Before 2009 comes to a close, I'd like to share more research on the decrease of blood flow in the MS brain. There are many researchers around the globe using new MRI technology to study slowed perfusion (slow travel time of blood) in MS brains.
Hypoperfusion (decreased blood flow) in MS- research break-down!
I would like to break down this one medical research paper for you, to show you how these researchers' findings can be linked what Dr. Zamboni has discovered- I will quote sections from the paper- and then we will discuss....
Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance
This work was supported by MS Anders (Amsterdam, The Netherlands).
Jacques De Keyser1,2, Christel Steen2, Jop P Mostert2 and Marcus W Koch2
1Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel,Brussels, Belgium
2Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Correspondence: Professor Dr J De Keyser, Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels 1090, Belgium. E-mail: email@example.com
Received 2 May 2008; Revised 13 June 2008; Accepted 16 June 2008; Published online 2 July 2008.
from the abstract:
"A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss."
-this means that in normal appearing white matter in MS brains, there is a slowing of blood flow which does not appear to be caused by axonal death. Something else is causing the slowed blood flow FIRST-because it shows up before we see lesions.
"The classic teaching is that MS is a T-cell-mediated autoimmune disorder of the central nervous system. However, a number of pathophysiological observations cannot be simply explained on the basis of autoimmune mechanisms. First, the progressive (neurodegenerative) component of the disease continues despite intense immunosuppressive interventions that effectively stop inflammatory disease activity (Coles et al, 1999; Metz et al, 2007; Roccatagliata et al, 2007; Samijn et al, 2006). Second, pathologic studies have shown that some demyelinating lesions develop without a preceding inflammatory reaction (Barnett and Prineas, 2004; Gay, 2007, 2006; Guseo and Jellinger, 1975; Lucchinetti et al, 2000). Third, another intriguing finding difficult to explain by autoimmune phenomena is the finding of a diffuse cerebral white matter hypoperfusion, which is the subject of this review."
-OK. This is basically saying that the prior thought has been that MS is a t-cell mediated disease, autoimmune, blah, blah...we've all heard this. HOWEVER, the researchers wonder, how can the autoimmune hypothesis explain what we (many other researchers) are observing?
1. Even when suppressing the immune system, damage continues in the MS brain
2. Demyelinating lesions appear BEFORE inflammation
3, There is a slowing down of blood flow in cerebral white matter in MS brains
"A number of studies using single photon emission computed tomography or positron emission tomography found reduced cerebral blood flow (CBF) in the gray and white matter of patients with MS, but these findings received little attention in terms of their possible pathophysiological significance (Brooks et al, 1984; Lycke et al, 1993; Sun et al, 1998; Swank et al, 1983)."
-Whaddya know! Researchers have noticed this before, even before the new MRI technologies...see Dr. Swank's name? Their discovery received little attention...but reduced cerebral blood flow in MS has been noted before.
"Ge et al (2005) interpreted the hypoperfusion in NAWM as a vasculopathy in the context of the perivascular inflammations that occur in focal MS lesions. However, although inflammatory infiltrates in MS are typically located around small- or medium-sized veins (Adams, 1989) and in the perivascular spaces surrounding arterioles (Gay, 2006; Gay et al, 1997), microvessel thrombosis is only exceptionally being observed within these lesions (Aboul-Enein and Lassmann, 2005; Wakefield et al, 1994). A primary vascular pathology, as seen in vasculitis, would lead to regional cerebral perfusion defects rather than a generalized microvascular hemodynamic impairment as observed in MS. Furthermore, the finding that enhancing white matter lesions show increased CBF and CBV, likely caused by inflammation-mediated vasodilatation (Ge et al, 2005; Wuerfel et al, 2004), strongly argues against inflammation as the causal factor. The absence of structural (peri)vascular pathology (Aboul-Enein and Lassmann, 2005) indicates that hypoperfusion of the cerebral white matter in MS has a functional origin."
-Here are some of the papers I linked to on the other post. Ge, Wuerfel, Lassmann- they've all noticed this slowed blood flow in the MS brain. These researchers take this further, by noting that the infiltrates are located around VEINS. If MS was a primary vascular disease, like vasculitis, you'd see inflammation all over the brain...but in MS, it's just around the VEINS- and looks to be a primary injury, not secondary to inflammation. This shows that the veins are implicated in this slowed perfusion.
"Accumulating evidence indicates that there is a decreased perfusion throughout the NAWM in patients with MS. It occurs in both relapsing–remitting and primary progressive MS, strongly suggesting that it represents an integral part of the disease process. Ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions). There appears to be a relationship between reduced white matter perfusion and cognitive dysfunction in patients with MS. We provide a hypothetical framework for the reduced perfusion, implicating a key role of astrocyte dysfunction, possibly related to a deficiency in 2-adrenergic receptors resulting in an impaired siphoning and release of K+ in the perivascular spaces. The underlying pathophysiological mechanisms need to be further elucidated as it could ultimately allow us to understand and treat this complex disease better."
-The researchers spend a great deal of time in the paper hypothesizing over causes for this slowed perfusion, and finally admit that there needs to be further study. They write about research into astrocyte (glial cells in the central nervous system) disfunction, but admit they don't really know what's going on. They haven't found the specific cause for this slowed perfusion and lack of oxygen in the MS brain, and further research needs to be done. The things they can show is that MS brains have slowed blood flow, damage due to lack of oxygen that is centered around the veins in the brain, and this happens before lesions form.
So, how does this link to Dr. Zamboni's research? If deoxygenated blood cannot leave the brain in a timely matter, due to blockage and reflux of the veins that drain the brain and spine, there will be damage to the white matter (myelin) because of ischemic or hypoxic injury (lack of oxygen.) Slowed perfusion simply means, slow blood in the brain. I believe Dr. Zamboni has found the mechanical cause for what researchers around the globe have been noticing in the MS brain. More research will tell the full story.
Now, we can look up more papers on "hypoperfusion and multiple sclerosis" and see that other researchers, around the world, are noticing this too-
Here's a mouse study where they actually gave mice optic neuritis and white matter lesions that looked like MS (in the corpus callosum!)- they did it by closing off the carotid arteries (oxygen going in) Doctors at Stanford are now trying to do it by closing the jugular veins in mice (deoxygenated blood leaving the brain, taking too long and slowing the delivery of oxygen in)- and seeing if mice get CCSVI.
-OK. I've got to get cooking for our New Year's Eve Party!!!!
Happy New Year to all. In 2010, my hope is that we get reading, study the recent MS research and become educated patients and care-givers. There will be many doctors coming forward, trying to disprove Dr. Zamboni's research, and using medical phraseology they think will intimidate us. If we have a grasp on the recent research, and know the vocabulary, we can counter their arguments.
The autoimmune theory is just a theory. Until we have facts, let's keep learning together-