MS is not a single disease. It is four at least.

A forum to discuss research on the origins of MS and its development.

MS is not a single disease. It is four at least.

Postby frodo » Wed Sep 06, 2017 2:37 pm

MS was defined in the XIX century as the presence of scars in the brain. They didn't know what was causing them, and they still don't know. There is no diagnosis test available except to observe the lesions via MRI or guess them via relapses. If your doctor finds that you have lesions distributed in time and space, then you have MS. There is no other criteria available.

In fact, some special cases previously considered MS, like NMO and anti-MOG encephalomyelitis, now are considered different diseases, just because somebody at some point has understood these disease's pathogenesis, but they would be still considered real MS if they were using as criteria the lesions distribution.

Since 1996 researchers know that there are four kind of lesions in MS, and that any given patient has only one of those types. Everybody involved wanted to claim that they were produced by four different underlying conditions, but until now there was no proof.

This week everything has changed. It seems now that MS is really four different diseases producing four kinds of different lesions.

The new research shows the following:

-Oligoclonal bands, which are supposed to be a marker of MS with more than 80% of specificity have been shown to be nearly absent in patterns II and III.
- Also the MRZ reaction (which we have spoken about here) reported in 80% of the patients, is also absent in patterns II and III.
- Finally, other specific biomarker named QAlb (albumin CSF/serum ratio) is higher in patterns II and III.

Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis
Source: https://jneuroinflammation.biomedcentra ... 017-0929-z

Background

The diagnosis of multiple sclerosis (MS) is currently based solely on clinical and magnetic resonance imaging features. However, histopathological studies have revealed four different patterns of lesion pathology in patients diagnosed with MS, suggesting that MS may be a pathologically heterogeneous syndrome rather than a single disease entity.

Objective

The aim of this study was to investigate whether patients with pattern I MS differ from patients with pattern II or III MS with regard to cerebrospinal fluid (CSF) findings, especially with reference to intrathecal IgG synthesis, which is found in most patients with MS but is frequently missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive encephalomyelitis.
Methods

Findings from 68 lumbar punctures in patients who underwent brain biopsy as part of their diagnostic work-up and who could be unequivocally classified as having pattern I, pattern II or pattern III MS were analysed retrospectively.

Results

Oligoclonal bands (OCBs) were present in 88.2% of samples from pattern I MS patients but in only 27% of samples from patients with pattern II or pattern III MS (P < 0.00004); moreover, OCBs were present only transiently in some of the latter patients. A polyspecific intrathecal IgG response to measles, rubella and/or varicella zoster virus (so-called MRZ reaction) was previously reported in 60–80% of MS patients, but was absent in all pattern II or III MS patients tested (P < 0.00001 vs. previous cohorts). In contrast, the albumin CSF/serum ratio (QAlb), a marker of blood–CSF barrier function, was more frequently elevated in samples from pattern II and III MS patients (P < 0.002). Accordingly, QAlb values and albumin and total protein levels were higher in pattern II and III MS samples than in pattern I MS samples (P < 0.005, P < 0.009 and P < 0.006, respectively).

Conclusions

Patients with pattern II or pattern III MS differ significantly from patients with pattern I MS as well as from previous, histologically non-classified MS cohorts with regard to both intrathecal IgG synthesis and blood–CSF barrier function. Our findings strongly corroborate the notion that pattern II and pattern III MS are entities distinct from pattern I MS.
Last edited by frodo on Wed Sep 06, 2017 11:55 pm, edited 4 times in total.
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Re: MS is not a single disease. It is four at least.

Postby frodo » Wed Sep 06, 2017 3:05 pm

Some previous research also supports this point:

- It was shown that pattern II is responsive to plasmapheresis, while others are not. (https://www.ncbi.nlm.nih.gov/pubmed/16099294), also reported at http://onlinelibrary.wiley.com/doi/10.1 ... 064.x/full)

- Pattern III has also previously been shown to be different from the others. See "Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity?" at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981817/

- A research group showed last year that pattern II is different from the others: See "Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions". Journal. 2 (9): 875–893. doi:10.1002/acn3.218." and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574805/

-Another group has developed a microarray able to tell the pathologic pattern of a patient (http://www.pnas.org/content/105/48/18889.short , also reported in http://ijmsc.org/doi/pdf/10.7224/1537-2073-14.S5.1). They found an antibody signature in blood and they were granted a patent available at https://www.google.com/patents/US9267945.
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Re: MS is not a single disease. It is four at least.

