CCSVI: study that fails to reproduce Zamboni's findings is now in print

Tsivgoulis et al. Extracranial venous hemodynamics in multiple sclerosis: A case-control study. Neurology. 2011 Sep 27;77(13):1241-5.

"This paper is now in print; I thought it may be worth reminding readers of its findings."

Background: A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of MS. The researchers performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria.

Methods: They prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva manoeuvre (straining to increase the pressure in the lungs).

Results: They recruited 42 patients with MS (mean age 39 ± 11 years, 17 men) and 43 control individuals (mean age 38 ± 12 years, 16 men). Very good/excellent intrarater and interrater agreement (κ values 0.82-1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during breath holding. After performing Valsalva maneuver to increase the pressure in the lung, they documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999).

Conclusions: With established reproducibility of venous ultrasound testing, these data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials.

"I have now lost count of all the studies that have not been able to reproduce Zamboni's data. Do we still need more data? It is becoming increasingly clear that CCSVI does not exist as a disease entity."