Man with rare blood-flow-to-brain disease gets MS

[cheerleader]

What's most interesting is that it is ischemic injury which activates the immune system and creates lesions in moyamoya disease....which is why it's a differential for MS.

We report a case of moyamoya disease in a young adult female, in whom the initial clinical and radiological features were considered to be compatible with multiple sclerosis. Magnetic resonance imaging (MRI) features of dilated collateral arteries were then recognized, and the initial MRI findings considered to represent demyelination were reinterpreted as areas of infarction. Although rare, moyamoya disease should be considered in the differential diagnosis in young patients presenting with symptoms and signs suggestive of multiple sclerosis. The diagnosis may be suggested by typical MRI findings.

http://www.ncbi.nlm.nih.gov/pubmed/2394073

Again, same MRI demyelination we see in stroke, cerebrovascular disease, and CCSVI. In this instance, it's slowed blood flow going into the brain, and opening the affected intracerebral arteries brings relief.

We believe that moyamoya disease should be considered in multiple sclerosis variants who present with paresthesias and do not respond to traditional immunosuppressive therapies.

Early diagnosis and revascularization procedures could help prevent further neurologic sequelae. Furthermore, subtle MRI findings should suggest obtaining a CTA/MRA or a formal angiogram to identify moyamoya vessels

thanks for linking the study over here, Cece. I find it less annoying (for myself) and less confusing to readers to write on Facebook, and appreciate you dealing with TIMS....
cheer

[Cece]

thanks for linking the study over here, Cece. I find it less annoying (for myself) and less confusing to readers to write on Facebook, and appreciate you dealing with TIMS....
cheer

Thanks, Cheer. The Facebook site seems like it would take a lot of time to manage.

I like the back-and-forth here at TIMS, up until stones start getting slung.

I look forward to us all having more of the answers than we do now. But looking back before CCSVI, dang! We had nothing. We had all the individual parts of the elephant and could not see how it all came together.

[scorpion]

What's most interesting is that it is ischemic injury which activates the immune system and creates lesions in moyamoya disease....which is why it's a differential for MS.

We report a case of moyamoya disease in a young adult female, in whom the initial clinical and radiological features were considered to be compatible with multiple sclerosis. Magnetic resonance imaging (MRI) features of dilated collateral arteries were then recognized, and the initial MRI findings considered to represent demyelination were reinterpreted as areas of infarction. Although rare, moyamoya disease should be considered in the differential diagnosis in young patients presenting with symptoms and signs suggestive of multiple sclerosis. The diagnosis may be suggested by typical MRI findings.

http://www.ncbi.nlm.nih.gov/pubmed/2394073

Again, same MRI demyelination we see in stroke, cerebrovascular disease, and CCSVI. In this instance, it's slowed blood flow going into the brain, and opening the affected intracerebral arteries brings relief.

We believe that moyamoya disease should be considered in multiple sclerosis variants who present with paresthesias and do not respond to traditional immunosuppressive therapies.

Early diagnosis and revascularization procedures could help prevent further neurologic sequelae. Furthermore, subtle MRI findings should suggest obtaining a CTA/MRA or a formal angiogram to identify moyamoya vessels

thanks for linking the study over here, Cece. I find it less annoying (for myself) and less confusing to readers to write on Facebook, and appreciate you dealing with TIMS....
cheer

As was pointed out....
The authors are not saying that the artery blockages caused demyelination. They are saying that the original plaques seen on MRI were thought to be demyelination characteristic of MS. After further angiographic tests (and the patient suffering a cerebral infarct), they changed their interpretation of the original MRI findings from demyelination to areas of infarct (tissue death due to a reduction of blood supply).

[cheerleader]

clarification....
Moyamoya is an ischemic demylinating disease
no need for an infarct.
There is still demylination, and white matter lesions.
Ischemic events create the same white matter lesions we see in MS...it is just that their cause is explainable.

