Cerebral and cervical venous outflow abnormalities are dynamic.

Abstract

I t was recently proposed that inflammation associated with multiple sclerosis (MS) is caused by chronic cerebrospinal venous insufficiency (CCSVI) owing to chronically elevated cerebral venous pressure that leads to disruption of the blood-brain barrier and entry of inflammatory mediators into the central nervous system. The results of the original studies that reported CCSVI in 100% of patients with MS (as demonstrated by specific venous ultrasonography abnormalities) have not consistently been replicated using sonography, magnetic resonance venography, or selective venography. Intracranial pressure measurements in patients with MS are no different from control subjects. In a 2011 study of US veterans with MS, we failed to show any association between cerebral venous ultrasonography abnormalities and MS. There was no significant difference between the number of ultrasonography abnormalities found in patients with MS compared with control subjects. In addition, none of the study subjects fulfilled criteria of CCSVI, defined as 2 or more ultrasonography abnormalities by proponents of the controversial CCSVI theory. Overall, currently there appears to be no scientific evidence to support CCSVI as an etiologic factor in MS. Nevertheless, both patients and practitioners continue to promote it and treat it as if it were. One possible reason to explain conflicting results from different research studies is the potentially low reliability and reproducibility of venous ultrasonography assessments owing to the plasticity of these vessels. We hypothesized that repeat studies would show intrapersonal variations with regard to venous diameter and blood flow. Therefore, all 8 study subjects of our original investigation with any abnormal ultrasonography results within the cervical or cerebral veins—including patients with a clinically isolated syndrome, relapsing-remitting MS, secondary progressive MS, or primary progressive MS— and healthy control subjects were reevaluated to determine whether the original findings could be replicated. Both the ultrasonography technician and interpreter were blinded to the subjects’ diagnosis. The ultrasonography technician did not have access to original study results, which were available to the ultrasonography interpreter. All repeat ultrasonography studies were normal (Table). These observations indicate that cerebral and cervical venous abnormalities as detected by ultrasonography may not always be persistent structural abnormalities and may further weaken the association of singular abnormal imaging findings and MS.