Neurological Sciences

, Volume 32, Issue 1, pp 17–21 | Cite as

Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis

  • A. GhezziEmail author
  • G. Comi
  • A. Federico
Review Article


Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.


Multiple sclerosis CCSVI Doppler sonography Extracranial venous stenosis MRI 


  1. 1.
    Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517CrossRefPubMedGoogle Scholar
  2. 2.
    Werner HL (2009) The challenge of multiple sclerosis: how do we cure chronic heterogeneous disease? Ann Neurol 65:239–248CrossRefGoogle Scholar
  3. 3.
    Ebers GC (2009) MS and autoimmune disorders. Neurogenetics 10:1–3CrossRefPubMedGoogle Scholar
  4. 4.
    Weinshenker BG, Bass B et al (1989) The natural history of multiple sclerosis: clinical course and disability. Brain 112:113–146CrossRefGoogle Scholar
  5. 5.
    Ebers G (1998) Natural history of multiple sclerosis. In: Mc Alpine Multiple Sclerosis. Churchill Livingstone, London Google Scholar
  6. 6.
    Amato MP, Ponziani G (2000) A prospective study on the prognosis of multiple sclerosis. Neurol Sci 21:S831–S838CrossRefPubMedGoogle Scholar
  7. 7.
    Trojano M, Liguori M, Bosco Zimatore G et al (2002) Age related disability in multiple sclerosis. Ann Neurol 51:475–480CrossRefPubMedGoogle Scholar
  8. 8.
    Confavreux C, Vokusic S, Moreau T, Adeleine P (2000) Relapses and progression of disability in multiple sclerosis. N Engl J Med 343:1430–1438CrossRefPubMedGoogle Scholar
  9. 9.
    De Jager PL, Jia X, Wang J, de Bakker PI et al (2009) Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 41:776–782CrossRefPubMedGoogle Scholar
  10. 10.
    Ascherio A, Munger KL (2007) Environmental risk factors for multiple sclerosis Part I: the role of infection. Ann Neurol 61:288–299CrossRefPubMedGoogle Scholar
  11. 11.
    Ascherio A, Munger KL (2007) Environmental risk factors for multiple sclerosis. Part II. Noninfectious factors. Ann Neurol 61:504–513CrossRefPubMedGoogle Scholar
  12. 12.
    Zamboni P, Menegatti E, Bartolomei I et al (2007) Current Neurovascular Research. Intracranial venous haemodynamics in multiple sclerosis 4:252–258Google Scholar
  13. 13.
    Zamboni P, Galeotti R, Menegatti E et al (2009) Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 80:392–399CrossRefPubMedGoogle Scholar
  14. 14.
    Zamboni P, Menegatti E, Galeotti R et al (2009) The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis. J. Neurol Sciences 282:21–27CrossRefGoogle Scholar
  15. 15.
    Zamboni P, Menegatti E, Weinstock-Guttman B et al (2009) The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol 24:133–138PubMedGoogle Scholar
  16. 16.
    Zamboni P (2006) The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J R Soc Med 99:589–593CrossRefPubMedGoogle Scholar
  17. 17.
    Singh AV, Zamboni P (2009) Anomalous venous blood flow and iron deposition in multiple sclerosis. J Cereb Blood Flow Metab 29:1867–1878CrossRefPubMedGoogle Scholar
  18. 18.
    Zamboni P, Consorti G, Galetti R et al (2009) Venous collateral circulation of the extracranial cerebrospinal outflow routes. Curr Neurovasc Res 6:204–212CrossRefPubMedGoogle Scholar
  19. 19.
    Zivadinov R, Schirda C, Dwyer MG et al (2010) Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case–control study. Int Angiol 29:158–175PubMedGoogle Scholar
  20. 20.
    Zamboni P, Menegatti E, Weinstock-Guttman B et al (2010) CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study. Int Angiol 29:140–148PubMedGoogle Scholar
  21. 21.
    Hojnacki D, Zamboni P, Lopez-Soriano A et al (2010) Use of neck magnetic resonance venography, Doppler sonography and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple sclerosis patients and healthy controls. Int Angiol 29:127–139PubMedGoogle Scholar
  22. 22.
    Menegatti E, Genova V, Tessari M et al (2010) The reproducibility of colour Doppler in chronic cerebrospinal venous insufficiency associated with multiple sclerosis. Int Angiol 29:121–126PubMedGoogle Scholar
  23. 23.
    Bartolomei I, Salvi F, Galeotti R et al (2010) Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis Correlation with symptoms at onset and clinical course. Int Angiol 29:183–188PubMedGoogle Scholar
  24. 24.
    Plasmati R, Pastorelli F, Fini N et al (2010) Chronic cerebro-spinal venous insufficiency: report of transcranial magnetic stimulation follow-up study in a patient with multiple sclerosis. Int Angiol 29:189–192PubMedGoogle Scholar
  25. 25.
    Malagoni AM, Galeotti R, Menegatti E et al (2010) Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study. Int Angiol 29:176–182PubMedGoogle Scholar
  26. 26.
