Current rationale for CCSVI treatment

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Current rationale for CCSVI treatment

Postby Cece » Tue May 14, 2013 7:52 am

http://www.sitesymposium.org/
https://www.facebook.com/notes/ccsvi-al ... 5820392783
from Dr. Zamboni, written for the 10th International Symposium of Endovascular Therapeutics in Barcelona, Spain, which was held this past weekend

Chronic cerebrospinal venous insufficiency (CCSVI) has been described as a vascular condition characterized by anomalies of the main extra-cranial cerebrospinal venous routes that interfere with normal venous outflow in patients with multiple sclerosis (MS). (1-4)Recent studies demonstrated that these venous abnormalities are not exclusive to MS patients, and that patients with other neurological diseases or even healthy individuals can present with these anomalies.(5-8) The clinical and MRI correlates of these findings are still unknown,and at this time it is not clear whether CCSVI may influence disease progression in MS (9-13) or play a role in CCSVI-induced cerebral hemodynamic alterations in MS and healthy individuals. (14)

Percutaneous transluminal angioplasty (PTA) for CCSVI-related abnormalities was introduced in an open-label study that evaluated its safety and efficacy on clinical and MRI outcomes in 65 MS patients over 18 (1) and 24 months of follow-up. (15) Additional open-label studies confirmed that the PTA procedures are relatively safe. (16-19) However,these studies were not blinded,controlled or randomized, and patients were not stratified with respect to their standard disease-modifying treatment (DMT) during the follow-up. Only one controlled pilot study investigated the safety and efficacy of PTA for CCSVI-related abnormalities in patients with relapsing-remitting (RR) MS. (20)While this small pilot study showed that PTA of CCSVI was related to partial improvement in clinical and MRI outcome measures of patients with MS, it could not recommend PTA as a treatment for MS, and warranted placebo-controlled trials with a larger number of patients and use of more advanced imaging techniques to assess cerebral fluid-dynamic changes after PTA.Therefore at this time, it is unknown whether PTA for CCSVI can improve CCSVI-induced cerebral fluid-dynamic abnormalities in patients with MS or with other neurologic diseases, or in healthy individuals.

Given that CCSVI is characterized by stenoses of the cerebral venous drainage system, there is reason to believe that the condition might induce subtle venous hypertension in the superior sagittal sinus (SSS),which in turn would tend to reduce the bulk flow of cerebrospinal fluid(CSF) into the sinus from the subarachnoid space – a finding that was shown in a recent pilot study including small number of MS patients and controls. (21) This has led us to hypothesize that CCSVI might be having an effect on the CSF-dynamics in patients with MS.

In order to explore this issue, the present study was designed to investigate whether PTA in patients with MS on standard DMT and diagnosed with CCSVI can modify characteristics of CSF flow and velocity outcomes.

Material and Methods:

This was a case-control MR blinded 12 months study that included 15 patients with RRMS who presented with significant stenoses (≥50%lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (cases), while7 had delayed PTA after 6 months of medical therapy alone (controls).CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle using a semi-automated method. Outcomes were compared between the two groups at baseline, 6 and 12 months of the study using mixed effect model analysis.

Results:

At baseline, no significant differences in CSF flow or velocity measures were detected between the 2 groups. At month 6, significant improvement in both flow and velocity outcomes were detected in the immediate compared to delayed groups, persisting to month 12. Within group flow comparisons from baseline to follow-up showed significant increase in immediate group (p=0.033), but decrease in delayed group (p=0.024). Altered CSF flow and velocity measures were associated with worsening of clinical and MRI outcomes in delayed group.

Conclusions:

PTA of MS patients with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.
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Re: Current rationale for CCSVI treatment

Postby ttucker3 » Tue May 14, 2013 10:51 am

Thanks for this Cece. Delighted to see mention of localized hypertension. Next question is what would the impact of elevated pressure on the permeability of the blood-brain-barrier to leukocytes?
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Re: Current rationale for CCSVI treatment

Postby Cece » Tue May 14, 2013 12:34 pm

CCSVI leads to localized hypertension leads to more permeable blood-brain barrier leads to leukocyte infiltration across blood-brain barrier. That should be researchable, I don't know if anyone is on it.

