Hypothalamic activation in cluster headache attacks

Lancet. 1998 Jul 25;352(9124):275-8. doi: 10.1016/S0140-6736(98)02470-2.


Background: Cluster headache, one of the most severe pain syndromes in human beings, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly half-sided pain syndrome cannot be readily explained by the vascular hypothesis. We aimed to assess changes in regional cerebral blood flow (rCBF) in patients with cluster headache.

Methods: We used positron emission tomography (PET) to assess the changes in rCBF, as an index of synaptic activity, during nitroglycerin-induced cluster headache attacks in nine patients who had chronic cluster headache. Eight patients who had cluster headache but were not in the bout acted as a control group.

Findings: In the acute pain state, activation was seen in the ipsilateral inferior hypothalamic grey matter, the contralateral ventroposterior thalamus, the anterior cingulate cortex, and bilaterally in the insulae. Activation in the hypothalamus was seen solely in the pain state and was not seen in patients who have cluster headache but were out of the bout.

Interpretation: Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache. We suggest that a radical reappraisal of this type of headache is needed and that it should in general terms, be regarded as a neurovascular headache, to give equal weight to the pathological and physiological mechanisms that are at work.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cerebrovascular Circulation / physiology
  • Circadian Rhythm / physiology
  • Cluster Headache / diagnostic imaging
  • Cluster Headache / etiology
  • Cluster Headache / physiopathology*
  • Humans
  • Hypothalamus / diagnostic imaging
  • Hypothalamus / physiopathology*
  • Male
  • Nitroglycerin
  • Tomography, Emission-Computed
  • Vasodilator Agents


  • Vasodilator Agents
  • Nitroglycerin