Abstract
This last decade has seen remarkable progess made toward unraveling the mystery of primary headache disorders like migraine and cluster. The vascular theory has been superseded by recognition that neurovascular phenomena seem to be the permissive and triggering factors in migraine and cluster headache. This understanding has been achieved through new imaging modalities such as positron emission tomography and functional magnetic resonance imaging. Prior to these imaging techniques it was impossible to study the primary headache disorders because these had no structural basis. There is now an increasing body of evidence that the brain is involved primarily in cluster and migraine and that vessel dilatation is an epiphenomenon.
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References and Recommended Reading
Ekbom K: A clinical comparison of cluster headache and migraine. Acta Neurol Scand 1970, 41:1–48.
Ekbom K: Patterns of cluster headache with a note on the relations to angina pectoris and peptic ulcer. Acta Neurol Scand 1970, 46:225–237.
Kudrow L: The cyclic relationship of natural illumination to cluster period frequency. Cephalalgia 1987, 7(suppl 6):76–77.
Kudrow L, Kudrow DB: Association of sustained oxyhemoglobin desaturation and onset of cluster headache attacks. Headache 1994, 30:400–407.
May A, Bahra A, Buchel C, Frackowiak RSJ, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet 1998, 351:275–278. Showed the first direct proof of neurologic dysfunction in cluster headache.
Ekbom K: Nitroglycerin as a provocative agent in cluster headache. Arch Neurol 1968, 19:487–493.
Fanciullacci M, Alessandri M, Figini M, et al.: Increases in plasma calcitonin gene-related peptide from extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain 1995, 60:119–123. Demonstrates the difference in pain processing and the specificity of hypothalamic activation in cluster headache.
May A, Kaube H, Buechel C, et al.: Experimental cranial pain elicited by capsaicin: a PET study. Pain 1998, 74:61–66.
Jones AK, Friston K, Frackowiak RSJ: Localization of responses to pain in human cerebral cortex. Science 1992, 255:215–216.
Casey KL, Minoshima S, Berger KL, et al.: Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli. J Neurophysiol 1994, 71:802–807.
Rosen SD, Paulesu E, Frith CD, et al.: Central nervous system pathways mediating angina. Lancet 1994, 344:147–150.
Hseih JC, Hannerz J, Ingvar M: Right-lateralized central processing for pain of nitroglycerin-induced cluster headache. Pain 1996, 67:59–68.
Casey KL, Coghill RC, Talbot JD, et al.: Distributed procession of pain and vibration by the human brain. J Neurosci 1994, 14:4095–4108. Specificity of different brain structures is demonstrated as specific to primary headache disorders.
Goadsby PJ: Current concepts of the pathophysiology of migraine. Neurol Clin North Am 1997, 15:27–41. Demonstrates a difference in the structure of the hypothalamus specific to cluster headache patients.
S, Morrow TJ, Koeppe RA, Casey KL: Involvement of the insular cortex in central autonomic regulation during painful thermal stimulation J Cereb Blood Flow 1995, 15(suppl 1):859.
Bahra A, Matharu MS, Buchel C, et al.: Brainstem activation specific to migraine headache. Lancet 2001, 357:1016–1017.
May A, Ashburner J, Buchel C, et al.: Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nat Med 1999, 5:836–838.
Waldenlind E, Facchinetti F, Nappi G, et al.: Reduced testosterone levels in CH, a stress-related phenomenon? Cephalalgia 1996, 2:29–34.
Polleri A, Nappi G, Murialdo G, et al.: Changes in the 24-hour prolactin pattern in CH. Cephalalgia 1982, 2:1–7.
Waldenlind E, Gustafsson SA: Prolactin in CH, diurnal secretion, response to thyrotropin-releasing hormone and relation to sex steroids and gonadotropins. Cephalalgia 1987, 7:43–54.
Waldenlind E, Gustafsson SA, Ekbom K, Wetterberg L: Circadian secretion of cortisol and melatonin in cluster headache during active cluster period and remission J Neurol Neurosurg Psychiatry 1987, 50:207–213.
Leone M, D’Amico D, Moschiano F, et al.: Melatonin versus placebo in the prophylaxis of cluster headache, a doubleblind pilot study with parallel groups. Cephalalgia 1996, 16:494–496.
Leone M, Attansio A, Croci D, et al.: The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity. Cephalalgia 1997, 17:666–672. Single case report showing relief of cluster headache with the implantation of an electrode in the hypothalamus.
D’Andrea G, Cananzi AR, Morra M, et al.: Platelet catecholamines in cluster headache. J Neurol Neurosurg Psychiatry 1992, 55:308–309.
Laudon ME, Waldenlind E, Marcus C: Altered nocturnal lipolysis in cluster headache. A sign of central autonomic dysfunction? [abstract] Cephalalgia 2001, 21:498.
Leone M, Franzine A, D’amico D, et al.: Intractable chronic cluster headache relieved by electrode implant to posterior hypothalamus [abstract]. Cephalalgia 2001, 21:503.
Wheeler SD, Carrazana EJ: Topiramate-treated cluster headache. Neurology 1999, 53:234–236.
Di Piero V, Fiacco F, Tombari D, Pantano P: Tonic pain: a SPECT study in normal subjects and cluster headache patients. Pain 1997, 70:185–191.
