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Neurotherapeutics

, Volume 7, Issue 2, pp 220–228 | Cite as

Deep brain stimulation in trigeminal autonomic cephalalgias

  • Massimo LeoneEmail author
  • Angelo Franzini
  • Alberto Proietti Cecchini
  • Eliana Mea
  • Giovanni Broggi
  • Gennaro Bussone
Review Article

Summary

Cluster headache (CH), paroxysmal hemicrania (PH), and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome) are primary headaches grouped together as trigeminal autonomic cephalalgias (TACs). All are characterized by short-lived unilateral head pain attacks associated with oculofacial autonomic phenomena. Neuroimaging studies have demonstrated that the posterior hypothalamus is activated during attacks, implicating hypothalamic hyperactivity in TAC pathophysiology and suggesting stimulation of the ipsilateral posterior hypothalamus as a means of preventing intractable CH. After almost 10 years of experience, hypothalamic stimulation has proved successful in preventing pain attacks in approximately 60% of the 58 documented chronic drug-resistant CH patients implanted at various centers. Positive results have also been reported in drug-resistant SUNCT and PH. Microrecording studies on hypothalamic neurons are increasingly being performed and promise to make it possible to more precisely identify the target site. The implantation procedure has generally proved safe, although it carries a small risk of brain hemorrhage. Long-term stimulation is proving to be safe: studies on patients under continuous hypothalamic stimulation have identified nonsymptomatic impairment of orthostatic adaptation as the only noteworthy change. Studies on pain threshold in chronically stimulated patients show increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. When the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, indicating that long-term hypothalamic stimulation is necessary to produce sensory and nociceptive changes, as also indicated by clinical experience that CH attacks are brought under control only after weeks of stimulation. Infection, transient loss of consciousness, and micturition syncope have been reported, but treatment interruption usually is not required.

Key Words

Cluster headache paroxysmal hemicrania SUNCT syndrome trigeminal autonomic cephalgias hypothalamus deep brain stimulation 

