Two recent posts on the ThisisMS website www.thisisms.com point to what Jung would call « Synchronicity » - a meaningful coincidence - the same ideas manifesting at the same time. EXCEPT it would seem they are disparate ideas. To my thinking, what unites them are the CCSVI theory.
On Sept 12, 2017 at 6 :50 a.m. 1eye posted « The Central Vein Sign ». Twenty-seven minutes later (7 :17 a.m.) Vesta (that’s me) responded to Frodo’s post « MS is not a single disease. It is Four at least ». Though not central to Frodo’s post, both suggest the CCSVI theory. That’s my conclusion as demonstrated by my Sept 12 response.
My post on the ThisisMS site under the « MS Etiology and Pathogenesis » unites the two :
« 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/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0116681&representation=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." Written by Dr. Michael Flanagan
Me again :
Rather than puncture more spines and brains, MS researchers should do structural analyses. And I suggest SIX CCSVI MS pathologies based on vein status, blood flow and CSF circulation.
1. Congenital 2) Developmental 3) Infectious 4) Toxic (Allergy) 5) Aging 6) Structural
Supplemental observations :
Type I exhibits MRZ (viral) reaction to infectious agents. Types II and III do not.
Types 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 types 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 ???
Best regards, Vesta
Some direct quotes from Frodo, posted on www.thisisMS.com September 6, 2017
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.
Quote:
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.
ME AGAIN:
O.K. We have at least 4 lesion patterns. At the same time it is now accepted that the Central Vein Sign is a marker for MS.
The Central Vein Sign (CVS) is now officially recognized as a marker for MS by the North American Imaging in Multiple Sclerosis Cooperative (NAIM)
(According to 1eye the (CSV) factor has been known by MRI rediologists for at least 30 years, but it took the Nature Review Neurology article to officialize it. Medical Doctors/Researchers are not very courageous. They are a conservative lot, they need group support/recognition/respectability to say anything. They here admit the veinous phenomena was seen as early as 1820.That’s why MSers need to act independently. We don’t have time. See the earth shaking conclusion below.)
https://www.ncbi.nlm.nih.gov/pubmed/27834394 -
Nat Rev Neurol. 2016 Dec;12(12):714-722. doi: 10.1038/nrneurol.2016.166. Epub 2016 Nov 1
« The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.
Sati P1, Oh J2,3, Constable RT4, Evangelou N5, Guttmann CR6, Henry RG7, Klawiter EC8, Mainero C9, Massacesi L10, McFarland H1, Nelson F11, Ontaneda D12, Rauscher A13, Rooney WD14, Samaraweera AP5, Shinohara RT15, Sobel RA16, Solomon AJ17, Treaba CA9, Wuerfel J18, Zivadinov R19, Sicotte NL20, Pelletier D21, Reich DS1; NAIMS Cooperative
Abstract Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS…
CONCLUSIONS ;
The NAIMS Cooperative has developed this Consensus Statement to better define and evaluate the CVS, as detected by MRI, for the diagnosis of MS. More precisely, our recommendations underscore the need for further investigation of the central vein in MS and its mimics. We have proposed a standard radiological definition of the central vein (Box 2), but we strongly recommend additional investigation to define the optimal CVS criteria. Our recommendations also promote standardization of MRI protocols and lesion selection criteria to assess central veins. Finally, we recommend investigation of the clinical value of the CVS through large multicentre studies involving patients with established diagnoses of MS and its mimics, as well as undiagnosed patients suspected of having MS.
Taken together, our recommendations provide a roadmap to help establish a high-impact role for the CVS in improving the diagnosis of MS. This Consensus Statement is in line with recent guidelines from the MAGNIMS group1, 4 and CMSC task force22, which both highlighted the potential of the CVS and its associated MRI acquisitions while calling for further research before considering an update of the diagnostic criteria. Overall, the NAIMS Cooperative is optimistic that the CVS will eventually find substantial clinical utility in daily practice, thus adding another layer of success to a technology that has changed the field
Joan Beal who writes the « Vascular Connection » already posted excellent information on the Central Vein Sign. ccsviinms.blogspot.com/.../the-central-vein-sign-and-new-research...
« The Central Vein Sign and New Research
September 20, 2013
It was 150 years ago, in 1863, when Eduard von Rindfleisch first peered through his microscope at an MS lesion and noted a vein inside the cerebral MS lesion.
