demyelinating brain lesions and starting Remicade treatment

5 yrs. diagnosed with demyelinating brain lesions.  51 yr. old female diagnosed Multiple Sclerosis and received treatment with Betaseron, Solumedrol, Novantrone. Treatment hasn't helped.  Brain lesions do not go away and I get a few new lesions each year. So I keep accumulating active brain lesions. MRI -Multiple small foci of bright FLAIR in the subcortical white matter of both hemispheres in relatively symmetric distribution. I am also diagnosed with Ankylosing Spondylitis and Ulcerative Colitis.  Need Remicade treatment but was told by one rheumatologist he wouldn't do it because of brain lesions-said I could die from Remicade activating further brain lesions. Saw another rheumatologist and she said yes to Remicade based on the brain lesions may not be demyelinating.  My symptoms are balance difficulties, Optic Neuritis, Uthoff's phenomenon, both legs w/weakness, muscle spasms, memory loss, arthritis of spine-hips-hands-feet, hearing loss. Waiting on a blood test for Myelin Basic Protein & Myelin Oligodendrocyte Glycoprotein. If this test comes out negative would it be safe to take Remicade? Have had blood tests several times for Lupus, Sarcoidosis, Lyme,etc. All negative but HLA-B27 positive. What should I do. Thank you.

[Joanna Fong, MD]

Your symptoms listed above are typical of multiple sclerosis.  However, without a full neurological examination and MRI films to review, it is difficult to answer your concerns with 100% certainty.  Here are the thoughts:

0) Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS).  
1)  Multiple sclerosis has many different types.  Some are progressive, some are relapsing-remitting course.  If your symptoms have been progressively worsen or with no improvements, this is likely a primary progressive.  Primary progressive MS (PPMS) represents only about 10 percent of cases at onset and is characterized by a steady decline in function from onset with no acute attacks.  Another progressive types are: "Progressive relapsing" — Progressive/relapsing MS (PRMS) begins with a progressive course, with occasional attacks superimposed upon the steadily progressive course.  "Secondary progressive" — Secondary progressive MS (SPMS) begins as relapsing-remitting disease (RRMS), but it later changes so that the course becomes characterized by a steady deterioration in function, unrelated to acute attacks. Typically, the attack rate is also reduced when the secondary progressive stage is reached. This type of MS, which ultimately develops in approximately 80 percent of RRMS patients, causes the greatest amount of neurologic disability.
2)  Number of brain lesions usually correlates with progression of disease (i.e. more symptoms).
3)  I understand that you had tried Betaseron, Solumedrol, Novantrone.  Treatment directed at the progressive phase of MS is typically more difficult than treatment of relapsing forms of MS.  Immunosuppressive therapies such as total lymphoid radiation (TLI), cyclosporine, methotrexate, 2-chlorodeoxyadenosine (2-CdA), cyclophosphamide, mitoxantrone, azathioprine, interferon, steroids, intravenous immune globulin (IVIG), and plasma exchange have shown at least some positive clinical effects in progressive disease.
4)  However, all of these nonspecific immunosuppressants suffer from the same basic defect; they may temporarily halt a rapidly progressive downhill course, but it is difficult or dangerous to employ them for more than a few months to a year or two. Thus, since MS is an illness of decades, not months, immunosuppressive therapy is only a temporary solution at best.
5)  It's a good idea to see a MS specialist.  We have Mellen Center here in the Cleveland Clinic (Cleveland, OH).  They'll be able to help you out more.
6)  Physical therapy is very important, especially you have weakness.
7)  Remicade is a Tumor Necrosis Factor (TNF) Blocking Agent - a disease modifying agent/immunosuppressive agent.  It is sometimes used in crohn's disease and Ankylosing spondylitis.  There are case reports of demyelinating disease of the central nervous system linked to anti-tumor necrosis factor alpha therapy such as Remicade.  It is also in the warning label for Remicade: "Warning: Concerns related to adverse effects:  Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop."

I hope they're helpful and answer some of your concerns.  It is still a good idea to see a MS specialist.  

Good luck.

[Quixotic1]

Wow, you are in a tough position.  I'm sorry to hear about your multiple illnesses.  The one thing that bothers me about what you wrote is that you say the "second rheumatologist" is willing to treat you "on the chance" that your CNS lesions are not a indication of a dymyelinating process.  Given your history which is classic for multiple sclerosis, what is the "chance" that those lesions are something else?  My gut reaction is that that chance is slim.  You didn't respond to the disease-altering meds, but, then, 30% or so do not.  That doesn't mean that you don't have MS.

