November 19, 2010 at 11:26am
from the V-Aware November issue.
Dr. Dake is the cardio-thoracic specialist I contacted with Dr. Zamboni's research in January 2009. He was our local doctor at Stanford University. The damage that Dr. Dake saw in Jeff's brain on MRI, and the damage he found in Jeff's jugular veins on MRV made sense to him. As a vascular doctor, he understands the correlation of venous drainage and disease.
Important Points to note in this article:
1. CCSVI resembles a known venous disease, superior vena cava syndrome. Symptoms related to this condition are similar to those in CCSVI. Relieving CCSVI via angioplasty produces similar results in angioplasty for superior vena cava occlusion.
2. CCSVI might account for the low flow states (hypoperfusion) found in pwMS.
3. Slowed blood flow changes the endothelial layer of blood vessels, allowing for a break in the blood brain barrier and immune cell penetration
4. Inflammation created by disturbed blood flow in CCSVI continues to damage the vein lining. Thus, CCSVI will progress with age of patient and length of disease.
Here is Dr. Dake on CCSVI---
Evidence presented recently in the medical literature proposes that patients with multiple sclerosis (MS) have a coexisting high frequency of obstruction to veins that drain the brain and spinal cord.
These data suggest that MS is associated with blockages in veins located in the neck or chest that alter cerebral venous hemodynamics, causing alterations in venous pressure and flow patterns. This venous obstruction is called chronic cerebrospinal venous insufficiency (CCSVI).
The alterations in venous drainage described above may occur in patients with MS by creating low flow states in the brain and spinal cord that enhance the ability of certain cells within the stagnant or slowly flowing blood to attach to the lining of the vein. Once they adhere to the lining—the so-called blood-brain barrier—immune cells are able to penetrate the wall of the vein and infiltrate the formerly protected brain tissue. After they are across the vein wall, immune cells release a variety of factors to further increase
the permeability of the vein wall, enhance migration of various cell types into the surrounding brain tissue, and promote the elaboration of tissue- damaging inflammatory elements.
This active phase of inflammation causes swelling and a high level of stress to the brain tissue that leads to demyelination. Eventually, as the inflammation subsides, the brain tissue resolves with fibrous tissue and plaque formation. In many cases, this situation results in compromised function in the area affected.
A STRONG ASSOCIATION
Dr. Paolo Zamboni and colleagues from Italy have marshaled compelling evidence for CCSVI associated with MS. Using duplex ultrasonography and transcranial Doppler studies, they have documented the frequent association of abnormal venous flow patterns with MS. In one study of 109 MS patients and 177 age- and gender-matched controls, subjects underwent a blinded assessment of five parameters related to cerebral venous outflow using transcranial and extracranial color-Doppler ultrasound examination (TCCS-ECD). In controls, only 2.7% of the measurements were abnormal, whereas in MS patients, 47% of measurements were abnormal. In a study comparing duplex ultrasound with contrast venography, 40% to 70% of patients with MS had evidence of flow disturbances or venous stenosis, or both, by TCCS-ECD. Contrast catheter venography found that 86% and 91% of these patients had obstructions of the azygous or internal jugular veins, respectively.
It is interesting to note that imaging with magnetic resonance shows a prolongation in the time it takes for blood to circulate in and out of the brain—the transit time—in MS patients when compared to patients who do not have MS. This suggests that the obstructions noted by Zamboni and others may have measurable effects on the physiological patterns of blood flow to the brain.
LOOKING AT CAUSES
Early observational experience using noninvasive imaging with ultrasound, magnetic resonance, and CT, as well as traditional catheter-based contrast venograms, all indicate that CCSVI includes a spectrum of locations and causes of obstructing venous lesions. The narrowing of a vein may occur at a variety of sites. For example, within the jugular veins in the neck, the obstructions may be high, mid, or low within the vein, and they often are diagnosed at multiple locations.
Similarly, the cause of the venous narrowing may be a range of abnormalities. Some are related to disease affecting the vein itself. These intrinsic vein lesions include thickening of the vein wall due to prior inflammation, scarring following trauma to the vein, and congenital abnormalities affecting a valve typically located within the lower end of the vein as it enters the chest. Alternatively, the vein may be grossly normal but simply narrowed by an extrinsic source, compressed by a structure outside the vein, such as a bone or artery that is anatomically located in a position that contacts the vein. We do not yet understand the relative importance of different sites of venous narrowing or causes of obstruction. It appears that the common thread that laces together all of the CCSVI observations is that venous obstruction exists—the exact location and the exact cause are non-specific.
It is intriguing to observe that some of the symptoms of MS mimic symptoms observed in patients with superior vena cava syndrome. Obstruction of the superior vena cava, usually caused by a tumor or radiation, impedes venous drainage of the head and neck. Relief of the obstruction with balloon angioplasty and stent placement, if required, provides swift and dramatic resolution of the symptoms of impaired cognition and fatigue. Thus, it is not surprising that patients with CCSVI associated with MS also report rapid relief of these nonlocalizing symptoms after treatment.
The general or global symptoms of fatigue, impaired cognitive performance, and heat intolerance often experienced by MS patients appear to respond to relief of CCSVI obstructions in certain patients. The precise response rate and expected duration of any improvement in symptoms after endovascular treatments are not well established, but numerous trials are actively under development to better define the potential benefits and possible complications of interventional management of CCSVI. Authorities agree that patients who decide to undergo an endovascular procedure should remain on their prescribed disease-modifying drug therapy regimen and not consider interventional therapy a replacement or substitute for established medical treatments.
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