Semin Neurol 2010; 30(2): 175-185
DOI: 10.1055/s-0030-1249226
© Thieme Medical Publishers

Cluster Headache: Diagnosis and Treatment

Rashmi Halker1 , Bert Vargas1 , David W. Dodick1
  • 1Department of Neurology, Mayo Clinic Arizona, Phoenix, Arizona
Further Information

Publication History

Publication Date:
29 March 2010 (online)

ABSTRACT

Cluster headache is a rare yet exquisitely painful primary headache disorder occurring in either episodic or chronic patterns. The unique feature of cluster headache is the distinctive circadian and circannual periodicity in the episodic forms. The attacks are stereotypic—they are of extreme intensity and short duration, occur unilaterally, and are associated with robust signs and symptoms of autonomic dysfunction. Although the pathophysiology of cluster headache remains to be fully understood, there have been a number of recent seminal observations. To exclude structural mimics, patients presenting with symptoms suggestive of cluster headache warrant at least a brain magnetic resonance imaging (MRI) scan in their work-up. The medical treatment of cluster headache includes acute, transitional, and maintenance prophylaxis. Agents used for acute therapy include inhalation of oxygen, triptans, such as sumatriptan, and dihydroergotamine. Transitional prophylaxis refers to the short-term use of fast-acting agents. This typically involves either corticosteroids or an occipital nerve block. The mainstay of prophylactic therapy is verapamil. Yet, other medications, including lithium, divalproex sodium, topiramate, methysergide, gabapentin, and even indomethacin, may be useful when the headache fails to respond to verapamil. For medically refractory patients, surgical interventions, occipital nerve stimulation, and deep brain stimulation remain an option. As the sophistication of functional neuroimaging increases, better insight into the pathophysiological mechanisms that underlie cluster headache is expected.

