Dr. Frohman and Normal Pressure Hydrocephalus

uprightdoc · Post by **uprightdoc** » Tue Jul 19, 2011 3:16 am

This is a terrific thread. My investigation into the role of upright posture in neurodegenerative diseases began back in 1984 while studying artificially deformed crania from the former indigenous people of Peru and Bolivia. The open state of their sutures (joints) in the skull suggested they had increased intracranial pressure. That's when I started looking into hydrocephalus, which led to normal pressure hydrocephalus, Alzheimer's, Parkionson's and multiple sclerosis.

Humans are predisposed to hydrocephalus due to the unqiue design of the skull, spine and circulatory system of the brain. Anything that impairs venous drainage of the brain at the same time decreases CSF flow. The large dural sinuses, however, are not true veins. They are much stronger and not likely to be compressed by excess CSF volume. On the other hand, there are many variations in the drainage system of the brain and some people are simply born with smaller (hypoplastic) veins and foramen (outlets) in the base of the skull used for drainage that result in decreased drainage capacity.

Currently NPH is associated with enlargement of the ventricles. The definition is open to debate and I believe that it needs to be changed to include any backup of CSF. For example, CSF can backup in the cisterns without enlargement of the ventricles and cause compression of the brainstem.

1eye · Post by **1eye** » Tue Jul 19, 2011 10:44 am

I think also Dr. Beggs was discussing the effects spinal fluid pressure and the pressure from the incoming pulses of blood in flexible arteries, conveyed through the medium of spinal fluid, might have on the resistance of the veins (Starling-type effects?).

To me, especially in the presence of atrophy which might result in deforming dilation, or absence of smooth muscle to prevent deforming contraction, the brain veins are especially vulnerable to Poiseuille’s Law, which is a more powerful effect than others by orders of magnitude. If there are Starling resistors, maybe the veins are being constricted at weaker points, stenosing them? Even if pathogens are at fault they could be working by stenosing veins.

uprightdoc · Post by **uprightdoc** » Tue Jul 19, 2011 11:35 am

Hello 1eye,

It's a good point. If interstitial/CSF pressure rises sufficiently it effects flow through both the smaller arteries and veins, which are easily compressible.

The larger dural sinuses however are not true veins. They are tunnels of dura mater, which is strong connective tissues, that are lined with endothelium (inside layer) of veins. The superior sagittal sinus drops from about 5- 10 mmHg in the supine position to negative value in the upright position. The negative pressure siphons arterial blood into the brain and increases brain blood flow. If it wasn't strong its walls would collapse, which is what I suspect happens in aging; that is the dura mater weakens, sags and loses its ability to stay open under negative pressure.

1eye · Post by **1eye** » Tue Jul 19, 2011 1:45 pm

The superior sagittal sinus drops from about 5- 10 mmHg in the supine position to negative value in the upright position

Why does that happen?

coach · Post by **coach** » Tue Jul 19, 2011 3:21 pm

I was just thinking about this the other day. Any chance that undersized posterior cranial fossa could play a role in this or am I totally missing the mark. I had shared with Dr. Flanagsn that both I and my daughter had postpartum optic neuritis and a sister that had c-sections with her two children had IIH. I didn't have high juglar stenosis but the AZY had a problem along with a couple of low IJV spots. Might that explain the 14 yr hiatus of MS symptoms after birth of first child. Also, some patients after initial improvements (myself included) lose some benefits. In my case walking and balance which never improved and have seem to grow worse.
What differentiates NPH from MS or can one have both?

cheerleader · Post by **cheerleader** » Tue Jul 19, 2011 6:57 pm

Coach--good question. Here are the things the NPH and MS share--
1. reduced cerebral blood flow or hypoperfusion
2. immunohistochemical changes in white matter
3. gait disturbances
4. cognitive problems
5. bladder incontinence
6. ischemic-like changes to white matter
7. progressive ventricular enlargement

Here is a great article summing up the research on what happens to the brain when cerebrospinal fluid becomes stagnated, due to blockage or inadequate uptake.
http://brain.oxfordjournals.org/content/127/5/947.full
cheer

cheerleader · Post by **cheerleader** » Tue Jul 19, 2011 7:40 pm

uprightdoc wrote: Currently NPH is associated with enlargement of the ventricles. The definition is open to debate and I believe that it needs to be changed to include any backup of CSF. For example, CSF can backup in the cisterns without enlargement of the ventricles and cause compression of the brainstem.

