Primary Headache Disorders and Circadian Biology: A Clinical, Imaging, and Therapy Perspective

Primary headache syndromes such as hypnic headache, and trigeminal autonomic cephalgias (TACs) such as cluster headache, paroxysmal hemicrania, and SUNCT (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing), are associated with varying degrees with attacks that occur with circadian rhythmicity. In hypnic headache, the attacks occur exclusively during sleep, and in cluster headache the attacks predominate in sleep in 75% of patients. The TACs, especially cluster headache and SUNCT, have been associated on functional imaging with activation of the hypothalamus during attacks. There is also evidence in patients with cluster headache of altered secretory rhythms of a variety of hypophyseal hormone systems including melatonin, cortisol, and others. Given the role of the suprachiasmatic nucleus in the diurnal cycle, the hypothalamus is implicated as a generator of headaches with a prominent circadian rhythm. This article discusses the physiological and biochemical mechanisms that implicate the hypothalamus in the generation of a variety of primary headache disorders.