A study, conducted by University at Buffalo ( UB ) researchers, published in the Neurology, the journal of the American Academy of Neurology, has found that CCSVI ( chronic cerebral venous insufficiency ) may be a result of multiple sclerosis, not a cause.
Robert Zivadinov is first author on the paper.

The results indicate that only 56.1% of multiple sclerosis patients and 38.1% of patients with a condition known as clinically isolated syndrome ( CIS ), an individual's first neurological episode, had CCSVI.
While this may suggest an association between the multiple sclerosis and CCSVI, association does not imply causality. In fact, 42.3% of participants classified as having other neurological diseases ( OND ), as well as 22.7% of healthy controls involved in the study, also presented with CCSVI.

These findings indicate that CCSVI does not have a primary role in causing multiple sclerosis; the findings are consistent with increased prevalence of CCSVI in multiple sclerosis, but substantially lower than the sensitivity and specificity rates in multiple sclerosis reported originally by the Italian investigators.

CCSVI is a complex vascular condition discovered and described by Paolo Zamboni, from Italy's University of Ferrara. It is characterized by narrowing of vessels draining blood from the cranium. Zamboni hypothesized that this narrowing restricts the normal outflow of blood from the brain, resulting in alterations in the blood flow patterns within the brain that eventually cause injury to brain tissue and degeneration of neurons, leading to multiple sclerosis.

Zamboni's original investigation in a group of 65 patients and 235 controls showed that CCSVI appeared to be strongly associated with multiple sclerosis, increasing the risk of having multiple sclerosis by 43 fold.

The results of the UB study are based on 499 participants in the Combined Transcranial and Extracranial Venous Doppler Evaluation ( CTEVD ) study, which began at the University in April 2009.
The study group consisted of 289 persons with multiple sclerosis,163 healthy controls, 26 with other neurological diseases and 21 with clinically isolated syndrome.

Multiple sclerosis patients also were defined by disease type: relapsing-remitting ( RR ), secondary progressive ( SP ), primary-progressive ( PP ), progressive-relapsing ( PR ) and multiple sclerosis with neuromyelitis optical ( NMO ), a type of multiple sclerosis that affects the optic nerves and spinal cord exclusively.

All patients underwent transcranial and extracranial echo-Doppler scans of the head and neck. Persons were considered CCSVI-positive if they met two or more of five venous hemodynamic criteria.

Prevalence rates were calculated in three groupings: only subjects with positive and negative CCSVI diagnoses; only borderline cases included in the negative group; and subjects who fulfilled any of the five criteria.

When only positive and negative CCSVI cases were considered, results showed a CCSVI prevalence of 62.5% in multiple sclerosis patients, 45.8% in those with other neurological diseases, 42.1% in clinically isolated syndrome, and 25.5% in healthy controls.

When borderline cases were included as negative for CCSVI, prevalence figures were 56.1% in multiple sclerosis patients, 42.3% in those with other neurological diseases, 38.1% with clinically isolated syndrome and 22.7% in healthy controls.

When all cases that met at least one of the five venous hemodynamic criteria were included in the analysis, CCSVI prevalence was 81.3% in multiple sclerosis cases, 76.2% in clinically isolated syndrome patients, 65.4% in other neurological diseases cases and 55.2% in healthy controls.

The highest prevalence was seen in relapsing primary-progressive multiple sclerosis ( 89.4% ), followed by non-relapsing secondary-progressive multiple sclerosis ( 67.2% ), neuromyelitis optical ( 66.6% ), primary-progressive multiple sclerosis ( 54.5% ) and relapsing-remitting multiple sclerosis ( 49.2% ).
CCSVI prevalence was substantially higher in progressive multiple sclerosis than in non-progressive multiple sclerosis patients.
In addition, patients with a progressive multiple sclerosis disease subtype had higher CCSVI prevalence than those with non-progressive multiple sclerosis.

The higher prevalence of CCSVI in progressive multiple sclerosis patients suggests that CCSVI may be a consequence, rather than a cause, of multiple sclerosis.

Several studies have reported that patients with progressive multiple sclerosis show decreased blood flow through the brain's neuronal tissue, indicating that CCSVI may be secondary to reduced perfusion. In addition, a pilot study has showen an association between the severity of CCSVI and reduced cerebral blood flow in brain parenchyma of multiple sclerosis patients.

Of the 10 pediatric multiple sclerosis patients who participated in the study, five presented with CCSVI ( 50% ), yielding prevalence similar to that in adult multiple sclerosis patients.
Although the sample size was too small to draw any firm conclusions, these results suggest that CCSVI is also present in children and is not the result of aging.

According to Zivadinov, the differences between UB study, the original Italian CCSVI study and other published studies also emphasize the need for a multimodal approach for the assessment of CCSVI. In addition to Doppler sonography, use of selective venography, magnetic resonance venography and intraluminal Doppler methods can provide more evidence for the true prevalence of CCSVI in multiple sclerosis.

Source: University at Buffalo, 2011

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