Professor Paolo Zamboni on current rationale for CCSVI treatment - facebook prikbord

The current rationale for CCSVI treatment: early clinical results from a pilot study by Prof Paolo Zamboni

written for the 10th International Symposium of Endovascular Therapeutics in Barcelona, Spain

http://www.sitesymposium.org

Chronic cerebrospinal venous insufficiency (CCSVI) has been described as a vascular condition characterized by anomalies of the main extra-cranial cerebrospinal venous routes that interfere with normal venous outflow in patients with multiple sclerosis (MS). (1-4)Recent studies demonstrated that these venous abnormalities are not exclusive to MS patients, and that patients with other neurological diseases or even healthy individuals can present with these anomalies.(5-8) The clinical and MRI correlates of these findings are still unknown,and at this time it is not clear whether CCSVI may influence disease progression in MS (9-13) or play a role in CCSVI-induced cerebral hemodynamic alterations in MS and healthy individuals. (14)

Percutaneous transluminal angioplasty (PTA) for CCSVI-related abnormalities was introduced in an open-label study that evaluated its safety and efficacy on clinical and MRI outcomes in 65 MS patients over 18 (1) and 24 months of follow-up. (15) Additional open-label studies confirmed that the PTA procedures are relatively safe. (16-19) However,these studies were not blinded,controlled or randomized, and patients were not stratified with respect to their standard disease-modifying treatment (DMT) during the follow-up. Only one controlled pilot study investigated the safety and efficacy of PTA for CCSVI-related abnormalities in patients with relapsing-remitting (RR) MS. (20)While this small pilot study showed that PTA of CCSVI was related to partial improvement in clinical and MRI outcome measures of patients with MS, it could not recommend PTA as a treatment for MS, and warranted placebo-controlled trials with a larger number of patients and use of more advanced imaging techniques to assess cerebral fluid-dynamic changes after PTA.Therefore at this time, it is unknown whether PTA for CCSVI can improve CCSVI-induced cerebral fluid-dynamic abnormalities in patients with MS or with other neurologic diseases, or in healthy individuals.

Given that CCSVI is characterized by stenoses of the cerebral venous drainage system, there is reason to believe that the condition might induce subtle venous hypertension in the superior sagittal sinus (SSS),which in turn would tend to reduce the bulk flow of cerebrospinal fluid(CSF) into the sinus from the subarachnoid space – a finding that was shown in a recent pilot study including small number of MS patients and controls. (21) This has led us to hypothesize that CCSVI might be having an effect on the CSF-dynamics in patients with MS.

In order to explore this issue, the present study was designed to investigate whether PTA in patients with MS on standard DMT and diagnosed with CCSVI can modify characteristics of CSF flow and velocity outcomes.

Material and Methods:

This was a case-control MR blinded 12 months study that included 15 patients with RRMS who presented with significant stenoses (=50%lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (cases), while7 had delayed PTA after 6 months of medical therapy alone (controls).CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle using a semi-automated method. Outcomes were compared between the two groups at baseline, 6 and 12 months of the study using mixed effect model analysis.

Results:

At baseline, no significant differences in CSF flow or velocity measures were detected between the 2 groups. At month 6, significant improvement in both flow and velocity outcomes were detected in the immediate compared to delayed groups, persisting to month 12. Within group flow comparisons from baseline to follow-up showed significant increase in immediate group (p=0.033), but decrease in delayed group (p=0.024). Altered CSF flow and velocity measures were associated with worsening of clinical and MRI outcomes in delayed group.

Conclusions:

PTA of MS patients with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.

References:

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