Neurological Sciences

, Volume 36, Supplement 1, pp 23–28 | Cite as

The role of intracranial hypertension in the chronification of migraine



Besides a similar clinical presentation, idiopathic intracranial hypertension (IIH) and chronic migraine (CM) also share relevant risk factors, show a higher prevalence of allodynic symptoms and both respond to topiramate. Moreover, sinus stenosis, a radiological marker of IIH, in CM patients is much more prevalent than expected. As a consequence of these striking similarities, IIH without papilledema (IIHWOP) may be easily misdiagnosed as CM. Actually, IIHWOP has been found in up to 14 % of CM clinical series. Considering that, on one hand, an asymptomatic sinus stenosis-associated raised intracranial pressure (ICP) may be highly prevalent in the general population, and on the other, that IIH clinical presentation with chronic headache may require a migraine predisposition, we have proposed that an overlooked IIHWOP could represent a risk factor for migraine progression. This hypothesis prompted us to investigate the prevalence of IIHWOP and its possible role in the process of migraine chronification in a consecutive series of CM patients selected for unresponsiveness to medical treatment and evidence of significant sinus stenosis. The main finding of our study is that the large majority of such patients actually suffer from a chronic headache secondary to IIHWOP. This implies that an IIHWOP mimicking CM is much more prevalent than believed, is commonly misdiagnosed as CM on the basis of ICHD criteria and is strictly predicted by refractoriness to preventive treatments. However, our data fully comply with the alternative hypothesis that an overlooked IIHWOP, although highly prevalent amongst healthy individuals, in migraine-prone subjects is a powerful (and modifiable) risk factor for the progression and the refractoriness of pain. The normalization of ICP by even a single LP with CSF withdrawal may be effective in a significant proportion of patients with a long history of refractory chronic headache, who represent about one-fifth of the patients screened in our study. We suggest that IIHWOP should be considered in all patients with almost daily migraine pain, with evidence of sinus stenosis and unresponsive to medical treatment, referred to specialized headache clinics.


Idiopathic intracranial hypertension Chronic migraine Risk factor Sinus venous stenosis 


  1. 1.
    Scher AI, Stewart WF, Liberman J, Lipton RB (2003) Prevalence of frequent headache in a population simple. Headache 43:336–342CrossRefGoogle Scholar
  2. 2.
    Natoli JL, Manack A, Dean B et al (2010) Global prevalence of chronic migraine: a systematic review. Cephalalgia 30:599–609PubMedGoogle Scholar
  3. 3.
    Headache Classification Committee of the International Headache Society (2013) The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 33(9):629–808CrossRefGoogle Scholar
  4. 4.
    Scher AI, Stewart WF, Ricci JA, Lipton RB (2003) Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain 106(1–2):81–89CrossRefPubMedGoogle Scholar
  5. 5.
    Cho SJ, Chu MK (2015) Risk factors of chronic daily headache or chronic migraine. Curr Pain Headache Rep 19(1):465CrossRefPubMedGoogle Scholar
  6. 6.
    Bigal ME, Lipton RB (2006) Modifiable risk factors for migraine progression. Headache 46(9):1334–1343CrossRefPubMedGoogle Scholar
  7. 7.
    Scher AI, Midgette LA, Lipton RB (2008) Risk factors for headache chronification. Headache 48:16–25CrossRefPubMedGoogle Scholar
  8. 8.
    Bigal ME, Lipton RB (2008) Concepts and mechanisms of migraine chronification. Headache 48:7–15CrossRefPubMedGoogle Scholar
  9. 9.
    Bigal ME, Lipton RB (2009) What predicts the change from episodic to chronic migraine? Curr Opin Neurol 22(3):269–276CrossRefPubMedGoogle Scholar
  10. 10.
    Lipton HL, Michelson PE (1972) Pseudotumor cerebri syndrome without papilledema. JAMA 220:1591–1592CrossRefPubMedGoogle Scholar
  11. 11.
    Marcelis J, Silberstein SD (1991) Idiopathic intracranial hypertension without papilledema. Arch Neurol 48:392–399CrossRefPubMedGoogle Scholar
  12. 12.
    Huff AL, Hupp SL, Rothrock JF (1996) Chronic daily headache with migrainous features due to papilledema-negative idiopathic intracranial hypertension. Cephalalgia 16:451–452CrossRefPubMedGoogle Scholar
  13. 13.
