Advances in the Treatment of Cluster Headache

Advances in the Treatment of Cluster Headache

Cohen Anna S, Goadsby Peter J
Published: European Neurological Review - Volume 3 - Issue I
download article

| More
dots

Cluster headache (CH) is one of the trigeminal autonomic cephalalgias (TACs), which are primary headache disorders characterised by unilateral head pain occurring in association with prominent ipsilateral cranial autonomic features, such as lacrimation, conjunctival injection or nasal symptoms.1,2 TACs include paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short-lasting unilateral neuralgiform headaches with cranial autonomic symptoms (SUNA). Whether hemicrania continua (HC) should be included is moot.3 Currently, TACs are grouped into section three of the revised International Classification of Headache Disorders (ICHD-III).4 TACs differ in attack duration and frequency, as well as response to therapy: CH has the longest attack duration and relatively low attack frequency; PH has intermediate duration and intermediate attack frequency; SUNCT has the shortest attack duration and the highest attack frequency; and HC is marked by continuous pain with exacerbations, which can include cranial autonomic symptoms as part of the phenotype. In this article, recent advances in CH will be set against the importance of first making the diagnosis and the distinction from other TACs, and then in terms of recent developments in therapy.

General Diagnostic Matters Concerning Trigeminal Autonomic Cephalalgias
Recently, some important diagnostic matters have arisen around TACs. These concerns include the clinical features at presentation, which greatly facilitate diagnosis, the investigation of the disorders and considerations that complicate the diagnosis.

The Attacks
At presentation the clinical features of the TACs are highly characteristic when typical (see Table 1). Large cohorts of patients with CH have been published,5,6 and we have supplemented this with our growing personal experience of more than 900 cases. Carefully characterised substantial cohorts are now available for PH7 and for SUNCT/SUNA.8 Drawing on this, material patterns have emerged, some of which run counter to the current International Headache Society (IHS) criteria4 in their detail. While these do not attempt to overturn the largest part of the criteria, they offer some clinical pointers. First, there is no typical form of pain in these syndromes: it may be throbbing, sharp or stabbing, and this may even vary from bout to bout and, indeed, between attacks. Second, while usually involving the ophthalmic division of the trigeminal nerve, the pain may also involve any part of the head and occasionally may not involve the ophthalmic division at all. Third, each of these syndromes produces what patients describe as severe pain, and for both CH and PH it is most commonly described as severe pain. CH patients whose diagnosis is safe will routinely describe the attack pain as their worst ever experience. Many PH patients say the same thing, and so do a number of SUNCT/ SUNA patients. The concept that pain character, distribution or severity exclusively defines these syndromes does not stand up in practice, so clinicians need to keep a broad view.

While attack frequency is a reasonable pointer to the diagnosis, there is considerable overlap. Although typical CH patients have one to two attacks a day, typical PH patients experience 10 and typical SUNCT/ SUNA patients suffer 50, there is a marked skew that favours a lower attack frequency in each of these conditions. Thus, having 20 CH attacks in a day is most exceptional, while having one to two PH attacks is less common but recognised.7 This fact suggests that, for example, clinicians need a low threshold for indomethacin testing in TACs. Another feature of attacks that is emerging in importance is the lateralisation of photophobia and phonophobia. In a cohort of consecutive patients, fewer than 5% of patients with unilateral migraine referred their photophobia or phonophobia to the side of the pain, whereas for TACs up to 10 times that proportion will say their photophobia or phonophobia, or both, is located ipsilateral to the pain.9 This can be a useful clinical pointer.

Interparoxysmal Pain and Allodynia in Trigeminal Autonomic Cephalalgias
While for HC it is clear that there is pain between attacks, this is now well recognised also in mainstream TACs. In a cohort of 52 patients with SUNCT/ SUNA, 22 had interparoxysmal pain.8 Most patients in that cohort who had interparoxysmal pain also had a personal or family history, or both, of migraine. Similarly, in a cohort of 31 PH patients, 18 had pain between attacks.7 This has been also been reported in smaller series10 and in 28 out of 84 patients in a retrospective series.11 Eight of the 18 in our series had medication overuse, and again the majority had a personal or family history, or both, of migraine. We have seen allodynia and hyperalgesia in each of the TACs, and again the largest group of affected patients have had migraine or a family history of migraine, or both. For CH, allodynia has been reported both to occur12 and not to be seen13 in small cohorts. Our belief is interparoxysmal pain and allodynia in TACs represent the co-existence of the TAC and migrainousness biology. The clinical importance is that one needs to be aware of these overlaps so as to identify the major presenting problem that requires treatment.

