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Cephalalgia. 2018 Apr;38(5):970-983. doi: 10.1177/0333102417716932. Epub 2017 Jul 5.

The pathophysiology of episodic cluster headache: Insights from recent neuroimaging research.

Yang FC1, Chou KH2,3, Kuo CY4, Lin YY2,5,6,7, Lin CP2,3,4,5, Wang SJ2,5,6,7.

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1 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
2 Brain Research Center, National Yang-Ming University, Taiwan.
3 Institute of Neuroscience, National Yang-Ming University, Taiwan.
4 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan.
5 Institute of Brain Science, National Yang-Ming University, Taiwan.
6 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
7 Neurological Institute, Taipei Veterans General Hospital, Taiwan.


Background Cluster headache is a disorder characterized by intermittent, severe unilateral head pain accompanied by cranial autonomic symptoms. Most cases of CH are episodic, manifesting as "in-bout" periods of frequent headache separated by month-to-year-long "out-of-bout" periods of remission. Previous imaging studies have implicated the hypothalamus and pain matrix in the pathogenesis of episodic CH. However, the pathophysiology driving the transition between in- and out-of-bout periods remains unclear. Methods The present study provides a narrative review of previous neuroimaging studies on the pathophysiology of episodic CH, addressing alterations in brain structures, metabolism, and structural and functional connectivity occurring between bout periods. Results Although the precise brain structures responsible for episodic CH are unknown, major roles are indicated for the posterior hypothalamus (especially in acute attacks), the pain neuromatrix with an emphasis on central descending pain modulation, and non-traditional pain processing networks including the occipital, cerebellar, and salience networks. These areas are potentially related to dynamic transitioning between in- and out-of-bout periods. Conclusion Recent progress in magnetic resonance imaging of episodic CH has provided additional insights into dynamic bout-associated structural and functional connectivity changes in the brain, especially in non-traditional pain processing network areas. These areas warrant future investigations as targets for neuromodulation in patients with CH.


Bout periods; diffusion tensor imaging; functional connectivity; magnetic resonance imaging; pain matrix; voxel-based morphometry

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