Deep Brain Stimulation for Medically Intractable Cluster Headache

  • Philip A. Starr
  • Andrew Ahn
Part of the Current Clinical Neurology book series (CCNEU)


Cluster headache (CH) is the most severe of the primary headache disorders. It affects approximately 1 in 1000 persons, and 20% of patients are significantly disabled in spite of optimal medical therapy (1). Peripheral nerve ablation procedures have been performed for CH, with little benefit. Positron emission tomography (PET) using H2 150 as the tracer has shown a focal increase in cerebral blood flow in the ipsilateral posterior hypothalamic region during a CH attack (2, 3). Based on this finding, in 2000 a promising new surgical procedure for severe CH was introduced in Milan, Italy: chronic deep brain stimulation (DBS) of the posterior hypothalamic region (4). Three open-label case series have been published, two from European centers and a third from our own (5, 6, 7). Additional scattered case reports are beginning to emerge (8, 9). In the three case series, most patients received major benefit, but approximately 25% of patients were nonresponders.

Many aspects of this novel therapy remain to be elucidated, including the actual proportion of patients who respond favorably, the degree and duration of response, presurgical predictors of outcome, the mechanism of action, the time course of onset and washout of the therapeutic effect, optimal programming parameters, and the the safety of the procedure. Currently, no commercial DBS device has U.S. or European regulatory approval for this emerging indication. This chapter reviews the relevant features of CH, surgical indications for DBS, surgical techniques, clinical outcomes, and possible mechanism of action.


