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Glossary Because blood thinners increase the risk of bleeding, patients should be monitored (via simple blood draws, usually a finger prick or draw from the arm) to ensure appropriate levels of the drug are present in the patient’s system.
Note that not all researchers and physicians have applied Dr. Zamboni et al.’s exact diagnostic definitions of CCSVI in their work, usually because the sophisticated duplex ultrasonography technology used by Dr. Zamboni’s team is not readily available, and physicians in the United States are not trained in duplex ultrasonography for CCSVI treatment. In the United States, CCSVI is typically indicated by confirmed blockages or severe stenosis in any/all of the major blood vessels draining the brain and spine, reflux, or significantly abnormal mean transit times. Please see Diagnostic Approaches in our Basics section for more information. CCSVI treatment An endovascular procedure employing balloon angioplasty or stent placement to reopen stenoses in veins. (Note that open surgery could also be performed to treat certain types of venous malformations.) Typically, the stenoses or blockages requiring treatment are initially identified via non-invasive CCSVI diagnosis (usually by Magnetic Resonance Venography, CT venography, or Duplex ultrasonography). Results are often confirmed via in-vein imaging using catheter venography. Once the stenosis is confirmed, the stent is placed or the balloon inflated in order to reopen the vein or clear the blockage. Clinical Type (also: MS Clinical Type) Generally, the four most common classifications of MS disease progression: Relapsing Remitting, Secondary Progressive, Progressive Relapsing (relatively rare), and Primary Progressive. Contrast Dye (also: contrast agent; contrast media) Any of several fluids injected into veins allowing imaging technologies to better reveal internal body organs and tissues. In x-ray technologies like CT scans and venograms, iodine or barium based dyes are typically used. In Magnetic resonance (MRI, MRV) technologies, gadolinium-based dyes are typically used. CT Venography (also: phlebography) A CT scan that combines a series of x-rays taken from a variety of angles to produce a detailed, cross-sectional view of the human body. Through the use of contrast agents, which are injected into the veins of the patient being imaged, CT scans can produce very precise images of the vascular system, including the veins associated with the CNS. Because CT scans use x-ray technology, they do expose the patient to radiation. Note that CT venography differs from catheter venography (also called “selective venography”) primarily in that selective venography employs a catheter to inject contrast media into very specific locations in the vein immediately prior to the x-rays being taken, whereas traditional venography uses a previously injected contrast dye that is not specific to any particular vein segment. Deep Cerebral Veins (DCVs) Any of a group of veins running primarily in the head and upper neck area that drain the internal or ‘deep’ parts of the brain. Disease Modifying Drugs (DMDs) FDA-approved pharmaceuticals used for the treatment of multiple sclerosis. Disease Modifying Therapies (DMTs) A term used by physicians, particularly neurologists, to describe disease modifying drugs. Technically, this term should also apply to non-pharmaceutical treatments such as micronutrient (e.g. vitamin D) intake, physical rehabilitation, endovascular treatments such as CCSVI, or any other method that has been shown to alter disease progression. However, in order to be consistent with neurological usage, CCSVI Alliance will use DMT and DMD interchangeably to mean FDA-approved pharmaceuticals for treating multiple sclerosis. Doppler Sonography (also: “Transcranial color-coded Doppler sonography”(TCCS); “Extracranial Doppler sonography” (ECD); “dopplers”) Also see “Duplex Ultrasonography” An ultrasound-based imaging technique that uses the Doppler principle to help generate images of blood flow within the vein. As a diagnostic tool for investigating CCSVI, Doppler imaging can create a moving picture of blood flow in a vein – such images, together with color-coded blood flow data, illustrate reflux or other abnormal hemodynamics associated with CCSVI. Duplex Ultrasonography A form of ultrasound used in CCSVI diagnosis that combines results from Doppler Ultrasound (which visualize blood flow within the vein), with a color-coded data representation (which visualizes venous hemodynamics - especially blood flow direction). This combined process allows highly trained CCSVI diagnosticians and physicians to identify all 5 types of venous obstructions defined in Dr. Zamboni’s technical criteria for CCSVI (see CCSVI above). Note that CCSVI literature often equates “Doppler Sonography” with “Duplex Ultrasonography,” because they are almost always combined for accurate CCSVI diagnosis. Further, the term “Doppler sonography” is more widely understood by non-professionals than Duplex Ultrasonography. For these reasons, CCSVI Alliance will use the two terms interchangeably except where otherwise indicated. Endothelium The thin layer of cells lining the inner wall of all blood vessels. The endothelium helps regulate blood pressure, coagulation, and inflammation, and is considered a compelling research candidate for investigating the relationship between vascular damage and immune response in MS. Endovascular procedure (also, “endovascular surgery”) A non-operative minimally invasive medical procedure performed inside the veins (or arteries). Typically, a very long narrow flexible plastic tube called a catheter is inserted into the vein via a pen-tip sized puncture or