References

  1. 1.
    Gildenberg PL. The history of stereotactic and functional neurosurgery. In: Gildenberg PL, Tasker RR, editors. Textbook of stereotactic and functional neurosurgery. 1st ed. New York: McGraw Hill, 1998: 5–20.Google Scholar
  2. 2.
    Bittar RG, Kar-Purkayastha I, Owen SL, Bear RE, Green A, Wang S, et al. Deep brain stimulation for pain relief: a meta-analysis. J Clin Neurosci 2005;12: 515–519.CrossRefPubMedGoogle Scholar
  3. 3.
    Veloso F, Kumar K, Toth C. Headache secondary to deep brain implantation. Headache 1998;38: 507–515.CrossRefPubMedGoogle Scholar
  4. 4.
    Young RF, Chambi VI. Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter: evidence for a non-opioid mechanism. J Neurosurg 1987;66: 364–371.CrossRefPubMedGoogle Scholar
  5. 5.
    Sano K, Sekino H, Hashimoto I, Amano K, Sugiyama H. Postero-medial hypothalamotomy in the treatment of tractable pain. Confin Neurol 1975;37: 285–290.CrossRefPubMedGoogle Scholar
  6. 6.
    Raskin NH, Hosobuchi Y, Lamb S. Headache may arise from perturbation of brain. Headache 1987;27: 416–420.CrossRefPubMedGoogle Scholar
  7. 7.
    Bittar RG, Nandi D, Carter H, Aziz TZ. Somatotopic organization of the human periventricular gray matter. J Clin Neurosci 2005;12: 240–241.CrossRefPubMedGoogle Scholar
  8. 8.
    Kumar K, Toth C, Nath R. Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery 1997;40: 736–746.CrossRefPubMedGoogle Scholar
  9. 9.
    May A. New insights into headache: an update on functional and structural imaging findings. Nat Rev Neurol 2009;5: 199–209.CrossRefPubMedGoogle Scholar
  10. 10.
    Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia 2004;24(Suppl 1):8–160.Google Scholar
  11. 11.
    May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet 1998;352: 275–278.CrossRefPubMedGoogle Scholar
  12. 12.
    May A, Bahra A, Büchel C, Turner R, Goadsby PJ. Functional MRI in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 1999;46: 791–794.CrossRefPubMedGoogle Scholar
  13. 13.
    Matharu MS, Cohen AS, Frackowiak RSJ, Goadsby PJ. Posterior hypothalamic activation in paroxysmal hemicrania. Ann Neurol 2006;59: 535–545.CrossRefPubMedGoogle Scholar
  14. 14.
    Matharu MS, Cohen AS, McGonigle DJ, Ward N, Frackowiak RS, Goadsby PJ. Posterior hypothalamic and brainstem activation in hemicrania continua. Headache 2004;44: 747–761.CrossRefPubMedGoogle Scholar
  15. 15.
    May A, Ashbumer J, Büchel C, McGonigle DJ, Fristen KJ, Frackowiak RS, et al. Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nat Med 1999;5: 836–838.CrossRefPubMedGoogle Scholar
  16. 16.
    Leone M, Franzini A, Bussone G. Stereotactic stimulation of posterior hypothalamic gray matter for intractable cluster headache. N Engl J Med 2001;345: 1428–1429.CrossRefPubMedGoogle Scholar
  17. 17.
    Kudrow L. Cluster headache, mechanism and management. New York: Oxford University Press, 1980.Google Scholar
  18. 18.
    Sjaastad O. Cluster headache syndrome. Major Problems in Neurology 23. London, Philadelphia, Toronto: WB Saunders, 1992.Google Scholar
  19. 19.
    Jarrar RG, Black DF, Dodick DW, Davis DH. Outcome of trigeminal nerve section in the treatment of chronic cluster headache. Neurology 2003;60: 1360–1362.CrossRefPubMedGoogle Scholar
  20. 20.
    O’Brien MD, Kirkpatrick PJ, McCabe JJ. Trigeminal nerve section for chronic migrainous neuralgia. In: Olesen J, Goadsby PJ, editors. Cluster headache and related conditions. Frontiers in Headache Research 9. Oxford: Oxford University Press, 1999: 291–295.Google Scholar
  21. 21.
    Donnet A, Valade D, Regis J. Gamma knife treatment for refractory cluster headache: prospective open trial. J Neurol Neurosurg Psychiatry 2005;76: 218–221.CrossRefPubMedGoogle Scholar
  22. 22.
    Matharu MS, Goadsby PJ. Persistence of attacks of cluster headache after trigeminal nerve root section. Brain 2002;125: 976–984.CrossRefPubMedGoogle Scholar
  23. 23.
    Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet Neurol 2007;6: 314–321.CrossRefPubMedGoogle Scholar
  24. 24.
    Leone M, May A, Franzini A, Broggi G, Dodick D, Rapoport A, et al. Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection. Cephalalgia 2004;24: 934–937.CrossRefPubMedGoogle Scholar
  25. 25.
    Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick D. Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia 2006;26: 1168–1170.CrossRefPubMedGoogle Scholar
  26. 26.
