New longitudinal study sheds light on the neurological consequences of narcolepsy with cataplexy. Childhood disease onset linked to faster cortical thinning.
Sleep scientists have long wondered about how narcolepsy progresses over time in the brain. Now a longitudinal study has recorded how structural changes manifest in the brain as people with narcolepsy age.
A team of researchers observed changes in 17 patients using MRI scans, in an about 5-year study looking at disease progression in narcolepsy patients’ brains, according to the journal Brain Imagining and Behavior.
The research showed that participants had widespread progressive cortical thinning in several areas, including in parts of the prefrontal cortex, responsible for executive functions, memory, cognition, and emotion. Structural abnormalities further extended to the hippocampus.
These findings were observed after two MRI [magnetic resonance imaging] scans were taken of each patient, one at the beginning of the study, followed by another five years later.
“We proved that there is disease progression,” says study coauthor Ho Sung Kim, PhD. “These patients had a great deal of cortical thinning.”
An assistant professor of neurology at the University of Southern California, Kim teamed up with collaborators at McGill University in Canada and Pusan National University in South Korea to execute the study.
It’s known that most people who have narcolepsy with cataplexy have a die-off of hypothalamic neurons. These neurons produce a neurotransmitter called hypocretin, associated with regulation of wakefulness and muscle tone. The lack of hypocretin (also known as orexin) results in lasting sleepiness and poor control of REM sleep. The sleep scientists in this latest study wanted to investigate if this could lead to other brain abnormalities.
The most surprising finding was that age of disease onset could have a large impact on how the disease manifests over time, says Kim.
Early age of onset led to a faster progression of cortical thinning and worse disease severity. This was seen in a subgroup of 9 participants, who experienced narcolepsy onset between the ages of 2 and 15 and had increased difficulty in getting and staying asleep during the night.
“We found that the patients who experienced early-onset in their childhood compared to those who had onset in their adulthood, they had actually faster cortical thinning compared to the other groups,” says Kim. “So if you actually start having this syndrome, your brain appears to be quickly, rapidly damaged.”
The study says that since these results are based on a small dataset, a more careful investigation of the underlying mechanism is needed. Further research could lead to better understanding of the biological mechanism behind early-onset and late-onset narcolepsy.
Kim says more research could eventually lead to more effective, individualized treatments for patients depending on their phenotype—and could lead to therapies to prevent progressive brain damage.
Lisa Spear is associate editor of Sleep Review.
Your study is based, I’m assuming on an early diagnosis of narcolepsy vs potential age at onset. How does one determine age of onset? I was officially diagnosed at age 45. I believe, however, that potential symptoms have been present since mid-teens, Would it be possible that the evaluation of my own potential symptoms as a teen be skewed now that a formal diagnosis has been obtained. Is there any way that a more accurate way to accurately determine age of onset?
This was a small study and I tend to doubt it. I was diagnosed with narcolepsy thirty five years ago, with symptoms onset as a child and a member of a cluster family with narcolepsy.
Due to other issues I have had about ten MRIs over the last four decades that were examined by top neurologists. None of them showed the type of damage indicated in this study.
Loss of hypocretin is a hypothesis that is touted as a definitive symptom of narcolepsy. It’s neither present in all people with narcolepsy nor specific to narcolepsy.
This leaves me with one question, does medication factor into this equation? If early onset is also equated with early treatment, is there a possibility that stimulant medication could cause said thinning?
Alternatively ….were the participants not on medications that controlled the condition? Perhaps lack of sleep or chaotic routines were the cause of the “thinning”
More questions than answers here.
Does this not include those without cataplexy?
I was wondering the same thing!
I was diagnosed with narcolepsy with cataplexy around 2011. I was around 41. However, symptoms were bothering me since my early 20s, and possibly teen years. My daddy had to retire from work, but could not get disability. Back then, they did not know what was wrong. He was actually diagnosed after I was. Was told that it was inherited. We recalled, his daddy, my grandfather, showing the same symptoms. I also want to stress that there is so much emphasis put on “sleep disorder ” For as long as I have suffered and watched my daddy suffer, I would like to say, it is so much more! Please tell me if anyone else is suffering from the following:
Of course extreme tiredness ALL the time, unless I take a Nuvigil. Slurred speech as if someone has drugged me. Feeling like something is squeezing my brain. Can not concentrate. Get confused. Depression, extreme depression. Blurred vision. Migraines. Can’t remember things. Just frustrated. Can’t take my Nuvigil every day due to heart condition
And let’s don’t even talk about the price. Can’t take the generic. I have had a couple of head traumas in early years. Seizures, and other neurological disorders run in family on both sides.
Just wanting to talk to someone going through the same thing other than having to worry my daddy.
I have N w/o C. If you are on Facebook there is a Group Page named Narcolepsy Support Group that I have found very beneficial. It includes people that have Narcolepsy with and without cataplexy, family members of diagnosed Narcoleptics, parents of minors diagnosed with Narcolepsy, etc. You can ask questions, vent, tell stories, etc. Your audience is people just like you and that sounds like exactly what you are looking for/need. Best wishes!
I’m interested to know, what kind of treatments did these patients receive during the 5 years between the baseline and follow up MRI?
Have you ever tried an opiate such as Codeine or Hydrocodone? I also have extreme difficulty taking stimulants. I have been switching back and forthe between the opiates for 25 years. Nothing has come close to working better for me. And I do not seem to have whatever it takes to get addicted to it. Only have tolorence problems.
I have been taking opiates for Narcolepsy for 25yrs ir more. It isn’t well known, YET that it works very well in controlling EDS and cataplexy.I would have had absolutely no life what so ever if it hadn’t been for my Dr who did the orginal research and prescribed them for me. I am way passed the point of needing an increase in dosage. With what is going on in addiction, My Dr is scared to do it. I don’t blame her. But I desperately want some kind of life back. I think it’s tragic that people could have some of their lives back and most don’t even know about it. I have never had problems with addiction or withdraws, it appears we are at very low risk for it because of the Narcolepsy.