    Wang SJ, Silberstein SD, Patterson S et al (1998) Idiopathic intracranial hypertension without papilledema: a case–control study in a headache center. Neurology 51:245–249CrossRefPubMedGoogle Scholar
  14. 14.
    Mathew NT, Ravishankar K, Sanin LC (1996) Coexistence of migraine and idiopathic intracranial hypertension without papilledema. Neurology 46:1226–1230CrossRefPubMedGoogle Scholar
  15. 15.
    De Simone R, Ranieri A, Cardillo G, Bonavita V (2011) High prevalence of bilateral transverse sinus stenosis-associated IIHWOP in unresponsive chronic headache sufferers: pathogenetic implications in primary headache progression. Cephalalgia 31(6):763–765CrossRefPubMedGoogle Scholar
  16. 16.
    De Simone R, Ranieri A, Montella S et al (2014) Intracranial pressure in unresponsive chronic migraine. J Neurol 261(7):1365–1373CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Digre KB, Nakamoto BK, Warner JE, Langeberg WJ, Baggaley SK, Katz BJ (2009) A comparison of idiopathic intracranial hypertension with and without papilledema. Headache 49(2):185–193CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Radhakrishnan K, Ahlskog JE, Cross SA, Kurland LT, O’Fallon WM (1993) Idiopathic intracranial hypertension (pseudotumor cerebri). Descriptive epidemiology in Rochester, Minn, 1976 to 1990. Arch Neurol 50(1):78–80CrossRefPubMedGoogle Scholar
  19. 19.
    Durcan FJ, Corbett JJ, Wall M (1998) The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol 45(8):875–877CrossRefGoogle Scholar
  20. 20.
    Craig JJ, Mulholland DA, Gibson JM (2001) Idiopathic intracranial hypertension; incidence, presenting features and outcome in Northern Ireland (1991–1995). Ulster Med J 70(1):31–35PubMedCentralPubMedGoogle Scholar
  21. 21.
    Raoof N, Sharrack B, Pepper IM, Hickman SJ (2011) The incidence and prevalence of idiopathic intracranial hypertension in Sheffield, UK. Eur J Neurol 18(10):1266–1268CrossRefPubMedGoogle Scholar
  22. 22.
    Quattrone A, Bono F, Oliveri RL et al (2001) Cerebral venous thrombosis and isolated intracranial hypertension without papilledema in CDH. Neurology 57(1):31–36CrossRefPubMedGoogle Scholar
  23. 23.
    Vieira DS, Masruha MR, Gonçalves AL et al (2008) Idiopathic intracranial hypertension with and without papilloedema in a consecutive series of patients with chronic migraine. Cephalalgia 28(6):609–613CrossRefPubMedGoogle Scholar
  24. 24.
    De Simone R, Marano E, Bilo L et al (2006) Idiopathic intracranial hypertension without headache. Cephalalgia 26(8):1020–1021CrossRefPubMedGoogle Scholar
  25. 25.
    Bono F, Cristiano D, Mastrandrea C et al (2010) The upper limit of normal CSF opening pressure is related to bilateral transverse sinus stenosis in headache sufferers. Cephalalgia 30:145–151CrossRefPubMedGoogle Scholar
  26. 26.
    De Simone R, Ranieri A, Montella S, Marchese M, Bonavita V (2012) Sinus venous stenosis-associated idiopathic intracranial hypertension without papilledema as a powerful risk factor for progression and refractoriness of headache. Curr Pain Headache Rep 16:261–269CrossRefPubMedGoogle Scholar
  27. 27.
    Karahalios DG, Rekate HL, Khayata MH et al (1996) Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies. Neurology 46:198–202CrossRefPubMedGoogle Scholar
  28. 28.
    Rohr A, Bindeballe J, Riedel C et al (2012) The entire dural sinus tree is compressed in patients with idiopathic intracranial hypertension: a longitudinal, volumetric magnetic resonance imaging study. Neuroradiology 54:25–33CrossRefPubMedGoogle Scholar
  29. 29.
    Stienen A, Weinzierl M, Ludolph A et al (2008) Obstruction of cerebral venous sinus secondary to idiopathic intracranial hypertension. Eur J Neurol 15:1416–1418CrossRefPubMedGoogle Scholar
  30. 30.
