Autonomic dysfunction: A unifying MS theory

[MSUK]

Autonomic dysfunction: A unifying MS theory, linking CCSVI, vitamin D3, and Epstein-Barr virus



Abstract
Multiple sclerosis (MS) is a disease with multiple etiologies. The most recent theory of the vascular etiology of MS, Chronic Cerebrospinal Venous Insufficiency (CCSVI), suggests that cerebral venous obstruction could lead to cerebral venous reflux, promoting local inflammatory processes.

This review article offers strong evidence that the route of the observed narrowing of cerebral veins arises from autonomic nervous system dysfunction, particularly cardiovascular autonomic dysfunction....Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2479

[MarkW]

A unifying theory for MS which does not explain the influence of genes in the etiology of MS. Not the whole puzzle, so incomplete.
MarkW

[Cece]

the direct link: http://www.sciencedirect.com/science/ar ... 7212000845

Multiple sclerosis (MS) is a disease with multiple etiologies. The most recent theory of the vascular etiology of MS, Chronic Cerebrospinal Venous Insufficiency (CCSVI), suggests that cerebral venous obstruction could lead to cerebral venous reflux, promoting local inflammatory processes.

This review article offers strong evidence that the route of the observed narrowing of cerebral veins arises from autonomic nervous system dysfunction, particularly cardiovascular autonomic dysfunction.

Ok, the authors have already gone wrong.

1) the stenoses are occuring in the jugular or azygous veins, not the cerebral veins
2) the cerebral veins or parenchyma are widened in MS patients, not narrowed, according to research presented at AAN, which fits with a model of downstream CCSVI blockages resulting in upstream congestion
3) there are valvular blockages and outflow obstructions and intraluminal abnormalities, which is a very different condition than the narrowing of the vein walls themselves; the latter could theoretically be due to autonomic dysfunction, but intraluminal abnormalities could not be due to autonomic dysfunction

Should I even keep reading? I am in agreement that there is autonomic nervous system dysfunction in MS patients, but research has not yet clarified whether the autonomic nervous system dysfunction is a result of the MS or the CCSVI. The immediacy of improvements such as warm feet and sudden ability to sweat after venoplasty would point to those dysfunctions being due to CCSVI.

[1eye]

A unifying theory for MS which does not explain the influence of genes in the etiology of MS. Not the whole puzzle, so incomplete.
MarkW

This link pointed to a lot of discussions of genetics: how rejection of non-self cells influences the immune response, etc. I think susceptibility to Epstein-Barr infections of different types and locations must be determined by genetics. Susceptibility to the varicosity and phlebosclerosis problems we have been discussing might be genetic or epigenetic, or susceptibility to infections which can cause them.

Age of onset sounds like it is genetic, as well as it being congenital. I think it must be like diabetes, which comes in the early and late-onset forms, determined by genes.

I think I agree with your point that we must not wait for research, if we have a treatment, no matter how permanent or impermanent it might be. Death is very permanent. If we had waited for research to further elucidate diabetes before allowing insulin to be used, a lot of people would have died by now.

I have been aware of CCSVI for about three years now. During that time, 1200 Canadians and I don't know how many, worldwide, have died of "MS". Maybe they couldn't all have been saved. But maybe some could.

Kurt Vonnegut wrote about what would happen if people started living too long. I do agree that it would not be a good thing. It's just that some things are more costly than others. That's why at one time the US Surgeon-General said that if smoking causes lung cancer, that might be ok, as it is a quicker and cheaper death.

[1eye]

Aren't the autonomic nerves contained in some kind of sheath with veins in the neck?

[gibbledygook]

I think this is interesting research. Linking autonomic dysfunction and impaired blood flow is entirely plausible when looking at the number of different articles in Pubmed which are related to the above citation. I've copied some from PubMed below which caught my eye. I think the linking of autonomic dysfunction and changes in pressure and venous problems are all somehow linked in a negative feedback loop.

