Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy

Cluster headache (CH) is characterized by severe unilateral orbital, supraorbital, and/or temporal pain associated with cranial ipsilateral parasympathetic activation and sympathetic deficit. Attacks last from 15 to 180 minutes, and there can be as many as eight per day. In episodic CH, attacks occur in clusters lasting 7 to 365 days separated by pain-free periods of >= 1 month. In chronic CH, affecting one-fifth of patients, attacks recur over > 1 year without remission periods or with remission periods lasting < 1 month. (1) The striking circadian rhythmicity of CH attacks has pointed to the hypothalamus as a strong candidate site for triggering the attack. Functional neuro-imaging studies performed using PET in patients with chronic CH during nitroglycerin-induced attacks showed increased blood flow in the ipsilateral hypothalamic gray matter. (2) Using a voxel-based morphometric (VBM) analysis of MRI, structural differences in gray matter density consistent with an increased volume have been detected bilaterally in the hypothalamus of patients with CH either in or outside a cluster. (3) Proton MR spectroscopy (H-1-MRS) allows the noninvasive and spatially resolved measurement of several brain compounds including N-acetylaspartate (NAA), a neuronal marker that is reduced when neuronal dysfunction or loss occurs. In this study, we used H-1-MRS to investigate whether biochemical abnormalities consistent with functional or structural changes are present in the hypothalamus of patients with CH.