123next ›last »
References:
  1. Goadsby PJ, Lipton RB, A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic features, including new cases, Brain, 1997;120: 193–209.
  2. Goadsby PJ, Cohen AS, Matharu MS, Trigeminal autonomic cephalalgias – diagnosis and treatment, Curr Neurol Neurosci Rep, 2007;7:117–25.
  3. Goadsby PJ, Cittadini E, Burns B, Cohen AS, Trigeminal autonomic cephalalgias- diagnostic and therapeutic developments, Curr Neurol Neurosci Rep, 2007;7(2):117–25.
  4. Headache Classification Committee of The International Headache Society, The International Classification of Headache Disorders (second edition), Cephalalgia, 2004;24 (Suppl. 1): 1–160.
  5. Bahra A, May A, Goadsby PJ, Cluster headache: a prospective clinical study in 230 patients with diagnostic implications, Neurology, 2002;58:354–61.
  6. Torelli P, Cologno D, Cademartiri C, Manzoni GC, Application of the International Headache Society classification criteria in 652 cluster headache patients, Cephalalgia, 2001;21:145–50.
  7. Cittadini E, Matharu MS, Goadsby PJ, Paroxysmal hemicrania: a prospective clinical study of thirty-one cases, Brain, 2008;131 (Pt 4):1142–55.
  8. Cohen AS, Matharu MS, Goadsby PJ, Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival injection and Tearing (SUNCT) or cranial Autonomic features (SUNA). A prospective clinical study of SUNCT and SUNA, Brain, 2006; 129:2746–60.
  9. Irimia P, Cittadini E, Paemeleire K, et al., Unilateral photophobia or phonophobia in migraine compared with trigeminal autonomic cephalalgias, Cephalalgia, 2008;28: 626–30.
  10. Zidverc-Trajkovic J, Pavlovic A, Mijajlovic M, et al., Cluster headache and paroxysmal hemicrania: differential diagnosis, Cephalalgia, 2005;25:244–8.
  11. Antonaci F, Sjaastad O, Chronic paroxysmal hemicrania (CPH): a review of the clinical manifestations, Headache, 1989;29: 648–56.
  12. Ashkenazi A, Young WB, Dynamic mechanical (brush) allodynia in cluster headache, Headache, 2004;44:1010–12.
  13. Ladda J, Straube A, Forderreuther S, et al., Quantitative sensory testing in cluster headache: increased sensory thresholds, Cephalalgia, 2006;26:1043–50.
  14. Irimia P, Gallego-Perez Larraya J, Martinez-Vila E, Seasonal periodicity in SUNCT syndrome, Cephalalgia, 2008;28:94–6.
  15. Levy M, Matharu MS, Meeran K, et al., The clinical characteristics of headache in patients with pituitary tumours, Brain, 2005;128:1921–30.
  16. Cohen AS, Goadsby PJ, Functional neuroimaging of primary headache disorders, Expert Rev Neurother, 2006;6: 1159–72.
  17. Leone M, Partuno G, Vescovi A, Bussone G, Neuroendocrine dysfunction in cluster headache, Cephalalgia, 1990;10:235–9.
  18. Favier I, van Vliet JA, Roon KI, et al., Trigeminal autonomic cephalgias due to structural lesions: a review of 31 cases, Arch Neurol, 2007;64:25–31.
  19. Sjaastad O, Chronic paroxysmal hemicrania, hemicrania continua and SUNCT: the fate of the three first described cases, J Headache Pain, 2006;7:151–6.
  20. Matharu MS, Levy MJ, Merry RT, Goadsby PJ, SUNCT syndrome secondary to prolactinoma, J Neurol Neurosurg Psychiat, 2003; 74:1590–92.
  21. Levy MJ, Matharu MS, Goadsby PJ, Prolactinomas, dopamine agonist and headache: two case reports, Eur J Neurol, 2003;10: 169–74.
  22. Monstad I, Krabbe A, Micieli G, et al., Pre-emptive oral treatment with sumatriptan during a cluster period, Headache, 1995;35:607–13.
  23. Evers S, Bauer B, Suhr B, Ergotamine-induced headache associated with cluster headache, Neurology, 1996;46:291.