Postby vesta » Tue Sep 12, 2017 6:17 am

frodo wrote:MS was defined in the XIX century as the presence of scars in the brain. They didn't know what was causing them, and they still don't know. There is no diagnosis test available except to observe the lesions via MRI or guess them via relapses. If your doctor finds that you have lesions distributed in time and space, then you have MS. There is no other criteria available.

In fact, some special cases previously considered MS, like NMO and anti-MOG encephalomyelitis, now are considered different diseases, just because somebody at some point has understood these disease's pathogenesis, but they would be still considered real MS if they were using as criteria the lesions distribution.

Since 1996 researchers know that there are four kind of lesions in MS, and that any given patient has only one of those types. Everybody involved wanted to claim that they were produced by four different underlying conditions, but until now there was no proof.

This week everything has changed. It seems now that MS is really four different diseases producing four kinds of different lesions.

The new research shows the following:

-Oligoclonal bands, which are supposed to be a marker of MS with more than 80% of specificity have been shown to be nearly absent in patterns II and III.
- Also the MRZ reaction (which we have spoken about here) reported in 80% of the patients, is also absent in patterns II and III.
- Finally, other specific biomarker named QAlb (albumin CSF/serum ratio) is higher in patterns II and III.

Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis
Source: https://jneuroinflammation.biomedcentra ... 017-0929-z

Background

The diagnosis of multiple sclerosis (MS) is currently based solely on clinical and magnetic resonance imaging features. However, histopathological studies have revealed four different patterns of lesion pathology in patients diagnosed with MS, suggesting that MS may be a pathologically heterogeneous syndrome rather than a single disease entity.

Objective

The aim of this study was to investigate whether patients with pattern I MS differ from patients with pattern II or III MS with regard to cerebrospinal fluid (CSF) findings, especially with reference to intrathecal IgG synthesis, which is found in most patients with MS but is frequently missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive encephalomyelitis.
Methods

Findings from 68 lumbar punctures in patients who underwent brain biopsy as part of their diagnostic work-up and who could be unequivocally classified as having pattern I, pattern II or pattern III MS were analysed retrospectively.

Results

Oligoclonal bands (OCBs) were present in 88.2% of samples from pattern I MS patients but in only 27% of samples from patients with pattern II or pattern III MS (P < 0.00004); moreover, OCBs were present only transiently in some of the latter patients. A polyspecific intrathecal IgG response to measles, rubella and/or varicella zoster virus (so-called MRZ reaction) was previously reported in 60–80% of MS patients, but was absent in all pattern II or III MS patients tested (P < 0.00001 vs. previous cohorts). In contrast, the albumin CSF/serum ratio (QAlb), a marker of blood–CSF barrier function, was more frequently elevated in samples from pattern II and III MS patients (P < 0.002). Accordingly, QAlb values and albumin and total protein levels were higher in pattern II and III MS samples than in pattern I MS samples (P < 0.005, P < 0.009 and P < 0.006, respectively).

Conclusions

Patients with pattern II or pattern III MS differ significantly from patients with pattern I MS as well as from previous, histologically non-classified MS cohorts with regard to both intrathecal IgG synthesis and blood–CSF barrier function. Our findings strongly corroborate the notion that pattern II and pattern III MS are entities distinct from pattern I MS.



Well, , it’s about time. It is obvious to me that « MS » is a grab bag description of multiple dysfunctions in the CNS. So now they have found 4 kinds of MS, and maybe more. So much for the vain hope of a « cure ». Rather than freeze up like hedgehogs in wait for the miracle drug it’s time for MSers to take the bull by the horns and act where we can, based on what we know. .

First off, ample studies have revealed that MS presents a problem with fluid circulation, in particular blood and cerebro-spinal fluid (and maybe glymphatic and lymphatic as well). Rather than obsess on cell and molecular biology, better diagnose the velocity of fluid flows, with particular attention to obstructions. As far as I know the FONAR upright MRI can detect obstructions in the CSF in the spine. Chiropractors and other body structure specialists, should be equipped to study the entire CNS fluid circulation and hopefully, once the problem has been identified, correct it if possible.
1). See the following study which reveals that blood circulates between the heart and brain at half the velocity in MSers as in normals.

*Cerebral Circulation Time is Prolonged and Not Correlated with EDSS in Multiple Sclerosis    Patients: A Study Using Digital Subtracted Angiography 
http://www.plosone.org/article/fetchObj ... tation=PDF

                    
2). The once a year conferences (since 2011) of International Society of Neurovascular Disease ISNVD https://isnvd.org/
have accumulated an important library on the subject. See Joan Beal’s the ‘Vascular Connection » for more research. ccsviinms.blogspot.com/

3). Chiropractor Dr. Michael Flanagan believed that up to 25% of MS cases originated in obstructed CSF and blood circulation impacting the CNS. (His death May 2015 was a terrible loss for me and other MSers, loss of a knowledgable, humane expert who generously answered questions and gave advice on individual cases.) His ThisisMS thread CCVBP under CCSVI remains highly informative. ) Dr. Flanagan commented on my post « MS : Positive Feedback Loop » thus :

In response to my request for a comment on this post, Chiropractor Dr. Michael Flanagan wrote on Thisisms.com December 14, 2014

Hello Vesta,

It would take too long to comment on all of them but you make some interesting points. 