MS is called a primary demylinating disease, because the cause is unknown. If the cause of demyelination can be detected, be it infectious or ischemic, the disease is called a secondary demyelinating disease. Once Moyamoya was detected, the demyelination was called secondary. But the lesions are still the same.

CCSVI may prove to be an ischemic demylinating disease. Obviously, more research is needed.
cheer

[cheerleader]

Here's a great paper explaining the different catagories of demylinating lesions. Moyamoya would be in the ischemic demylinating diseases, along with carbon monoxide poisoning, vasculitis and cerebrovascular disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860500/
cheer

[frodo]

Here's a great paper explaining the different catagories of demylinating lesions. Moyamoya would be in the ischemic demylinating diseases, along with carbon monoxide poisoning, vasculitis and cerebrovascular disease.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860500/
cheer

A big part of the problem is the "clinical definition" for MS. Cases like Moyamoya patients with demyelinating lesions are not included inside the MS spectrum just because the McDonald criteria imposes that no explanation should exists for the lesions to be MS.

McDonald criteria should be considered just some clinical test and a pathological definition for MS should be used instead. I am not the only one saying that. There are some others, like Lassmann, thinking the same:

http://brain.oxfordjournals.org/content ... 17.extract

[Cece]

What would the pathological definition of MS be? My understanding is that, as a disease of exclusion, there is no exact way to diagnose MS.

[frodo]

What would the pathological definition of MS be? My understanding is that, as a disease of exclusion, there is no exact way to diagnose MS.

Any definition would be good as long as it is consistent. If moyamoya lesions are equal than those in unexplained MS, both should be clasified as the same condition. Even if their ethiologies were different.

I would say that defining MS by the presence of T-cells mediated diffused demyelinating lesions would be a good approach for a definition.

[cheerleader]

I would say that defining MS by the presence of T-cells mediated diffused demyelinating lesions would be a good approach for a definition.

Frodo---but these t-cell mediated demylinating lesions are present in cerebrovascular disease, dementia, ischemic disease, carbon monoxide poisoning, etc. The t-cells react the exact same way.

This is from a Facebook note I wrote up on this problem of defining MS by t-cell activation.

Here is a study where the CSF of patients with cerebrovascular disease is tested. And those with MS and CVD have the same range of MBP reactive T-cells in the CSF. This leads the researchers to posit that this immune reaction is secondary to damage in the CNS. Which makes me wonder....is the CSF of stroke patients and those with hypoxia or ischemic events regularly tested? And if so, are these people told they have an immune system disease? Obviously, the answer is no.


Myelin antigen reactive T cells in cerebrovascular diseases
W.Z.WANG,T.OLSSON,V.KOSTULAS,B.HOJEBERG,H.P.EKRE&H.LINK
Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden

Quote:
INTRODUCTION In acute ischaemic cerebrovascular diseases (CVD), mononuclear cells appear in the brain parenchyma within 1-2 days and increase in number over the ensuing 5-30 days[1].Also in cerebrospinal fluid (CSF), elevated numbers of mononuclear cells may be detected. These cells are considered to mainly represent monocytes-macrophages, but there are no detailed studies on their lineage with,e.g.,antibodies to different cell surface markers. Oligoclonal IgG bands are present in the CSF while missing in corresponding serum, in about 10% of patients with CVD [2,3].A local B cell response directed to neurotropic viruses,as in patients with multiple sclerosis, has been reported in those patients with CVD who displayed oligoclonal IgG bands in CSF [4].Taken together,these observations indicate that patients with acute CVD may display an intrathecal immune response......

The strong increases in numbers of MBP, MBP peptide and PLP reactive T cells in blood, and of MBP reactive T cells in CSF, which we here report in our patients with Cerebro Vascular Disease, are in the same range as we have previously observed in MS [10,11].Thus, both diseases are accompanied by an expanded pool of myelin autoreactive T cells and they may well be secondary to damage to the central nervous system.