Thanks for all of your research and writings, Dr. Flanagan. I feel like there is still so much to understand--it's all fascinating--I've heard many of the neurologists say that NPH is not like MS, in that pwMS do not show signs of increased pressure on their lumbar punctures, but this comment is wrong-- neither do people with NPH. The lumbar puncture pressure readings are normal. Thus the name, normal pressure hydocephalus.

The ‘normal pressure’ aspect of NPH is something of a misnomer. While CSF pressure may be within the normal range when measured by manometry at lumbar puncture, continuous CSF pressure measurements reveal waves of increased pressure, particularly during rapid eye movement (REM) sleep, and CSF infusion studies reveal abnormal CSF circulation.

This reminds me of Dr. Beggs discussion on injurious waves of CSF pressure due to CCSVI.

And some pwMS do have are enlarged ventricles, just like pwNPH-

In 13 of 23 patients with multiple sclerosis, studied with computerized tomography (C.T.) the lateral ventricles were found to be enlarged.

http://www.sciencedirect.com/science/ar ... 677880016X

Nineteen patients were found to have mildly dilated ventricles and another nine patients had moderate to severe ventricular enlargement. Performance on memory and intelligence testing was related to the degree of ventriculomegaly. Three linear CT measurements were also recorded. [b'Using this method, the width of the third ventricle proved to be the best indicator of intellectual and memory dysfunction. [/b]Measures of cognition and ventricular size did not correlate with length of illness or overall disability as rated by the Kurtzke Disability Status Score.

http://archneur.ama-assn.org/cgi/conten ... t/42/7/678

cheer

uprightdoc · Post by **uprightdoc** » Wed Jul 20, 2011 2:20 am

coach wrote: Any chance that undersized posterior cranial fossa could play a role in this or am I totally missing the mark. I had shared with Dr. Flanagsn that both I and my daughter had postpartum optic neuritis and a sister that had c-sections with her two children had IIH. I didn't have high juglar stenosis but the AZY had a problem along with a couple of low IJV spots. Might that explain the 14 yr hiatus of MS symptoms after birth of first child. Also, some patients after initial improvements (myself included) lose some benefits. In my case walking and balance which never improved and have seem to grow worse.
What differentiates NPH from MS or can one have both?

Hello Coach,
An undersized posterior fossa plays a role in Chiari malformations which obstructs CSF flow. It can certainly play a role in NPH as well. Female cranial capacity tends to be 10-20 percent smaller than males. I suspect the size of the cranial vault is the reason why females are much more susceptible to certain neurodegenerative diseases such as MS. Post partum optic neuritis can be caused by Valsalva maneuvers during delivery. The fact that your sister has IIH would make matters far worse. In your particular case, I believe you have structural problems that impede CSF flow. It would be terrific if we could find someone with a Cox 7 or similar decompression table to work on you.

uprightdoc · Post by **uprightdoc** » Wed Jul 20, 2011 2:32 am

Hello Cheerleader,
One of the problems I have with the current definition of NPH is that it has to be associated with ventriculomegaly. It's a topic I cover thoroughly in my book because I disagree with the definition. I have seen many cases with normal size ventricles and excess CSF volume in the cisterns or in the spaces at the top of the brain that are not considered to be NPH.

Whether the ventricles enlarge or not depends on internal versus external ventricular pressures. The worst cases of Alzheimer's are associated with low CSF flow and pressure. If CSF pressure is very low the ventricles won't necessarily enlarge. NPH occurs when CSF backs up regardless of whether the ventricles enlarge or not.