I don't mean to toot my own horn but I started my researh in 1984 and published my first paper on the role of the vertebral veins in neurodegenerative diseases in 1987 long before Zamboni published his research. At the same time I described the role of the perivascular pathways and CSF as the lymph system of the brain and its importance to removal of wastes etc, decades before anything was mentioned about the glymphatic system. Considering Zamboni's theory versus mine, there are far more potential causes of venous insufficiency of the vertebral veins due to malformations, misalignments and deformation of the upper cervical spine than venous insufficiency due to malformation and blockage of the jugulars. Moreover, the vertebral veins are the primary drainage routes of the brain used during upright posture, not the jugulars and upright posture is used two-thirds of every day. 

It was Schelling who introduced the term venous back jets not Zamboni. He attributed the violent back jets to trauma.  

In addition to muscle spasms, muscle weakness can cause deformation of the spine. Most primary malformations, misalignments and deformation of the upper cervical spine, however, and spondylosis, scoliosis and stenosis in the lower spine in patients with MS are due to other causes not muscle spasms or weakness. Spasms and weaknesses cause secondary deformation.

It is wise to make every effort to enhance blood and cerebrospinal fluid circulation in all neurodegenerative diseases to provide nutrients and eliminate wastes, as well as inflammation.

Swimming and aqua therapy are terrific for many neurological disorders."



Me again :



Rather than puncture more spines and brains, MS researchers should do structural analyses. And I suggest SIX CCSVI MS conditions based on vein status, blood flow and CSF circulation.

1) Congenital 2) Developmental 3) Infectious 4) Toxic (Allergy) 5) Aging 6) Structural

Supplemental observations :
Pattern I exhibits MRZR (viral) reaction to infectious agents. Types II and III do not.
Patterns II and III reveal CSF anomalies Type I does not.
Now we can see why there are so many different effective alternative treatments. 

One danger in all this is that the test tube fanatics will start puncturing more spines to analyse which of the 4 patterns one has and then try to find a drug to attack it. First let the researchers take seriously the fluid circulation issue. There is something downright sadistic in MS research. Brain biopsy ???

Thanks Frodo, great info.

Best regards, Vesta

(Parts of this previously published on my site http://www.mscureenigmas.net)
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Re: MS is not a single disease. It is four at least.

Postby frodo » Wed Oct 04, 2017 12:27 pm

Maybe benign MS is also a different disease and can be diagnosed by OCT:

https://www.ncbi.nlm.nih.gov/pubmed/28966652

Optical coherence tomography and T cell gene expression analysis in patients with benign multiple sclerosis.

Abstract

Benign multiple sclerosis is a retrospective diagnosis based primarily on a lack of motor symptom progression. Recent findings that suggest patients with benign multiple sclerosis experience non-motor symptoms highlight the need for a more prospective means to diagnose benign multiple sclerosis early in order to help direct patient care. In this study, we present optical coherence tomography and T cell neurotrophin gene analysis findings in a small number of patients with benign multiple sclerosis. Our results demonstrated that retinal nerve fiber layer was mildly thinned, and T cells had a distinct gene expression profile that included upregulation of interleukin 10 and leukemia inhibitory factor, downregulation of interleukin 6 and neurotensin high affinity receptor 1 (a novel neurotrophin receptor). These findings add evidence for further investigation into optical coherence tomography and mRNA profiling in larger cohorts as a potential means to diagnose benign multiple sclerosis in a more prospective manner.
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Re: MS is not a single disease. It is four at least.

Postby David1949 » Tue Oct 17, 2017 3:10 pm

In my opinion MS is at least two diseases, relapsing remitting and primary progressive. Other types could be secondary progressive, and benign. That would make 4 altogether. I wonder if those relate to any of the types they mention.

But a bigger question is; can they cure any of them?
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Re: MS is not a single disease. It is four at least.

Postby frodo » Sun Oct 22, 2017 11:10 pm

David1949 wrote:But a bigger question is; can they cure any of them?


That's just a secondary question. The main questions are, what the hell are they? why they do appear? how they do evolve? and how can we interfere with their natural evolution?
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