Published online before print March 21, 2013, doi: 10.3174/ajnr.A3563
AJNR 2013 34: E70

D.J. Radak^a, N. Ilijevski^a and S. Tanaskovic^a
a“Dedinje” Cardiovascular Institute
Vascular Surgery Clinic
School of Medicine, Belgrade University
Belgrade, Serbia

We would like to comment on the recently published study entitled “Mystery of Chronic Cerebrospinal Venous Insufficiency: Identical Venographic and Ultrasound Findings in Patients with MS and Controls” by McAuliffe and Kermode.1

The study aimed to analyze a very interesting and controversial topic that recently produced much debate in medical and patients’ circles. In our opinion, to achieve their goal, the authors used questionable design and methodology, which resulted in numerous limitations of their study.1

Namely, the limited number of the patients and control subjects included makes the whole series inconclusive. Data were missing about the training of actual investigators concerning chronic cerebrospinal venous insufficiency (CCSVI), keeping in mind that the patients examined were their initial 30 cases.1

The authors found internal jugular vein narrowing in 8 of 9 patients without MS by use of venography, but they did not perform sonography (ultrasound) examination before catheterization to determine if these patients might have CCSVI without MS. Therefore, they did not confirm or exclude the presence of CCSVI by ultrasound examination in these patients. Venography performed in these patients only describes the similarity of internal jugular vein narrowing seen in patients with CCSVI and other pathologies. Similarly, by use of ultrasound examination, the authors found no case of CCSVI in the MS group of patients or healthy control subjects, but they did not confirm the absence of CCSVI with catheter venography.1

We do not know if MS is connected with CCSVI, yet morphologic and hemodynamic abnormalities of jugular veins have been seen in patients with MS as well.2

Considering that CCSVI is a new entity and has yet to be defined, besides the ultrasound, we have used MDCT angiography to register and evaluate extracranial venous pathway obstruction in patients with MS.3 MDCT proved to be a very reliable procedure for extracranial venous intraluminal obstruction and extraluminal compression diagnosis.3

In addition to MDCT, during venous percutaneous angioplasty we measured gradient pressures before and after the venoplasty at various obstruction levels to confirm hemodynamic significance of the diagnosed lesions.3

Whether in patients with MS or healthy control subjects, ultrasound, MDCT, or catheter venography and gradient pressure measurement should be performed before the final diagnosis of CCSVI can be made.

Finally, multicentric prospective studies with long-term follow-up are necessary to resolve numerous questions concerning CCSVI that many patients with MS and their physicians pose daily.

References

1. McAuliffe W, Kermode AG. Mystery of chronic cerebrospinal venous insufficiency: identical venographic and ultrasound findings in patients with MS and controls. AJNR Am J Neuroradiol January 31, 2013. [Epub ahead of print] » Search Google Scholar
2. Radak DJ, Kolar J, Tanaskovic S, et al. Morphological and haemodynamic abnormalities in the jugular veins of patients with multiple sclerosis.Phlebology 2012;27:168–72 » Abstract/FREE Full Text
3. Radak D, Tanaskovic S, Antonic Z, et al. Compressive syndrome of internal jugular veins in multiple sclerosis: does it matter? Phlebology September 7,2012. [Epub ahead of print] » Search Google Scholar

Reply

Published online before print March 21, 2013, doi: 10.3174/ajnr.A3579
AJNR 2013 34: E71

W. McAuliffe^a
aNeurological Intervention and Imaging Service of Western Australia
Sir Charles Gairdner Hospital
Nedlands, Perth, Australia

A. Kermode^b
bCentre for Neuromuscular and Neurological Disorders
Australian Neuromuscular Research Institute
Sir Charles Gairdner Hospital
Nedlands, Perth, Australia

We read with interest the letters by Djordje et al and Bavera concerning our article “Mystery of Chronic Cerebrospinal Insufficiency: Identical Venographic and Ultrasound Findings in Patients with MS and Controls.” The correspondents noted the relatively small sample size and the fact the patients with MS did not undergo venography as they did not have 2 abnormal criteria. The venographic findings were also not correlated with sonography. All are true, but the important points of the article are inviolate. The starting point of the chronic cerebrospinal venous insufficiency (CCSVI) entity lies on semiobjective nonvalidated sonographic findings1 obtained by operators who are not blinded to the patient’s condition. This is compounded by a significant trend in the methodology in many articles to consider additional subjective findings of the internal jugular vein valvular appearance as being abnormal. We have indeed cited protocol guidelines that are well-accepted.2 The application of these subjective nonvalidated, nonblinded techniques results in a positive result in 1 defined group, and the subsequent venographic findings are confirmatory. We suggest that the difficulty here is that most humans will demonstrate the venographic findings considered abnormal in CCSVI papers. Any prevenographic screening test that defines a group, be it sonography by specially trained individuals (that cannot be replicated by others3,4), blood tests (in our cases, the prevenogram patients having a high parathyroid hormone or adrenocorticotropic hormone), or perhaps a genetic “profile”, will inevitably result in these “positive” venogram findings. The validity and accuracy of the screening test and the venographic appearance are, in our opinion, unrelated.

The venous system is not analogous to the arterial tree, with marked differences in the number of collaterals, function and drainage in the erect and supine position, the presence of valves, capacitance, and the role of the thoracic cage volume changes. Moreover, the neuroscience community has extensive experience in studying diseases in which there are definite acquired venous stenoses combined with intracranial arterial hypervolemia/hypertension (cerebral dural arteriovenous fistula and arteriovenous malformations), with these cases never having images compatible with cerebral demyelination on cranial MR imaging.

The calling for randomized trials is well in advance of reality. The role of a randomized trial is to compare therapies with scientific bases to establish equivalency/superiority or the safety of one therapy over another action (or inaction). CCSVI, as defined, is not a syndrome, disease, or, we would purport, a medical entity. If the proponents of venous angioplasty wish to support the therapy in the treatment of MS, it cannot be on the basis of “angioplastying” venographic findings seen in the healthy population and purporting them to be pathologic in patients with MS. It must be on the basis of unknown, perhaps humorally mediated, sequelae of subjecting internal jugular vein walls to high-pressure balloon angioplasty. A trial of sham angioplasty versus angioplasty (not easy because awake patients can often see the screen and are aware of their surroundings and operator movements) would be one way of assessing placebo-versus-real sustained improvement in a disease process that waxes and wanes in its effects on patients with time as a matter of course. We would submit such a trial is difficult to mount at this time on the basis of the evidence at hand.

References

1. Baracchini C, Valdueza JM, Del Sette M, et al. CCSVI and MS: a statement from the European Society of Neurosonology and Cerebral Hemodynamics. J Neurol 2012;259:2585–89 » CrossRef » Medline
2. Simka M, Kostecki J, Zaniewski M, et al. Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insufficiency in the patients with multiple sclerosis. Int Angiol 2010;29:109–14 » Medline
3. Mayer CA, Pfeilschifter W, Lorenz MW, et al. The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry 2011;82:436–40 » Abstract/FREE Full Text
4. Doepp F, Paul F, Valdueza JM, et al. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010;68:173–83 » Medline