Neuromodulation for Trigeminal Autonomic Cephalalgias

  • Tsinsue Chen
  • Manjit Matharu
  • Ludvic ZrinzoEmail author


Trigeminal autonomic cephalalgias (TAC) include chronic cluster headache (CCH), short lasting unilateral neuralgiform headaches with autonomic symptoms (SUNHA), paroxysmal hemicrania and hemicrania continua. Neuromodulation for the treatment of TACs can involve both peripheral and central targets. Peripheral targets include stimulation of the sphenopalatine ganglion and the greater occipital nerve. Central targeting includes deep brain stimulation of ventral tegmental area, which has also been described as the “posterior hypothalamus”, as well as high cervical spinal cord stimulation. This chapter explores the mechanisms, operative techniques and clinical evidence supporting each method, with an emphasis on central neuromodulation techniques.


Trigeminal autonomic cephalgia Chronic cluster headache SUNCT SUNHA SUNA Hemicrania continua Paroxysmal hemicrania Deep brain stimulation Spinal cord stimulation Occipital nerve stimulation Sphenopalatine ganglion stimulation Sphenopalatine ganglion ablation 


  1. 1.
    Magis D, Schoenen J. Advances and challenges in neurostimulation for headaches. Lancet Neurol. 2012;11(8):708–19.CrossRefPubMedGoogle Scholar
  2. 2.
    Lambru G, Trimboli M, Palmisani S, Smith T, Al-Kaisy A. Safety and efficacy of cervical 10 kHz spinal cord stimulation in chronic refractory primary headaches: a retrospective case series. J Headache Pain. 2016;17(1):66.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    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(2):115–27.CrossRefPubMedGoogle Scholar
  4. 4.
    Miller S, Sinclair AJ, Davies B, Matharu M. Neurostimulation in the treatment of primary headaches. Pract Neurol. 2016;16(5):362–75.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Schoenen J, Jensen RH, Lanteri-Minet M, Lainez MJ, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816–30.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Barloese MC, Jurgens TP, May A, Lainez JM, Schoenen J, Gaul C, et al. Cluster headache attack remission with sphenopalatine ganglion stimulation: experiences in chronic cluster headache patients through 24 months. J Headache Pain. 2016;17(1):67.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Jurgens TP, Schoenen J, Rostgaard J, Hillerup S, Lainez MJ, Assaf AT, et al. Stimulation of the sphenopalatine ganglion in intractable cluster headache: expert consensus on patient selection and standards of care. Cephalalgia. 2014;34(13):1100–10.CrossRefPubMedGoogle Scholar
  8. 8.
    Devoghel JC. Cluster headache and sphenopalatine block. Acta Anaesthesiol Belg. 1981;32(1):101–7.PubMedGoogle Scholar
  9. 9.
    Sanders M, Zuurmond WW. Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headache: a 12- to 70-month follow-up evaluation. J Neurosurg. 1997;87(6):876–80.CrossRefPubMedGoogle Scholar
  10. 10.
    Narouze S, Kapural L, Casanova J, Mekhail N. Sphenopalatine ganglion radiofrequency ablation for the management of chronic cluster headache. Headache. 2009;49(4):571–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Bendersky DC, Hem SM, Yampolsky CG. Unsuccessful pulsed radiofrequency of the sphenopalatine ganglion in patients with chronic cluster headache and subsequent successful thermocoagulation. Pain Pract. 2015;15(5):E40–5.CrossRefPubMedGoogle Scholar
  12. 12.
    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(9567):1099–106.CrossRefPubMedGoogle Scholar
  13. 13.
    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(4):314–21.CrossRefPubMedGoogle Scholar
  14. 14.
    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(1–2):126–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Ambrosini A, Vandenheede M, Rossi P, Aloj F, Sauli E, Pierelli F, 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):92–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Anthony M. Headache and the greater occipital nerve. Clin Neurol Neurosurg. 1992;94(4):297–301.CrossRefPubMedGoogle Scholar
  17. 17.
    Bartsch T, Goadsby PJ. Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain. 2002;125(Pt 7):1496–509.CrossRefPubMedGoogle Scholar
  18. 18.
    Bartsch T, Goadsby PJ. Increased responses in trigeminocervical nociceptive neurons to cervical input after stimulation of the dura mater. Brain. 2003;126(Pt 8):1801–13.CrossRefPubMedGoogle Scholar
  19. 19.