« If one looks carefully at freshly altered parts of the white matter ...one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood...All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation. »
Rindfleisch E. - "Histologisches detail zu der grauen degeneration von gehirn und ruckenmark". Archives of Pathological Anatomy and Physiology. 1863;26:474–483.
We've known for over a century that MS lesions are perivenous, meaning lesions form around a vein. There is a vein in the center of almost every cerebral MS lesion, and this makes the MS lesion unique.
So, it was interesting to see THREE brand new papers on this topic in 2013, coming from neurological research.
Here's one from July 2013, published in "Frontiers of Neurology"--suggesting that these central veins and perivenous lesions, which are now very clear on 7Tesla MRI, might be helpful in making an MS diagnosis.
« Venocentric Lesions: an MRI marker in MS?
In the past decade, numerous studies have explored a promising biomarker for MS: MRI-detectable veins within lesions.This biomarker is well established as detectable at 3 and 7T and efforts should be made to identify/optimize clinically practical methods for its evaluation. Prospective studies have shown that the presence of venocentric lesions at an early but ambiguous clinical presentation is highly predictive of future MS diagnosis. Work remains to be done to confirm or exclude lesions of common MS mimics as venocentric. Common imaging practice and lesion-rating paradigms should be adopted by scientists working in this field.
http://www.frontiersin.org/Multiple_Sclerosis_and_Neuroimmunology/10.3389/fneur.2013.00098/full »
Here's another paper entitled "The Central Vein Sign: is there a place for susceptibility weighted imaging in possible multiple sclerosis." (Readers of this page know that CCSVI investigator, Dr. Mark Haacke, is the inventor of SWI. He has noted these central veins and iron deposition in the MS brain for almost a decade now, and linked their presence to CCSVI.)
« Susceptibility weighted imaging (SWI) may have the potential to depict the perivenous extent of white matter lesions (WMLs) in multiple sclerosis (MS). We aimed to assess the discriminatory value of the "central vein sign" (CVS). »
The "central vein sign" was predominantly seen in MS lesions. The "central vein sign" helps discriminate between MS and non-MS lesions.
http://www.ncbi.nlm.nih.gov/pubmed/23436147 »
Here's yet another study published in the Journal of Neuroimmunology in May 2013 which notes the central veins visible in MS lesion.
« Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions.
In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms
.
http://www.ncbi.nlm.nih.gov/pubmed/23529352 »
+++++++++++++++++++++++++++++
These papers are no surprise--researchers have been noting these veins inside MS lesions for over a century. But what continues to shock me is that researchers aren't asking WHY?
Rindfleisch, with his microscope in 1863, was wondering why there was a change in the blood vessels in the MS brain.
Here is Dr. C.W. Adams in 1987, looking at autopsied brain tissue in the hopes of understanding the mechanism of lesion formation in MS.
« The periventricular region was studied in the brains of 129 cases of multiple sclerosis, with the purpose of establishing the mechanism and order of events in the development of the periventricular plaque, and deciding whether there is any relationship between granular ependymitis and such plaques. Periventricular plaques were found in 82.2% of cases. Observation and computerized morphology showed that the early stage of the periventricular plaque is the formation of a lesion around a subependymal vein and that adjacent lesions later coalesce ».
(Subependymal means below the ependymal zone, in the lateral ventricles of the brain.)
http://www.ncbi.nlm.nih.gov/pubmed/3614542
++++++++++++++++++++++++++++++
One cardiovascular doctor has asked why, and utilized Dr. Zamboni's research to explain the central vein found in MS lesions.
Here's Dr. Michael Dake's illuminating powerpoint presentation, explaining how CCSVI would create vessel wall breakdown, due to disturbed venous blood flow, microbleeds and perivenous fibrin cuffs, activating the inflammatory process. This would lead to adhesion molecule and cytokine expression, oxidative stress and reduced NOS activity--endothelial dysfunction and a breech in the blood brain barrier. We know how this happens in chronic venous disease in other parts of the body. Laminar, or smooth blood flow, maintains the endothelium. Disturbed blood flow leads to a break down.
This would explain the central vein inside the lesion.
http://www.ucsfcme.com/2011/slides/MSU11003/14DakeCurrentStatusOfChronicCerebrospinalVenousInsufficiencyInMS.pdf
Perhaps neurologists do not want to ask why there is a central vein; because they know the answer points to a vascular connection to multiple sclerosis. Their studies are looking at this central vein in MS lesions as purely a means to aid MS diagnosis, so they might begin disease modifying medications in their patients.
