There is a new study published in Neurology that attempts to prove there is no such thing as CCSVI in MS. The neurologists in this new study measure ferritin levels in cerebral spinal fluid and do not find high levels of ferritin in the CSF in pwMS. Ferritin is a protein that binds to iron in the body. Since there is not a lot of ferritin (but there is some!) in the spinal fluid of pwMS the neurologists conclude there is no iron deposition in MS brains. But they are looking at the wrong biomarker.....
Here's the study abstract:
Normal CSF ferritin levels in MS suggest against etiologic role of chronic venous insufficiency
V. Worthington, PhD, J. Killestein, MD, PhD, M.J. Eikelenboom, MD, PhD, C.E. Teunissen, PhD,F. Barkhof, MD, PhD, C.H. Polman, MD, PhD, B.M.J. Uitdehaag, MD, PhD and A. Petzold, MD, PhD
From the Department of Neuroimmunology (V.W., A.P.), UCL Institute of Neurology, Queen Square, London, UK; and MS Center Amsterdam (J.K., M.J.E., C.E.T., F.B., C.H.P., B.M.J.U., A.P.), Free University Medical Center, Amsterdam, the Netherlands
Address correspondence and reprint requests to Dr. Axel Petzold, Free University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam, the Netherlands a.petzold@vumc.nl ora.petzold@ion.ucl.ac.uk
Objectives: Chronic cerebrospinal venous insufficiency has been suggested to be a possible cause of multiple sclerosis (MS). If the presumed mechanism of venous stasis–related parenchymal iron deposition and neurodegeneration were true, then upregulation of intrathecal iron transport proteins may be expected.
Methods: This was a cross-sectional (n = 1,408) and longitudinal (n = 29) study on CSF ferritin levels in patients with MS and a range of neurologic disorders.
Results: Pathologic (>12 ng/mL) CSF ferritin levels were observed in 4% of the control patients (median 4 ng/mL), 91% of patients with superficial siderosis (75 ng/mL), 73% of patients with a subarachnoid hemorrhage (59 ng/mL), 10% of patients with relapsing-remitting MS (5 ng/mL), 11% of patients with primary progressive MS (6 ng/mL), 23% of patients with secondary progressive MS (5 ng/mL), and 23% of patients with meningoencephalitis (5 ng/mL). In MS, there was no significant change of CSF ferritin levels over the 3-year follow-up period.
Conclusion: These data do not support an etiologic role for CCSVI-related parenchymal iron deposition in MS.
http://www.neurology.org/cgi/content/abstract/WNL.0b013e3181fb449ev1?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=ferritin+CCSVI&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
Note that the researchers find ferritin in 91% of the patients with siderosis and subarachnoid hemorrhage--that's because these are major brain infarctions, and ferritin is a terrific measure for people who suffer strokes and bleeding on the brain. But it is NOT a measure of ongoing chronic venous disease.
Dr. Zamboni writes about this in his Big Idea paper. He discusses how an appropriate measure is not ferritin levels, but hemosiderin levels. Here he discusses increased iron in the legs in chronic venous disease--
"The origin of increased leg iron stores is extravasation of red blood cells (erythrocytes) in conditions of significant venous stasis. Erythrocytes are degraded by the interstitial macrophages, with the released iron incorporated into ferritin. Over time, with increasing overload of iron, the structure of ferritin changes to haemosiderin.4-9 In 1988, Ackermann found a twenty-fold higher average concentration of iron in lower limbs affected by venous ulcers as compared to the upper arm of the same subjects.8 The phenomenon of leg haemosiderin deposits seems to be significant for the entire body, since this protein has been demonstrated in the urine of patients affected by CVD.9"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/
So, hemosiderin is the more appropriate measure of long-standing venous disease, like CCSVI...because ferritin changes over time to hemosiderin. And CCSVI is a chronic, on-going disease. As a matter of fact, Dr. Zamboni measured hemosiderin in pwMS, and guess what? He found, by doing a simple urine test, that pwMS had high levels of hemosiderin! Just like those with chronic venous disease in their legs.
Dr. Zamboni writes about how the appropriate measure for chronic venous disease is hemosiderin, NOT ferritin....and yet, here's a new study saying the ferritin levels in CSF prove there's no CCSVI.
I'm sorry, but I'm just a slightly bright person with no medical training who knows how to read medical journals, and even I can see that this new study is using the WRONG biomarker. How can these neurologists continue to publish this tripe, which, in this instance, is looking at the wrong biomarkers for chronic venous disease? How can they get away with this?
Ah, yes...here's a name I recognize. One of the researchers in the study is Dr. Frederik Barkhof. Dr. Barkhof was one of the authors with Dr. Khan in the Annals of Neurology opinion piece earlier in the year. Dr. Barkhoff was also a member of the NMSS "CCSVI - International Scientific Panel Formed to Expedite Review of Submitted CCSVI Research Proposals" last March. The panel that only approved research proposals submitted by other neurologists, not vascular doctors or anyone who had any knowledge of CCSVI. And last, but certainly not least--- Dr Barkhof has received research support from the Dutch MS Research Foundation and Merck- Serono; consultancy and speaking honoraria from EMD Merck-Serono, Bayer-Schering Pharma, Biogen-Idec, UBC, Sanofi-Aventis, Novo-Nordisk.
Does anyone else see a pattern emerging? "Research" papers that are rushed to publication, that DO NOT follow Dr. Zamboni's protocol and say there is no CCSVI. Papers that are written by the same cast of characters, the same good old boys club that works together and votes to give each other research grants and meets up at the pharmaceutical conventions time and time again. How can this charade continue?
I'm hoping that medical professionals will speak out...that vascular doctors will take Dr. Zamboni's suggestion and MEASURE HEMOSIDERIN LEVELS IN URINE of pwMS. How hard it that? Certainly a lot easier than taking spinal fluid and measuring the WRONG marker for chronic venous disease. I know Jeff's levels were sky high prior to angioplasty. How about yours?
Any takers? Let's get out the paper cups.
Joan