    Biousse V, Bruce BB, Newman NJ (2012) Update on the pathophysiology and management of idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 83:488–494CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Farb RI, Vanek I, Scott JN et al (2003) Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology 60:1418–1424CrossRefPubMedGoogle Scholar
  32. 32.
    Friedman DI, Liu GT, Digre KB (2013) Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 81(13):1159–1165CrossRefPubMedGoogle Scholar
  33. 33.
    King JO, Mitchell PJ, Thomson KR et al (2002) Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology 58:26–30CrossRefPubMedGoogle Scholar
  34. 34.
    Ahmed R, Friedman DI, Halmagyi GM (2011) Stenting of the transverse sinuses in idiopathic intracranial hypertension. J Neuroophthalmol 31:374–380CrossRefPubMedGoogle Scholar
  35. 35.
    Kumpe DA, Bennett JL, Seinfeld J et al (2012) Dural sinus stent placement for idiopathic intracranial hypertension. J Neurosurg 116:538–548CrossRefPubMedGoogle Scholar
  36. 36.
    Fields JD, Javedani PP, Falardeau J et al (2013) Dural venous sinus angioplasty and stenting for the treatment of idiopathic intracranial hypertension. J Neurointerv Surg 5:62–68CrossRefPubMedGoogle Scholar
  37. 37.
    De Simone R, Ranieri A, Montella S, Bilo L, Cautiero F (2014) The role of dural sinus stenosis in idiopathic intracranial hypertension pathogenesis: the self-limiting venous collapse feedback-loop model. Panminerva Med 56(3):201–209PubMedGoogle Scholar
  38. 38.
    Higgins JNP, Pickard JD (2004) Lateral sinus stenosis in idiopathic intracranial hypertension resolving after CSF diversion. Neurology 2:1907–1908CrossRefGoogle Scholar
  39. 39.
    Baryshnik DB, Farb RI (2004) Changes in the appearance of venous sinuses after treatment of disordered intracranial pressure. Neurology 62:1445–1446CrossRefPubMedGoogle Scholar
  40. 40.
    De Simone R, Marano E, Fiorillo C et al (2005) Sudden re-opening of collapsed transverse sinuses and longstanding clinical remission after a single lumbar puncture in a case of idiopathic intracranial hypertension: pathogenetic implications. Neurol Sci 25:342–344CrossRefPubMedGoogle Scholar
  41. 41.
    Scoffings DJ, Pickard JD, Higgins JNP (2007) Resolution of transverse sinus stenoses immediately after CSF withdrawal in idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 78:911–912CrossRefPubMedCentralPubMedGoogle Scholar
  42. 42.
    Lee SW, Gates P, Morris P, Whan A, Riddington L (2009) Idiopathic intracranial hypertension; immediate resolution of venous sinus “obstruction” after reducing cerebrospinal fluid pressure to 10 cmH2O. J Clin Neurosci 16:1690–1692CrossRefPubMedGoogle Scholar
  43. 43.
    Bono F, Messina D, Giliberto C et al (2008) Bilateral transverse sinus stenosis and idiopathic intracranial hypertension without papilledema in chronic tension-type headache. J Neurol 255(6):807–812CrossRefPubMedGoogle Scholar
  44. 44.
    Silberstein S, Diener HC, Lipton R, Goadsby P, Dodick D, Bussone G et al (2008) Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate. Headache 48:1087–1095CrossRefPubMedGoogle Scholar
  45. 45.
    Wall M (2008) Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep 8:87–93CrossRefPubMedGoogle Scholar
  46. 46.
    Marcus DM, Lynn J, Miller JJ, Chaudhary O, Thomas D, Chaudhary B (2001) Sleep disorders: a risk factor for pseudotumor cerebri? J Neuroophthalmol 21:121–123CrossRefPubMedGoogle Scholar
  47. 47.
    Cooke L, Eliasziw M, Becker WJ (2007) Cutaneous allodynia in transformed migraine patients. Headache 47(4):531–539PubMedGoogle Scholar
  48. 48.
