Course of disease in cluster headache is reflected by distinct gray matter transformation

Objective: To identify gray matter changes in episodic and chronic cluster headache.

Background: Cluster headache (CH) is a rare primary headache disorder and usually follows a distinct course of disease with pain free episodes (outside bout) and periods with headache attacks attacks (inside bout). Some patients have no pain free episodes and are considered to have chronic CH (CCH). A pivotal role of the hypothalamus in the pathophysiology of CH was suggested, but data are controversial. The involvement of other parts of the pain network and especially changes in regard to different states of disease is hardly investigated.

Design/methods: We investigated 75 CH patients (22 episodic CH (ECH) inside bout, 35 ECH outside bout and 18 CCH) and 61 age and gender matched healthy controls using Voxel Based Morphometry (VBM).

Results: Patient recently suffered from CH attacks (CCH + ECH inside bout) showed the most prominent GM loss in major parts of the central pain network. In CCH additionally alterations in the anterior cingulate cortex (ACC), amygdala and secondary somatosensory cortex were observed. In ECH outside bout no gray matter changes were detected. Neither overall nor subgroup analysis did reveal any changes in the hypothalamic region.

Conclusions: Our findings showed a gray matter loss within the central pain network in CH, most pronounced in the chronic subtype but no changes in the hypothalamic area. Similar gray matter changes were observed in other chronic pain disorders. As there are no changes outside bout gray matter changes in CH are presumably reversible but longitudinal trials will be needed to confirm this hypothesis. The exclusive alteration of amygdale, S2 and ACC in chronic course of disease prompts at a role of these structures in chronification of CH. The role of the hypothalamus in CH has to be discussed again based on our results.