    Magis D, Bruno MA, Fumal A, Gerardy PY, Hustinx R, Laureys S, et al. Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study. BMC Neurol. 2011;11:25.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Burns B, Watkins L, Goadsby PJ. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology. 2009;72(4):341–5.CrossRefPubMedGoogle Scholar
  21. 21.
    de Quintana-Schmidt C, Casajuana-Garreta E, Molet-Teixido J, Garcia-Bach M, Roig C, Clavel-Laria P, et al. Stimulation of the occipital nerve in the treatment of drug-resistant cluster headache. Rev Neurol. 2010;51(1):19–26.PubMedGoogle Scholar
  22. 22.
    Fontaine D, Christophe Sol J, Raoul S, Fabre N, Geraud G, Magne C, et al. Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation. Cephalalgia. 2011;31(10):1101–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Fontaine D, Blond S, Lucas C, Regis J, Donnet A, Derrey S, et al. Occipital nerve stimulation improves the quality of life in medically-intractable chronic cluster headache: Results of an observational prospective study. Cephalalgia. 2017;37(12):1173–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Leone M, Proietti Cecchini A, Messina G, Franzini A. Long-term occipital nerve stimulation for drug-resistant chronic cluster headache. Cephalalgia. 2017;37(8):756–63.CrossRefPubMedGoogle Scholar
  25. 25.
    Miller S, Watkins L, Matharu M. Treatment of intractable chronic cluster headache by occipital nerve stimulation: a cohort of 51 patients. Eur J Neurol. 2017;24(2):381–90.CrossRefPubMedGoogle Scholar
  26. 26.
    Mueller O, Diener HC, Dammann P, Rabe K, Hagel V, Sure U, et al. Occipital nerve stimulation for intractable chronic cluster headache or migraine: a critical analysis of direct treatment costs and complications. Cephalalgia. 2013;33(16):1283–91.CrossRefPubMedGoogle Scholar
  27. 27.
    Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic headache—long-term safety and efficacy. Cephalalgia. 2007;27(2):153–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Burns B, Watkins L, Goadsby PJ. Treatment of hemicrania continua by occipital nerve stimulation with a bion device: long-term follow-up of a crossover study. Lancet Neurol. 2008;7(11):1001–12.CrossRefPubMedGoogle Scholar
  29. 29.
    Lambru G, Shanahan P, Watkins L, Matharu MS. Occipital nerve stimulation in the treatment of medically intractable SUNCT and SUNA. Pain Physician. 2014;17(1):29–41.PubMedGoogle Scholar
  30. 30.
    Van Buyten JP, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. Neuromodulation. 2013;16(1):59–65; discussion 65–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Al-Kaisy A, Van Buyten JP, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain Med. 2014;15(3):347–54.CrossRefPubMedGoogle Scholar
  32. 32.
    Al-Kaisy A, Palmisani S, Smith T, Harris S, Pang D. The use of 10-kilohertz spinal cord stimulation in a cohort of patients with chronic neuropathic limb pain refractory to medical management. Neuromodulation. 2015;18(1):18–23.CrossRefPubMedGoogle Scholar
  33. 33.
    Wolter T, Kiemen A, Kaube H. High cervical spinal cord stimulation for chronic cluster headache. Cephalalgia. 2011;31(11):1170–80.CrossRefPubMedGoogle Scholar
  34. 34.
    May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet. 1998;352(9124):275–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Leone M, Franzini A, Bussone G. Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. N Engl J Med. 2001;345(19):1428–9.CrossRefPubMedGoogle Scholar
  36. 36.
    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(5):1095–9; discussion 9–101.PubMedGoogle 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(Pt 4):940–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Leone M, Franzini A, Broggi G, Bussone G. Hypothalamic stimulation for intractable cluster headache: long-term experience. Neurology. 2006;67(1):150–2.CrossRefPubMedGoogle Scholar
  39. 39.
    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(6):999–1005.CrossRefPubMedGoogle Scholar
  40. 40.
    Owen SL, 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(10):955–60.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(3):285–95.CrossRefPubMedGoogle Scholar
  42. 42.
    Bartsch T, Paemeleire K, Goadsby PJ. Neurostimulation approaches to primary headache disorders. Curr Opin Neurol. 2009;22(3):262–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Hidding U, May A. Mere surgery will not cure cluster headache—implications for neurostimulation. Cephalalgia. 2011;31(1):112–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Fontaine D, Lazorthes Y, Mertens P, Blond S, Geraud 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(1):23–31.CrossRefPubMedGoogle Scholar