Ann Biomed Eng. 1985;13(3-4):311-20.
Cerebrovascular transmural pressure and autoregulation.
Wagner EM, Traystman RJ.
Abstract
The cerebral blood flow (CBF) response to changes in perfusion pressure mediated through decreases in arterial pressure, increases in cerebrospinal fluid (CSF) pressure and increases in jugular venous pressure was studied in anesthetized dogs. A preparation was developed in which each of the three relevant pressures could be controlled and manipulated independently of each other. In this preparation, the superior vena cava and femoral vein were cannulated and drained into a reservoir. Blood was pumped from the reservoir into the right atrium. With this system, mean arterial pressure and jugular venous pressure could be independently controlled. CSF pressure (measured in the lateral ventricle) could be manipulated via a cisternal puncture. Total and regional CBF responses to alterations in perfusion pressure were studied with the radiolabelled microsphere technique. Each hemisphere was sectioned into 13 regions: spinal cord, cerebellum, medulla, pons, midbrain, diencephalon, caudate, hippocampus, parahippocampal gyrus, and occipital, temporal, parietal and frontal lobes. Despite 30 mm Hg reductions in arterial pressure or increases in jugular venous pressure or CSF pressure, little change in CBF was observed provided the perfusion pressure (arterial pressure minus jugular venous pressure or CSF pressure depending on which pressure was of greater magnitude) was greater than the lower limit for cerebral autoregulation (approximately 60 mm Hg). However, when the perfusion pressure was reduced by any of the three different methods to levels less than 60 mm Hg (average of 48 mm Hg), a comparable reduction (25-35%) in both total and regional CBF was obtained. Thus comparable changes in the perfusion pressure gradient established by decreasing arterial pressure, increasing jugular venous pressure and increasing CSF pressure resulted in similar total and regional blood flow responses. Independent alterations of arterial and CSF pressures, and jugular venous pressure produce opposite changes in vascular transmural pressure yet result in similar CBF responses. These results show that cerebral autoregulation is a function of the perfusion pressure gradient and cannot be accounted for predominantly by myogenic mechanisms.
PMID: 4037460 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/4037460

Am J Physiol. 1988 Dec;255(6 Pt 2):H1516-24.
Effect of jugular venous pressure on cerebral autoregulation in dogs.
McPherson RW, Koehler RC, Traystman RJ.
Source
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Abstract
We determined the importance of a myogenic sensor of cerebral autoregulation by assessing the effect of vascular transmural pressure on cerebral blood flow (CBF) as cerebral perfusion pressure (CPP) was decreased. Decreasing CPP by decreased arterial pressure (Pa) or increased intracranial pressure (Pcsf) decreases transmural pressure, whereas increased jugular venous pressure (Pjv) increases transmural pressure. Regional CBF was measured in barbiturate-anesthetized dogs using radiolabeled microspheres. In group 1 (n = 5), CPP was decreased by decreasing Pa; in group 2 (n = 5), CPP was decreased by increasing Pcsf (Pa = 80 mmHg); and in group 3 (n = 5) CPP was decreased by increasing Pjv (Pa = 80 mmHg). CPP was reduced from 80 to 30 mmHg in 10-mm increments in each group. In groups 1 and 2 regional CBF was maintained as CPP was decreased to 40 mmHg; however, at CPP of 30 mmHg, blood flow to cerebrum, caudate, and periventricular white matter decreased, whereas flow to cerebellum and medulla remained unchanged. In group 3 regional CBF was unchanged as CPP decreased from 80 to 50 mmHg but decreased in all regions as CPP decreased further. In all three groups, cerebrovascular resistance continuously declined as CPP was decreased. In all groups, cerebral O2 uptake was unaltered. Autoregulation fails at a higher CPP with increased Pjv than with decreased Pa or increased Pcsf, particularly in brain stem. We conclude that metabolic autoregulation predominates over the myogenic mechanism until CPP is low.
PMID: 3144187 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/3144187

