Neuroimaging and clinical neurophysiology in cluster headache and trigeminal autonomic cephalalgias

Functional anatomy of headache: hypothalamus

“…The clinical manifestation of hemicrania continua overlaps with that of other trigeminal autonomic headaches and migraine, and activations observed in the hypothalamus and dorsal rostral pons, respectively, appear to play an important pathophysiological role. (1,2,(20)(21)(22)(23) Functional brain imaging has demonstrated significant activation of the ipsilateral dorsal rostral pons in association with the headache attacks of hemicrania continua. (20,21) There was also a significant activation of the contralateral posterior hypothalamus and ipsilateral ventrolateral midbrain, which extended over the red nucleus, the substantia nigra and the pontomedullary junction.…”

“…(24) Clinical use of deep brain stimulation (DBS) was based on the theory of posterior hypothalamic nucleus dysfunction as the cause of cluster headache attacks. (1,2,10,11,(20)(21)(22) In a recent publication Seijo and colleagues (24) implanted five patients with a tetrapolar electrode (always ipsilateral to the pain side) into the hypothalamus, using the stereotaxic coordinates of 4 mm lateral to the third ventricle wall, 2 mm behind the midintercommissural point and 5 mm under the intercommissural line. An improvement of the headache was obtained in all patients.…”

“…There is now compelling evidence that the hypothalamus exerts a major role in the mechanism of headache triggering. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) Pain and concomitant changes in the hormonal secretory pattern occur during an attack of headache when hypothalamic structures are involved. (5) For instance, the hypothalamus, especially in the posterior region, is activated during attacks of trigeminal autonomic headaches, such as cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), while during migraine attacks the activation occurs preponderantly in the brainstem (e.g., dorsal pontine region), but hypothalamic activation also occurs.…”

“…(5) For instance, the hypothalamus, especially in the posterior region, is activated during attacks of trigeminal autonomic headaches, such as cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), while during migraine attacks the activation occurs preponderantly in the brainstem (e.g., dorsal pontine region), but hypothalamic activation also occurs. (1,2) The hypothalamus and the adjacent brainstem form a complex interconnected structure responsible for the chronobiological features of some types of primary headache, especially sleep-related attacks, a characteristic feature of trigeminal autonomic headaches, hypnic headache and migraine. (12) The hypothalamus, through hormonal and autonomic regulation, controls a number of physiological functions, such as blood pressure, fluid and electrolyte balance, body temperature, and body weight, maintaining a fairly constant value known as the "set point".…”