You need to talk with a third specialist about the true danger of taking the Remicade if, indeed, you do have MS.  That's why you're posting here of course, but the neuro here is almost a full month behind in answering.  Once you know that risk, then you have to weigh it against not treating the other two diseases and what further disability they will inflict.  If the risk is potentially fatal with Remicade, then this is a situation where I would definitely seek a third opinion from the best source I could get access to.

I think you need a team conference of Neurology, Immunology, and Rheumatology at a major teaching center or major university medical center to discuss all of the options.  This is far too complex for you to sort it out by going from one doctor to another.  (I don't know if that is what your are doing).  I am a physician and, if it were me, I would demand such a team approach.

I have another question if you would be so kind as to answer it.  I was under the impression that using the the anti-MOG and anti-MBP antibody tests were still in research.  Are they performing these on your blood?  Are they doing it especially for you or are these tests now available for use in diagnosing others?  Where are you having the tests done?  I was assuming that you had not had a lumbar puncture because of the AS.  Thank you, Quix

[dittledittle]

I learned of those blood tests from reading archive posts from this forum.  The neurologist replied to someone saying to do those tests and if negative to seek more of a rheumatological cause.  I contacted my Neurologist with this info and I located a lab in California thru contacting Cleveland Clinic lab. My neurologist filled out the test request form and will know the results in another week.  I had a lumber puncture 5 yrs. ago and everything was normal.  The Ankylosing Spondylitis has gotten worse and the pain is becoming too much. NSAIDs are not helping much. The Ulcerative Colitis is under control.  My neurologist says I don't fit the typical brain lesion locations.  None in the Dawson fingers location and the lesions remain active where they should become inactive after a period of time as I am told.  I have had every blood test for rheumatological causes including Lyme.  All negative.  Do you have MS?  

[Quixotic1]

I see what you are saying about the lesions.  I have a lot to learn about neurology and brain lesions.  I'm sorry if I seemed presumptuous.  You are clearly receiving good care.  I have researched the anti-MOG and anti-MBP and can't find any data newer than 2004 on these and nothing on their current use in actually diagnosing MS.  (Except for two articles this year which did not find them that useful.  However, they were only being used to determine which people with a CIS would be most likely to convert to clinically definite MS )  If you can give me any more specific info, I'd appreciate it.  I recently told someone that this test didn't appear to exist and I need to retract that, along with my apology.

I can't help but wonder why it isn't being used more in people with classic signs and symptoms, but non-diagnostic MRI's.  We know that a huge number of the lesions in MS are still not being picked up by current MRI machines.  The newer T3 machines are better, but aren't yet widely in use.  Yes, I am newly diagnosed with MS.  I went from 0 spinal lesions to 7 just in switching to the T3 machine.

Quix

[dittledittle]

Please do not apologize.  I appreciate your advice and was thinking I'm going to need to seek a team of physicians to get this figured out.  I search the internet for info that maybe would help determine my situation.  One of the labs that processes MBP & MOG is Immunosciences Lab., Inc.  There is another lab in California too and I think one in Buffalo, NY.  I don't know why it isn't used more but took the opportunity in hopes that it might help my situation.  Can I ask what does a physician in Immunology do?  Sorry to hear of your diagnosis. It would be really great if there can be a cure to all of these autoimmune illnesses.  Are you receiving medications that work for you? How long did it take to get your diagnosis.  Do you have other autoimmune illnesses too?

[karzme]

I was diagnosed with MS on June 28th. Found out it's what I could have on April 23rd. I have alot of tingling and numbness in left arm. I know it's suppose to be symptoms of MS, but drs are telling me, they don't think it has to do with MS. I have seen my MRI's and I have many lesions on brain and spinal cord.  I also am having throbbing pain in my left thigh. Drs don't have answers to this either.

Am also getting sharp pains up and down spine. Went to ER and had x-rays of spine. All they told me was, I had some arthritis in lower spine. No other explanations. Is it possible that pain in arm and thigh (can feel nots in them sometimes), isn't MS related? Could it be a pinched nerve or maybe cancer? The drs I've seen aren't giving me much advice.

Also was wondering , how helpful are copaxone and other injectables? I am not on any currently, but am considering copaxone, because insurance pays most. Would only have to pay co-pay. I've heard there is alternative meds, but that my insurance and most insurance doesn't cover them. I REALLY hate needles, but would do it if had to. Any suggestions or advice would be helpful. Thanks.

[Quixotic1]

There is a great overlap between Immunology and Rheumatology, but the Immunologist tend to be university and research-based and cross cover the diseases of immunocompromise.  I recommend seeing one because of the potential for harm if the "guess" is wrong and Remicade could cause really severe CNS damage.

