This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.

Thesis submitted in fulfilment of the requirements for the degree Master of Technology: Radiography in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology Supervisor: Ms. Ferial Isaacs Co-supervisor: Prof. Susan J. Van Rensburg Bellville September 2013 / Multiple Sclerosis (MS) is characterised by demyelination within the central nervous system (CNS), which may result in neurological disabilities over time, causing considerable hardship to patients and their families, in addition to being costly to treat. Recent studies have linked MS to impaired cerebral blood flow, called chronic cerebrospinal venous insufficiency (CCSVI). Anecdotal evidence has suggested that surgical correction thereof results in improvement of symptoms experienced by MS patients. To my knowledge, no information is available in the literature on carotid artery disease in MS. The USA National MS Society has therefore called for more research to be done in this area. This cross-sectional observational sub-study will determine, by ultrasound (B-Mode, Colour and Pulsed-wave Doppler), the prevalence of chronic venous insufficiency (CCSVI) and carotid artery disease in the selected sample of MS patients within the region of the Western Cape, South Africa. Biochemical data; lifestyle factors such as physical activity and smoking; and nutritional status of MS patients were determined from the main study entitled: “The development of a comprehensive gene-based, pathology supported intervention program for improved quality of life in patients diagnosed with multiple sclerosis” (Division of Chemical Pathology, NHLS, Tygerberg Hospital, and University of Stellenbosch). Twenty-nine (29) patients were aged between 28-64years and they suffered from MS for 0.83-27years. A larger proximal and mid cross-sectional diameter (CSD) of the right IJV compared to the left (differences significant, P= 0.026 and P=0.023) was demonstrated. Increased intima media thickness (IMT) was present in 13.33% of the non-smoking MS group and 20% in the smoking MS group. IJV reflux was evident in 13.33% of the MS group. A significant reduction of cross-sectional diameters of the IJV’s was evident in smoking MS patients; suggesting that smoking is not only a risk factor for atherosclerotic disease but could also be related to narrowing of the major neck veins. This study also supports findings of other studies viz that there’s no significant correlation between extracranial venous abnormalities and MS. Early carotid artery disease was noted in smoking and non-smoking MS patients, however the findings were non-significant.

No / 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.

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.