Professional Documents
Culture Documents
E Mark Haacke
Director, The MRI Institute for Biomedical Research and Director, MR Research Fa
cility, Wayne State University, MI, USA
nmrimaging@aol.com
From
Expert
Review
of
Neurotherapeutics
Abstract
and
Introduction
Abstract
Recently, it has been demonstrated that there is reduced perfusion and even loss
of small medullary vein visibility in MS.[8] Juurlink
discusses the role of hypoperfusion in MS.[25] He comments that the reduced perf
usion can be detrimental to oligodendrocytes,
preferentially affects white matter, causes demyelination and leads to microglia
l activity. He notes that these can be most marked in
the optic nerve and tract. He then states: "There is now ample evidence that isc
hemic insults of sufficient severity can cause
upregulation of cell adhesion molecules onto the endothelial cells, thus allowin
g infiltration of leukocytes into the brain parenchyma,
resulting in an inflammatory lesion." He goes on to point out that hypertension
of genetically susceptible lesions leads to vascular
damage, which in turn leads to ischemia. There is actually a body of evidence su
ggesting reduced perfusion in MS patients. Back in
the 1980s, Swank et al. found that past the age of 40 years, MS patients had mar
kedly reduced blood flow compared with normal
individuals.[26] Using MRI, there has been a thrust in the last 10 years to stud
y perfusion in MS. The work of Meng Law[27] and others
[28 32] demonstrates that there is reduced perfusion as a function of severity of
disease. Law et al. reported a significant decrease of
cerebral blood flow and a prolongation of mean transit time in the normal-appear
ing white matter (NAWM) at the level of the lateral
ventricles in MS patients.[27] These reductions often appear in the basal gangli
a and thalamus and have been related to fatigue.
[30,31,33] A study of seven patients with relapsing remitting MS revealed decrease
d relative cerebral blood volume (CBV) in chronic
lesions and further reduced relative CBV in one acute lesion in white matter com
pared with that in gray matter.[27] Haselhorst et al.
examined 25 patients with MS and found that acute lesions had significantly high
er relative CBV than NAWM and that chronic
plaques had significantly lower relative CBV than NAWM.[34] Inflammatory activit
y can cause compensative vasodilatation and result
in increased cerebral blood flow and CBV, which is found in enhancing lesions. O
n the other hand, any evidence of increased
perfusion in some chronic nonenhancing lesions can be explained by lesion reacti
vity with new vascular inflammatory changes.
Clinical
Evidence
of
Venous
Abnormalities
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Chronic Cerebral Spinal Venous Insufficiency in Multiple Sclerosis (printer-frie
ndly) Pagina 5 di 6 -friendly) Pagina 5 di 6
Figure 1. A magnetic resonance venogram from a multiple sclerosis patient showin
g a tight stenosis (long, thin arrow) of the
left internal jugular vein in the region of the confluence of a vertebral vein (
short, thick arrow) into the trunk of the left internal
jugular vein.
Conclusion
The above discussions provide varied evidence that the venous system plays a maj
or role, or in the least is associated with, MS.
Past efforts in immunology have been impressive. More recent efforts in understa
nding how vascular abnormalities lead to
immunological effects are suggestive. Perhaps it is time to be thinking of a 'va
scular immunology' focus in the study of neurological
disease, an interesting marriage between cardiovascular and neurodegenerative re
search. A recent review has promoted this
concept as it relates to vascular endothelial health[47] and is written focusing
on MS as a vascular disease. It behooves us to follow
this advice, especially in light of the work of Zamboni and now many others foll
owing in his footsteps worldwide that suggest the
venous vascular system may be strongly associated with MS.
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Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organi
zation or entity with a financial interest in or financial conflict with the sub
ject
matter or materials discussed in the manuscript. This includes employment, consu
ltancies, honoraria, stock ownership or options, expert testimony, grants
or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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