I've continued to look at the use of the anti-myelin antibodies and have concluded that, while they are commercially available, they have not been shown to be statisitically helpful in in diagnosing MS.  Which is why the MS specialists aren't including them in the MS diagnostic protocols.  Now, that does not mean that in any "individual" case that they won't bring some more information to the table.  Your case is so complex and worrisome that I would look for and use all pieces of info available.  Here is the New England Journal of Medicine article from Jan 2007 that found no association between the anti-mylelin antibodies and progression to MS.  It doesn't really apply to your case.

http://content.nejm.org/cgi/content/abstract/356/4/371

I am a former pediatrician who was disabled in 2001 by Autoimmune Inner Ear Disease with severe, intractable vertigo.  At that time there was very good evidence that my problem was with the peripheral vestibular system, not the CNS.  We have not found anything that treats the vertigo effectively.  About 2 and a half years ago I developed right leg weakness and spasticity, severe fatigue and heat intolerance, then incontinence, and then weakness and spasticity of my right arm.  My neurologist ignored a classic brain lesion and basically accused me of faking my symptoms (spasticity??)  So I found an MS specialist who confirmed the diagnosis last March.  I am on Avonex and it's too early to know if it will help.

I miss being useful and practicing medicine, so I hang around the forums answering questions when I think I can help.  I would very much like to find out what happens with you and what you/they decide to do.  Mostly I hang out over on the MS Forum here on MedHelp trying to help people navigate the diagnostic maze.

Quix

[que03]

Do you know of the facilities that have the T3 MRI's?  Dx'ed with MS or something similiar in 2005.  On Rebif since Dec. 05.  Started adding IVIG this year back in Mar.  It seems to help.  Unfortunately, I haven't been able to do any exercise since Mar due to extreme nerve pain in legs after 15 mins., or I get hot. Last triathlon done in Oct 06, when I had to hang up bike.  Last marathon done in Feb. 07.  Boy, was it pitiful too!!!  I am still having trouble accepting DX and feel like solely bulging disc or something simple, like hypocalcemia.  Nothing in brain looks like MS.  "something" in basal ganglia--probably "nothing to worry about"  but like person above it doesnot change, it stays bright.  Neurologist feels like problem in upper spine but unable to see on MRI.  I am resigned to accept it b/c if I have any other problems the other Drs blame MS and go on.  If I had physical proof of lesions on sc MRI I think I might accept DX--whether that is good or bad, I don't know.  My neurologist has also mentioned Remicade.  Why is it bad?  Doc acted like it was the "magic" I needed.  Thx for your input. que

[Quixotic1]

Well, here you are again.  Sorry I missed you, I don't spend as much time over here any more.

I have seen Remicade mentioned in a couple of medical articles for CAUSING Multiple Sclerosis-like symptoms.  The problem is that MS responds to things like Interferon.  Interferon "modulates" a crtical part of the immune system, that part which is felt to be near the source of the problem in the demyelination procress.  Interferon is actually a byproduct of the action of the immune system.  It does not suppress the immune system, contrary to what a lot of people seem to believe.  I question your doc considering it.

Remicade is a direct supressant of the immune system, basically shutting it down.  MS apparently needs at least a partially functionl immune system to stay in check.

Like I said to you in another post, if your disease responds well to IVIG, then could you possibley have CIDP instead of MS.  Do you  know if you have decreased knee and ankle reflexes or normal or hyperactive?

Quix

[dittledittle]

I got the test results for the MBP & MOG and it was negative.  My doctor says it still doesn't help much but gives us some information.  I was reading your response to que03 and wanted to state that I am seeing the rheumatologist this coming Fri. to talk more about treatment for arthritis of the spine.  Just to say something here I have decreased knee and ankle reflexes too.  Was wondering if que03 does too.  My reflexes have been decreased since the beginning of symptoms.  Maybe que03 and myself have some common ground.  Are you responding to your treatment?

[Quixotic1]

I actually have MS and have spasticity with very hyperative reflexes, but the CIDP is demyelinated peripheral nerves and typically has decreased or absent reflexes.  Dx is made by seeing characteristic changes on NCS and on elevated protein in CSF.  It is rare, but felt to be under recognized, thus under diagnosed.  It is an autoimmune disease and responds well to IVIG, plasma pheresis and other treatments.