opening made near the patient’s groin. Using contrast dye and imaging, the tip of the catheter can be threaded through the vein(s) to the desired location. Modern endovascular procedures were developed over 30 years ago as a way to diagnose problems in blood vessels. CCSVI Treatment is a form of endovascular procedure, as are angiograms and catheter venograms. Etiology (ee-tee-ol-uh-jee) The causes or origin of a disease or disorder. The etiology of stenosis in the jugular and/or azygos and related veins is an active area of inquiry among CCSVI researchers. Flow Quantification In CCSVI, flow quantification may refer to any of various techniques used to measure blood flow through the venous system. Duplex ultrasonography, MRV with Time-of-Flight compensation, and catheter-based manometers can all be used to help quantify blood flow. Hemodynamics The dynamics of blood flow. In CCSVI, the effect of venous obstruction on blood flow rates and blood flow direction are active areas of investigation. Note that the hemodynamics of the vascular system is highly complex and varies across individuals. Venous hemodynamics relies on and may be affected by all aspects of the cardiovascular system, including the condition of the heart, lungs, vessel tissues, endothelium, blood viscosity, the patient’s age, and other factors. Hypoplasia A type of venous abnormality where long vein segments are incompletely formed or developed. Like agenesis, hypoplasia is a potentially severe type of venous obstruction. Treatment of some cases of hypoplasia, agenesis, and atresia are not currently amenable to CCSVI treatment procedures. Hypoxia Pathological oxygen deprivation to body tissues. Interventional radiologist A subspecialty of radiology whose practitioners are trained in, among other specialties, endovascular procedures. Institutional Review Board (IRB) [also: Independent Ethics Committee (IEC) or Ethical Review Board (ERB)] A committee formally designated to review, approve, and monitor any medical and behavioral research that includes human beings as subjects or participants. The IRB's goal is to ensure that medical and behavioral research is being performed ethically, and that the rights and welfare of human participants are being protected. All institutions performing biomedical or behavioral research and receiving funding from the Department of Health and Human Services (HHS, which includes the Food and Drug Administration) are required by federal mandate to have an IRB. Most university research institutes (including hospitals) and public/private hospitals have an IRB. The IRB must be staffed by at least five members, and members must have sufficient education, expertise, and diversity to make reasonable and informed bioethical decisions. The IRB must include at least one scientist and one non-scientist. Intracranial Compartment The area inside the skull. Internal jugular veins (juhg-yuh-ler) [also: IJVs] The internal jugular veins (left and right), collect and drain blood from the brain, the outside of the face, and the neck. The internal jugular veins (IJV’s) connect to the superior vena cava, which carries blood to the heart. Jugular foramen (fuh-rey-muhn) A large opening at the base of the skull formed by the jugular notches of the temporal and occipital bones. In CCSVI, Dr. Zamboni’s transcranial Doppler protocol can image reflux from the jugular foramen and back toward the brain; extracranial Doppler techniques generally cannot reach the jugular foramen, as it is too far up toward the skull. Liberation Procedure, Liberation Treatment The term for CCSVI treatment coined by Italian neurologist Dr. Salvi and subsequently used by Dr. Zamboni. See CCSVI Treatment. Also, please see our FAQ for an explanation of why the CCSVI-Alliance does not use the term “Liberation Treatment.” Lumen The space inside of blood vessels and other tubular structures. Magnetic Resonance Venography (MRV) A type of magnetic resonance imaging (MRI) used to produce images of the venous system. Typically, MRV is performed using the same imaging equipment used during a standard MRI. MRVs using contrast dyes and state-of-the-art imaging techniques and equipment can provide high resolution three-dimensional images of veins, thus helping document areas of stenosis. Specific technical variations of MRV (e.g. Time-of-Flight compensation) can also capture blood flow rate and direction. Manometer (muh-nom-i-ter) An instrument for measuring pressure; for example, blood pressure. Mean Transit Time A measurement of the mean amount of time required for blood to flow through specified areas of the circulatory system. In CCSVI, venous stenoses and other blockages are thought to inhibit blood flow through the venous system, thus potentially prolonging circulatory times or causing reflux and/or an increase of deoxygenated blood in the CNS. Mean transit times can be measured by blood flow rate and patterns. Minimally Invasive Procedure A medical procedure or surgery not requiring any large incision into the body, and/or not creating any large openings of the body or any body cavity. Instead, the procedure is performed through a very small, often pencil-tip sized, perforation or opening in the skin. For most patients, minimally invasive procedures require substantially less recovery time than open or invasive procedures, and are much less painful. Many endovascular procedures are good examples of minimally invasive procedures. Note that “minimally invasive” does not automatically mean that the overall surgery or procedure has minimal risk; it refers only to the process by which the procedure is performed - the procedure itself (for example, stent placement or balloon angioplasty) may carry a separate set of risks. Open Label Study (also: