ago, looking at normal sleep study, like overnight sleep study parameters. This was a daytime sleep study parameter with the MSLT. We're looking at other potentially other publications for other daytime tests, and other forms of sleep testing, that would be a good next future step of research. But also, how can we make diagnoses of narcolepsy earlier? A lot of that is education among patients, but even also among doctors too because unfortunately a lot of patients with narcolepsyare not diagnosed early. They suffer for many years with their diagnosis and people call them lazy or just unmotivated or depressed. Unfortunately, it calls for a larger picture. Now, we'd like to have earlier detection and treatment of patients with narcolepsy which probably goes for all sleep disorders. If someone has a sleep problem, they should try to get checked out right away, see their doctor and get evaluated right off the bat to improve quality of life overall.

Do you think there is a stigma associated with this sleep disorder?

Exactly, there is a stigma attached with narcolepsy because people are just sleeping so it seems like this person is lazy or they stayed up all day or they're not focused. But the truth is that it's a disease just like if someone walks into a room with a broken arm, we're not going to think less of them with a physical ailment. But with a physical ailment that manifests sleepiness is often misconstrued as being like something else, like lazy or unmotivated, or depressed or other. Or they use their time poorly, they stayed up all night, and so they can't stay up for class. The truth is, they just can't stay awake. It's truly a brain disorder and nothing of their choice.

Transcript edited for clarity.

REFERENCES
1. Biabani N, Birdseye A, Higgins S, et al. The neurophysiologic landscape of the sleep onset: a systematic review. J Thorac Dis. 2023;15(8):4530-4543. doi:10.21037/jtd-23-325
2. Iskander A, Jairam T, Wang C, Murray BJ, Boulos MI. Normal multiple sleep latency test values in adults: A systematic review and meta-analysis. Sleep Med. 2023;109:143-148. doi:10.1016/j.sleep.2023.06.019