Galeotti N, Ghelardini C, Zoppi M, et al.: Hypofunctionality of Gi proteins as aetiopathogenic mechanism for migraine and cluster headache. Cephalalgia 2001, 21:38–45.
Silberstein SD, Niknam R, Rozen TD, Young WB: Cluster headache with aura. Neurology 2000, 54:219–222.
Montagna P, Lodi R, Cortelli P, et al.: Phosphorous magnetic resonance spectroscopy in cluster headache. Neurology 1997, 48:113–118.
Graham JR: Cluster headache. Headache 1972, 11:175–185.
Lozza A, Schoenen J, Delwaide PJ: Inhibition of the blink reflex R2 component after supraorbital and index finger stimulation is reduced in cluster headache: an indication for both segmental and suprasegmental dysfunction. Pain 1997, 71:81–88.
Evers S, Bauer B, Suhr B, et al.: Cognitive processing is involved in cluster headache but not in chronic paroxysmal hemicrania. Neurology 1999, 53:357–363.
D’Amico D, Leone M, Moschiano F, Bussone G: Familial cluster headache: report of three families. Headache 1996, 36:41–43.
Sjaastad O, Shen JM, Stovner LJ, Elsas T: Cluster headache in identical twins. Headache 1993, 33:214–217.
Russell MB, Andersson PG, Thomsen LL, Iselius L: Cluster headache is an autosomal dominantly inherited disorder in some families: a complex segregation analysis. J Med Genet 1995, 32:954–956.
Leone M, Russell MB, Rigamonti A, et al.: Increased familial risk of cluster headache. Neurology 2001, 56:1233–1236.
D’ Amico D, Centonze V, Grazzi L, et al.: Coexistence of migraine and cluster headache: a report of 10 cases and possible pathogenetic implications. Headache 1997, 37:21–25.
Sjostrand C, Giedraitis V, Ekbom K, et al.: CACNA1A gene polymorphisms in cluster headache [abstract]. Cephalalgia 2001, 21:497.
Goadsby PJ, Edvinsson L: The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993, 33:48–56.
Goadsby PJ, Edvinsson L: Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 1988, 23:193–196.
Goadsby PJ, Edvinsson L: Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain 1994, 117:427–434.
Fanciullacci M, Alessandri M, Figini M, et al.: Increases in plasma calcitonin gene-related peptide from extracerebral circulation during nitroglycerin-induced cluster attack. Pain 1995, 60:119–123.
Treatment of acute cluster headache with sumatriptan. The Sumatriptan Cluster Headache study group [no authors listed]. N Engl J Med 1991, 325:322–326.
van Vilet JA, Bahra A, Martin V, et al.: Intranasal sumatriptan is effective in the treatment of acute cluster headache-a double-blind placebo-controlled study. Cephalalgia 2001, 21:270–271.
Kudrow L: The pathogenesis of cluster headache. Curr Opin Neurol 1994, 7:278–282.
Norris JW, Hachiniski VC, Cooper PW: Cerebral blood flow changes in cluster headache. Acta Neurol Scand 1976, 54:371–374.
Sakai P, Meyer JS: Regional cerebral hemodynamics during migraine and cluster headaches measured by the 133-Xe inhalation method. Headache 1978, 18:122–132.
Nelson RF, du Boulay GH, Marshall J, et al.: Cerebral blood flow studies in patients with cluster headache. Headache 1980, 20:184–189.
Henry PY, Vernhiet J, Orgoogozo JM, Caille JM: Cerebral blood flow in migraine and cluster headache. Compartmental analysis and reactivity to anaesthetic depression. Res Clin Stud Headache 1978, 6:81–88.
Krabbe AA, Henriksen L, Olesen J: Tomographic determination of cerebral blood flow during attacks of cluster headache. Cephalalgia 1984, 4:17–23.
Dahl A, Russell D, Nyberg-Hansen R, Rootwelt K: Cluster headache: transcranial doppler ultrasound and rCBF studies. Cephalalgia 1990, 10:87–94.
Tegeler CH, Davidai G, Gengo FM, et al.: Middle cerebral artery velocity correlates with nitroglycerin-induced headache onset. J Neuroimaging 1996, 6:81–86.
Harbedo JE: How cluster headache is explained as an intracavernous inflammatory process lesioning sympathetic fibres. Headache 1994, 34:125–131.
Hannerz J, Ericson K, Bergstrand G: Orbital phlebography in patients with cluster headache. Cephalalgia 1987, 7:207–211.
Bovin G, Jenssen G, Ericson K: Orbital phlebography: a comparison between cluster headache and other headaches. Headache 1992, 32:408–412.
Afra J, Proietti Cecchini A, Schoenen J: Craniometric measures in cluster headache patients. Cephalalgia 1998, 18:143–145.
Sjaastad O, Rinck P: Cluster headache: MRI studies of the cavernous sinus and the base of the brain. Headache 1990, 30:350–351.
Drummond PD, Anthony M: Extracranial vascular responses to sublingual nitroglycerin and oxygen inhalation in cluster headache patients. Headache 1985, 25:70–74.
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Aurora, S.K. Etiology and pathogenesis of cluster headache. Current Science Inc 6, 71–75 (2002). https://doi.org/10.1007/s11916-002-0027-4
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DOI: https://doi.org/10.1007/s11916-002-0027-4