REFERENCES

  • 1 Irimia P, Cittadini E, Paemeleire K, Cohen A S, Goadsby P J. Unilateral photophobia or phonophobia in migraine compared with trigeminal autonomic cephalalgias.  Cephalalgia. 2008;  28(6) 626-630
  • 2 Wilbrink L A, Ferrari M D, Kruit M C, Haan J. Neuroimaging in trigeminal autonomic cephalgias: when, how, and of what?.  Curr Opin Neurol. 2009;  22(3) 247-253
  • 3 Akerman S, Holland P R, Lasalandra M P, Goadsby P J. Oxygen inhibits neuronal activation in the trigeminocervical complex after stimulation of trigeminal autonomic reflex, but not during direct dural activation of trigeminal afferents.  Headache. 2009;  49(8) 1131-1143
  • 4 Ekbom K. The Sumatriptan Cluster Headache Study Group . Treatment of acute cluster headache with sumatriptan.  N Engl J Med. 1991;  325(5) 322-326
  • 5 Ekbom K, Krabbe A, Micieli G et al.. Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg).  Cephalalgia. 1995;  15 230-236
  • 6 Göbel H, Lindner V, Heinze A, Ribbat M, Deuschl G. Acute therapy for cluster headache with sumatriptan: findings of a one-year long-term study.  Neurology. 1998;  51(3) 908-911
  • 7 Hardebo J E, Dahlöf C. Sumatriptan nasal spray (20 mg/dose) in the acute treatment of cluster headache.  Cephalalgia. 1998;  18(7) 487-489
  • 8 van Vliet J A, Bahra A, Martin V et al.. Intranasal sumatriptan in cluster headache: randomized placebo-controlled double-blind study.  Neurology. 2003;  60(4) 630-633
  • 9 Bahra A, Gawel M J, Hardebo J E et al.. Oral zolmitriptan is effective in the acute treatment of cluster headache.  Neurology. 2000;  54(9) 1832-1839
  • 10 Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby P J. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study.  Arch Neurol. 2006;  63(11) 1537-1542
  • 11 Rapoport A M, Mathew N T, Silberstein S D et al.. Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study.  Neurology. 2007;  69(9) 821-826
  • 12 Kudrow L. Cluster Headache: Mechanisms and Management. Oxford/New York; Oxford University Press 1980
  • 13 May A, Leone M, Afra J EFNS Task Force et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias.  Eur J Neurol. 2006;  13(10) 1066-1077
  • 14 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(1-2) 92-96
  • 15 Antonaci F, Costa A, Candeloro E, Sjaastad O, Nappi G. Single high-dose steroid treatment in episodic cluster headache.  Cephalalgia. 2005;  25(4) 290-295
  • 16 Cianchetti C, Zuddas A, Marchei F. High dose intravenous methylprednisolone in cluster headache.  J Neurol Neurosurg Psychiatry. 1998;  64(3) 418
  • 17 Prusinski A, Kozubski W, Szulc-Kuberska J. Steroid treatment in the interruption of clusters in cluster headache.  Cephalalgia. 1987;  6 332-333
  • 18 Couch Jr J R, Ziegler D K. Prednisone therapy for cluster headache.  Headache. 1978;  18(4) 219-221
  • 19 Jammes J L. The treatment of cluster headaches with prednisone.  Dis Nerv Syst. 1975;  36(7) 375-376
  • 20 Leone M, D'Amico D, Attanasio A et al.. Verapamil is an effective prophylactic for cluster headache: results of a double-blind multicenter study versus placebo. In: Olesen J, Goadsby PJ Cluster Headache & Related Conditions. Oxford/New York; Oxford University Press 1999: 296-299
  • 21 Ekbom K. Lithium for cluster headache: review of the literature and preliminary results of long-term treatment.  Headache. 1981;  21(4) 132-139
  • 22 Bussone G, Leone M, Peccarisi C et al.. Double blind comparison of lithium and verapamil in cluster headache prophylaxis.  Headache. 1990;  30(7) 411-417
  • 23 Steiner T J, Hering R, Couturier E GM, Davies P T, Whitmarsh T E. Double-blind placebo-controlled trial of lithium in episodic cluster headache.  Cephalalgia. 1997;  17(6) 673-675
  • 24 Dodick D W, Rozen T D, Goadsby P J, Silberstein S D. Cluster headache.  Cephalalgia. 2000;  20(9) 787-803
  • 25 Storer R J, Akerman S, Shields K G, Goadsby P J. GABAA receptor modulation of trigeminovascular nociceptive neurotransmission by midazolam is antagonized by flumazenil.  Brain Res. 2004;  1013(2) 188-193
  • 26 Pascual J, Láinez M JA, Dodick D W, Hering-Hanit R. Antiepileptic drugs for the treatment of chronic and episodic cluster headache: a review.  Headache. 2007;  47(1) 81-89
  • 27 Storer R J, Goadsby P J. Trigeminovascular nociceptive transmission involves N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptors.  Neuroscience. 1999;  90(4) 1371-1376
  • 28 Mitsikostas D D, Sanchez del Rio M, Waeber C, Huang Z, Cutrer F M, Moskowitz M A. Non-NMDA glutamate receptors modulate capsaicin induced c-fos expression within trigeminal nucleus caudalis.  Br J Pharmacol. 1999;  127(3) 623-630
  • 29 Rogawski M A, Löscher W. The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions.  Nat Med. 2004;  10(7) 685-692