    Leone M, Proietti Cecchini A, Mea E, D’Amico D, Tullo V, Grazzi L, et al. Therapeutic neurostimulation in chronic headaches: problems of patient selection. Neurol Sci 2008;29: S59-S61.CrossRefPubMedGoogle Scholar
  27. 27.
    Sumaptriptan Cluster Headache Study Group. Treatment of acute cluster headache with sumatriptan. N Engl J Med 1991;325: 322–326.CrossRefGoogle Scholar
  28. 28.
    Turhal NS. Sumatriptan overdose in episodic cluster headache: a case report of overuse without event. Cephalalgia 2001;21: 700.CrossRefPubMedGoogle Scholar
  29. 29.
    May A, Leone M, Áfra J, Linde M, Sándor PS, Evers S, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol 2006;13: 1066–1077.CrossRefPubMedGoogle Scholar
  30. 30.
    Lipton RB, Micieli G, Russell D, Solomon S, Tfelt-Hansen P, Waldenlind E. Guidelines for controlled clinical trials of drugs in cluster headache. Cephalalgia 1995;15: 452–462.CrossRefPubMedGoogle Scholar
  31. 31.
    Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients. Lancet 2007;369: 1099–1106.CrossRefPubMedGoogle Scholar
  32. 32.
    Leone M, Franzini A, Cecchini AP, Broggi G, Bussone G. Stimulation of occipital nerve for drug-resistant chronic cluster headache. Lancet Neurol 2007;6: 289–291.CrossRefPubMedGoogle Scholar
  33. 33.
    Leone M, Franzini A, Broggi G, Mea E, Cecchini AP, Bussone G. Acute hypothalamic stimulation and ongoing cluster headache attacks. Neurology 2006;67: 1844–1845.CrossRefPubMedGoogle Scholar
  34. 34.
    Franzini A, Ferroli P, Leone M, Broggi G. Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: first reported series. Neurosurgery 2003;52: 1095–1099.CrossRefPubMedGoogle Scholar
  35. 35.
    Franzini A, Ferroli P, Leone M, Bussone G, Broggi G. Hypothalamic deep brain stimulation for the treatment of chronic cluster headaches: a series report. Neuromodulation 2004;7: 1–8.CrossRefGoogle Scholar
  36. 36.
    Leone M, Franzini A, Broggi G, May A, Bussone G. Long-term follow up of bilateral hypothalamic stimulation for intractable cluster headache. Brain 2004;127: 2259–2264.CrossRefPubMedGoogle Scholar
  37. 37.
    Schoenen J, Di Clemente L, Vandenheede M, Fumal A, De Pasqua V, Mouchamps M, et al. Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain 2005;128: 940–947.CrossRefPubMedGoogle Scholar
  38. 38.
    Leone M, Franzini A, Broggi G, Bussone G. Hypothalamic stimulation for intractable cluster headache: long-term experience. Neurology 2006;67: 150–152.CrossRefPubMedGoogle Scholar
  39. 39.
    Owen SLF, Green AL, Davies P, Stein JF, Aziz TZ, Behrens T, et al. Connectivity of an effective hypothalamic surgical target for cluster headache. J Clin Neurosci 2007;14: 955–960.CrossRefPubMedGoogle Scholar
  40. 40.
    Starr PA, Barbaro NM, Raskin NH, Ostrem JL. Chronic stimulation of the posterior hypothalamic region for cluster headache: technique and 1-year results in four patients. J Neurosurg 2007;106: 999–1005.CrossRefPubMedGoogle Scholar
  41. 41.
    Bartsch T, Pinsker MO, Rasche D, Kinfe T, Hertel F, Diener HC, et al. Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series. Cephalalgia 2008;28: 285–295.CrossRefPubMedGoogle Scholar
  42. 42.
    D’Andrea G, Nordera GP, Piacentino M. Effectiveness of hypothalamic stimulation in two patients affected by intractable chronic cluster headache. Neurology 2006;66(Suppl 2): A140 (abstract).Google Scholar
  43. 43.
    Benabid AL, Chabardés S, Scigneuret E, Torres N. Intraventricular stimulation for targets close to the midline: periaqueductal gray, posterior hypothalamus, anterior hypothalamus, subcommissural structures. Acta Neurochir (Wien) 2006;148: i-lxiv (abstract).Google Scholar
  44. 44.
    Mateos V, Scijo F, Lozano B, Álvarez Vega M, Fernández González F. Deep brain stimulation in refractory chronic cluster headache: first national cases [Estimulacion cerebral profunda en cefalea en racimos crónica refractaria primeros casos nationales] [In Spanish]. Neurologia 2007;22: 96 (abstract).Google Scholar
  45. 45.
    Fontaine D, Lazorthes Y, Mertens P, Blond S, Géraud G, Fabre N, et al. Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension. J Headache Pain 2010;11: 23–31.CrossRefPubMedGoogle Scholar
  46. 46.
    Sillay KA, Sani S, Starr PA. Deep brain stimulation for medically intractable cluster headache. Neurobiol Dis 2009 Jun 6 [Epub ahead of print].Google Scholar
  47. 47.
    Brittain J-S, Green AL, Jenkinson N, Ray NJ, Holland P, Stein JF, et al. Local field potentials reveal a distinctive neural signature of cluster headache in the hypothalamus. Cephalalgia 2009;29: 1165–1173.CrossRefPubMedGoogle Scholar