But the looming question remains....why the central vein?
The answer will provide healing for those with MS.
Joan
PS--for those who wish to learn more about this history, Dr. Schelling has written the most comprehensive and thorough evaluation of the history of MS lesion studies.
http://www.ms-info.net/ms_040504.pdf
Posted by Joan at 11:27 AM
MS CURE ENIGMAS AGAIN:
ANOTHER REASON TO THINK THAT MS IS A VASCULAR DISEASE : BIRTH CONTROL PILLS (ESTROGEN)
I noted several years ago that Professor George Ebers had observed that around 50-60 years ago MS afflicted males and females alike, in the same ratio. Now there are up to 2, 3, even 4 times as many female MSers as male. What changed nearly 60 years ago ? Answer : The birth control pill, launched in 1960. And now the research is coming in.
"Lead researcher Dr Kerstin Hellwig said: ‘These findings suggest that using hormonal contraceptives may be contributing at least in part to the rise in the rate of MS among women.’
Read more: http://www.dailymail.co.uk/health/article-2569855/Multiple-sclerosis-linked-contraceptive-pill-Risk-50-higher-women-taken-it.html#ixzz4sfGYne6N
Follow us: @MailOnline on Twitter | DailyMail on Facebook Study examined 305 U.S. women
Read more: http://www.dailymail.co.uk/health/article-2569855/Multiple-sclerosis-linked-contraceptive-pill-Risk-50-higher-women-taken-it.html#ixzz4sfGlkVOY
Follow us: @MailOnline on Twitter | DailyMail on Facebook
www.dailymail.co.uk/.../Multiple-sclerosis-linked-contraceptive-pil...
One final note. Not only does Estrogen increase the risk of MS, it, increases the risk of Stroke and Migraines.
And research has shown that Interferon B used to treat MS ALSO increases the risk of stroke and migraines. It would appear that this drug, with only minor effectiveness as an MS treatment, also impacts the vascular system. Details later.
Tags : MS, CCSVI, Estrogen, Central Vein Sign, Dr. Michael Dake, Dr. Michael Flanagan, Dr. Schelling, Dr. George Ebers, NAIMS, Joan Deal
.
On Sept 12, 2017 at 6 :50 a.m. 1eye posted « The Central Vein Sign ». Twenty-seven minutes later (7 :17 a.m.) Vesta (that’s me) responded to Frodo’s post « MS is not a single disease. It is Four at least ». Though not central to Frodo’s post, both suggest the CCSVI theory. That’s my conclusion as demonstrated by my Sept 12 response.
My post on the ThisisMS site under the « MS Etiology and Pathogenesis » unites the two :
« 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/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0116681&representation=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." Written by Dr. Michael Flanagan
Me again :
Rather than puncture more spines and brains, MS researchers should do structural analyses. And I suggest SIX CCSVI MS pathologies based on vein status, blood flow and CSF circulation.
1. Congenital 2) Developmental 3) Infectious 4) Toxic (Allergy) 5) Aging 6) Structural
Supplemental observations :
Type I exhibits MRZ (viral) reaction to infectious agents. Types II and III do not.
Types 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 types 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 ???
Best regards, Vesta
Some direct quotes from Frodo, posted on www.thisisMS.com September 6, 2017
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.
Quote:
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.
ME AGAIN:
O.K. We have at least 4 lesion patterns. At the same time it is now accepted that the Central Vein Sign is a marker for MS.
The Central Vein Sign (CVS) is now officially recognized as a marker for MS by the North American Imaging in Multiple Sclerosis Cooperative (NAIM)
(According to 1eye the (CSV) factor has been known by MRI rediologists for at least 30 years, but it took the Nature Review Neurology article to officialize it. Medical Doctors/Researchers are not very courageous. They are a conservative lot, they need group support/recognition/respectability to say anything. They here admit the veinous phenomena was seen as early as 1820.That’s why MSers need to act independently. We don’t have time. See the earth shaking conclusion below.)
https://www.ncbi.nlm.nih.gov/pubmed/27834394 -
Nat Rev Neurol. 2016 Dec;12(12):714-722. doi: 10.1038/nrneurol.2016.166. Epub 2016 Nov 1
« The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.