    Lee AB, Laredo J, Neville R (2010) Embryological background of truncular venous malformation in the extracranial venous pathways as the cause of chronic cerebro spinal venous insufficiency. Int Angiol 29:95–108PubMedGoogle Scholar
  27. 27.
    Al-Omari MH, Rousan LA (2010) Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. Int Angiol 29:115–120PubMedGoogle Scholar
  28. 28.
    Simka M, Kostecki J, Zaniewski M et al (2010) Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis. Int Angiol 29:109–114PubMedGoogle Scholar
  29. 29.
    Khan O, Filippi M, Freedman MS et al (2010) Chronic cerebrospinal venous insufficiency and multiple sclerosis. Ann Neurol 67:286–290CrossRefPubMedGoogle Scholar
  30. 30.
    Qiu J (2010) Venous abnormalities and multiple sclerosis: another breakthrough claim? Lancet Neurol 9:464–465CrossRefPubMedGoogle Scholar
  31. 31.
    Zivadinov R (2010) CCSVI and MRI outcomes in MS. Oral presentation at American Academy of Neurology, TorontoGoogle Scholar
  32. 32.
    Zivadinov R, Cutter G, Marr K et al (2010) MRI result of blinded chronic cerebrospinal venous insufficiency study in patients with multiple sclerosis. Mult Scler P318Google Scholar
  33. 33.
    Weinstock-Guttman B, Cutter G, Marr K et al (2010) Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis Mult Scler 2010:653Google Scholar
  34. 34.
    Doepp F, Paul F, Valdueza JM et al (2010) No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 68:173–183PubMedGoogle Scholar
  35. 35.
    Sundsrom P, Wahlin A, Ambarki K et al (2010) Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol 68:255–259CrossRefGoogle Scholar
  36. 36.
    Worthington V, Killestein J, Eikelenboom MJ et al (2010) Normal CSF ferritin levels in MS suggest against etiologic role of chronic venous insufficiency. Neurology 75 (in press)Google Scholar
  37. 37.
    Sander D, Winbeck K, Etgen T et al (2000) Disturbance of venous flow patterns in patients with transient global amnesia. Lancet 356:1982CrossRefPubMedGoogle Scholar
  38. 38.
    Wattjes MP, Oosten BW, de Graaf W et al (2010) No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study. J Neurol Neurosurg Psych. doi: 10.1136/jnnp2010.223479
  39. 39.
    Yamout B, Herlopian A, Issa Z et al (2010) Extracranial venous stenosis is an unlikely cause of MS. Mult Scler 16:1341–1348CrossRefPubMedGoogle Scholar
  40. 40.
    Baracchini C, Perini P, Calabrese M et al No evidence of al.chronic cerebrospinal venous insufficiency in clinically isolated syndrome suggestive of MS Ann Neurol (in press)Google Scholar
  41. 41.
    Alikhani K, Kremenchutzky MC (2010) Magnetic resonance venography findings of the veins in patients followed at the MS clinic in London, Ontario. Mult Scler P778Google Scholar
  42. 42.
    Khalil M, Langkammer C, Ropele S et al (2010) Increased brain iron levels by R2 relaxometry in relation to cognitive deficits in MS. Mult Scler P315Google Scholar
  43. 43.
    Simka M, Ludyga T, Kazibudzki M et al (2010) Correlation of localisation and severity of extracranial venous lesions with clinical status of multiple sclerosis. Mult Scler P641Google Scholar
  44. 44.
    Zamboni P, Galeotti R, Menegatti E et al (2009) J Vasc Surg. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency 50:1348–1358Google Scholar
  45. 45.
    Simka M, Ludyga T, Kazibudizki M et al (2010) Safety and complications to endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis patients. Mult Scler P914Google Scholar
  46. 46.
    Samson K (2010) Experimental MS vascular shunting procedure halted at Stanford. Ann Neurol 67:A14Google Scholar
  47. 47.
    Briggs FB, Bartlett SE, Goldstein BA (2010) Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12, 566 individuals. Hum Mol Genet 19(21):4286–4295CrossRefPubMedGoogle Scholar
  48. 48.
    International Multiple Sclerosis Genetics Consortium (IMSGC), Bush WS, Sawcer SJ, de Jager PL et al (2010) Evidence for polygenic susceptibility to multiple sclerosis—the shape of things to come. Am J Hum Genet 86:621–625CrossRefPubMedGoogle Scholar
  49. 49.
    International Multiple Sclerosis Genetics Consortium (IMSGC) (2010) Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci. Hum Mol Genet 19:953–962CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Centro Studi Sclerosi MultiplaOspedale di Gallarate, Coordinator of Multiple Sclerosis Study Group, Italian Society of NeurologyGallarateItaly
  2. 2.Dipartimento di NeurologiaUniversità Vita-Salute San Raffaele, Elected President of Italian Society of NeurologyMilanoItaly
  3. 3.Dipartimento di Scienze NeurologicheNeurochirurgiche e del Comportamento, Università degli Studi di Siena, President of Italian Society of NeurologySienaItaly
  4. 4.Centro Studi Sclerosi MultiplaOspedale S. Antonio AbateGallarateItaly

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