  48. 48.
    Black D, Bartleson JD, Torgrimson SM, Davis DH. Two cases of chronic cluster headache treated successfully with hypothalamic deep brain stimulation. Neurology 2007:P07.065 (abstract).Google Scholar
  49. 49.
    Swaab DF. The human hypothalamus: basic and clinical aspects; Part II: Neuropathology of the human hypothalamus and adjacent structures. Handbook of clinical neurology. Handbook of Clinical Neurology 80 (3rd series, vol. 2). Amsterdam: Elsevier, 2003–2004.Google Scholar
  50. 50.
    Sherrington CS. The integrative action of the nervous system. 2nd ed. New Haven, CT: Yale University Press, 1947: 1.Google Scholar
  51. 51.
    Loewy AD. Forebrain nuclei involved in autonomic control. Prog Brain Res 1991;87: 253–268.CrossRefPubMedGoogle Scholar
  52. 52.
    Cortelli P, Guaraldi P, Leone M, Pierangeli G, Barletta G, Grimaldi D, et al. Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients. Eur J Neurol 2007;14: 1008–1015.CrossRefPubMedGoogle Scholar
  53. 53.
    Benarroch EE. Homeostasis, immunomodulation and antinociception. In: Central autonomic network: functional organization and clinical correlations. Armonk, NY: Futura Publishing, 1997: 405–443.Google Scholar
  54. 54.
    Abrahamson EE, Moore RY. The posterior hypothalamic area: chemoarchitecture and afferent connections. Brain Res 2001;889: 1–22.CrossRefPubMedGoogle Scholar
  55. 55.
    Vetrugno R, Pierangeli G, Leone M, Bussone G, Franzini A, Brogli G, et al. Effect on sleep of posterior hypothalamus stimulation in cluster headache. Headache 2007;47: 1085–1090.CrossRefPubMedGoogle Scholar
  56. 56.
    Talairach J, Tournoux P. Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system: an approach to cerebral imaging. Stuttgart: G. Thieme Verlag, 1988.Google Scholar
  57. 57.
    Cordella R, Carella F, Leone M, Franzini A, Broggi G, Bussone G, et al. Spontaneous neuronal activity of the posterior hypothalamus in trigeminal autonomic cephalalgias. Neurol Sci 2007;28: 93–95.CrossRefPubMedGoogle Scholar
  58. 58.
    Sani S, Shimamoto S, Turner RS, Levesque N, Starr PA. Micro-electrode recording in the posterior hypothalamic region in humans. Neurosurgery 2009;64(3 Suppl): 161–167.CrossRefPubMedGoogle Scholar
  59. 59.
    Malick A, Strassman AM, Burstein R. Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J Neurophysiol 2000;84: 2078–2112.PubMedGoogle Scholar
  60. 60.
    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
  61. 61.
    Jürgens T, Leone M, Proietti-Cecchini A, Busch V, Mea E, Bussone G, et al. Hypothalamic deep-brain stimulation modulates thermal sensitivity and pain thresholds in cluster headache. Pain 2009;146: 84–90.CrossRefPubMedGoogle Scholar
  62. 62.
    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: 2746–2760.CrossRefPubMedGoogle Scholar
  63. 63.
    Black DF, Dodick DW. Two cases of medically and surgically intractable SUNCT: a reason for caution and an argument for a central mechanism. Cephalalgia 2002;22: 201–214.CrossRefPubMedGoogle Scholar
  64. 64.
    Leone M, Franzini A, D’Andrea G, Broggi G, Casucci G, Bussone G. Deep brain stimulation to relieve severe drug-resistant SUNCT. Ann Neurol 2005;57: 924–927.CrossRefPubMedGoogle Scholar
  65. 65.
    Lyons MK, Dodick DW, Evidente VG. Responsiveness of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing to hypothalamic deep brain stimulation. J Neurosurg 2009;110: 279–281.CrossRefPubMedGoogle Scholar
  66. 66.
    Walcott BP, Bamber NI, Anderson DE. Successful treatment of chronic paroxysmal hemicrania with posterior hypothalamic stimulation: technical case report. Neurosurgery 2009;65: E997.CrossRefPubMedGoogle Scholar
  67. 67.
    May A, Leone M, Boecker H, Sprenger T, Juergens T, Bussone G, et al. Hypothalamic deep brain stimulation in positron emission tomography. J Neurosci 2006;26: 3589–3593.CrossRefPubMedGoogle Scholar
  68. 68.
    Leone M, Bussone G. Pathophysiology of trigeminal autonomic cephalalgias. Lancet Neurol 2009;8: 755–764.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Massimo Leone
    • 1
    Email author
  • Angelo Franzini
    • 2
  • Alberto Proietti Cecchini
    • 1
  • Eliana Mea
    • 1
  • Giovanni Broggi
    • 2
  • Gennaro Bussone
    • 1
  1. 1.Headache Center, Neuromodulation Unit, Department of NeurologyFondazione I.R.C.C.S. Istituto Neurologico Carlo BestaMilanItaly
  2. 2.Department of NeurosurgeryFondazione I.R.C.C.S. Istituto Neurologico Carlo BestaMilanItaly

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