Sati P1, Oh J2,3, Constable RT4, Evangelou N5, Guttmann CR6, Henry RG7, Klawiter EC8, Mainero C9, Massacesi L10, McFarland H1, Nelson F11, Ontaneda D12, Rauscher A13, Rooney WD14, Samaraweera AP5, Shinohara RT15, Sobel RA16, Solomon AJ17, Treaba CA9, Wuerfel J18, Zivadinov R19, Sicotte NL20, Pelletier D21, Reich DS1; NAIMS Cooperative
Abstract Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS…
CONCLUSIONS ;
The NAIMS Cooperative has developed this Consensus Statement to better define and evaluate the CVS, as detected by MRI, for the diagnosis of MS. More precisely, our recommendations underscore the need for further investigation of the central vein in MS and its mimics. We have proposed a standard radiological definition of the central vein (Box 2), but we strongly recommend additional investigation to define the optimal CVS criteria. Our recommendations also promote standardization of MRI protocols and lesion selection criteria to assess central veins. Finally, we recommend investigation of the clinical value of the CVS through large multicentre studies involving patients with established diagnoses of MS and its mimics, as well as undiagnosed patients suspected of having MS.
Taken together, our recommendations provide a roadmap to help establish a high-impact role for the CVS in improving the diagnosis of MS. This Consensus Statement is in line with recent guidelines from the MAGNIMS group1, 4 and CMSC task force22, which both highlighted the potential of the CVS and its associated MRI acquisitions while calling for further research before considering an update of the diagnostic criteria. Overall, the NAIMS Cooperative is optimistic that the CVS will eventually find substantial clinical utility in daily practice, thus adding another layer of success to a technology that has changed the field
Joan Beal who writes the « Vascular Connection » already posted excellent information on the Central Vein Sign. ccsviinms.blogspot.com/.../the-central-vein-sign-and-new-research...
« The Central Vein Sign and New Research
September 20, 2013
It was 150 years ago, in 1863, when Eduard von Rindfleisch first peered through his microscope at an MS lesion and noted a vein inside the cerebral MS lesion.
« If one looks carefully at freshly altered parts of the white matter ...one perceives already with the naked eye a red point or line in the middle of each individual focus,.. the lumen of a small vessel engorged with blood...All this leads us to search for the primary cause of the disease in an alteration of individual vessels and their ramifications; All vessels running inside the foci, but also those which traverse the immediately surrounding but still intact parenchyma are in a state characteristic of chronic inflammation. »
Rindfleisch E. - "Histologisches detail zu der grauen degeneration von gehirn und ruckenmark". Archives of Pathological Anatomy and Physiology. 1863;26:474–483.
We've known for over a century that MS lesions are perivenous, meaning lesions form around a vein. There is a vein in the center of almost every cerebral MS lesion, and this makes the MS lesion unique.
So, it was interesting to see THREE brand new papers on this topic in 2013, coming from neurological research.
Here's one from July 2013, published in "Frontiers of Neurology"--suggesting that these central veins and perivenous lesions, which are now very clear on 7Tesla MRI, might be helpful in making an MS diagnosis.
« Venocentric Lesions: an MRI marker in MS?
In the past decade, numerous studies have explored a promising biomarker for MS: MRI-detectable veins within lesions.This biomarker is well established as detectable at 3 and 7T and efforts should be made to identify/optimize clinically practical methods for its evaluation. Prospective studies have shown that the presence of venocentric lesions at an early but ambiguous clinical presentation is highly predictive of future MS diagnosis. Work remains to be done to confirm or exclude lesions of common MS mimics as venocentric. Common imaging practice and lesion-rating paradigms should be adopted by scientists working in this field.
http://www.frontiersin.org/Multiple_Sclerosis_and_Neuroimmunology/10.3389/fneur.2013.00098/full »
Here's another paper entitled "The Central Vein Sign: is there a place for susceptibility weighted imaging in possible multiple sclerosis." (Readers of this page know that CCSVI investigator, Dr. Mark Haacke, is the inventor of SWI. He has noted these central veins and iron deposition in the MS brain for almost a decade now, and linked their presence to CCSVI.)
« Susceptibility weighted imaging (SWI) may have the potential to depict the perivenous extent of white matter lesions (WMLs) in multiple sclerosis (MS). We aimed to assess the discriminatory value of the "central vein sign" (CVS). »
The "central vein sign" was predominantly seen in MS lesions. The "central vein sign" helps discriminate between MS and non-MS lesions.
http://www.ncbi.nlm.nih.gov/pubmed/23436147 »
Here's yet another study published in the Journal of Neuroimmunology in May 2013 which notes the central veins visible in MS lesion.
« Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions.
In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms
.
http://www.ncbi.nlm.nih.gov/pubmed/23529352 »
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These papers are no surprise--researchers have been noting these veins inside MS lesions for over a century. But what continues to shock me is that researchers aren't asking WHY?
Rindfleisch, with his microscope in 1863, was wondering why there was a change in the blood vessels in the MS brain.
Here is Dr. C.W. Adams in 1987, looking at autopsied brain tissue in the hopes of understanding the mechanism of lesion formation in MS.
« The periventricular region was studied in the brains of 129 cases of multiple sclerosis, with the purpose of establishing the mechanism and order of events in the development of the periventricular plaque, and deciding whether there is any relationship between granular ependymitis and such plaques. Periventricular plaques were found in 82.2% of cases. Observation and computerized morphology showed that the early stage of the periventricular plaque is the formation of a lesion around a subependymal vein and that adjacent lesions later coalesce ».
(Subependymal means below the ependymal zone, in the lateral ventricles of the brain.)
http://www.ncbi.nlm.nih.gov/pubmed/3614542
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One cardiovascular doctor has asked why, and utilized Dr. Zamboni's research to explain the central vein found in MS lesions.
Here's Dr. Michael Dake's illuminating powerpoint presentation, explaining how CCSVI would create vessel wall breakdown, due to disturbed venous blood flow, microbleeds and perivenous fibrin cuffs, activating the inflammatory process. This would lead to adhesion molecule and cytokine expression, oxidative stress and reduced NOS activity--endothelial dysfunction and a breech in the blood brain barrier. We know how this happens in chronic venous disease in other parts of the body. Laminar, or smooth blood flow, maintains the endothelium. Disturbed blood flow leads to a break down.
This would explain the central vein inside the lesion.
http://www.ucsfcme.com/2011/slides/MSU11003/14DakeCurrentStatusOfChronicCerebrospinalVenousInsufficiencyInMS.pdf
Perhaps neurologists do not want to ask why there is a central vein; because they know the answer points to a vascular connection to multiple sclerosis. Their studies are looking at this central vein in MS lesions as purely a means to aid MS diagnosis, so they might begin disease modifying medications in their patients.
But the looming question remains....why the central vein?
The answer will provide healing for those with MS.
Joan
PS--for those who wish to learn more about this history, Dr. Schelling has written the most comprehensive and thorough evaluation of the history of MS lesion studies.
http://www.ms-info.net/ms_040504.pdf
Posted by Joan at 11:27 AM
MS CURE ENIGMAS AGAIN:
ANOTHER REASON TO THINK THAT MS IS A VASCULAR DISEASE : BIRTH CONTROL PILLS (ESTROGEN)
I noted several years ago that Professor George Ebers had observed that around 50-60 years ago MS afflicted males and females alike, in the same ratio. Now there are up to 2, 3, even 4 times as many female MSers as male. What changed nearly 60 years ago ? Answer : The birth control pill, launched in 1960. And now the research is coming in.
"Lead researcher Dr Kerstin Hellwig said: ‘These findings suggest that using hormonal contraceptives may be contributing at least in part to the rise in the rate of MS among women.’
Read more: http://www.dailymail.co.uk/health/article-2569855/Multiple-sclerosis-linked-contraceptive-pill-Risk-50-higher-women-taken-it.html#ixzz4sfGYne6N
Follow us: @MailOnline on Twitter | DailyMail on Facebook Study examined 305 U.S. women
Read more: http://www.dailymail.co.uk/health/article-2569855/Multiple-sclerosis-linked-contraceptive-pill-Risk-50-higher-women-taken-it.html#ixzz4sfGlkVOY
Follow us: @MailOnline on Twitter | DailyMail on Facebook
www.dailymail.co.uk/.../Multiple-sclerosis-linked-contraceptive-pil...
One final note. Not only does Estrogen increase the risk of MS, it, increases the risk of Stroke and Migraines.
And research has shown that Interferon B used to treat MS ALSO increases the risk of stroke and migraines. It would appear that this drug, with only minor effectiveness as an MS treatment, also impacts the vascular system. Details later.
Tags : MS, CCSVI, Estrogen, Central Vein Sign, Dr. Michael Dake, Dr. Michael Flanagan, Dr. Schelling, Dr. George Ebers, NAIMS, Joan Deal
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