Understanding the Mechanisms of Pediatric Narcolepsy

Kiran Maski, MD, MPH

Although progress has been made in the scientific understanding of the less-than-common condition of pediatric narcolepsy, for Kiran Maski, MD, MPH, there is still a long way to go to complete the medical community’s knowledge of it.

Not only is delayed diagnosis an issue, but misdiagnosis is common for the disorder, with many of its symptoms—cataplexy and sleepiness, for example—causing clinicians to confuse it for other conditions such as depression or attention-deficit/hyperactivity disorder. In order to better address the diagnosis and treatment of pediatric narcolepsy, Maski pointed to a need for improved understanding of the condition as a whole.

The director of the sleep clinic and assistant professor of neurology at Harvard Medical School spoke with NeurologyLive in an interview to further discuss what has been learned about the condition in the last decade, as well as what questions remain unanswered.

NeurologyLive: What do we know now about pediatric narcolepsy that we did not 10 years ago?

Kiran Maski, MD, MPH: We’re still trying to understand the mechanisms that cause narcolepsy. We think of it as an autoimmune condition in type 1, where have been associations with specific viruses and specific vaccinations and specific bacteria like strep that precede narcolepsy onset. The majority of patients with narcolepsy type 1 are positive for a specific haplotype—the HLA DQB-0602 haplotype—and so we think there must be some interaction between these agents, such as sort of an environmental stressor and then a genetic propensity to have narcolepsy. It’s sort of a series of unfortunate events, if you will, that can cause it, but we’re still trying to tease apart all the details of that interaction. Narcolepsy type 2, which is considered a milder form of narcolepsy without catalepsy, we really don’t know what causes that at all.

In terms of the most recent information, we have there was a recent article published in Nature highlighting the role of these specific T cells—anti-hypocretin cells—which does that suggest there may be some role of innate immunity in the development of narcolepsy.

What other questions are unanswered in pediatric narcolepsy?

In terms of how our other medications are performing, there’s really no comparative effectiveness studies. In fact, even though the only medication that we have are stimulants, there is no randomized medication control trial or, really, any efficacy study done of these drugs for children with narcolepsy. This is really important because, essentially, we are using really high doses of stimulant medications, so we don’t know what the long-term cardiovascular effects of this are in this population. To me, that’s concerning, and I think parents are very concerned about addiction possibilities with the use of chronic stimulants. Essentially, this is life-long stimulant use, but fortunately, we don’t see high degrees of addiction or problematic behaviors related to stimulants in the narcolepsy population.

What’s the key message about managing narcolepsy for you?

In terms of managing narcolepsy, it’s to say that the treatments—meaning the drugs themselves—are not going to be 100% effective. There is always going to be a degree of symptom burden for patients, so management oftentimes includes a lot of behavioral supports. Having a nap schedule during the day is really helpful just to kind of dissipate that buildup of daytime sleepiness and providing accommodations in school—the ability to get up and walk around and come back, keep cool water by you, chew gum—they’re all really little things that I think practitioners can use to make a big difference.

Are there other sleep disorders common in pediatrics that clinicians should be aware of?

Probably the most common in children is insomnia, just the ability to fall asleep or maintain sleep. Somewhere between 20% to 25% of kids are going to experience insomnia at some point in their lives—probably more. Parasomnia, sleepwalking sleep talking kind of behaviors, at some point kids are going to experience that—it’s almost like an 80% prevalence. That’s the bread and butter of what you’ll see in a clinical setting.

Transcript edited for clarity.