Small internal jugular veins with restricted outflow are associated with severe multiple sclerosis: a sonographer-blinded, case–control ultrasound study

BACKGROUND Recent evidence has indicated an association between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis. Small internal jugular veins (IJVs) (with a cross-sectional area of less than 0.4 cm²) have been previously described as difficult to catheterize, and their presence may potentially affect cerebrospinal venous drainage. In this blinded extracranial color-Doppler study we had two principal aims: first, to assess prevalence of CCSVI among Serbian MS patients compared to healthy controls; and second, to assess prevalence of small IJVs (with a CSA ≤ 0.4 cm²) among MS patients and controls. METHODS The sixty seven unrelated patients with clinical isolated syndrome (CIS), relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP) multiple sclerosis and 21 healthy controls were examined by high-resolution color-Doppler. RESULTS The ultrasonographic criteria of CCSVI (according to Zamboni) were positive in 11.9% of the patients and in none of the control subjects. The CCSVI-positive patients had significantly longer disease durations and were significantly more disabled (measured by their Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) scores), but after adjustment for gender and disease duration, CCSVI was not an independent risk factor for multiple sclerosis severity. The small IJVs were found in 28.4% of the patients and 28.6% of the controls. The patients with small IJVs were associated with decreased venous outflow from the brain and presented with longer disease durations and significantly higher EDSS and MSSS scores compared to patients without small IJVs. A multivariate logistic regression analysis adjusted for gender and disease duration showed that small IJV is an independent factor associated with multiple sclerosis severity (EDSS ≥6) (adjusted OR = 8.9, 95% CI: 1.8-45.6, p = 0.007). Among patients with small IJVs the 36.84% were also CCSVI positive. CONCLUSIONS Both, CCSVI and small IJVs seem to influence or follow MS severity, but only small IJVs turned out to be an independent factor in this study. Thus, small IJVs with restricted outflow, which might be aspects of CCSVI different from the criteria originally described by Zamboni, emerge as a cofactor in the multifactorial pathophysiology of multiple sclerosis.