Published in the Annals of Neurology-

http://www.ncbi.nlm.nih.gov/pubmed/21061390

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.

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

LETTER

VC 2010 American Neurological Association 1

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