Functional and structural neuroimaging in trigeminal autonomic cephalalgias

  • Manjit MatharuEmail author
  • Arne May


The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterized by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features. They include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing. Until recently, primary headache disorders, including the TACs, were widely considered to be caused by peripheral mechanisms such as vascular changes or neurogenic inflammation. Developments in neuroimaging are revolutionizing our understanding of the pathophysiology of primary headache syndromes. Functional imaging studies have demonstrated hypothalamic activation in all the TACs. Furthermore, neuroimaging studies using voxel-based morphometry and magnetic resonance spectroscopy techniques have demonstrated structural and biochemical alterations, respectively, in the hypothalamus of patients with cluster headache. These studies suggest that the hypothalamus plays a crucial role in the pathophysiology of TACs, thereby supporting the notion that these disorders are primarily due to central rather than peripheral mechanisms.


Cluster Headache Cavernous Sinus Primary Headache Disorder Paroxysmal Hemicrania Hypothalamic Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Recommended Reading

  1. 1.
    Headache Classification Committee of The International Headache Society: The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004, 24(Suppl 1):1–195.Google Scholar
  2. 2.
    May A, Kaube H, Buchel C, et al.: Experimental cranial pain elicited by capsaicin: a PET study. Pain 1998, 74:61–66.CrossRefPubMedGoogle Scholar
  3. 3.
    Kupers RC, Svensson P, Jensen TS: Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study. Pain 2004, 108:284–293.CrossRefPubMedGoogle Scholar
  4. 4.
    Peyron R, Laurent B, Garcia-Larrea L: Functional imaging of brain responses to pain. A review and meta-analysis. Neurophysiol Clin 2000, 30:263–288.CrossRefPubMedGoogle Scholar
  5. 5.
    Derbyshire SW: Exploring the pain “neuromatrix.” Curr Rev Pain 2000, 4:467–477.PubMedGoogle Scholar
  6. 6.
    Goadsby PJ, Duckworth JW: Locus coeruleus stimulation leads to reduction in regional cerebral blood flow in the cat. J Cereb Blood Flow Metab 1987, 7:S221.Google Scholar
  7. 7.
    May A, Buchel C, Turner R, Goadsby PJ: Magnetic resonance angiography in facial and other pain: neurovascular mechanisms of trigeminal sensation. J Cereb Blood Flow Metab 2001, 21:1171–1176.CrossRefPubMedGoogle Scholar
  8. 8.
    May A: Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005, 366:843–855.CrossRefPubMedGoogle Scholar
  9. 9.
    Matharu M, Goadsby P: Trigeminal autonomic cephalalgias: diagnosis and management. In Wolff’s Headache and Other Head Pain, edn 8. Edited by Silberstein S, Lipton R, Dodick D. New York: Oxford University Press; 2007:379–430.Google Scholar
  10. 10.
    Moskowitz MA: Cluster headache: evidence for a pathophysiologic focus in the superior pericarotid cavernous sinus plexus. Headache 1988, 28:584–586.CrossRefPubMedGoogle Scholar
  11. 11.
    Gawel MJ, Krajewski A, Luo YM, Ichise M: The cluster diathesis. Headache 1990, 30:652–655.CrossRefPubMedGoogle Scholar
  12. 12.
    Sianard-Gainko J, Milet J, Ghuysen V, Schoenen J: Increased parasellar activity on gallium SPECT is not specific for active cluster headache. Cephalalgia 1994, 14:132–133.PubMedGoogle Scholar
  13. 13.
    Schuh-Hofer S, Richter M, Israel H, et al.: The use of radiolabelled human serum albumin and SPECT/MRI coregistration to study inflammation in the cavernous sinus of cluster headache patients. Cephalalgia 2006, 26:1115–1122.CrossRefPubMedGoogle Scholar
  14. 14.
    Moore-Ede MC: The circadian timing system in mammals: two pacemakers preside over many secondary oscillators. Fed Proc 1983, 42:2802–2808.PubMedGoogle Scholar
  15. 15.
    Leone M, Bussone G: A review of hormonal findings in cluster headache. Evidence for hypothalamic involvement. Cephalalgia 1993, 13:309–317.CrossRefPubMedGoogle Scholar
  16. 16.
    Hsieh JC, Hannerz J, Ingvar M: Right-lateralised central processing for pain of cluster headache. Pain 1996, 67:59–68.CrossRefPubMedGoogle Scholar
  17. 17.
    May A, Bahra A, Buchel C, et al.: Hypothalamic activation in cluster headache attacks. Lancet 1998, 352:275–278.CrossRefPubMedGoogle Scholar
  18. 18.
    May A, Bahra A, Buchel C, et al.: PET and MRA findings in cluster headache and MRA in experimental pain. Neurology 2000, 55:1328–1335.PubMedGoogle Scholar
  19. 19.
    Weiller C, May A, Limmroth V, et al.: Brain stem activation in spontaneous human migraine attacks. Nat Med 1995, 1:658–660.CrossRefPubMedGoogle Scholar
  20. 20.
    Goadsby PJ: Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol 2002, 1:251–257.CrossRefPubMedGoogle Scholar
  21. 21.
