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Wednesday, November 10, 2010

Dr. Zamboni's published letter in response to the Doepp study

November 10, 2010 at 2:00pm

Published in the Annals of Neurology-

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.3,4

There 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.5
The 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.


To put this in layman's terms---Dr. Zamboni is suggesting that the Doepp study actually proved CCSVI.  
Here's how:  The researchers noted a much larger blood flow volume difference in normal subjects compared to MS patients when the subjects go from a lying down to an upright position.    

What Dr. Zamboni is saying is that normal people have a larger blood flow volume change thru their jugulars when going from lying down to sitting up and the Doepp study proved this!  Dr. Zamboni suggests this might be because of webs, stenosis of faulty valves, like the ones he sees all the time in CCSVI.  

FIGURE 1: High resolution B-Mode image of the internal jugular vein (IJV), in longitudinal access. An intraluminal septum/malformed valve (arrow) causing a significant stenosis, with flow block and increased resistance at the junction with the brachiocephalic venous trunk (BCT), is showed. Intraluminal septation is the most frequent stenosing lesion in course of CCSVI and does not involve the reduction of the vessel cross-sectional area. It can be detected by the means of a probe capable to explore the supraclavicular fossa.

Potential Conflicts of Interest
Nothing to report.
Vascular Diseases Center, University of Ferrara, Ferrara, Italy References
1. Doepp F, Friedemann P, Valdueza JM, et al. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010; DOI: 10.1002/ana.22085.
2. Gisolf, J, van Lieshout JJ, van Heusden K, et al. Human cerebral venous outflow pathway depends on posture and central venous pressure. J Physiol 2004;560:317–327.
3. Zamboni P, Galeotti R, Menegatti E, et al. A prospective open- label study of endovascular treatment of chronic cerebrospinal ve- nous insufficiency. J Vasc Surg 2009;50:1348–1358.
4. Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392–399.
5. Law M, Saindane AM, Ge Y, et al. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology 2004;231:645–652.
DOI: 10.1002/ana.22152
VC 2010 American Neurological Association 1

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