Coverage from EHF 2019

The role of hypothalamus in cluster headache is well established. In his presentation at the 13th annual congress of the European Headache Federation, Prof. Arne May (University of Hamburg, Germany) gave an overview of the role of the hypothalamus in cluster headache and recent clinical research into the nature of hypothalamic involvement in migraine.

“Migraine is defined by the attack phase, however, the brain of migraineurs is also different from that of healthy controls outside of the attack.” 

– Arne May, University of Hamburg, Germany

Chronic headache and the hypothalamus

Prof. May started his presentation with an overview of the role of the hypothalamus in cluster headache. Trigeminal autonomic cephalgias (TAC), which include cluster headache and paroxysmal hemicrania, show a circadian and circannual rhythm of attack implicating the hypothalamus as a disease modulator. He continued by illustrating how hypothalamic activity is increased in chronic headache.1 Indeed, all TAC show hypothalamic activation in the acute headache phase. While alcohol and histamine provoke attacks, Prof. May indicated that this is only the case during active phases of the disease. He added that this observation could translate into optimised treatment. Medication scheduling could be tailored to coincide with active disease phases as a means to decrease treatment burden on patients. Prof. May concluded the first part of his presentation by indicating that the hypothalamus plays a crucial role in attack generation in cluster headache.

Migraine and the hypothalamus

Transitioning into hypothalamic involvement in migraine, Prof. May stressed that previously, only the brainstem was linked to migraine neurobiology. However, hypothalamic involvement in migraine was suspected since migraineurs experience premonitory symptoms.2,3 Initially demonstrated by Denuelle et al. in 2007,4 hypothalamic activity during migraine attacks was observed.5 Prof. May highlighted research from his laboratory in which episodic migraineurs, chronic migraineurs and healthy controls received painful ammonia stimulation alongside simultaneous recording of brain activity using magnetic resonance imaging (MRI).6 Increased activity of the posterior hypothalamus was observed during the acute pain stage of migraineurs, while increased activity in the anterior hypothalamus was observed during attack generation and chronification. This research into the distinct roles of subregions of the hypothalamus builds on earlier research in which altered connectivity between the hypothalamus and specific subregions of the brainstem (dorsal rostral pons and spinal trigeminal nuclei) was observed in the brain of a migraine patient in the 24 hours immediately preceding a migraine attack.7 Combined, these results suggest that while the brainstem may be the ‘migraine generator’, the hypothalamus may play the role of mediator in the pathophysiology of migraine.

Prof. May concluded that the different subregions of the hypothalamus play different roles in migraine – the anterior hypothalamus might be the driver of attacks, while the posterior hypothalamus is involved in acute migraine headache. Additionally, he indicated that beta-blockers, but not topiramate, may have an effect on hypothalamic control, which could, in turn, inform treatment decisions.


  1. May A, et al. Hypothalamic activation in cluster headache attacks. Lancet1998;352:275–278.
  2. Giffin NJ, et al. Premonitory symptoms in migraine – An electronic diary study. Neurology. 2003;60:935–940.
  3. Quintela E, et al. Premonitory and resolution symptoms in migraine: A prospective study in 100 unselected patients. Cephalalgia. 2006;26:1051–1060.
  4. Denuelle M, et al. Hypothalamic activation in spontaneous migraine attacks. Headache. 2007;47:1418-1426.
  5. Maniyar FH, et al. The premonitory phase of migraine – What can we learn from it? Headache. 2015;55:609–620.
  6. Schulte LH, et al. Hypothalamus as a mediator of chronic pain. Evidence from high resolution fMRI. Neurology. 2017;88:2011–2016.
  7. Schulte LH, et al. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139:1987–1993.