THE IMPACT OF CHRONIC CEREBROSPINAL VENOUS INSUFFICIENCY ON INTRACRANIAL
PHYSIOLOGY IN HEALTHY INDIVIDUALS
Clive B. Beggs, PhD, Christopher Magnano, MS, Simon J. Shepherd, PhD, Karen
Marr, RVT, Vesela Valnarov, MD, David Hojnacki, MD, Niels Bergsland, BS, PavelBelov, Steven Grisafi, Michael G. Dwyer, MS, Ellen Carl, Bianca WeinstockGuttman, MD, Robert Zivadinov, MD, PhD
1Centre for Infection Control and Biophysics, University of Bradford, Bradford, West Yorkshire, Bradford, UK
2Buffalo Neuroimaging Analysis Center, University at Buffalo, Buffalo, NY, USA
3Jacobs MS Comprehensive and Research Center, University at Buffalo, Buffalo, NY, USA
In recent years it has been observed that many patients with multiple sclerosis (MS) exhibit stenosis of the extra-cranial venous pathways from the brain , resulting in extensive collateral rerouting of the blood back to the heart . Given that this condition, known as chronic cerebrospinal venous insufficiency (CCSVI), is associated with alterations in the cerebral vascular bed  and CSF dynamics , there is reason to believe that occlusion of the extra-cranial venous pathways might cause subtle changes of the cerebral hydrodynamic system. If this were the case, then one would expect these changes to be evident in healthy individuals, with no neurological disorder, who are diagnosed with CCSVI. Therefore, in this study we investigated this possibility and present the results of a preliminary study designed to establish whether or not CCSVI is associated with hemodynamic and structural brain parenchyma changes in healthy individuals.
Materials & Methods
25 CCSVI negative and 15 CCSVI positive age- and sex-matched healthy individuals with no known neurological disease underwent Doppler sonography (DS) and MRI scan with cine phase contrast imaging for cerebrospinal fluid (CSF) flow estimation. CSF net negative flow (NNF), net positive flow (NPF), peak positive velocity (PPV) and peak negative velocity (PNV), T2 lesion number (T2-LN) and volume (T2-LV) and normalized gray matter volume (GMV), white matter volume (WMV), lateral ventricle volume (LVV) and cortical volume (CV) were collected. Univariate and multivariate (MANOVA) statistical analysis of the data was undertaken, together with principal component analysis (PCA), logistic regression analysis (LRA) and singular value decomposition (SVD) cluster analysis to identify differences between the two study groups.
LRA revealed a combination of NPF (p = 0.009), T2-LN (p = 0.009) and T2-LV (p = 0.007) to be the best discriminator between the CCSVI positive and negative cohorts, achieving sensitivity and specificity scores of 73.3% and 80.0%, respectively. SVD analysis confirmed this result (sensitivity = 80.0%; specificity = 88.0%). PCA revealed marked differences in the system dynamics between the CCSVI positive and negative groups; a finding confirmed by the results of the MANOVA (p = 0.033). CCSVI was associated with increased NPF (p = 0.037; Mann-Whitney U-test) and NNF (p = 0.086; Mann-Whitney U-test). In the CCSVI negative group the correlation between normalized LVV and T2-LN was very weak (r = 0.152, p = 0.469), whereas in the CCSVI positive group this relationship was much stronger (r = 0.662, p = 0.007).
CCSVI appears to be associated with systemic changes in the intracranial physiology of healthy individuals, which alters the relationship between the CSF flow, enlargement of LVV and T2 lesion formation. CCSVI negative individuals exhibit a complex intracranial dynamic, which appears to simplify in CCSVI positive individuals. Correlations between key MRI variables are much stronger in the CCSVI positive group compared with the negative group, suggesting that some intracranial variables have become more dominant. In particular, relationships involving LVV and other MRI variables significantly altered in the CCSVI positive group. The results of the study mirror those of other researchers who observed increased CSF pulsatility in MS patients [4, 5] – something that appears to be associated with CCSVI . Although not statistically significant, CSF net flow (sum of NNF and NPF) was 27.1% lower in the CCSVI positive group compared with the CCSVI negative group. As such, this finding is consistent with the model that CCSVI induces hypertension in the dural sinuses, something that is known to inhibit CSF absorption from the sub-arachnoid space .
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