    Filatova E, Latysheva N, Kurenkov A (2008) Evidence of persistent central sensitization in chronic headaches: a multi-method study. J Headache Pain 9:295–300CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Ashkenazi A, Sholtzow M, Shaw JW, Burstein R, Young WB (2007) Identifying cutaneous allodynia in chronic migraine using a practical clinical method. Cephalalgia 27:111–117CrossRefPubMedCentralPubMedGoogle Scholar
  50. 50.
    Ekizoglu E, Baykan B, Orhan EK et al (2012) The analysis of allodynia in patients with idiopathic intracranial hypertension. Cephalalgia 32:1049–1058CrossRefPubMedGoogle Scholar
  51. 51.
    Diener HC, Bussone G, Van Oene JC et al (2007) Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 27:814–823CrossRefPubMedGoogle Scholar
  52. 52.
    Diener HC, Dodick DW, Goadsby PJ et al (2009) Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia 29:1021–1027CrossRefPubMedGoogle Scholar
  53. 53.
    Dodgson SJ, Shank RP, Maryanoff BE (2000) Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia 41(Suppl):S35–S39CrossRefPubMedGoogle Scholar
  54. 54.
    Celebisoy N, Gokcay F, Sirin H, Akyurekli O (2007) Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study. Acta Neurol Scand 116:322–327CrossRefPubMedGoogle Scholar
  55. 55.
    Bono F, Salvino D, Tallarico T et al (2010) Abnormal pressure waves in headache sufferers with bilateral transverse sinus stenosis. Cephalalgia 30(12):1419–1425CrossRefPubMedGoogle Scholar
  56. 56.
    Valk J, van Vucht N, Pevenage P (2011) MR venographic patterns in chronic intractable headache. Neuroradiol J 24(1):13–19CrossRefPubMedGoogle Scholar
  57. 57.
    Fofi L, Giugni E, Vadalà R et al (2012) Cerebral transverse sinus morphology as detected by MR venography in patients with chronic migraine. Headache 52(8):1254–1261CrossRefPubMedGoogle Scholar
  58. 58.
    Headache Classification Subcommittee of the International Headache Society (2004) The International Classification Of Headache Disorders second Edition. Cephalalgia 24(Suppl 1):9–160Google Scholar
  59. 59.
    Doepp F, Schreiber SJ, Dreier JP et al (2003) Migraine aggravation caused by cephalic venous congestion. Headache 43:96–98CrossRefPubMedGoogle Scholar
  60. 60.
    Chou CH, Chao AC, Lu SR et al (2004) Cephalic venous congestion aggravates only migraine-type headaches. Cephalalgia 24:973–979CrossRefPubMedGoogle Scholar
  61. 61.
    Burstein R, Cutrer MF, Yarnitsky D (2000) The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain 123:1703–1709CrossRefPubMedGoogle Scholar
  62. 62.
    Burstein R, Yarnitsky D, Goor-Aryeh I et al (2000) An association between migraine and cutaneous allodynia. Ann Neurol 47:614–624CrossRefPubMedGoogle Scholar
  63. 63.
    Bendtsen L (2000) Central sensitization in tension-type headache—possible pathophysiological mechanisms. Cephalalgia 20:486–508CrossRefPubMedGoogle Scholar
  64. 64.
    Ashkenazi A, Young WB (2004) Dynamic mechanical (brush) allodynia in cluster headache. Headache 44:1010–1012CrossRefPubMedGoogle Scholar
  65. 65.
    Rozen TD, Haynes GV, Saper JR et al (2005) Abrupt onset and termination of cutaneous allodynia (central sensitization) during attacks of SUNCT. Headache 45:153–155CrossRefPubMedGoogle Scholar
  66. 66.
    Bigal ME, Ashina S, Burstein R et al (2008) Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology 70:1525–1533CrossRefPubMedCentralPubMedGoogle Scholar
  67. 67.
    Louter MA, Bosker JE, van Oosterhout WP et al (2013) Cutaneous allodynia as a predictor of migraine chronification. Brain 136:3489–3496CrossRefPubMedGoogle Scholar
  68. 68.
    Bonavita V, De Simone R (2010) Is chronic migraine a primary or a secondary condition? Neurol Sci 31(Suppl 1):S45–S50CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Department of Neurosciences, Headache CentreUniversity “Federico II” of NaplesNaplesItaly
  2. 2.Istituto di Diagnosi e Cura Hermitage CapodimonteNaplesItaly

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