J Neurosurg. 1998 Jul;89(1):118-24.
Local cerebral blood flow autoregulation following "asymptomatic" cerebral venous occlusion in the rat.
Nakase H, Nagata K, Otsuka H, Sakaki T, Kempski O.
Source
Department of Neurosurgery, Nara Medical University, Kashihara, Japan.
Abstract
OBJECT:
Maintenance of cerebral blood flow (CBF) autoregulation in the brain is of major importance for patient outcome in various clinical conditions. The authors assessed local autoregulation after "asymptomatic" cortical vein occlusion.
METHODS:
In Wistar rats, a single cortical vein was occluded photochemically by using rose bengal and fiberoptic illumination. In rats with bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension. Local CBF at each pressure level was assessed by performing laser Doppler (LD) scanning at 25 (5 x 5) locations within bilateral cranial windows. In this manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm Hg in both right and left hemispheres in Group A (five rats), in which the animals received illumination without rose bengal and had no venous occlusion. Of the 11 rats that underwent vein occlusion, three developed severe reductions in local CBF and/or a growing venous thrombus and were distinguished as Group C (symptomatic; three rats); from previous work we know that those animals are bound to experience venous infarction. The remaining rats formed Group B (asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the left hemisphere without occlusion, whereas, in the right cortex with the occluded vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly ischemic range than that in the opposite normal hemisphere.
CONCLUSIONS:
The results of the present study suggest that cerebral venous circulation disorders are manifested via additional pathways, that is, from a partially impaired local autoregulation in the vicinity of the occluded vein, even under conditions in which the vein occlusion itself does not cause brain damage. Care should be taken in the control of blood pressure in patients with this pathological condition.
PMID: 9647182 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9647182

[Cece]

Ann Biomed Eng. 1985;13(3-4):311-20.
Cerebrovascular transmural pressure and autoregulation.
Wagner EM, Traystman RJ.
Abstract
The cerebral blood flow (CBF) response to changes in perfusion pressure mediated through decreases in arterial pressure, increases in cerebrospinal fluid (CSF) pressure and increases in jugular venous pressure was studied in anesthetized dogs. A preparation was developed in which each of the three relevant pressures could be controlled and manipulated independently of each other. In this preparation, the superior vena cava and femoral vein were cannulated and drained into a reservoir. Blood was pumped from the reservoir into the right atrium. With this system, mean arterial pressure and jugular venous pressure could be independently controlled. CSF pressure (measured in the lateral ventricle) could be manipulated via a cisternal puncture. Total and regional CBF responses to alterations in perfusion pressure were studied with the radiolabelled microsphere technique. Each hemisphere was sectioned into 13 regions: spinal cord, cerebellum, medulla, pons, midbrain, diencephalon, caudate, hippocampus, parahippocampal gyrus, and occipital, temporal, parietal and frontal lobes. Despite 30 mm Hg reductions in arterial pressure or increases in jugular venous pressure or CSF pressure, little change in CBF was observed provided the perfusion pressure (arterial pressure minus jugular venous pressure or CSF pressure depending on which pressure was of greater magnitude) was greater than the lower limit for cerebral autoregulation (approximately 60 mm Hg). However, when the perfusion pressure was reduced by any of the three different methods to levels less than 60 mm Hg (average of 48 mm Hg), a comparable reduction (25-35%) in both total and regional CBF was obtained. Thus comparable changes in the perfusion pressure gradient established by decreasing arterial pressure, increasing jugular venous pressure and increasing CSF pressure resulted in similar total and regional blood flow responses. Independent alterations of arterial and CSF pressures, and jugular venous pressure produce opposite changes in vascular transmural pressure yet result in similar CBF responses. These results show that cerebral autoregulation is a function of the perfusion pressure gradient and cannot be accounted for predominantly by myogenic mechanisms.
PMID: 4037460 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/4037460

It's a tipping point. That has a lot of possible implications.
It also says that alteration of jugular venous pressure can independently result in cerebral blood flow impairment.
'Cerebral autoregulation is a function of the perfusion pressure gradient.' Interesting.

[gibbledygook]

I've just spent about 2 hours trying to find an article in PubMed which I'm sure was a related citation to the above. It discussed venous closure and cerebral autoregulation. If I recall correctly it suggested that the veins close up owing to changes in pressures and autonomic dysregulation. However as I cannot find the article I may have been imagining it!

[Cece]

I can't look for it now but I'll later. Maybe cheer or someone else knows?

[SammyJo]

Autonomic Dysregulation in MS now seems to be an accepted concept.
Here is a full paper

[PDF] Autonomic Dysregulation in Multiple Sclerosis - MDPI.com
http://www.mdpi.com/1422-0067/16/8/16920/pdf
Multidisciplinary Digital Publishing Institute
by A Pintér - ‎2015

"Prevalent and clinically relevant autonomic disturbances include
neurogenic lower urinary tract dysfunction, symptoms of cardiovascular and gastrointestinal dysregulation as well as sudomotor (sweating) and pupillomotor dysfunction."
Of course the author dismisses CCSVI, but it does go into a few remedial therapies that won't fix the root cause but could alleviate symptoms.