    Sprenger T, Boecker H, Tolle TR, et al.: Specific hypothalamic activation during a spontaneous cluster headache attack. Neurology 2004, 62:516–517.PubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedGoogle Scholar
  23. 23.
    Wang SJ, Lirng JF, Fuh JL, Chen JJ: Reduction in hypothalamic 1H-MRS metabolite ratios in patients with cluster headache. J Neurol Neurosurg Psychiatry 2006, 77:622–625.CrossRefPubMedGoogle Scholar
  24. 24.
    Lodi R, Pierangeli G, Tonon C, et al.: Study of hypothalamic metabolism in cluster headache by proton MR spectroscopy. Neurology 2006, 66:1264–1266.CrossRefPubMedGoogle Scholar
  25. 25.
    Micieli G, Cavallini A, Facchinetti F, et al.: Chronic paroxysmal hemicrania: a chronobiological study (case report). Cephalalgia 1989, 9:281–286.CrossRefPubMedGoogle Scholar
  26. 26.
    Matharu MS, Cohen AS, Frackowiak RS, Goadsby PJ: Posterior hypothalamic activation in paroxysmal hemicrania. Ann Neurol 2006, 59:535–545.CrossRefPubMedGoogle Scholar
  27. 27.
    May A, Bahra A, Buchel C, et al.: Functional magnetic resonance imaging in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 1999, 46:791–794.CrossRefPubMedGoogle Scholar
  28. 28.
    Cohen A, Matharu M, Kalisch R, et al.: Functional MRI in SUNCT shows differential hypothalamic activation with increasing pain. Cephalalgia 2004, 24:1098–1099.CrossRefGoogle Scholar
  29. 29.
    Cohen AS: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. Cephalalgia 2007, 27:824–832.CrossRefPubMedGoogle Scholar
  30. 30.
    Sprenger T, Valet M, Platzer S, et al.: SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression. Pain 2005, 113:422–426.CrossRefPubMedGoogle Scholar
  31. 31.
    Sprenger T, Valet M, Hammes M, et al.: Hypothalamic activation in trigeminal autonomic cephalgia: functional imaging of an atypical case. Cephalalgia 2004, 24:753–757.CrossRefPubMedGoogle Scholar
  32. 32.
    Matharu M, Goadsby P: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome. In Chronic Daily Headache for Clinicians. Edited by Goadsby PJ, Silberstein SD, Dodick DW. London: Decker Inc.; 2005:89–103.Google Scholar
  33. 33.
    Goadsby PJ, Lipton RB: A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain 1997, 120:193–209.CrossRefPubMedGoogle Scholar
  34. 34.
    May A, Goadsby PJ: The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Metab 1999, 19:115–127.CrossRefPubMedGoogle Scholar
  35. 35.
    Goadsby PJ, Matharu MS, Boes CJ: SUNCT syndrome or trigeminal neuralgia with lacrimation. Cephalalgia 2001, 21:82–83.CrossRefPubMedGoogle Scholar
  36. 36.
    Malick A, Burstein R: Cells of origin of the trigeminohypothalamic tract in the rat. J Comp Neurol 1998, 400:125–144.CrossRefPubMedGoogle Scholar
  37. 37.
    Rainero I, Gallone S, Valfre W, et al.: A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache. Neurology 2004, 63:1286–1288.PubMedGoogle Scholar
  38. 38.
    Baumber L, Sjostrand C, Leone M, et al.: A genome-wide scan and HCRTR2 candidate gene analysis in a European cluster headache cohort. Neurology 2006, 66:1888–1893.CrossRefPubMedGoogle Scholar
  39. 39.
    Bartsch T, Levy MJ, Knight YE, Goadsby PJ: Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area. Pain 2004, 109:367–378.CrossRefPubMedGoogle Scholar
  40. 40.
    Holland PR, Akerman S, Goadsby PJ: Hypothalamic neuropeptides orexin A and B modulation of central and peripheral pathways in the pathophysiology of migraine. Cephalalgia 2005, 25:857.Google Scholar
  41. 41.
    Holland PR, Akerman S, Goadsby PJ: Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur J Neurosci 2006, 24:2825–2833.CrossRefPubMedGoogle Scholar
  42. 42.
    Bartsch T, Levy MJ, Knight YE, Goadsby PJ: Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus. Pain 2005, 117:30–39.CrossRefPubMedGoogle Scholar
  43. 43.
    Matharu MS, Levy MJ, Meeran K, Goadsby PJ: Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study. Ann Neurol 2004, 56:488–494.CrossRefPubMedGoogle Scholar
  44. 44.
    Sprenger T, Willoch F, Miederer M, et al.: Opioidergic changes in the pineal gland and hypothalamus in cluster headache: a ligand PET study. Neurology 2006, 66:1108–1110.CrossRefPubMedGoogle Scholar
  45. 45.
    Matharu MS: The hypothalamus, pain, and primary headaches. Headache 2007, 47:963–968.CrossRefGoogle Scholar
  46. 46.
    Leone M: Deep brain stimulation in headache. Lancet Neurol 2006, 5:873–877.CrossRefPubMedGoogle Scholar
  47. 47.
    Leone M, May A, Franzini A, et al.: Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection. Cephalalgia 2004, 24:934–937.CrossRefPubMedGoogle Scholar
  48. 48.
    May A, Leone M, Boecker H, et al.: Hypothalamic deep brain stimulation in positron emission tomography. J Neurosci 2006, 26:3589–3593.CrossRefPubMedGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Headache GroupInstitute of Neurology, Queen SquareLondonUK

Personalised recommendations