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Med Hypotheses. 2010 Apr 16. [Epub ahead of print]

A possible haemodynamic mechanism for Amyotrophic Lateral Sclerosis.
Arhart RW.

2117 Belaire Drive, Salt Lake City, UT 84109, USA.

Abstract
The hypothesis proposed in this article is that a haemodynamic mechanism may cause Amyotrophic Lateral Sclerosis (ALS). The hypothesis is synthesized from three separate streams of medical research: (1) multiple sclerosis (MS) research; (2) ALS research; (3) atherosclerosis research. Each research stream was reviewed as prerequisite for proposing the hypothesis. A vascular mechanism for MS was first advanced in the medical literature 130years ago. Seventy years ago researchers knew that the plaques aligned along a central vein, and the wall of that central vein was damaged and leaky. Twenty-five years ago the refluxing blood mechanism was proposed. Zamboni imaged the veins of MS patients in 2007 and saw stenoses, twistings, and membrane blockages in the jugular, azygous, and vertebral veins, and refluxing venous blood upstream of the constrictions. The refluxing blood damages the blood-brain-barrier (BBB) of the veins. Leakage of blood components into the central nervous system then causes the plaques in the brains of MS people. Zamboni dilated the venous constrictions endovascularly, and the MS symptoms and brain plaques diminished dramatically. ALS research has recently revealed that this disease is started by blood-spinal cord-barrier (BSCB) damage. The ALS mutant mouse shows BSCB damage and down regulation of tight junction proteins Occludin and ZO-1 before motor neuron harm. Samplings of ALS patients' spinal cords show downregulation of mRNA for tight junction proteins compared to controls. Atherosclerosis research provides the mechanism for how the refluxing blood breaks the tight junctions between the endothelial cells of the veins. Atherosclerosis research on blood flow effects shows that normal pulsatile laminar blood flow is necessary for maintenance of the tight junctions between endothelial cells. Abnormal flow conditions, such as turbulent, stopped, or reversed flow, cause downregulation of tight junction proteins Occludin and ZO-1. Blood flow (haemodynamic) effects explain the BBB damage in MS and may explain the BSCB damage in ALS. The hypothesis: ALS is caused by constrictions in veins draining the spinal cord and brain, which cause venous reflux, which downregulates tight junction proteins Occludin and ZO-1, which leads to breaks in the tight junctions between endothelial cells in the veins, which leads to leakage of toxic blood components into CNS tissue. The consequences of the hypothesis are discussed. If a venous constriction can be reached endovascularly it can be dilated, and such dilation may constitute cure of ALS. Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20400230 [PubMed - as supplied by publisher]

cheerleader wrote:We had a thread going on ALS and that paper a couple of weeks ago...

The hypothesis: ALS is caused by constrictions in veins draining the spinal cord and brain, which cause venous reflux, which downregulates tight junction proteins Occludin and ZO-1, which leads to breaks in the tight junctions between endothelial cells in the veins, which leads to leakage of toxic blood components into CNS tissue.

gibbledygook wrote:Hi,

Sorry I can't keep up with all the posting either!!
Yes, I think Prof Dake said it was arterial blockages in the shoulder of an astrophysicist. I do so hope they start checking the possibility that these neurological diseases may have perfectly simple mechanical/structural explanations or contributions.


I'm due to have a c-section on the 24th june but I may have it earlier as the obstetrician was today concerned that the baby may not be growing so well as my tummy was only 32cm rather than 34/35cm. My blood pressure has also collapsed again to 70/30 and he is worried about placental hypoperfusion. On the other hand 2 days ago the ultrasound sonographer gave the baby a very good weight so I'm not sure that either of them have accurate means of determining the baby's weight/growth! I can't wait for it to be over though. Pregnancy has been a heck of a lot tougher than I thought it would be.