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BOLD fMRI responses during cognitive tasks in Multiple Sclerosis and effects of angioplasty
Buracas G1, Ponec D2, Gooding J2, Saxon R2, Haacke M3, Sauder H4, Hubbard D4 1Dept Radiology, University of California, San Diego, 2North County Radiology, SanDiego, 3Wayne State U, Detroit MI, 4Applied fMRI Institute, San Diego

Abstract
Introduction
There is renewed interest in the hypothesis that multiple sclerosis may be associated with impaired clearance or insufficient CNS venous drainage - chronic cerebrospinal venous insufficiency (CCSVI). FMRI BOLD offers the possibility to evaluate both neuronal population responses and cortical hemodynamics. Specifically, venous drainage from cortex can be assessed directly by measuring the component of the BOLD hemodynamic
response (HDR) known as the venous undershoot.

Methods
20 patients with multiple sclerosis and 20 normal controls were studied by functional MRI.
The cognitive task was designed to activate a maximum number of cortical and subcortical regions while still being intuitive to an untrained person. The MS patients were re-tested after undergoing internal jugular venoplasty. MR venography, flow quantification and fMRI were conducted on a Siemens 3T scanner.

Results
In healthy control subjects, the task evoked activation in an extensive set of brain areas (task-positive network), including visual, parietal, temporal and frontal cortices. In MS patients the task showed significantly reduced (30-70%) activations compared to normal controls. The default (task-negative) network, in particular the medial prefrontal, posterior cingulate and cuneus cortices, also showed pronounced differences in MS patients compared to the normal controls. Specifically, these areas were not suppressed during task performance in contrast to the expected suppression seen in the normal controls. The time course of the BOLD response showed greater decay and a more pronounced undershoot as compared to the control group. Venoplasty resulted in recovery of the task-negative effects in the default network such that the comparison between controls and post-venoplasty MS patients showed no significant differences (t-test, p<0.05). The pair wise t-test of pre- and
post-venoplasty activations confirmed that the default network suppression was increased post-venoplasty as compared to pre-venoplasty in the same subjects. The task-positive network on the other hand, did not show significant changes as a result of the procedure.
Conclusions
The finding of significant differences between normal controls and MS patients in BOLD response patterns associated with a cognitive task in both task-positive and task-negative cortical networks sheds light on neuronal mechanisms of cognitive impairment in MS patients. Most remarkably, the inhibition of the default network appears to be impaired in posterior parietal and anterior medial prefrontal cortex and this impairment is reversed and in fact normalized by venoplasty. Since BOLD response is a function of cerebral blood flow and volume, and also oxygen metabolism rate, the reduced BOLD responses in both task positive and task-negative networks may reflect not only altered neuronal function but also change in cortical venous blood volume in MS. Thus the recovery of the suppression
in the default network by angioplastic treatment may reflect recovered neuronal and/ or vascular function. Moreover the increase in the venous undershoot component of the BOLD response in MS as compared to controls and its reduction after venoplasty provides evidence of impaired clearance and CNS venous insufficiency and holds out the promise
that this method may provide an objective diagnostic test.
References
Buxton RB, Uluda􀀃 K, Dubowitz DJ, Liu TT. (2004) Modeling the hemodynamic response to brain
activation. Neuroimage, 23 Suppl 1:S220-33.
Zamboni P, Menegatti E, Bartolomei I, Galeotti R, Malagoni AM, Tacconi G, et al.
Intracranial venous haemodynamics in multiple sclerosis. Curr Neurovasc Res 2007;4:252-8.

If you are seeking balanced information on balloon venoplasty go to
www.ccsvi.org and read the info many times over. Listening to the naysayers is dangerous as they appear to raise doubts by asking questions but are naysayers.

Scientists know that nothing is ever proven. Balloon venoplasty for stenosed veins is a personal choice based on your MS and ability to pay. Read my story if you wish.

MarkW

For the sake of this post not turning into an angry tirade against the "naysayer" this will be my last post on this thread.

While I'm among the loudest critics of going by what "seems" to be the case it does "seem" that those not finding benefit from "liberation" are increasingly losing their fear of posting their results and it seems to me they are in the majority here at thisisms recently.

What I find most interesting and confusing is that most of them remain die hard believers despite the loss of cash and lack of (positive) results.

Do you have any liberation studies contrary?

You're asking if I have scientific papers showing that an unproven theory is an unproven theory?

We're learning more about hypoxia and venous undershoot via BOLD technology. BOLD stands for Blood Oxygenation Level Dependent, and it gives a good picture of how the brain uses (or doesn't use) blood. What is of interest is that after venoplasty (not calle Liberation anymore) the pwMS had the same level of respone to testing and BOLD levels as normals.

1)ANY "improvement" they experience is immediately credited to the angioplasty procedure. MS is called relapsing remitting because symptoms wax and wane so a symptom that recedes six months after angioplasty MAY be the result of the natural course of someone's disease.

What about patients who are progressive who show improvements? We have seen such outcomes. It is hard to argue that this would have been the natural course of their disease.

My own improvements were dramatic enough, it would be hard to believe that seeing new degrees of brightness in colors, such as I haven't seen before, was going to happen that week regardless of whether I had the procedure or not. I'd also been getting worse this past year, not better.

I wish there was a way we could erase all preconceptions and inital expectations of the "liberation procedure" so we can better get a handle on what has occurred since Zamboni released his "groundbreaking" study over a year and a half ago. It does seem the miracle recoveries have slowed down which maybe means that we are getting closer to the truth about whether the liberation procedure has any effect on the progression of MS or not. What concerns me are two assumptions that I see continually occurring over and over as people try to accurately report what effect angioplasty has had on their MS.

1)ANY "improvement" they experience is immediately credited to the angioplasty procedure. MS is called relapsing remitting because symptoms wax and wane so a symptom that recedes six months after angioplasty MAY be the result of the natural course of someone's disease.

2)Any studies not reinforcing the validity of CCSVI are flawed. There must come a time that people start recognizing the issue of venous blockage in MS (if it occurs at all) is not as clear cut as Zamboni and some others would like us to believe. It is time people allow science to dictate the direction of CCSVI and not emotionally charged postings on internet websites.

The longer we allow the "myths" surrounding CCSVI to linger the longer it will take for us to get clear cut answers as to the validity of CCSVI.