This Is MS Multiple Sclerosis Community: Knowledge & Support

Unlike previous reports of hypoxic-ischemic demyelination, our patient lacked any cortical abnormalities, presumably due to isolated white matter changes. This report alerts physicians to the possibility of hypoxic-ischemic demyelination due to global hypoxia-ischemia as an etiologic factor for neurogenic bladder.

A 40-year-old male presented with acutely oncoming neuropsychiatric symptoms in the form of extrapyramidal disturbances, personality change, behavior changes and urinary incontinence. One month prior to this symptomatology, he had been found unconscious in his closed room where a coal fire was burning overnight. He recovered completely in two days with supportive therapy. Magnetic resonance imaging during this presentation showed bilateral white matter changes suggestive of demyelination.

The potential for hypoxia and other cardiovascular issues to cause demyleinating lesions as described by Zamboni et al seems intuitively plausible enough.

However, does anyone have any thoughts on the mechanism by which a cardiovascular abnormality would lead to the CSF abnormalities--oligoclonal bands, IgG/albumin ratio, protein synthesis rate, etc.--seen by many/most MS sufferers?

This part is puzzling to me.

Would be interesting to see a new lumbar puncture from him....but I doubt he'll do it!

Cerebrospinal fluid which contains higher weight proteins (IgG, IgA, IgM) shows the diffusion of plasma across an altered blood brain barrier. CSF with oligoclonal bands shows intrathecal synthesis. All of these changes to the CSF can occur when the blood brain barrier is breached.

Right...I know how the lumbar puncture works. All I'm saying is that the bands that show antibodies from myelin being destroyed inside the CNS are ultimately due to the break in the blood brain barrier, and how this fits with the CCSVI research.

As far as I know, the antibody bands seen in the CSF are not a result of demyelination. They are a marker for MS, but I don't think anyone knows why the antibodies are in the CSF.

By the way, unless I missed it, I don't think Zamboni mentions hypoxia in any of his papers.

At high altitudes, the reactive oxygen species are continuously generated as a consequence of low oxygen partial pressure (hypoxia), which causes tissue damage. The body's defence system to combat the oxidative stress (e.g., anti-oxidant enzymes, free radical scavengers such as vitamin C, vitamin E, beta-carotene, reduced glutathione and minerals such as selenium, etc.) may diminish. In the present study, the antioxidant effect of selenium (Se) in reducing the hypoxia-induced oxidative stress was evaluated by exposing male albino rats to hypoxic stress in a decompression chamber. Exposure to hypoxia resulted in an increase in malondialdehyde (MDA) levels in plasma and tissues and a concurrent decrease in blood glutathione (GSH), glutathione peroxidase (GPx), plasma protein and plasma selenium content when compared with controls. Haemoglobin concentration (Hb%), red blood corpuscles (RBC) and white blood corpuscles (WBC) count were also increased in the hypoxia-exposed group. Selenium supplementation to animals reversed the trend. There was a significant decrease (P < 0.001) in MDA and subsequent increase in plasma and tissue GSH levels. Similarly the blood and tissue GPx and plasma protein also increased significantly in the Se supplemented animals compared with control animals. The Hb%, RBC and WBC counts showed no significant difference between Se-fed and control rats. These results suggest that selenium may help in reducing the lipid peroxidation during hypoxia.

One specific pattern of demyelination is defined by an oligodendrogliopathy, primarily affecting the most distant processes of these cells and leading to apoptotic cell death of oligodendrocytes at later stages of lesion development (Lucchinetti et al., 2000). These alterations of oligodendrocytes and myelin are similar to those present in acute ischaemic white matter damage and are associated with nuclear expression of hypoxia‐inducible factor‐1α (HIF‐1α).

T cell reactivities to the putative autoantigens myelin basic protein (MBP), MBP peptides with amino acid residues 110-128 and 148-165, and myelin proteolipid protein (PLP) were examined in patients with acute ischaemic cerebrovascular disease (CVD) and, for comparison, in patients with inflammatory neurological diseases and other neurological diseases. A quantitative measure of these T cell reactivities was obtained by assessing numbers of T cells among blood and cerebrospinal fluid (CSF) mononuclear cells that secreted IFN-gamma in response to antigen in vitro. Higher numbers of T cells reactive with each of these four antigens were detected in peripheral blood from patients with CVD compared with patients of the two control groups. Among blood cells from the CVD patients, their average number was 2.3-4.2/10(5) mononuclear cells. MBP reactive T cells were several-fold enriched in the CSF of CVD patients. The findings strongly suggest that brain damage in context with acute CVD leads to an in vivo expansion of myelin reactive T cells.

To date, there has been little interest in exploring the possibility that autoimmune responses to brain antigens might affect outcome from stroke. There are, however, studies that document the fact immune responses to brain antigens do occur following stroke. For instance, lymphocytes from stroke survivors show more activity against MBP than the lymphocytes from patients with multiple sclerosis.18,19 In addition, myelin-reactive T cells are found in higher numbers among patients with cerebrovascular disease.20

These data thus provide evidence that a cellular immune response to brain antigens occurs following stroke. Furthermore, there are increased titers of antibodies to brain antigens, including neurofilaments and portions of N-methyl-D-aspartate receptor, following stroke, indicating that there is also the development of a humoral response to these antigens.21,22 The immune response to CNS antigens after stroke is likely just an epiphenomena of stroke given that cerebral ischemic injury to the blood–brain barrier allows for the systemic immune system to come into contact with the antigens that are normally sequestered from it. Nonetheless, it is possible that this response leads to "collateral damage"; whether these immune responses affect outcome from stroke is largely an unanswered question.