  24. Hering-Hanit R, Alteration in nature of cluster headache during subcutaneous administration of sumatriptan, Headache, 2000; 40:41–4.
  25. Gobel H, Lindner A, Heinze A, et al., Acute therapy for cluster headache with sumatriptan: findings of a one year long-term study, Neurology, 1998;51:908–11.
  26. Dousset V, Chrystome V, Ruiz B, et al., Does repeated subcutaneous administration of sumatriptan produce an unfavorable evolution in cluster headache?, J Headache Pain, 2004;5:110–14.
  27. Rossi P, Lorenzo GD, Formisano R, Buzzi MG, Subcutaneous sumatriptan induces changes in frequency pattern in cluster headache patients, Headache, 2004;44:713–18.
  28. Hardebo JE, Subcutaneous sumatriptan in cluster headache: A time study in the effect of pain and autonomic symptoms, Headache, 1993;33:18–21.
  29. Paemeleire K, Bahra A, Evers S, et al., Medication-overuse headache in cluster headache patients, Neurology, 2006; 67:109–13.
  30. Goadsby PJ, Is medication-overuse headache a distinct biological entity?, Nat Clin Pract Neurol, 2006;2:401.
  31. Bahra A, Walsh M, Menon S, Goadsby PJ, Does chronic daily headache arise de novo in association with regular analgesic use?, Headache, 2003;43:179–90.
  32. Wilkinson SM, Becker WJ, Heine JA, Opiate use to control bowel motility may induce chronic daily headache in patients with migraine, Headache, 2001;41:303–9.
  33. Sjaastad O, Bakketeig LS, Cluster headache prevalence. Vaga study of headache epidemiology, Cephalalgia, 2003;23:528–33.
  34. Evers S, Fischera M, May A, Berger K, Prevalence of cluster headache in Germany: results of the epidemiological DMKG study, J Neurol Neurosurg Psychiatry, 2007;78:1289–90.
  35. Ford HL, Gerry E, Johnson M, Williams R, A prospective study of the incidence, prevalence and mortality of multiple sclerosis in Leeds, J Neurol, 2002;249:260–65.
  36. Ekbom K, Monstad I, Prusinski A, et al., Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study, Acta Neurologica Scandinavica, 1993;88: 63–9.
  37. Ekbom K, The Sumatriptan Cluster Headache Study Group. Treatment of acute cluster headache with sumatriptan, New Eng J Med, 1991;325:322–6.
  38. Wendt J, Cady R, Singer R, et al., A randomized, double-blind, placebo-controlled trial of the efficacy and tolerability of a 4mg dose of subcutaneous sumatriptan for the treatment of acute migraine attacks in adults, Clin Ther, 2006;28:517–26.
  39. van Vliet JA, Bahra A, Martin V, et al., Intranasal sumatriptan in cluster headache – randomized placebo-controlled double-blind study, Neurology, 2003;60:630–33.
  40. Cittadini E, May A, Straube A, et al., Effectiveness of intranasal zolmitriptan in acute cluster headache. A randomized, placebocontrolled, double-blind crossover study, Arch Neurol, 2006;63: 1537–42.
  41. Rapoport AM, Mathew NT, Silberstein SD, et al., Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study, Neurology, 2007;69:821–6.
  42. Afridi SK, Shields KG, Bhola R, Goadsby PJ, Greater occipital nerve injection in primary headache syndromes – prolonged effects from a single injection, Pain, 2006;122:126–9.
  43. Ambrosini A, Vandenheede M, Rossi P, et al., Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study, Pain, 2005;118:92–6.
  44. Busch V, Jakob W, Juergens T, et al., Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink reflexes, Cephalalgia, 2006;26:50–55.
  45. Fogan L, Treatment of cluster headache: a double blind comparison of oxygen vs air inhalation, Arch Neurol, 1985; 42:362–3.
  46. Kudrow L, Response of cluster headache attacks to oxygen inhalation, Headache, 1981;21:1–4.