Here is the full paper in PDF form.
http://www.ncbi.nlm.nih.gov/pmc/article ... 8-0161.pdf

The only difference between any of these cerebrovascular diseases (like Moyamoya) and MS is that the cause of this immune activation is not known in MS....that's why it's called a primary demylinating disease and Moyamoya is a secondary demylinating disorder. But what if the cause of immune activation is venous congestion and ischemic injury due to CCSVI? Why should MS be the ONE disease that is autoimmune, if the t-cell activation is the EXACT SAME in other cerebrovascular diseases? Ockham's razor comes to mind,
cheer

[frodo]

Frodo---but these t-cell mediated demylinating lesions are present in cerebrovascular disease, dementia, ischemic disease, carbon monoxide poisoning, etc. The t-cells react the exact same way.

That is not a problem. Then we would speak about carbon monoxide induced MS, ischemic MS and cerebrovascular infarct induced MS, and maybe CCSVI induced MS.

Sometimes it would sound weird but such a extension is required to maintain consistency with a pathological definition, which I consider necessary.

[Cece]

I don't quite follow this. Carbon monoxide poisoning, for example, has its specific treatment plan and prognosis. There can be sustained neurological damage after carbon monoxide poisoning, but, unlike MS, it is a one-time event. Carbon monoxide poisoning is named for the cause of the damage, which would be the carbon monoxide.

MS is named for the damage itself, probably because the cause was elusive. But there is a specific disorder called MS that we have all suffered from in its various forms. Now things are in upheaval because of the possibility that what we knew about it (autoimmune) is false and what we didn't know (vascular involvement) has implications in treatment and understanding of the disease.

The name MS is not important, but it is important that there be a name for the disease that we suffer. If it is true that CCSVI is the cause of MS, then we can drop the MS and just call it CCSVI!

[cheerleader]

right, Cece.
there are many demyelinating diseases, all have demyelination as a reaction to some insult of the CNS...ischemic, viral, bacterial, toxic, metabolic disorder, etc.

There's no need to place other demyelinating diseases under an "MS umbrella", Frodo. These other diseases can be explained and categorized by the known injury. Demyelination is secondary. The pathology is consistent....it's called demyelination.

There is only one demyelinating disease of unknown aetiology, it is called MS.

cheer

[frodo]

right, Cece.
there are many demyelinating diseases, all have demyelination as a reaction to some insult of the CNS...ischemic, viral, bacterial, toxic, metabolic disorder, etc.

There's no need to place other demyelinating diseases under an "MS umbrella", Frodo. These other diseases can be explained and categorized by the known injury. Demyelination is secondary. The pathology is consistent....it's called demyelination.

There is only one demyelinating disease of unknown aetiology, it is called MS.

cheer

MS is a demyelinating disease of unknown aetiology, but it must be secondary to something. Therefore I still see no difference between MS and the other disorders you propose.

EDIT: Anyway even if my pathological definition is not good, there is still need for a pathological definition

[ikulo]

I found this interesting...

Distinction of demyelination [in MS] from destructive processes such as infarction depends largely on the demonstration of axons within regions of white matter that are devoid of myelin. This distinction is more obvious when grey matter is affected: in multiple sclerosis neurones are preserved (fig 1F​1F),), but this is not the case for infarction or other destructive processes that cause loss of myelin

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860500/

... because neurons are not really preserved in MS.

[Cece]

I found this interesting...

Distinction of demyelination [in MS] from destructive processes such as infarction depends largely on the demonstration of axons within regions of white matter that are devoid of myelin. This distinction is more obvious when grey matter is affected: in multiple sclerosis neurones are preserved (fig 1F​1F),), but this is not the case for infarction or other destructive processes that cause loss of myelin

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860500/

... because neurons are not really preserved in MS.

This is from 2006, which is fairly recent. I looked thinking maybe it was older, since it's only been in recent years that it was discovered that axons and gray matter were affected by MS early in the disease process.