Using virtually identical ultrasound techniques to try and reproduce the results by Dr Zamboni, Florian Doepp and colleagues in Berlin have not been able to reproduce the results that put CCSVI on the map. Their results seriously challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS.
What are the implications of these findings for people with MS?
Clearly we need to wait for other studies in this area to clarify the discrepency in the results of these studies. From a clinical perspective we continue to advise against undergoing any interventional therapy until there is clarity on whether or not CCSVI is a real entity or not.
Dr. Zamboni responds to the Doepp CCSVI study results Regarding ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis. Intraluminal Jugular Septation’’ Paolo Zamboni, MD I read with interest the article titled ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis’’ by Doepp and coworkers.1 Contrary to their conclusions, I believe that the authors’ results are a further validation of venous flow irregularities in multiple sclerosis (MS) patients.One of the major regulators of cerebral venous outflow is posture, due to the gravitational gradient between the cerebral parenchymal veins and the base of the neck (␣30mmHg).2 The authors demonstrate a much larger change in blood flow volume in normal subjects compared to MS patients when the subjects go from a supine to an upright position. They find a change of 128ml/min and 56ml/min for the right and left sides, respectively, for MS patients. But they find a much larger change of 266ml/min and 105ml/min for their normal subjects. This result actually suggests the presence of chronic cerebrospinal venous insufficiency (CCSVI). Possible causes include intra-luminal septum, membrane, and immobile valve affecting the hydrostatic pressure gradient in the upright position. The presence of such blockages in the extracranial and extravertebral cerebral veins has been proven also by using catheter venography, the unquestionable gold standard in medicine.3,4There was a trend toward significance (0.06) when comparing the mean global cerebral blood flow (CBF) in MS patients with that in controls. However, the level of significance is under- estimated by the low control sample, 20 versus 56 patients. The reduction in CBF in MS, meaning in practical terms stasis, might become significant by simply increasing the control sample.Both the above-reported results correspond with the reduction in CBF and in cerebral blood volume with increased mean transit time, assessed by means of magnetic resonance imaging (MRI) perfusion study.5The authors failed to demonstrate CCSVI through the assessment of the criteria originally proposed by our group. However, it seems the latter were not precisely assessed. For instance, the authors exchange the parameter for defining stenosis we used in angiographic studies (>50% lumen reduction) with those used in Doppler ultrasonography. In addition, the frequent detection of intraluminal jugular septation is not described by the authors. The latter is the most common cause of flow blockage, and can only be diagnosed with high resolution ultrasonographic probes capable to explore the jugular in the supraclavicular fossa (Fig. 1) 3-4. Clearly, a complete understanding of the system is required before drawing conclusions about the lack of venous abnormalities, and this requires ultra- sound, MRI, and catheter venography. This underscores the urgency of establishing an internationally accepted protocol. In the attempt to achieve this cultural osmosis, my group is available to travel to Berlin and rescan with German colleagues the entire series by the means of the proposed methodology.Source: Annals of Neurology 2010 Nov 8 © 2010 American Neurological Association & Pubmed PMID: 21061390 (11/11/10)
Dr Zamboni has responded to this study in Annals of Neurology 2010 Nov 8 2010. This has also been published on the MSRC website: http://www.msrc.co.uk/index.cfm/fuseaction/show/pageid/2944/Zamboni states:I read with interest the article titled ‘‘No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis’’ by Doepp and coworkers. Contrary to their conclusions, I believe that the authors’ results are a further validation of venous flow irregularities in multiple sclerosis (MS) patients.” He has also offered to travel with his group to Berlin and rescan the subjects of the study with the authors. This is exactly the sort of collaboration needed to help sort the ‘wheat from the chaff’ on this area of research. I would implore Dr Klaus Schmierer to be at the forefront on this issue and to take up this offer from Dr Zamboni.