  47. Cohen AS, Matharu MS, Burns B, Goadsby PJ, Randomized double-blind, placebo-controlled trial of high-flow inhaled oxygen in acute cluster headache, Cephalalgia, 2007;27: 1188.
  48. Gabai IJ, Spierings ELH, Prophylactic treatment of cluster headache with verapamil, Headache, 1989;29:167–8.
  49. Leone M, D’Amico D, Frediani F, et al., Verapamil in the prophylaxis of episodic cluster headache: A double-blind study versus placebo, Neurology, 2000;54:1382–5.
  50. Bussone G, Leone M, Peccarisi C, et al., Double blind comparison of lithium and verapamil in cluster headache prophylaxis, Headache, 1990;30:411–17.
  51. Olesen J, Goadsby PJ, Cluster Headache and Related Conditions. In: Olesen J (ed.), Frontiers in Headache Research, vol. 9, Oxford: Oxford University Press, 1999.
  52. Silberstein SD, Pharmacological management of cluster headache, CNS Drugs, 1994;2:199–207.
  53. Singh BN, Nademanee K, Use of calcium antagonists for cardiac arrhythmias, Am J Cardiol, 1987;59:153B–162B.
  54. Naylor WG, Calcium Antagonists, London: Academic Press, 1988.
  55. Cohen AS, Matharu MS, Goadsby PJ, Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy, Neurology, 2007;69:668–75.
  56. Matharu MS, van Vliet JA, Ferrari M, et al., Verapamil-induced gingival enlargement in cluster headache, J Neurol Neurosurg Psychiat, 2005;76:124–7.
  57. Goadsby PJ, Schoenen J, Ferrari MD, et al., Towards a definition of intractable headache for use in clinical practice and trials, Cephalalgia, 2006;26:1168–70.
  58. Mathew NT, Hurt W, Percutaneous radiofrequency trigeminal gangliorhizolysis in intractable cluster headache, Headache, 1988;28:328–31.
  59. Kirkpatrick PJ, O’Brien M, MacCabe JJ, Trigeminal nerve section for chronic migrainous neuralgia, Br J Neurosurg, 1993;7: 483–90.
  60. Jarrar RG, Black DF, Dodick DW, Davis DH, Outcome of trigeminal nerve section in the treatment of chronic cluster headache, Neurology, 2003;60:1360–62.
  61. May A, Bahra A, Buchel C, et al., Hypothalamic activation in cluster headache attacks, Lancet, 1998;352:275–8.
  62. Leone M, Deep brain stimulation in headache, Lancet Neurol, 2006;5:873–7.
  63. Schoenen J, Di Clemente L, Vandenheede M, et al., Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action, Brain, 2005;128:940–47.
  64. Bartsch T, Goadsby PJ, Anatomy and physiology of pain referral in primary and cervicogenic headache disorders, Headache, 2005;2:42–8.
  65. Matharu MS, Bartsch T, Ward N, et al., Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study, Brain, 2004;127:220–30.
  66. Burns B, Watkins L, Goadsby PJ, Successful treatment of medically intractable cluster headache using occipital nerve stimulation (ONS), Lancet, 2007;369:1099–1106.
  67. Magis D, Allena M, Bolla M, et al., Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study, Lancet Neurol, 2007;6:314–21.
  68. Burns B, Watkins L, Goadsby PJ, Treatment of medically intractable cluster headache by occipital nerve stimulation: long term follow up 13 patients, Cephalalgia, 2007;27:1190.
  69. Goadsby PJ, Neurostimulation in primary headache syndromes, Expert Rev Neurother, 2007;7:1785–9.
  70. Cohen AS, Matharu MS, Goadsby PJ, Suggested guidelines for treating SUNCT and SUNA, Cephalalgia, 2005;25:1200.
  71. Cohen AS, Matharu MS, Goadsby PJ, Trigeminal autonomic cephalalgias: current and future treatments, Headache, 2007;47:969–80.

Copyright® 2012 Touch Group PLC. All rights reserved.
Touch Neurology is for informational purposes and should not be considered medical advice, diagnosis or treatment recommendations.