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Blood Brain Barrier
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Blood Brain Barrier

Does anyone know what a doctor is looking for in a MRI when he says we will do an MRI to see where the blood brain barrier has been compromised?
Last October 09 I had an MRI which was clear apart from an questionable area of inflammation in thorasic cord. In Nov 09 I had a positive spinal tap for oligoclonal bands in CSF but not in serum and slightly raised protein .
A year later , Oct 10, the MS neuro said he wanted to do another MRI to see where the blood brain barrier had been compromised. This MRI was completely normal.
It has just left me questioning why nothing would show up? Ive had all the MS mimics ruled out  and am relapsing every 4 months or so.
I am due to see a new MS specialist neurologist for second opinion today and hopefully he can shed some light on this.
So far Ive had a diagnosis from 3 different neuros, one of Transverse Myelitis ? MS, then a diagnosis of MS, then the MS specialist say no to MS due to clear MR who has sent me away back to the second neuro who thinks it is MS but cant prescribe DMDs due to the MS specialist saying no.
Any advice would be greatly appreciated.   Thanks Heather
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1466984_tn?1310564208
Hi Heather,
The MRI is an issue that comes up on this site a lot.

The MRI dectects lesions caused by MS - but lesions can be caused by other things as well.  No lesions does NOT necessarily mean no MS.  Here is a good link about MS lesions:

http://www.medhelp.org/tags/health_page/7687/Multiple-Sclerosis/How-MRIs-Show-Lesions-in-MS?hp_id=23

If you had your MRI done on a 3T machine, that will pick up more lesions.  Do you have copies of your MRI reports?  If I were you I would get copies of all tests.  The dx of MS can take a long time - sometimes those pesky lesions don't show themselves for a while - and keep asking questions.  I had a similar issue of being DX, then having the MS expert say he wasn't quite so sure - but didn't know what else it could be.
I was already on meds from my original neuro so I went back to my original guy, and stayed on meds .  I do have lesions, but am missing some of the other "classic" things for MS - but my neuro felt that I had enough going on that he was confident in starting me on the MS meds.

I wonder why your first doc who thinks MS can't prescribe.  Docs disagree on this stuff all the time!  Not that you want to be treated if it's not MS -

Here is the link to the McDonald Criteria to dx MS:
http://www.mult-sclerosis.org/DiagnosticCriteria.html

Any evoked potentials done ? Good luck.  I hope you get to the bottom of this soon!
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1466984_tn?1310564208
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1453990_tn?1329235026
BBB stability is why they use contrast.  If the lesion "enhances" under T1 sequences (post-GAD), that indicates that the BBB is allowing vascular components (GAD Contrast, White Blood Cells, etc) to "leak" into the brain.

Enhancing Lesions = Leaky BBB.
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572651_tn?1333939396
to finish Bob's equation,

Leaky BBB = active MS.  

Good luck with finding answers and treatment,
Lulu
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1045086_tn?1332130022
I thought contrast was specific only for recent breaks in the BBB.  

Other than that, I confess, I am at a complete loss as to why so many people have symptoms and positive results on various differential tests that are helpful in establishing a MS diagnosis, but still have "clear" MRI.  

I'm forced into thinking #1 - there may be diseases/conditions medical science hasn't even defined yet that explains these findings or #2 - the knowledge and standards for MRI interpretation (in general and specifically for MS) remain in the infancy of development.  Perhaps their meaning isn't as clear as we or the medical professionals would like to believe.

So Heather, who treats your symptoms when they appear?  Please don't tell me they send you away with no help.  I think I'd try to pin them down for a better plan and MAYBE consider a different opinion.  

I don't know if the MS specialist you saw is right or not.  I do know they are not all created equal and one that dismisses a patient based on MRI alone always makes me suspicious.

Mary
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1453990_tn?1329235026
You can have lesions without activity.  That means the BBB is intact.  If you have a lesions that enhances , the BBB has to leak for the Gadolinium to get out of the blood stream and enhance on the lesions.  If the BBB is healthy, nothing should enhance on the T1 sequences.
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Thanks everyone for your comments.
The reason the 2nd neurologist could not start DMDs is - in the UK each Health Board has a neuro in charge of the MS clinic and only he/she can prescribe these drugs as they are costly and they need to follow strict protocols before they are prescribed. I will not qualify for them as this neuro does not think I have MS due to clear MRI.
.  
On a good note, I saw a new neurologist this afternoon in a different health board  and I was very happy with him. He looked at my recent MRIs and said the quality was very poor and could not possible be used to dismiss a diagnosis of MS.  
He has ordered a new MRI specifically looking at the areas where he thinks would show lesions due to my recent relapse symptoms. He also noted a spot in the brain which is suspect.
I am very fortunate to have a great GP (family doctor) who has supported me through the past year and a half.  She did not hesitate to write the referal letter to a different health board after hearing how I have been treated.
I am so glad I decided to switch health boards and would highly recommend to anyone here to seek a second opinion or a 4th in my case! Mary you are right not all MS specialists are created equal.
Im still not sure why the last neuro thought he would see where the blood brain barrier had been compromised a year after my positve spinal tap?? Yes, I guess if  MS was still active or new lesions show, who knows.  
So does that mean if they had done the MRI with contrast at the time of the positive spinal tap it would have shown where the BBB had been compromised. Sorry I just find this all very confusing.
Best wishes Heather
  .
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1045086_tn?1332130022
Maybe I'm being dense, but I'm not following.  There can be lesions without what kind of activity?  

