Dr. Frohman and Normal Pressure Hydrocephalus

[cheerleader]

Wanted to bump this thread....there is much more research now, with the Fonar upright MRI and Dr. Rosa's study. The connection of CSF flow, perfusion and venous health is becoming clearer. Only 3 years since I first heard Dr. Frohman refer to NPH in Bologna...so things are, thankfully, moving ahead. Thanks to Dr. Flanagan, Dr. Rosa and all the other researchers joining their efforts to understand neurodegenerative disease.
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[dania]

Glad you bumped it!!!

[1eye]

There is never any extra room in the cranial vault. It's always filled with brain, blood and CSF. If one of those three things goes up in volume, something else goes down in volume. If the brain shrinks, CSF moves in. If CSF volume in cranial vault increases it compresses the brain. The brain gets comressed in both Chiari malformations and NPH.

Well, since this thread is bumped: aside from brain shrinkage, there must be, and is, an increase in oxygenated blood volume whenever the heart pumps blood into the head. This happens on every heartbeat, and causes an equal outflow of deoxygenated blood. I think we must distinguish between the instantaneous and the steady-state. Does the spinal fluid react to every heartbeat? I somehow doubt it. But I would not be surprised if the steady state changed, on average, over times longer than a heartbeat, in response to, say, exercise.

[cheerleader]

Does the spinal fluid react to every heartbeat?

It actually does. Dr. Flanagan explains it quite well on his webpage---

When the heart contracts a considerable amount of blood is driven into the brain, which compresses the brain, veins and CSF pathways. This drives venous blood and CSF out of the cranial vault and brain. When the heart relaxes, the brain, veins and CSF pathways expand which draws blood into the tissues of the brain, and pulls waste out of tissue spaces and into the drainage system ready to be removed on the next cycle. The heart thus causes the brain to rhythmically expand and contract.

Problems occur when waves get out of control. I liken them to rogue waves and describe them in more detail on my prior post. When CSF volume gets out of control it can damage the brain. Likewise, when CSF waves get out of control they can damage the brain as well. The basal cisterns (wells) that surround the brainstem and cerebellum with CSF, are the first place to experience the brunt of rogue waves and the most likely to suffer the consequences. I suspect that chronic pounding from rogue waves can cause damage.

http://uprightdoctor.wordpress.com/2011 ... -and-flow/

Here's a video showing these CSF pulsations.


but, we do not know enough about CSF flow.

The accumulation of any substance transported through the CSF is governed to a large extent by the pulsatile dynamics of this fluid. Surprisingly, little detail is known about CSF flow. This can be attributed to the fact that potentially accurate invasive flow measurements necessarily alter its motion, and that non-invasive studies are limited in resolution and accuracy, except in areas of well-defined shape with CSF motion along a predominant axis such as in the aqueduct of Sylvius, in the superior part of the spinal subarachnoid space (SAS) and, to a certain extent, in some planes within the various cranial cisterns.

I think you'll like this paper, 1eye
http://rsif.royalsocietypublishing.org/ ... .0033.full
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[dania]

Does the spinal fluid react to every heartbeat?

When I was having my Fonar MRI in Dr Rosa's study they put a pulse ox monitor on my finger. I was told that the CSF goes along with our heartbeat.

[1eye]

It's funny to see this discussion. Quite a few years ago now, I expressed to my sister wonder about the absence of any mechanical pump for CSF, and she said, there is too, it's called a sodium pump. I think this must figure into all this somewhere.

[gibbledygook]

I read recently that the MS brain is absolutely stuffed full of sodium...let me check pubmed.

[gibbledygook]

Radiology. 2012 Jul 17. [Epub ahead of print]
Distribution of Brain Sodium Accumulation Correlates with Disability in Multiple Sclerosis: A Cross-sectional 23Na MR Imaging Study.
Zaaraoui W, Konstandin S, Audoin B, Nagel AM, Rico A, Malikova I, Soulier E, Viout P, Confort-Gouny S, Cozzone PJ, Pelletier J, Schad LR, Ranjeva JP.
Source
CRMBM, no. 7339, Aix-Marseille University, CNRS, Marseille, France; Department of Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany; Division of Clinical Neurosciences, Department of Neurology, APHM, Hôpital de La Timone, Marseille, France.
Abstract
Purpose:To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging.Materials and Methods:This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration <5 years) and 12 with advanced RR MS (disease duration >5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed.Results:TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks.Conclusion:TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.© RSNA, 2012Supplemental material: http://radiology.rsna.org/lookup/suppl/ ... 2680/-/DC1.
PMID: 22807483 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22807483

[cheerleader]

thanks for the paper, Gibbs. We discussed it on the general thread, where I mentioned this process is seen in venous insufficiency. http://www.thisisms.com/forum/general-d ... 20410.html

There's a lot of stuff accumulating in the MS brain which increases during disease progression- Iron, sodium, EBV, bacteria, toxins, metals....
Researchers can spend the next century looking at each individual item through the microscope and making mouse models
OR they could study the clearance system for the brain---cerebrospinal fluid and venous bloodflow.
We see these same biomarkers in dementia, Alzheimers and normal pressure hydrocephalus (the start of this thread, thanks to Dr. Frohman.)