  45. 45.
    Seijo F, Saiz A, Lozano B, Santamarta E, Alvarez-Vega M, Seijo E, et al. Neuromodulation of the posterolateral hypothalamus for the treatment of chronic refractory cluster headache: experience in five patients with a modified anatomical target. Cephalalgia. 2011;31(16):1634–41.CrossRefPubMedGoogle Scholar
  46. 46.
    Chabardes S, Carron R, Seigneuret E, Torres N, Goetz L, Krainik A, et al. Endoventricular deep brain stimulation of the third ventricle: proof of concept and application to cluster headache. Neurosurgery. 2016;79(6):806–15.CrossRefPubMedGoogle Scholar
  47. 47.
    Akram H, Miller S, Lagrata S, Hyam J, Jahanshahi M, Hariz M, et al. Ventral tegmental area deep brain stimulation for refractory chronic cluster headache. Neurology. 2016;86(18):1676–82.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Bartsch T, Falk D, Knudsen K, Reese R, Raethjen J, Mehdorn HM, et al. Deep brain stimulation of the posterior hypothalamic area in intractable short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). Cephalalgia. 2011;31(13):1405–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Leone M, Franzini A, D'Andrea G, Broggi G, Casucci G, Bussone G. Deep brain stimulation to relieve drug-resistant SUNCT. Ann Neurol. 2005;57(6):924–7.CrossRefPubMedGoogle Scholar
  50. 50.
    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(2):279–81.CrossRefPubMedGoogle Scholar
  51. 51.
    Miller S, Akram H, Lagrata S, Hariz M, Zrinzo L, Matharu M. Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks. Brain. 2016;139(Pt 10):2631–40.CrossRefPubMedGoogle Scholar
  52. 52.
    Walcott BP, Bamber NI, Anderson DE. Successful treatment of chronic paroxysmal hemicrania with posterior hypothalamic stimulation: technical case report. Neurosurgery. 2009;65(5):E997; discussion E.CrossRefPubMedGoogle Scholar
  53. 53.
    Matharu MS, Zrinzo L. Deep brain stimulation in cluster headache: hypothalamus or midbrain tegmentum? Curr Pain Headache Rep. 2010;14(2):151–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Zrinzo L, Foltynie T, Limousin P, Hariz MI. Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review. J Neurosurg. 2012;116(1):84–94.CrossRefPubMedGoogle Scholar
  55. 55.
    Chen T, Mirzadeh Z, Chapple K, Lambert M, Ponce FA. Complication rates, lengths of stay, and readmission rates in “awake” and “asleep” deep brain simulation. J Neurosurg. 2017;127(2):360–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Fenoy AJ, Simpson RK Jr. Risks of common complications in deep brain stimulation surgery: management and avoidance. J Neurosurg. 2014;120(1):132–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Patel DM, Walker HC, Brooks R, Omar N, Ditty B, Guthrie BL. Adverse events associated with deep brain stimulation for movement disorders: analysis of 510 consecutive cases. Neurosurgery. 2015;11(Suppl 2):190–9.PubMedGoogle Scholar
  58. 58.
    Leone M, Franzini A, Cecchini AP, Bussone G. Efficacy of hypothalamic stimulation for chronic drug-resistant cluster headache. Cephalalgia. 2012;32(4):267–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Holl EM, Petersen EA, Foltynie T, Martinez-Torres I, Limousin P, Hariz MI, et al. Improving targeting in image-guided frame-based deep brain stimulation. Neurosurgery. 2010;67(2 Suppl Operative):437–47.PubMedGoogle Scholar
  60. 60.
    Foltynie T, Zrinzo L, Martinez-Torres I, Tripoliti E, Petersen E, Holl E, et al. MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety. J Neurol Neurosurg Psychiatry. 2011;82(4):358–63.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Tsinsue Chen
    • 1
    • 2
  • Manjit Matharu
    • 3
    • 4
  • Ludvic Zrinzo
    • 1
    • 5
    Email author
  1. 1.Victor Horsley Department of NeurosurgeryNational Hospital of Neurology and NeurosurgeryLondonUK
  2. 2.Division of NeurosurgeryBarrow Neurological Institute, St. Joseph’s Hospital and Medical CenterPhoenixUSA
  3. 3.Department of NeurologyNational Hospital of Neurology and NeurosurgeryLondonUK
  4. 4.UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Headache GroupLondonUK
  5. 5.Unit of Functional Neurosurgery, Department of Movement DisordersUCL Institute of Neurology, University College LondonLondonUK

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