open label trial) A scientific study or clinical trial, typically carried out in early phases of research, where both the researchers and patients know which treatment is being administered. The purpose of such studies include safety validation, dosage determination, trial methodological testing, data collection and analysis validation, analysis of result trends, and other data collection necessary for planning later-stage clinical trials. For example, open label studies often precede and inform subsequent single and double blinded clinical trials. Osseous Occlusion (os-ee-uhs) A bony structure, for example the cervical vertebrae, which may impinge on the jugular veins, potentially contributing to stenosis. Patency (peyt-n-see, pat-n-see) The degree of openness, or lack of obstruction. (The opposite of stenosis.) In CCSVI treatment, patency is a measure of the effectiveness treatment, indicating whether the vein has been successfully opened, or the degree to which the vein remains open, or patent, over time. Phlebology The study of veins, particularly varicose, spidery, and other venous malformations or problems. Reflux A condition of reversed blood flow where deoxygenated blood that should be leaving the brain and spine and moving toward the heart is in fact flowing back toward the brain and spine. Reflux can be a consequence of stenosis of the primary pathways (left and right jugulars, azygos, lumbar, vertebral, and others) that drain blood from the brain and spine. Restenosis A condition where a previously treated vein segment becomes re-occluded. Restenosis may occur, for example, due to scarring or tissue growth at the point of treatment (when stents are used), or muscle or vein weakness/abnormality and collapse at the point of treatment after angioplasty (veins cannot re-collapse over stents). Septum A wall-like formation of tissue inside the vein. Abnormally located septum(s) may block or inhibit blood flow through a vein. In particular, Dr. Zamboni et al. describe septum/valve malformations specifically at the point where the internal jugular veins connect with the Superior Vena Cava. Statistical Significance Used to indicate whether an experimental procedure (e.g. a new pharmaceutical, CCSVI treatment, etc.) is responsible for a measured outcome, statistical significance describes the probability that the result of an experiment occurred by chance. If the odds of an outcome occurring by chance are extremely low, then the researchers can conclude that the outcome was likely caused by the experiment/treatment rather than by random chance alone. The statistical measure of the odds of an event happening by chance is called the P-value. In scientific research, a P-value of 5% or less is accepted as a statistically legitimate finding (that is, if a measured outcome would occur by chance only 5% of the time, the researchers can feel fairly comfortable that the outcome was caused by their experiment or treatment, and not merely by chance). A P-value of 1% is considered more significant, as it indicates a lower probability of the event occurring by chance. In scientific journal articles, statistical significance is written in a specific format – for example: “P.01” indicate that there is a 5% and a 1% probability that a result occurred by chance. Stenosis [stenoses] Literally, a “narrowing.” A stricture in a vein caused by an abnormal narrowing of the vein itself, or by the protrusion or impinging of some other anatomical component against the vein. More broadly, stenosis often refers to a larger range of venous problems prohibiting normal or efficient blood drainage from the brain and spine back to the heart. Dr. Zamboni et al. have documented many distinct types of stenosis and other venous problems causing obstructed blood flow:
A manufactured metal-mesh tube that can be inserted into the vein to prevent, or counteract, a localized flow constriction or stenosis. Stents are placed during endovascular procedures using stent-delivery catheters. Stents are manufactured from state-of-the-art metals (for example, so-called “memory metals” that automatically reshaped themselves to their initially defined dimensions after being flexed or torqued). Stents come in a wide range of diameters and lengths. Superior Vena Cava (also: Precava) The superior vena cava is a thick, short vein that carries deoxygenated blood from the upper part of the body and brain back to the heart. Primary cerebrospinal pathways, including the internal jugular veins and the azygos vein, carry blood from the brain and spine into the superior vena cava. Susceptibility Weighted Imaging (SWI) SWI is a highly specialized type of MRI using susceptibility (magnetic variance of a given material when exposed to a magnetic field) in conjunction with particular MRI techniques to generate images that are extremely sensitive to venous blood, hemorrhage, and iron deposition. Valsalva Maneuver Forcible exhalation against a closed airway. Vein, Venous System The blood vessels that carry deoxygenated blood from bodily organs back to the heart. Veins differ from arteries in that veins are more pliable and elastic while arteries are generally more rigid and durable. Venocentric (also: perivenous) Centered or located around veins. Venography See Catheter Venography, or CT Venography. Venous Obstruction Any type of stenosis, blockage, malformation, or other abnormality in the vein that significantly impedes venous blood flow. To be considered significant, a venous obstruction must impede ≥50% of the blood flow through the vein. Vertebral veins A pair of veins that contribute to the deoxygenated blood return system from the spinal cord. These are smaller in diameter than than the internal jugular veins and the azygos vein. |