The article discusses orthostatic hypertension and POTS, topics Dr. Diane Driscol has written about extensively regarding treatment b/c she suffers from it herself. I have improved many of these symptoms myself with various alternative treatments I've done (LDN, cannabis oil, CCSVI tx, stem cells, ketogenic diet, mythelation/nutrigenomics). Some gave me amazing recovery then faded, but much has lasted, especially after stem cells. Still in a wheelchair, but I've been on a remission streak since May 2014, heat tolerance to 85 F, can sweat again, able to exercise, can get out of my wheelchair and walk on occasion especially on a niacin flush. Don't feel sick and miserable anymore, fatigue is down, but when I stand the orthostatic hypertension is very limiting.

I have never been evaluated for POTS or orthostatic hypertension on a tilt table by MS doctors, so I'm going to send this to my doctor and see what the response is. Has anyone else tried discussing Autonomic Dysregulation in MS with their MS doctor?

[1eye]

Sit-to-stand from a medium chair (arms folded, don't fall back) might help core strength and/or ortho problems. I still think biotin has helped me with this: I can now do 30+ of these and can get down and up from my trike by myself.

Wouldn't ask my GP for anything invasive or possibly harmful. Why don't hydro-dynamics and math modelling folks look at this? Ballooning problem-free veins sounds like voodoo to me but who am I?

[cheerleader]

SammyJo---that niacin flush could well be contributing to orthostatic hypotension...since it quickly vasodilates your vessels. Something to consider. I LOVE 1eye's sit stand exercise suggestion!

Orthostatic hypotension is also a problem in the elderly population---as the body becomes less active, blood levels become lower (due to hydration issues, hypovolemia, lack of shear stress on endothelial cells)
Here's a really good explanation of the different causes and issues
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888469/

I've had postural hypotension all my life, had tilt table test---mine is due to very low blood pressure, not specifically autonomic dysfunction. Not on any meds, never intervention. A niacin flush would knock me out! My doctor tells me to make sure I remain hydrated (to keep blood volume up and not become hypovolemic), watch it on coffee intake (dehydrating) and recommends I include a lil' bit of salt in my diet and stay as active as possible, to keep blood volume high. You'll see all of these suggestions in the link I posted (...and as y'all know, I don't have MS..)

The heart and brain are connected, and communicate continually. But there is lots that can be done w/lifestyle, nutrition and movement to deal with heart/brain health.
HTH!
cheer

[1eye]

If you have heart trouble, don't mess with anything that might lower your blood pressure too much.

A niacin flush would knock me out!

I had to take an ambulance ride and stay in emerg for 12 hours and it was all because I had a twinge while climbing stairs (possible angina). I responded by taking nitro (more below). Feeling a lot of anxiety, I took a lorazepam, and some sativex spray, and lay down. In the ambulance, they said, if my blood pressure were any lower, it would be game over. They told me both lorazepam and sativex lower blood pressure. They also told me, if I ever take anything sublingual with a metered dose by spray, especially nitro, spray it once away from myself once before taking it, to prime the pump. I had probably had too much, of both nitro and sativex, because of accidental overdose. And never combine anything with nitro. Especially viagra. BTW it seems one of the nicer ways to commit suicide, on the surface of it. Might be traumatic for the survivor, though.

The oxygen in the ambulance worked wonders...

[SammyJo]

Great suggestions! Thank you 1eye and cheerleader!
I've already started on the extra water and salt. Doubt I will try any other meds, as long as I keep making improvements. 1eye I've been doing sit-stand too, usually 29-30 a day. This morning on a niacin flush I was able to do it 10 times without using my hands

I forgot to list oxygen, hyperbaric O2 has always helped me, and it was obvious the benefit I got from better blood flow getting O2 into brain after CCSVI tx. I was told I had the veins of an end stage renal patient, that is why they kept collapsing a few months after angioplasty. I am looking forward to the day when MS patients first get stem cells to calm the immune system and strengthen vein tissue, then get venoplasty to correct stenosis. cheerleader I REALLY appreciate everything you continue to do for CCSVI awareness.
SammyJo