Say there is an enhancing lesion indicating a break in the BBB.  Three months later the lesion is still there but doesn't enhance anymore.  What does that say about the BBB?  Is it intact again until another invasion creates a new lesion?

So enhanced lesions indicate a recent break in BBB and non-enhanced lesions indicate a previous break in the BBB.  Is that right?  And we all know our symptoms can get worse (a lot worse) even without an increase in visible MRI lesions of any sort.  So what does that say?

Besides, I was under the impression that MS damage is an ongoing process.  That it happens independent of my awareness of it's activity.  And where does any of this leave Heather who reorts a clear MRI when her doc is looking to see "where the BBB has been compromised".   That sounds like he knows it's there.

I really don't want to argue.  I just like things to make logical sense and heavy reliance on MRI to diagnosis or track progress in MS has never really made sense to me.  It's an excellent tool.  It just doesn't seem to have the reliability factor yet.

I apologize Heather if I have complicated things instead of getting you the simple answer you were probably looking for.  I usually try to suppress these questions in myself that usually cause more dancing than answering.

Mary

Mary
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Avatar_f_tn
Thanks Mary for your questions. Like you I am very confused and I did mention this to my new neuro but unfortunately he didnt really answer. If anyone can clarify please jump in.
Heather
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1453990_tn?1329235026
This is the short version of how I understand this.  Quix  would do better at this than I am going to do.

The endothelium of the vessel is inflamed and allows WBCs and other immune components outside the vessel.  This is the break down in the BBB.  Those immune components attack the the myelin,  That is when the lesion begins.  When the BBB is compromised, GAD can also leak through the vessel wall.  This is the time when the lesion will enhance.  As the endothelium heals, the BBB stabilizes and and intravascular immune components stop passing through the BBB. This is the point when GAD no longer passes from the blood to the lesion.   The components that have passed through the BBB remain active and B-cells, etc. continue to provoke a response and generate antibodies in the brain that are not in the blood.  Damage at the site continues and the lesions can grow bigger, but at that point the BBB is no longer involved.

Quix knows the immunology better than I do and neuroimmunology is even stranger because once the B-cells, CD-4 and other cells are in the brain, they begin to function independent of the immune system in the rest of the body.  The BBB is a barrier between the CNS immune system and the rest of the immune system.  OC Bands in CSF, not in blood is a direct result of that separation and the unique antibodies forming in the CNS.

There is an editorial that explains this pretty well: "The use of MRI in monitoring the treatment of multiple sclerosis "   http://www.springerlink.com/content/p09345337p722m11/
GAD is technically referred to as a "surrogate marker."  We can't see the BBB, but when we see GAD enhance, that means that the BBB leaks.  That is really what GAD is used for in MS imaging.  

Bob
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1045086_tn?1332130022
Despite my little side rant, what I really wanted you to explain was your statement that "BBB stability is why they use contrast".  

A break in the BBB is a vital part of the disease process of MS.  It's why lesions appear at all and why they do MRI to aid diagnosis.  To differentiate new lesions (ie: recent new disease activity) is why they use contrast.  That's why contrast isn't essential for diagnosis but is helpful in locating lesions to track disease progression.

Mary
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1045086_tn?1332130022
Heather, I was wondering about today's visit.  I came back and realized we posted at about the same time.  I had completely missed your report.  That is wonderful news.  

I too have had tremendous support from my PCP.  She has been willing to support me in whatever was necessary to find answers and doesn't hesitate to say when consulted docs aren't making sense.  She has balls not usually seen in the fairer gender.  

We are both very fortunate to have found these talented doctors who know us as individuals and are committed to directing us to quality health care.

I'm thinking the MS specialist used some obscure terminology to describe what he was talking about.  The Blood Brain Barrier isn't a visible structure that can appear or be evaluated directly on MRI.  A lesion is the evidence it has been violated.

The BBB is microscopic.  It exists to monitor the gate separating the bloodstream and the brain/spinal fluid.  Normally, it allows free passage to some substances but stops others cold.  It "leaks" when some process makes it ineffective at it's job.

To "see where the BBB has been compromised" you wouldn't expect to see something to evaluate directly, as if you were looking at the Great Wall of China on satellite pictures.  It's more like hoping to spot individual illegal immigrants who slipped past sleeping guards at unmarked borders and took up residence at the first convenient place offering food and shelter.

I hope that helps because I sure did surprise myself by writing it.  Somebody must be in my head helping tonight.  It sure would be great if Quix came by and verified it though.

Mary
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1453990_tn?1329235026
Emmanuelle Waubant while at the UCSF MS Center in San Francisco called MS a disease of the Blood Brain Barrier rather than a disease of the CNS.  The failure of the BBB was the root cause that enabled T-lymphocytes to attack the myelin.  If the BBB was working correctly, the T-lymphocytes would never make it into the CSF to attack the myelin.

Disease Markers, IOS Press, Volume 22, Number 4/2006.  pp 235-244
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1045086_tn?1332130022
I understand that.  That's why I said it's the reason lesions appear at all.  Thanks Bob.  I think I've got it as clear as possible for me at the moment.

Others may still have specific questions though.  I hope I haven't discouraged them from looking here and asking you if they do.

Mary
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