Rolf Fronczek, PhD, MD

“It's very interesting that there's a relationship between severe headache attacks, really severe headache attacks and sleep."

The exact connection between cluster headache and (REM)-sleep has never been fully clarified, however, recent work has demonstrated that the anterior part of the hypothalamus, the location of the biological clock, is enlarged during cluster headache.

To provide more insight into the association between cluster headaches and sleep, 

spoke with Rolf Fronczek, PhD, MD, Department of Neurology, Leiden University Medical Centre, Sleep-Wake Centre SEIN, 24

 Congress of the European Sleep Research Society in Basel, Switzerland.

Fronczek emphasized that clinicians need to be aware that sleep problems can be associated with cluster headaches and to follow-up with patients, and if necessary, refer them to a sleep specialist. A majority of patients with cluster headache, Fronczek added, suffer from insomnia.

The episodic and circadian nature of cluster headache, the association with sleep as well as neuroimaging data suggest a role between the hypothalamus and its biological clock, which still needs to be explored further.

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Recent work demonstrates that the anterior part of the hypothalamus is enlarged in cluster headache.

Rolf Fronczek, PhD, MD: Cluster Headaches and Sleep

“This could also have clinical implications not only for opiate users, maybe as an explanation for their addiction, but also for narcolepsy, maybe as a treatment.”

Rolf Fronczek, PhD, MD, Department of Neurology, Leiden University Medical Centre, Sleep-Wake Centre SEIN, sat with 

 Congress of the European Sleep Research Society in Basel, Switzerland, to discuss the connection between narcolepsy and opiates.

In a collaboration with researchers from UCLA, Fronczek and colleagues examined a number of hypocretin neurons in postmortem brains and found that some individuals presented with an unexpectedly large cell number increase. Looking back, researchers discovered that those patients were opiate addicts. Similar increases in hypocretin-producing cells were induced in a mouse model by administration of morphine.

With an interest in these findings, Fronczek and colleagues examined cases of individuals with narcolepsy from the Dutch Brain Bank. Similar to previous findings, researchers found that in 1 patient where hypocretin neurons were present, the individual did in fact use opiates and experienced an improvement in narcolepsy symptoms during the time period. There was about a 50% return of hypocretin neurons compared to a typical narcoleptic brain where there are hardly any neurons left.

The clinical implications of these findings may not only be relevant for opiate users, as an increased number of hypocretin-producing cells may play a role in maintaining opiate addiction, but also raises the question about a potential treatment option for narcolepsy.

Thannickal T, John J, Shan L, et al. Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy. 

The neurologist discussed an analysis of findings suggesting that opiate agonists may have a role in the treatment of narcolepsy.

Author | Rolf Fronczek, PhD, MD

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Rolf Fronczek, PhD, MD: Cluster Headaches and Sleep

Rolf Fronczek, PhD, MD: Narcolepsy and Opiates