  • 30 Freitag F G, Diamond S, Diamond M L, Urban G, Peepr B. Divalproex sodium in the preventive treatment of cluster headache.  Headache. 2000;  40 408-411
  • 31 Gallagher R M, Mueller L L, Freitag F G. Divalproex sodium in the treatment of migraine and cluster headaches.  J Am Osteopath Assoc. 2002;  202 92-94
  • 32 Hering R, Kuritzky A. Sodium valproate in the treatment of cluster headache: an open clinical trial.  Cephalalgia. 1989;  9(3) 195-198
  • 33 Wheeler S D, Carrazana E J. Topiramate-treated cluster headache.  Neurology. 1999;  53(1) 234-236
  • 34 Cohen A S, Matharu M S, Goadsby P J. Trigeminal autonomic cephalalgias: current and future treatments.  Headache. 2007;  47(6) 969-980
  • 35 Pascual J, Láinez M J, Dodick D, Hering-Hanit R. Antiepileptic drugs for the treatment of chronic and episodic cluster headache: a review.  Headache. 2007;  47(1) 81-89
  • 36 Leandri M, Luzzani M, Cruccu G, Gottlieb A. Drug-resistant cluster headache responding to gabapentin: a pilot study.  Cephalalgia. 2001;  21(7) 744-746
  • 37 Schuh-Hofer S, Israel H, Neeb L, Reuter U, Arnold G. The use of gabapentin in chronic cluster headache patients refractory to first-line therapy.  Eur J Neurol. 2007;  14(6) 694-696
  • 38 Leone M, Lucini V, D'Amico D et al.. Twenty-four-hour melatonin and cortisol plasma levels in relation to timing of cluster headache.  Cephalalgia. 1995;  15(3) 224-229
  • 39 Leone M, D'Amico D, Moschiano F, Fraschini F, Bussone G. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups.  Cephalalgia. 1996;  16(7) 494-496
  • 40 Mather P J, Silberstein S D, Schulman E A, Hopkins M M. The treatment of cluster headache with repetitive intravenous dihydroergotamine.  Headache. 1991;  31(8) 525-532
  • 41 Diamond S, Freitag F G, Prager J, Gandhi S. Treatment of intractable cluster.  Headache. 1986;  26(1) 42-46
  • 42 Taha J M, Tew Jr J M. Long-term results of radiofrequency rhizotomy in the treatment of cluster headache.  Headache. 1995;  35(4) 193-196
  • 43 Ford R G, Ford K T, Swaid S, Young P, Jennelle R. Gamma knife treatment of refractory cluster headache.  Headache. 1998;  38 3-9
  • 44 McClelland III S, Tendulkar R D, Barnett G H, Neyman G, Suh J H. Long-term results of radiosurgery for refractory cluster headache.  Neurosurgery. 2006;  59(6) 1258-1262, discussion 1262–1263
  • 45 McClelland III S, Barnett G H, Neyman G, Suh J H. Repeat trigeminal nerve radiosurgery for refractory cluster headache fails to provide long-term pain relief.  Headache. 2007;  47(2) 298-300
  • 46 Onofrio B M, Campbell J K. Surgical treatment of chronic cluster headache.  Mayo Clin Proc. 1986;  61(7) 537-544
  • 47 Kirkpatrick P J, O'Brien M D, MacCabe J J. Trigeminal nerve section for chronic migrainous neuralgia.  Br J Neurosurg. 1993;  7(5) 483-490
  • 48 Weiner R L, Reed K L. Peripheral neurostimulation for control of intractable occipital neuralgia.  Neuromodulation. 1999;  2 217-221
  • 49 Schwedt T J, Dodick D W, Trentman T L, Zimmerman R S. Occipital nerve stimulation for chronic cluster headache and hemicrania continua: pain relief and persistence of autonomic features.  Cephalalgia. 2006;  26(8) 1025-1027
  • 50 Schwedt T J, Dodick D W, Hentz J, Trentman T L, Zimmerman R S. Occipital nerve stimulation for chronic headache—long-term safety and efficacy.  Cephalalgia. 2007;  27(2) 153-157
  • 51 Burns B, Watkins L, Goadsby P J. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients.  Lancet. 2007;  369(9567) 1099-1106
  • 52 Burns B, Watkins L, Goadsby P J. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients.  Neurology. 2009;  72(4) 341-345
  • 53 Bartsch T, Paemeleire K, Goadsby P J. Neurostimulation approaches to primary headache disorders.  Curr Opin Neurol. 2009;  22(3) 262-268
  • 54 Magis D, Allena M, Bolla M, De Pasqua V, Remacle J M, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study.  Lancet Neurol. 2007;  6(4) 314-321
  • 55 Matharu M S, Bartsch T, Ward N, Frackowiak R S, Weiner R, Goadsby P J. Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study.  Brain. 2004;  127(Pt 1) 220-230
  • 56 Goadsby P J, Bartsch T, Dodick D W. Occipital nerve stimulation for headache: mechanisms and efficacy.  Headache. 2008;  48(2) 313-318
  • 57 May A. Hypothalamic deep-brain stimulation: target and potential mechanism for the treatment of cluster headache.  Cephalalgia. 2008;  28(7) 799-803
  • 58 Leone M. Deep brain stimulation in headache.  Lancet Neurol. 2006;  5(10) 873-877
  • 59 Lanteri-Minet M, Fontaine D, Fabre N et al.. Refractory chronic cluster headache treated by deep brain stimulation: a French multicentric randomized placebo-controlled double-blind trial.  Neurology. 2009;  72(11, Suppl 3) A252

David W DodickM.D. 

Department of Neurology, Mayo Clinic Arizona

5777 East Mayo Blvd., Phoenix, AZ 85054

Email: dodick.david@mayo.edu

    >