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Chronic Migraine with Medication Overuse

Cephalalgia; ePub 2019 Mar 5; Lerebours, et al

An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse, a recent study found. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase. Researchers compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n=25) to age- and sex-matched patients with episodic migraine in the interictal phase (n=22). They also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. They found:

  • All patients with chronic migraine had medication overuse.
  • There was a significant connectivity between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these 2 regions were not connected in the episodic group.
  • The strength of connectivity was not correlated with pain intensity.
  • In the seed-to-voxel analysis, 3 regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei, the right dorsal anterior insula, and the right caudate.


Lerebours F, Boulanouar K, Barège M, et al. Functional connectivity of hypothalamus in chronic migraine with medication overuse. [Published online ahead of print March 5, 2019]. Cephalalgia. doi:10.1177%2F0333102419833087.


Schulte and May, in a seminal trial (Brain 2016: 139:1987–1993), obtained daily morning functional MRIs (fMRI) in a single subject who experienced three spontaneous episodic migraine attacks during that time. They reported increasing hypothalamic activity during the 24 hours prior to the next attack, increasing until the attack occurred. They also described altered functional coupling between the hypothalamus, the spinal trigeminal nuclei, and the dorsal rostral pons during the pre-ictal day and the pain phase of the migraine attacks and speculated that the real driver of attacks might be functional changes in hypothalamo–brainstem connectivity. Stankewitz et al. reported activity of spinal trigeminal nuclei activity increased as a new episodic migraine approached and the “distance to the next headache attack was predictable by the height of the signal intensities in the spinal nuclei.” (J Neurosci 2011;31:1937–1943). The current study extends this understanding of migraine pathophysiology, confirming hypothalamus-brainstem connectivity for more severe, chronic migraine with medication overuse, and raises the question of limbic involvement as well. —Stewart J. Tepper, MD, FAHS, Professor of Neurology, Geisel School of Medicine at Dartmouth, Director, Dartmouth Headache Center, Dartmouth-Hitchcock Medical Center, Lebanon