The choke point for CSF flow is through the subarachnoid space of the upper cervical spine. Rises and falls in CSF volume and pressure as a result of arterial and respiratory waves must be compensated for and are vented through the upper cervical spine.

uprightdoc · Post by **uprightdoc** » Thu Jul 21, 2011 4:52 am

1eye wrote:
The superior sagittal sinus drops from about 5- 10 mmHg in the supine position to negative value in the upright position
Why does that happen?

Hello 1eye,

The main drainage outlet for the brain is the superior sagittal sinus located at the top of the brain when the head is held upright. The upright position creates a waterfall in the brain that increases CSF and venous outflow, which increases cerebral perfusion pressure and arterial flow. The increase in brain blood flow however depends on the ability to maintain negative pressure in the superior sagittal sinus without collapsing during upright posture.

cheerleader · Post by **cheerleader** » Thu Jul 21, 2011 8:14 am

uprightdoc wrote:Hello Cheerleader,
I have seen many cases with normal size ventricles and excess CSF volume in the cisterns or in the spaces at the top of the brain that are not considered to be NPH.

Whether the ventricles enlarge or not depends on internal versus external ventricular pressures. The worst cases of Alzheimer's are associated with low CSF flow and pressure. If CSF pressure is very low the ventricles won't necessarily enlarge. NPH occurs when CSF backs up regardless of whether the ventricles enlarge or not.

Thank you Dr. Flanagan. I'm getting your book. Will this excess CSF show up on MRI? What is the quantification? How do we know if this is occurring in an MS brain? Neurologists insist NPH has nothing to do with MS....what is their evidence? What could be our evidence?
thanks,
cheer

uprightdoc · Post by **uprightdoc** » Thu Jul 21, 2011 9:20 am

cheerleader wrote: ... Will this excess CSF show up on MRI? What is the quantification? How do we know if this is occurring in an MS brain? Neurologists insist NPH has nothing to do with MS....what is their evidence? What could be our evidence?

Your welcome Cheerleader,
Aside from enlargement of the ventricles called ventriculomegaly, other evidence of NPH also includes enlarged spaces, fissures and sulci in the brain. Further evidence for obstruction to CSF flow is right around the corner in the form of cine upright MRI.

1eye · Post by **1eye** » Thu Jul 21, 2011 12:00 pm

So could you have both? I've seen my MRIs and I could have another look or send them out if I knew who to send them to.

uprightdoc · Post by **uprightdoc** » Thu Jul 21, 2011 1:13 pm

Absolutely. You can have both ventriculomegaly and an increase in the size of the spaces, fissures and sulci. I have in fact seen some cases of MS that looked more like NPH than MS.

If you would like me to look at your brain scan I will PM you with my email and mailing address.

HappyPoet · Post by **HappyPoet** » Thu Jul 21, 2011 4:48 pm

uprightdoc wrote:
cheerleader wrote: ... Will this excess CSF show up on MRI? What is the quantification? How do we know if this is occurring in an MS brain? Neurologists insist NPH has nothing to do with MS....what is their evidence? What could be our evidence?
Your welcome Cheerleader,
Aside from enlargement of the ventricles called ventriculomegaly, other evidence of NPH also includes enlarged spaces, fissures and sulci in the brain. Further evidence for obstruction to CSF flow is right around the corner in the form of cine upright MRI.

Hi cheer,
As Dr. Flanagan said, upright MRI is "right around the corner," and for me, an upright MRI literally is right around the corner from my home. In fact, I just participated in a 41-patient randomized, blinded study at this facility in Albany, NY. The study is designed to evaluate CSF flows, quantified by upright MRI, before and after Atlas Orthogonal adjustment. After my adjustment (non-sham arm), a "notable" increase in my CSF flow was measured. Placebo patients required a third MRI after their true adjustment.

The same investigators, my AO chiro, Dr. Wehrenberg; Michelle's AO chiro, Dr. Bender; Dr. Scott Rosa; and a radiologist, are now designing another trial for an MS-only cohort in which Michelle and I plan to participate.

Edit - to correct the record regarding Michelle (bestadmom) as not being in the first study with me. Sorry, Michele, and thanks for letting me know!