I'm glad that BNAC is looking at perfusion levels and CSF flow in pwMS.

Significantly decreased CSF net flow was detected in MS patients compared to HC (-3.7 vs. -7.1 μL/beat, P = 0.005). CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

http://www.ncbi.nlm.nih.gov/pubmed/22733409

Low flow means less clearance. It's that simple-
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[Sharon]

The reference to the quote from the study published in the Journal of Royal Society

The accumulation of any substance transported through the CSF is governed to a large extent by the pulsatile dynamics of this fluid. Surprisingly, little detail is known about CSF flow. This can be attributed to the fact that potentially accurate invasive flow measurements necessarily alter its motion, and that non-invasive studies are limited in resolution and accuracy, except in areas of well-defined shape with CSF motion along a predominant axis such as in the aqueduct of Sylvius, in the superior part of the spinal subarachnoid space (SAS) and, to a certain extent, in some planes within the various cranial cisterns.

The CSF flow patterns and measurements were imaged on a recumbant MRI. The upright MRI is offering new information to CSF flow dynamics and to cerebral venous drainage. Here is an interesting publication "Position Dependent Changes of the Cerebral Venous Drainage - Implications for the Imaging of the Cervical Spine"
https://www.thieme-connect.de/ejournals ... 30-1253348

Sharon

[1eye]

I would have thought if the CSF motion depends on sodium that would be a good way to track it. Can it be dyed with radioactivity? It is common almost everywhere in the body, because blood is salty. Do these molecules get past the normal BBB?

We see these same biomarkers in dementia, Alzheimers and normal pressure hydrocephalus (the start of this thread, thanks to Dr. Frohman.)

Aren't these now being suspected of vascular involvement?

[cheerleader]

The answer to your question miraculously appeared in the news today, one eye
There is a brand new technique for monitoring CSF flow thru the living (animal) brain--
and, apparently, CSF is even more important than we thought.

Scientists have known that cerebrospinal fluid or CSF plays an important role cleansing brain tissue, carrying away waste products and carrying nutrients to brain tissue through a process known as diffusion. The newly discovered system circulates CSF to every corner of the brain much more efficiently, through what scientists call bulk flow or convection........

How has this system eluded the notice of scientists up to now?
The scientists say the system operates only when it's intact and operating in the living brain, making it very difficult to study for earlier scientists who could not directly visualize CSF flow in a live animal, and often had to study sections of brain tissue that had already died. To study the living, whole brain, the team used a technology known as two-photon microscopy, which allows scientists to look at the flow of blood, CSF and other substances in the brain of a living animal.
While a few scientists two or three decades ago hypothesized that CSF flow in the brain is more extensive than has been realized, they were unable to prove it because the technology to look at the system in a living animal did not exist at that time.
"It's a hydraulic system," said Nedergaard. "Once you open it, you break the connections, and it cannot be studied. We are lucky enough to have technology now that allows us to study the system intact, to see it in operation."

"Understanding how the brain copes with waste is critical. In every organ, waste clearance is as basic an issue as how nutrients are delivered. In the brain, it's an especially interesting subject, because in essentially all neurodegenerative diseases, including Alzheimer's disease, protein waste accumulates and eventually suffocates and kills the neuronal network of the brain," said Iliff.

http://www.sciencedaily.com/releases/20 ... science%29

wow!
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[1eye]

Except today I saw another one that said astrocytes are the janitors... Bulk flow by convection sounds an awful lot like it doesn't work so well when you're lying down, is very (critically?) temperature-dependent, and could possibly come into conflict with the "sodium pump". I felt more confident when I thought it was respiration-driven. Back to the drawing-board, Lord.

[1eye]

Once you open it, you break the connections, and it cannot be studied.

So medicine starts to catch up with quantum mechanics. The uncertainty principle is very widespread, isn't it?

[cheerleader]

Ha! Not as bad as Heisenberg, eye....they were just referring to the fact that when you open a hydrolic system in a living creature, you can no longer study it. But they did study it with this new technology, in vivo.
I look at this as a positive sign for the plumbers and hydrolic scientists Where's Dr. Beggs? He'd love this!
Here's more info on the mechanisms of capillary exchange, which includes diffusion, and our newly discovered CSF system of bulk flow (convection). We know how this works in the cardiovascular system, which manages in supine or upright positions, so that' s plus. And it most certainly ties in with the start of this thread which was restricted venous return and NPH.
http://www.cvphysiology.com/Microcirculation/M016.htm
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