The purpose of this article is to investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA). This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS 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 (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis. At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group. PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.
Beggs, Clive B.; Chung, C.P.; Bergsland, N.; Wang, P.N.; Shepherd, Simon J.; Cheng, C.Y.; Dwyer, Michael G.; Hu, H.H.; Zivadinov, R. (2013)
To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR-positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema.
Zamboni, P.; Menegatti, E.; Conforti, P.; Shepherd, Simon J.; Tessari, M.; Beggs, Clive B. (2012)
BACKGROUND: Magnetic resonance imaging and echo color Doppler (ECD) scan techniques do not accurately assess the cerebral venous return. This generated considerable scientific controversy linked with the diagnosis of a vascular syndrome known as chronic cerebrospinal venous insufficiency (CCSVI) characterized by restricted venous outflow from the brain. The purpose of this study was to assess the cerebral venous return in relation to the change in position by means of a novel cervical plethysmography method. METHODS: This was a single-center, cross-sectional, blinded case-control study conducted at the Vascular Diseases Center, University of Ferrara, Italy. The study involved 40 healthy controls (HCs; 18 women and 22 men) with a mean age of 41.5 +/- 14.4 years, and 44 patients with multiple sclerosis (MS; 25 women and 19 men) with a mean age of 41.0 +/- 12.1 years. All participants were previously scanned using ECD sonography, and further subset in HC (CCSVI negative at ECD) and CCSVI groups. Subjects blindly underwent cervical plethysmography, tipping them from the upright (90 degrees ) to supine position (0 degrees ) in a chair. Once the blood volume stabilized, they were returned to the upright position, allowing blood to drain from the neck. We measured venous volume (VV), filling time (FT), filling gradient (FG) required to achieve 90% of VV, residual volume (RV), emptying time (ET), and emptying gradient (EG) required to achieve 90% of emptying volume (EV) where EV = VV - RV, also analyzing the considered parameters by receiver operating characteristic (ROC) curves and principal component mathematical analysis. RESULTS: The rate at which venous blood discharged in the vertical position (EG) was significantly faster in the controls (2.73 mL/second +/- 1.63) compared with the patients with CCSVI (1.73 mL/second +/- 0.94; P = .001). In addition, respectively, in controls and in patients with CCSVI, the following parameters were highly significantly different: FT 5.81 +/- 1.99 seconds vs 4.45 +/- 2.16 seconds (P = .003); FG 0.92 +/- 0.45 mL/second vs 1.50 +/- 0.85 mL/second (P < .001); RV 0.54 +/- 1.31 mL vs 1.37 +/- 1.34 mL (P = .005); ET 1.84 +/- 0.54 seconds vs 2.66 +/- 0.95 seconds (P < .001). Mathematical analysis demonstrated a higher variability of the dynamic process of cerebral venous return in CCSVI. Finally, ROC analysis demonstrated a good sensitivity of the proposed test with a percent concordant 83.8, discordant 16.0, tied 0.2 (C = 0.839). CONCLUSIONS: Cerebral venous return characteristics of the patients with CCSVI were markedly different from those of the controls. In addition, our results suggest that cervical plethysmography has great potential as an inexpensive screening device and as a postoperative monitoring tool.
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