Given that CCSVI is characterized by stenoses of the cerebral venous drainage system, there is reason to believe that the condition might induce subtle venous hypertension in the superior sagittal sinus (SSS),which in turn would tend to reduce the bulk flow of cerebrospinal fluid(CSF) into the sinus from the subarachnoid space – a finding that was shown in a recent pilot study including small number of MS patients and controls.

CCSVI leads to localized hypertension in the SSS leads to reduction of cerebrospinal fluid flow into the SSS.
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Re: Current rationale for CCSVI treatment

Postby 1eye » Wed May 15, 2013 6:03 pm

CSF flow is also affected when there is a problem with drainage (CCSVI) of the head, because the CSF drains into the veins. There is an endoscopic procedure which involves an improvement to the CSF drainage, which is used in Normal Pressure Hydrocephalus. This involved making a drainage hole in the ventricle wall. I would like to learn more of the difference(s) between normal and high pressure hydrocephalus, and their origins. When NPH happens it can bring with it many of the symptoms of MS. This endoscopic drainage procedure can improve walking disability and the recipient may walk normally again.

I would like to see PTA and possibly the endoscopic procedure become first-line therapies for CCSVI.

I would volunteer as a subject for any study of this, since venous drainage may be a common thread in all my family's various auto-immunities, of which there are/were many. My brother was born with high pressure hydrocephalus, and has had a shunt all his life (now in has forties). My mother was on dialysis due to damage from vasculitis.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
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Re: Current rationale for CCSVI treatment

Postby ttucker3 » Thu May 16, 2013 11:13 am

I don't know of anyone who is on it either Cece. But as a footnote, I suspect Zamboni of being a master of understatement. I suspect over-pressure in the SSS that is not subtle at all, but perhaps 80% above normal. This can't be measured directly by any method that I know, but, theoretically, could be measured indirectly with 4D flow quantification MRI. This would measure flow velocity fields and the data then entered into the Navier-Stokes equations to solve for pressure distributions. Not straight forward since boundary values would need to be entered as well, which would include compliance of the veins and venules - not straight forward.
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Re: Current rationale for CCSVI treatment

Postby Anonymoose » Thu May 16, 2013 12:39 pm

Superior Sagittal Sinus Pressure and jugular vein compression (and head elevation/IBT).
http://www.ncbi.nlm.nih.gov/m/pubmed/3522822/
Air embolism is a potential hazard during craniotomy whenever intracranial venous pressure is subatmospheric. In order to better understand both the risk of air embolism and its treatment in neurosurgical patients, the authors have investigated the relationship of superior sagittal sinus pressure (SSP) to head position in 15 children and examined the effects of both jugular venous compression and positive end-expiratory airway pressure (PEEP) on SSP. Progressive head elevation significantly decreased mean SSP and, in five patients, SSP was less than 0 mm Hg at 90 degrees torso elevation. A PEEP of 10 cm H2O was ineffective in significantly increasing SSP at any degree of head elevation, whereas bilateral internal jugular compression always caused a significant increase in SSP. The authors conclude that children are at risk for venous air embolism when undergoing suboccipital craniectomy in the sitting position because intracranial venous pressure is often subatmospheric when the head is elevated. Furthermore, maintaining PEEP does not appear to be a reliable treatment for increasing SSP, whereas bilateral internal jugular compression is effective.

1986!!! Why does it take us so long to make the connections? (Maybe this is already posted on tims...didn't do my homework). It seems like this should make it easy to prove the value of ccsvi PTA. Woohoo??
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Re: Current rationale for CCSVI treatment

Postby Anonymoose » Thu May 16, 2013 1:20 pm

More. Not proof but the suspicion has been there for a while.
http://www.ajnr.org/content/21/8/1497.long
It has been postulated that hydrocephalus in achondroplasia results from elevated SSS pressure, which in turn results from diminished venous outflow through the small jugular foramen (10, 11, 13–15, 27). This increase in SSS pressure is believed to lead to a reduced pressure gradient across the arachnoid villi, from the subarachnoid spaces to the SSS. When the suture is open in infancy, the resultant increased intracranial pressure results in expansion of the calvarium and ventricles until the pressure normalizes (28, 29). Although our study does not offer direct evidence of increased SSS pressure, the results are consistent with the hypothesis that increased pressure of the SSS attributable to restricted venous outflow causes hydrocephalus in achondroplasia.
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