cluster headache deep brain stimulation hypothalamus stereotactic neurosurgery 


  1. 1.
    Russell MB (2004) Epidemiology and genetics of cluster headaches. Lancet Neurol 3:279–283.PubMedCrossRefGoogle Scholar
  2. 2.
    May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ (1998) Hypothalamic activation in cluster headache attacks. Lancet 352(9124):275–278.PubMedCrossRefGoogle Scholar
  3. 3.
    May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ (2000) PET and MRA findings in cluster headache and MRA in experimental pain. Neurology 55:1328–1335.PubMedGoogle Scholar
  4. 4.
    Leone M, Franzini A, Bussone G (2001) Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. N Engl J Med 345:1428–1429.PubMedCrossRefGoogle Scholar
  5. 5.
    Leone M, Franzini A, Broggi G, Bussone G (2006) Hypothalamic stimulation for intractable cluster headache: long-term experience. Neurology 67(1):150–152.PubMedCrossRefGoogle Scholar
  6. 6.
    Schoenen J, DiClemente L, Vandenheede M, Fumal A, Pasqua VD, Mouchamps M, Remacle JM, Noordhout AMD (2005) Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain 128:940–947.PubMedCrossRefGoogle Scholar
  7. 7.
    Starr PA, Barbaro N, Raskin N, Ostrem JL (in press) Chronic stimulation of the posterior hypothalamic region for cluster headache: technique and one-year results in four patients. J Neurosurg.Google Scholar
  8. 8.
    Wilkinson SB, Dafer R, Overman J (2004) Posterior hypothalamic stimulation benefits intractable cluster headaches. In: American Society for Stereotactic and Functional Neurosurgery, Cleveland, OH.Google Scholar
  9. 9.
    Rasche D, Foethke D, Gliemroth J, Tronnier VM (2006) Deep brain stimulation in the posterior hypothalamus for chronic cluster headache Case report and review of the literature. Schmerz.Google Scholar
  10. 10.
    The International Headache Society (2004) The international classification of headache disorders. Cephalalgia 24(Suppl 1):44–46.Google Scholar
  11. 11.
    May A, Leone M (2003) Update on cluster headache. Curr Opin Neurol 16:333–340.PubMedCrossRefGoogle Scholar
  12. 12.
    May A (2005) Cluster headache: pathogenesis, diagnosis, and management. Lancet 366(9488):843–855.PubMedCrossRefGoogle Scholar
  13. 13.
    Manzoni GC, Micieli G, Granella F, Tassorelli C, Zanferrari C, Cavallini A (1991) Cluster headache—course over ten years in 189 patients. Cephalalgia 11(4):169–174.PubMedCrossRefGoogle Scholar
  14. 14.
    Jarrar RG, Black DF, Dodick DW, Davis DH (2003) Outcome of trigeminal nerve section in the treatment of chronic cluster headache. Neurology 60:1360–1362.PubMedCrossRefGoogle Scholar
  15. 15.
    Donnet A, Valade D, Regis J (2005) Gamma knife treatment for refractory cluster headache: prospective open trial. J Neurol Neurosurg Psychiatry 76:218–221.PubMedCrossRefGoogle Scholar
  16. 16.
    Matharu MS, Goadsby PJ (2002) Persistence of attacks of cluster headache after trigeminal nerve root section. Brain 125:976–984.PubMedCrossRefGoogle Scholar
  17. 17.
    Leone M, Franzini A, Broggi G, May A, Bussone G (2004) Long-term follow-up of bilateral hypothalamic stimulation for intractable cluster headache. Brain 127:2259–2264.PubMedCrossRefGoogle Scholar
  18. 18.
    May A, Ashburner J, Buchel C, McGonigle DJ, Friston KJ, Frackowiak RS, Goadsby PJ (1999) Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nature Med 5:836–838.PubMedCrossRefGoogle Scholar
  19. 19.
    Sprenger T, Boecker H, Tolle TR, Bussone G, May A, Leone M (2004) Specific hypothalamic activation during a spontaneous cluster headache attack. Neurology 62(3):516–517.PubMedGoogle Scholar
  20. 20.
    May A (2003) Headache: lessons learned from functional imaging. Brit Med Bull 65:223–234.PubMedCrossRefGoogle Scholar
  21. 21.
    May A, Bahra A, Buchel C, Turner R, Goadsby PJ (1999) Functional magnetic resonance imaging in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 46(5):791–794.PubMedCrossRefGoogle Scholar
  22. 22.
    Sprenger T, Valet M, Platzer S, Pfaffenrath V, Steude U, Tolle TR (2005) SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression. Pain 113(3):422–426.PubMedCrossRefGoogle Scholar
  23. 23.
    Sprenger T, Valet M, Hammes M, Erhard P, Berthele A, Conrad B, Tolle TR (2004) Hypothalamic activation in trigeminal autonomic cephalgia: functional imaging of an atypical case. Cephalalgia 24(9):753–757.PubMedCrossRefGoogle Scholar
  24. 24.
    Leone M, May A, Franzini A, Broggi G, Dodick D, Rapoport A, Goadsby PJ, Schoenen J, Bonavita V, Bussone G (2004) Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection. Cephalalgia 24(11):934–937.PubMedCrossRefGoogle Scholar
  25. 25.
    Starr PA (2003) Placement of deep brain stimulators into the subthalamic nucleus or globus pallidus internus: technical approach. Stereotact Funct Neurosurg 79:118–145.CrossRefGoogle Scholar
  26. 26.
    Franzini A, Ferroli P, Leone M, Broggi G (2003) Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: First reported series. Neurosurgery 52:1095–1101.PubMedCrossRefGoogle Scholar
  27. 27.
    Schaltenbrand G, Wahren W (1977) Introduction to stereotaxis with an atlas of the human brain. Stuttgart: Georg Thieme.Google Scholar
  28. 28.
    Swaab DF (2003) The human hypothalamus: basic and clinical aspects, Part I. Amsterdam: Elsevier.Google Scholar
  29. 29.
    Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Stuttgart: Thieme.Google Scholar
  30. 30.
  31. 31.
    Rezai AR, Phillips M, Baker KB, Sharan AD, Nyenhuis J, Tkach J, Henderson J, Shellock FG (2004) Neurostimulation system used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations. Invest Radiol 39(5):300–303.PubMedCrossRefGoogle Scholar
  32. 32.
    Franzini A, Ferroli P, Leone M, Bussone G, Broggi G (2004) Hypothalamic deep brain stimulation for the treatment of chronic cluster headaches: A series report. Neuromodulation 7:1–8.CrossRefGoogle Scholar
  33. 33.
    May A, Leone M, Boecker H, Sprenger T, Juergens T, Bussone G, Tolle TR (2006) Hypothalamic deep brain stimulation in positron emission tomography. J Neurosci 26(13):3589–3593.PubMedCrossRefGoogle Scholar
  34. 34.
    Young RF, Kroening R, Fulton W (1985) Electrical stimulation of the brain in treatment of chronic pain. J Neurosurg 47:178–194.Google Scholar
  35. 35.
    Baskin DS, Mehler WR, Hosobuchi Y, Richardson DE, Adams JE, Flitter MA (1986) Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central gray in humans. Brain Res 371(2):231–236.PubMedCrossRefGoogle Scholar
  36. 36.
    Sano K, Sekino H, Hashimoto I, Amano K, Sugiyama H (1975) Posteromedial Hypothalamotomy in the treatment of intractable pain. Confin Neurol 37(1–3):285–290.PubMedCrossRefGoogle Scholar
  37. 37.
    Whittle IR, Jenkinson JL (1995) CT-guided stereotactic antero-medial pulvinotomy and centromedian-parafascicular thalamotomy for intractable malignant pain. Br J Neurosurg 9:195–200.PubMedCrossRefGoogle Scholar
  38. 38.
    Jeanmonod D, Magnin M, Morel A (1993) Thalamus and neurogenic pain: physiological, anatomical and clinical data. Neuroreport 4:475–478.PubMedCrossRefGoogle Scholar
  39. 39.
    Young RF, Jacques DS, Rand RW, Copcutt BC, Vermeulen SS, Posewitz AF (1995) Technique of stereotactic medial thalamotomy with the Leksell Gamma Knife for treatment of chronic pain. Neurol Res 17:59–65.PubMedGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Philip A. Starr
    • 1
  • Andrew Ahn
    • 1
  1. 1.Department of NeurosurgeryUniversity of CaliforniaSan FranciscoUSA

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