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.