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Brain Advance Access published online on December 5, 2005
Brain, doi:10.1093/brain/awh691
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 6, 2005
Revised August 31, 2005
Accepted October 20, 2005

Article

Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine

Arnaud Fumal 1 * {dagger}, Steven Laureys 2 {dagger}, Laura Di Clemente 3, Mélanie Boly 2, Valentin Bohotin 3, Michel Vandenheede 3, Gianluca Coppola 3, Eric Salmon 2, Ron Kupers 4, and Jean Schoenen 1

1 Department of Neurology, University of Liège, Liège, Belgium; Department of Neuroanatomy, University of Liège, Liège, Belgium
2 Department of Neurology, University of Liège, Liège, Belgium; Department of Cyclotron Research Center, University of Liège, Liège, Belgium
3 Department of Neurology, University of Liège, Liège, Belgium
4 Aarhus University and University Hospital of Aarhus, Center for Functionally Integrative Neuroscience (CFIN), Aarhus, Denmark

* To whom correspondence should be addressed.
Arnaud Fumal, E-mail: arnaud.fumal{at}ulg.ac.be


  Abstract

The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs with analgesic overuse before and 3 weeks after medication withdrawal and compared the data with those of a control population (n = 68). Before withdrawal, the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus, insula/ventral striatum and right inferior parietal lobule were hypometabolic, while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered to almost normal glucose uptake after withdrawal of analgesics, except the OFC where a further metabolic decrease was found. A subanalysis showed that most of the orbitofrontal hypometabolism was due to eight patients overusing combination analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache is thus associated with reversible metabolic changes in pain processing structures like other chronic pain disorders, but also with persistent orbitofrontal hypofunction. The latter is known to occur in drug dependence and could predispose subgroups of migraineurs to recurrent analgesic overuse.

Keywords: PET; orbitofrontal cortex; migraine; addiction; medication overuse headache.
{dagger}Both these authors contributed equally to this work.
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