J Neurol Neurosurg Psychiatry 80:392-399 doi:10.1136/jnnp.2008.157164
  • Research paper

Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

Open Access
  1. P Zamboni1,
  2. R Galeotti1,
  3. E Menegatti1,
  4. A M Malagoni1,
  5. G Tacconi1,
  6. S Dall’Ara1,
  7. I Bartolomei2,
  8. F Salvi2
  1. 1
    Vascular Diseases Center, University of Ferrara, Ferrara, Italy
  2. 2
    Department of Neurology, Bellaria Hospital, Bologna, Italy
  1. Professor P Zamboni, Vascular Diseases Center, University of Ferrara, 44100 Ferrara, Italy; zmp{at}
  • Received 2 July 2008
  • Revised 7 November 2008
  • Accepted 10 November 2008
  • Published Online First 5 December 2008


Background: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated.

Methods: Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement.

Results: CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher.

Conclusion: CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.


  • Competing interests: None.

  • Funding: Research supported by the Italian Ministry for University and Scientific Research and by the Foundation Cassa di Risparmio di Ferrara.

  • Ethics approval: Ethics approval was provided by the Ethics Committee of the Ferrara University Hospital.

  • See Editorial Commentary, p 358

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