I've been lurking through the CCSVI discussion and it seems to me a facet of CCSVI that doesn't seem to have received a lot of attention yet is the whole concept of slowed or "hypoperfusion" and its relationship to MS. I've found it's a pretty fascinating topic.
Per Cheer in the "Just the Facts" thread,
Blood that stays in the brain too long creates “slowed perfusion”...a delay in deoxyginated blood leaving the head. This can cause a lack of oxygen (hypoxia) in the brain. This slowed perfusion has been linked to fatigue in MS patients.
This "slowed perfusion" has also been linked to other MS symptoms, disability levels, and, in relationship to the perpetual "chicken and egg" questions in MS, there's preliminary research indicating that it starts early (in CIS) and potentially "jump starts" the pathological process in MS. A little bit about each topic.
First off, from Wikipedia a definiton of hypoperfuison aka ischemia: "Ischemia in brain tissue, for example due to stroke or head injury, causes a process called the ischemic cascade to be unleashed, in which proteolytic enzymes, reactive oxygen species, and other harmful chemicals damage and may ultimately kill brain tissue." Now, some research in the other areas.
Hypoperfusion and Other MS Symptoms
there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.
Our results suggest a role for tissue perfusion impairment in NP dysfunction in MS.
Hypoperfusion in Normal Appearing White Matter (NAWM), RRMS, PPMS and Link to Disability Levels
Compared to controls, CBF and CBV were significantly lower in all NAWM regions in both PP-MS patients (p values from <0.0001 to 0.001) and RR-MS (p values from <0.0001 to 0.020).
Compared to RR-MS, PP-MS patients showed significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in the periventricular and frontal NAWM (p values: 0.0029 and 0.022).
EDSS was significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038, respectively).
This study suggests that the hemodynamic abnormalities of NAWM have clinical relevance in patients with MS. DSC perfusion MRI might provide a relevant objective measure of disease activity and treatment efficacy.
Maybe an MRI outcome measure of stenting should be results from "DSC perfusion" MRI--just a thought.
Hypoperfusion Starts Early-Present in Normal Appearing White Matter in People with CIS and RRMS
White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis
Hypoperfusion has been reported in lesions, normal-appearing white (NAWM) and gray matter (NAGM) of patients with clinically definite multiple sclerosis (MS) by using perfusion MRI. However, it is still unknown how early such changes in perfusion occur.
CONCLUSIONS: CBF was decreased in the NAWM of both CIS and RR-MS patients and in the subcortical NAGM of RR-MS patients suggesting a continuum of tissue perfusion decreases beginning in white matter and spreading to gray matter, as the disease progresses.
Hypoperfusion and Early MS Pathology
This topic is a bit trickier and I'm not into debating the "auto-immune" vs. not topic. This is just some fairly current MS research that could be relevant to a discussion of CCSVI, hypoperfusion and MS.
First off, there's substantial research evidence indicating that there are pathological changes in normal appearing white matter(NAWM) and gray matter in people with MS prior to lesion formation--here's some recent info on the "NAWM".
Preactive Lesions in MS
RECENT FINDINGS: Compelling evidence is accumulating for pathological changes in normal-appearing white matter of MS patients, which occur before the actual development of the active demyelinating lesion. Focal disorder has been documented in normal-appearing white matter of MS months to years before the appearance of gadolinium-enhancing lesions.
SUMMARY: Preactive lesions in MS represent early stages in the formation of destructive MS lesions. As many of them spontaneously resolve, they are expected to hold important clues to stop the inflammatory process in MS.
Now, here's info connecting "hypoperfusion" with this initial MS pathology in the NAWM.
Support for Primary Hypoperfusion in MS
This article (freely available) notes the research re NAWM and diffuse abnormalities prior to lesion formation, and indicates that "the underlying basis for hypoperfusion in MS may be related to ischemia from a primary vascular pathology, or, secondary to decreased metabolic demanded from processes such as wallerian degeneration (WD) of axons transected in distant lesions. The distinction between these mechanisms has potentially important implications, because ischemia may be an early and potentially reversible finding, whereas hypometabolism from axonal degeneration would represent advanced and irreversible disease."
Conclusion:......These findings support the concept of primary ischemia in MS rather than secondary hypoperfusion as a result of WD.
And, don't forget, earlier in this post there's the research that the tissue perfusion starts in the white matter before it proceeds to the sub-cortical gray matter.
All very interesting IMO....hypoperfusion, a side effect if you will of CCSVI, has been linked to MS symptoms (fatigue, cognitive, neuropsychiatric), to RRMS, PPMS and disability levels, has been identified in people with CIS (i.e.,early in the disease process) and early research found the pathological changes in NAWM that precede lesion formation to be attributable to hypoperfusion rather than Wallerian degeneration (which I think would be the most typical MS explanation.)
Comments, observations or other thoughts or ideas on this topic anyone?
I really appreciate all the work and effort Marie, Cheer and others have put into this and want to thank all the "pioneers" as well. Take care all