In queste settimane stampa specializzata e non si sono focalizzate sui risultati di una metodica di chirurgia non invasiva messa a punto presso la Divisione di Chirurgia Vascolare dell’Óspedale di Ferrara dal Dr. Zamboni. Il dato per certi aspetti “sorprendente” e´che questo intervento non ha come obbiettivo una patologia vascolare ma la Sclerosi Multipla.

 

 

 

 

 

 

 

On January 25, Drs. Zamboni and Salvi joined a scientific panel of the Italian Multiple Sclerosis Foundation to share and discuss data on the etiopathogenetic relevance and therapeutic implications of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS).

 

Dr. Zamboni reviewed evidence suggesting that CCSVI may participate in causing the disease rather than being a consequence of it: data from a small number of biopsies taken from patients with MS suggest that a subversion of the normal vessel architecture may take place since components of the tunica media such as smooth muscle cells and vasa vasorum are found in the adventitia. Furthermore, jugular veins have “inverted” valves and vessel walls are not infiltrated by mononuclear cells. According to Dr. Zamboni it is hard to imagine that such alterations are a consequence of the neurological disease. They may rather participate in determining the central nervous system damage: besides the hypothesis put forward in the early papers, mainly linked to iron deposition, it has now been suggested that a chronic oscillatory (rather than laminar) flow may have proinflammatory effects at the level of post-capillary venules through the activation of NFkB via fibronectin.

All participants shared the impression that much work remains to be done to fully understand how a condition such as CCSVI, that appears to be relatively well compensated, can cause a severe disease such as MS. Also the “static” features of CCSVI alterations do not easily explain a central nervous system involvement that can typically migrate from one neurological system to another during the course of the disease. Furthermore, severe venous thromboses of the jugular veins, such as those that complicate major cardiac surgery, do not seem to lead to pathology that resembles MS. Dr. Zamboni suggested that the truncular location of the stenoses, besides being an element of specificity of CCSVI in MS (asymmetries, hypoplasias and stenoses are frequent intracranially in healthy individuals but are never seen at the truncular level), may induce flow alterations that are indeed consistent, at sites where high blood volumes have to be dealt with. However, there appears to be neither correlation between lesion load and severity of CCSVI nor between side of the lesion and lateralization of symptoms. On the contrary, data from Dr. Zamboni’s group support a linear correlation between venous hemodynamic severity score and MRI measures of cerebrospinal fluid flux and parenchyma volume at the posterior fossa level.

 

Technical aspects were also discussed including intra- inter-observer reproducibility. It was felt that further efforts are required in order to optimize an aspect that is crucial for subsequent studies that should be ideally carried out at different research centres on large numbers of subjects. According to Dr. Zamboni, a good agreement can be reached after a 15-day training period if the trainee is already familiar with arterial dopplersonography. Dr. Zamboni was also willing to provide such training in view of future collaborative studies. Also in view of future studies, the possibility o simplifying the assessment of CCSVI was taken into consideration. It emerged that transcranial dopplersonography is relevant for a 10% of all the diagnoses, all restricted to patients with the primary progressive form of the disease. Participants also discussed whether MRI venography could add information to dopplersonography and selective venography. In Dr. Zamboni’s opinion, the possibility of false positives and negatives and its failure to image the azygous vein hamper the use of this technique for the assessment of CCSVI.

 

Results of the open label study of endovascular treatment of CCSVI were also discussed. All participants agreed that the results of this trial have to be regarded as preliminary.  Study design, outcome measures, patient selection were felt to be insufficient to provide information on the effects of the procedure.

 

Dr. Zamboni and the Commission agreed that CCSVI does not represent the cure of multiple sclerosis. The results obtained so far deserve a thorough attention from the scientific community since CCSVI has the potential to offer new tools to the treatment of MS.

 

The Panel of Italian MS Foudation in a following meeting expressed an answer to three key questions on the subject.

 

Q) Are the technical aspects of the assessment of CCSVI enough clear and defined to be used in different laboratories?

 

A) The technique proposed and the scoring and validation system need to be confirmed in other laboratories in order to be widely accepted.

 

Q) Are epidemiological data enough clear to refer to an association between CCSVI and multiple sclerosis?

 

A) Available evidences suggest that MS is a multifactorial disease. The role of CCSVI is an intriguing observation which need to be further explored (larger sample size, appropriate control groups including other inflammatory and neurological diseases, more pathophysiological data, longitudinal studies, to assess also correlation with disease courses and severity).

 

Q) Is the present knowledge on CCSVI sufficient to promote clinical trials in MS patients at this stage?

 

A) In the absence of the evidences required above, it is considered premature to embark now on clinical trials.

The acquisition of new information as required in part 1 and 2, may in a short time open the opportunity for the assessment of the value of endovascular treatment of CCSVI with appropriate controlled clinical trials design.