This Is MS Multiple Sclerosis Community: Knowledge & Support

You can't just release fibrinogen, you have to release fibrinogen in the specific environment created by CCSVI hemodynamics.

Let's say the fibrinogen is a trigger leading to inflammation and white matter lesions and that the fibrinogen is a result of the weakened blood-brain barrier as a result of CCSVI hemodynamics/focal hypertension/lack of shear stress. Those same dynamics are also causing a reduction in the transfer of solutes across the blood-brain barrier, and slowed cerebrospinal fluid flow, and maybe some CSF pressure on the brain stem, and reduced oxygen, nutrients and waste removal, and the totality of all these effects is what makes MS be like MS. Theoretically. A complex outcome with a simple solution: venoplasty.

For my edification . . .

I thought that in 2006 Dr. Z speculated that reflux led to a breach of the BBB and consequently the deposition of iron, not fibrinogen. Since Charcot we have noted the peri-venular iron deposition in the brain. As I understand it, both fibrin and iron can can trigger an autoimmune response. Is there some relationship between iron and fibrin?

Fibrin cuffs are not an exclusive finding of CVD, but are commonly visible around cerebral veins in the course of MS and today they are interpreted as ongoing reparative processes20,21 (Figure 1B). MRI venography confirms in vivo the close relationship between the main cerebral veins and the inflammatory plaques. In 94/95 MS lesions, a central vein was visible.22 When cortical lesions occur, they arise within the territory of the principal cortical veins.23,24 In another study, contrast MRI allowed documentation of the break-down of the blood-brain barrier (BBB). Such an injury preceded other MRI abnormalities and the clinical evidence of a new lesion. This supports the view that a defect in the BBB, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of a new lesion in MS.2

For my edification . . .

I thought that in 2006 Dr. Z speculated that reflux led to a breach of the BBB and consequently the deposition of iron, not fibrinogen. Since Charcot we have noted the peri-venular iron deposition in the brain. As I understand it, both fibrin and iron can can trigger an autoimmune response. Is there some relationship between iron and fibrin?

A question was raised elsewhere that seems relevant: if fibrinogen is the trigger, then why wouldn't any insult that released fibrinogen result in the same lesion? So stroke, etc, would look like MS.

Ischemic stroke triggers an acute phase response resulting in a rise of circulating inflammatory markers.19 The induction of tissue injury in the vasculature triggers inflammatory response which activates upregulation of hepatic fibrinogen and initiates coagulation cascade. Because fibrinogen is an acute phase protein, the high concentrations associated with stroke and with its risk factors could at least in part be a response to brain damage and the underlying vessel wall disease. It is, however, a mistake to assume that this detracts from the value of measuring fibrinogen for clinical purposes or from the pathogenetic importance of raised concentrations. Levels of fibrinogen are strongly associated with stroke severity in almost all studied populations.6 Because stroke severity is also strongly associated with mortality and functional outcome after stroke, it is not surprising that fibrinogen is also associated with mortality and outcome. Fibrinogen remains independently associated with mortality and outcome even after adjusting for stroke severity; it seems that this marker may provide additional general prognostic information.

In particular, the effects on stroke prognosis of lowering raised fibrinogen concentrations have not yet been established. There is currently no definitive evidence that lowering fibrinogen will necessarily improve prognosis. However, many secondary prevention interventions have been linked to lower fibrinogen levels. In particular, diet, exercise, and smoking cessation all lead to both reduced fibrinogen levels and reduced vascular risk. Several pharmacological agents proven to reduce vascular risk influence fibrinogen levels. Apart from ancrod,41 which is given intravenously and only in acute situations, there are at present no selective fibrinogen-lowering agents. If and when these do become available, their long-term safety as well as their effectiveness will have to be established to identify the best therapeutic regimen based on fibrinogen concentrations integrated with clinical findings and objective imaging.

J Neuroimmunol. 2010 Dec 15;229(1-2):180-91. doi: 10.1016/j.jneuroim.2010.08.011. Epub 2010 Sep 15.

Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE.

Bennett J, Basivireddy J, Kollar A, Biron KE, Reickmann P, Jefferies WA, McQuaid S.

Source
University of British Columbia, Biomedical Research Centre, Vancouver, British Columbia, Canada.
Abstract
Multiple sclerosis (MS) is a demyelinating disease characterized by the breakdown of the blood-brain barrier (BBB), and accumulation of inflammatory infiltrates in the central nervous system. Tight junctions are specialized cell-cell adhesion structures and critical components of the BBB that have previously been shown to be abnormally distributed in MS tissue. To evaluate whether experimental autoimmune encephalomyelitis (EAE) provides a suitable model for this aspect of MS disease, we examined the expression and distribution of ZO-1 over the course of disease in EAE. We observed a dramatic relocalization of ZO-1 which precedes overt clinical disease and correlates with the sites of inflammatory cell accumulation. Treatment of in vitro cultures of murine brain endothelial cells with components of EAE induction provided similar findings, with relocalization of ZO-1 and increased permeability of endothelial monolayers. BBB disruption in the EAE model appears to parallel disease progression in MS, with direct effects on the cerebrovascular endothelium, making it an ideal tool for future evaluation of tight junction breakdown and repair in MS-like pathology.

For my edification . . .

I thought that in 2006 Dr. Z speculated that reflux led to a breach of the BBB and consequently the deposition of iron, not fibrinogen. Since Charcot we have noted the peri-venular iron deposition in the brain. As I understand it, both fibrin and iron can can trigger an autoimmune response. Is there some relationship between iron and fibrin?

Fibrinogen Level Tied to Poorer PCI Outcomes

http://www.medpagetoday.com/Cardiology/PCI/36734

Thought that Clopidogrel (plavix) is still used by some docs . . in CCSVI venoplasty - but only after the procedure? Perhaps some prescribe for pre-procedure use? Pradaxa would have a similar effect re: fibrinogen I think. This must be standard procedure? I was on Pradaxa for a month post procedure.