Chronic cerebrospinal venous insufficiency is not more prevalent in patients with mild multiple sclerosis: a sonographer-blinded, case-control ultrasound study

Mult Scler. 2013 May;19(6):749-56. doi: 10.1177/1352458512459986. Epub 2012 Sep 7.


Objectives: We designed a prospective case-control study of patients with clinically isolated syndrome (CIS) and Relapsing-Remitting Multiple Sclerosis (RRMS) with an Expanded Disability Status Score (EDSS) of ≤2, compared with age-and-sex-matched healthy controls, to test the hypothesis that chronic cerebrospinal venous insufficiency (CCSVI) is more prevalent in patients with CIS or mild MS.

Methods: All subjects were examined using a Siemens Antares duplex ultrasound machine. The internal jugular, vertebral and intracranial veins were studied in subjects in both supine and sitting postures. The sonographer was blind to the subject's clinical status. Measures included the criteria proposed by Zamboni and volume flow. Presence of CCSVI was defined as ≥2 Zamboni criteria.

Results: Seventy patient-control pairs were recruited, with 11 males and 59 females in each group. Only one subject, a control, satisfied the Zamboni definition of CCSVI; however, 19 patients and 13 controls had abnormalities as defined by Zamboni, the difference largely caused by a higher prevalence in patients of internal jugular vein (IJV) stenosis, defined as a cross-sectional area ≤0.3cm(2). This difference disappeared with a more rigorous stenosis definition. Further analysis revealed there was IJV valve variation in seven patients and one control.

Conclusions: Our findings indicate that CCSVI, as defined by the Zamboni ultrasound criteria, is not present in CIS and mild RRMS (EDSS ≤2), providing further evidence that CCSVI does not have a causal role in MS; however, we found an apparent increase in IJV variation in patients with CIS or mild MS that would warrant further investigation.

Keywords: Causality; Relapsing–Remitting Multiple Sclerosis; Zamboni criteria; chronic cerebrospinal venous insufficiency; clinically isolated syndrome; jugular vein stenosis; multiple sclerosis; ultrasound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia / epidemiology
  • Case-Control Studies
  • Cerebral Veins / diagnostic imaging*
  • Cerebral Veins / physiopathology
  • Cerebrovascular Circulation
  • Cerebrovascular Disorders / diagnostic imaging*
  • Cerebrovascular Disorders / epidemiology*
  • Cerebrovascular Disorders / physiopathology
  • Chronic Disease
  • Constriction, Pathologic
  • Demyelinating Diseases / diagnosis
  • Demyelinating Diseases / epidemiology*
  • Disability Evaluation
  • Female
  • Humans
  • Jugular Veins / diagnostic imaging*
  • Jugular Veins / physiopathology
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / epidemiology*
  • Patient Positioning
  • Predictive Value of Tests
  • Prevalence
  • Prospective Studies
  • Regional Blood Flow
  • Risk Factors
  • Severity of Illness Index
  • Spinal Cord / blood supply*
  • Supine Position
  • Ultrasonography, Doppler, Duplex*
  • Venous Insufficiency / diagnostic imaging*
  • Venous Insufficiency / epidemiology*
  • Venous Insufficiency / physiopathology