Posterior hypothalamic activation in paroxysmal hemicrania

Ann Neurol. 2006 Mar;59(3):535-45. doi: 10.1002/ana.20763.


Objective: Paroxysmal hemicrania (PH) is a severe, strictly unilateral headache that lasts 2 to 30 minutes, occurs more than five times daily, is associated with trigeminal autonomic symptoms, and is exquisitely responsive to indomethacin. The purpose of the study was to determine the brain structures active in PH.

Methods: Seven PH patients were studied using positron emission tomography (PET). Each patient was scanned in three states: (1) acute PH attack-off indomethacin; (2) pain-free-off indomethacin; and (3) pain-free after administration of intramuscular indomethacin 100 mg. The scan images were processed and analyzed using SPM99.

Results: The study showed no significant activations during state 1 compared with state 2, but there was relative activation of the pain neuromatrix in both states 1 and 2 compared with state 3. This suggests that there is persistent activation of the pain neuromatrix during acute PH attacks and during interictal pain-free states off indomethacin that is deactivated by the administration of indomethacin. In addition, the untreated PH state was associated with significant activation of the contralateral posterior hypothalamus and contralateral ventral midbrain, which extended over the red nucleus and the substantia nigra.

Interpretation: These activated subcortical structures may play a pivotal role in the pathophysiology of this syndrome.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biophysical Phenomena
  • Biophysics
  • Brain Mapping
  • Female
  • Functional Laterality
  • Humans
  • Hypothalamus, Posterior / drug effects
  • Hypothalamus, Posterior / physiopathology*
  • Image Processing, Computer-Assisted / methods
  • Indomethacin / therapeutic use
  • Male
  • Middle Aged
  • Paroxysmal Hemicrania / drug therapy
  • Paroxysmal Hemicrania / pathology*
  • Positron-Emission Tomography / methods
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology*
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Indomethacin