I bring it up, only because it mimics other diseases like MS in symptoms, but is treatable.  Quix

[que03]

Yes, dr thought 1st time they saw me I had brachial neuritis/CIDP.  Had normal reflexes that visit.  Over the next couple of years and several attacks, one-by-one reflexes have turned hyper and clonus both legs but no babinski.  1 1/2 years later l. arm  EXTREME pain, worse than anything I have ever experienced(mom of 3 kiddos).  Dr thought another brachial neuritis/CIDP.  After shots in ER and RX meds went home.  Neuro treated with IVIG among other things and truly felt this worked.    After about 3 weeks off most meds. Most of my function normal, just a little weakness in lat. and p.minor on r. side.  Here is the problem--reflexes don't go eith CIDP as you well know.  Now, when I get hot, my lower legs anteriorly on shin feel like I have a thousand fire ants biting. Dr says this happens with any spinal cord damage.  Have horrible constipation(Zelnorm off market is the worst!).  And urinary dysfunction(I can't remember what they called it).  These don't go with CIDP,right?  To make this more interesting, my dad has had something similiar that has been going on since I was in H.S.  He gave up after Mayo clinic dx'ed by exclusion MS.  One interesting thing that came out was a Ca channel ab. type N that was 325.(I think under 16 was normal).  Normally this is seen in LEMS or lung ca which according to Mayo he has neither.  So what does all this mean?   Dr believes it is something R/R, autoimmune that is causing nerve damage.  Is it a subset of MS or completely different? My EMGs have been reported to me verbally as "fine".  Do you have an email?  Normally don't ever comment.  I just surf to find if someone sounds like me and what dr says to them.  I was tuned in b/c of Remicade.  I will heed your warning.  Thx.

[Quixotic1]

Que, Hi, I don't mean to pass myself off as an expert here.  I am probably meddling in someone's proper care.  I have also found that some people with MS also respond to IVIG.  So it isn't cut and dried.  As far as the T3 MRI's they are definitely popping up in the newer and bigger imaging centers.  I don't think they are rare, but they are still outnumbered by the older, less powerful machines.

Autonomic neuropathy (which can cause gastrointestinal abnormalities, like diarrhea or constipation), cardiac and blood pressure abnormalities and problems with vascular instability and temperature instability can be SEEN IN CIDP.  In fact, autonomic neuropathy is a subset of CIDP.  People who deal with CIDP feel that anyone in whom this Dx is even considered should be given a course of therapy, eg. IVIG or plasmapheresis.  The thinking is that CIDP in most of it's forms responds very well to treatment and the other options (MS) don't.  Again, typically the spinal fluid will have an elevated protein.  There are also a couple serum antibody markers for some of the variants.

Again, I am not a neurologist and actually can barely understand the genetics immunological and biochemical discussions of CIDP.  But, it seems to me that I see quite a bit of symptomatology here that fits with CIDP and may be being missed.

As I understand it, hyperactive reflexes would not fit CIDP (I don't know if this is hard and fast).  The heat intolerance and also generalized fatigue is frequent in CIDP.  I recently looked this up.  There are many variants of CIDP and many of them include paresthesias (sensory CIDP).  So Yes, the urinary, constipation, heat intolerance and "fire ants" could fit CIDP also.

About the Ca channel finding - I am totally ignorant on this topic.  sorry

If either of you want to contact me you can do so at my nickname neuroquix and I use the gmaildotcom program.

Dittle, I realize that you have AS and that may make an LP difficult.  I have garden variety osteo (not even in the same category!) but they did my LP under fluoroscopy guidance, working painlessly around the osteophytes and my LP was slow, but a total breeze.  Would a repeat LP give you any more info?  From your descriptions I can't believe they don't think you have MS.  On MRI scarred lesions don't go away, but may eventually leave "black holes."  Are they saying that they think you have a vasculitis causing the constant appeareance of new lesions?  And is that characteristic of AS???????

I remain worried by your statement that the rheumatologist is willing to use Remicade as the lesions "may not" be demyelinating.  But, what if they are?  Would IVIG or plasmaphoresis be beneficial for any of your illnesses, IBS or AS?

Quix

[que03]

From what I have seen, IVIG is good for IBS and AS.  It helps calm the autoimmune response by temporarily saturating your system.  I am doing 4 days in a row every 6 weeks.  The time frame can be anywhere from 4 wks to 3 months depending on how things are going with you.  It is much better to treat a little earlier than necessary so you don't get behind 8 ball and then have to dig out of flair.  Because it is not specific it can be helpful in many autoimmune things.  

[dittledittle]

Blood test for Myelin Basic Protein & Myelin Oligodendrocyte Glycoprotein came back negative.  I am presently trying Methotrexate and taking folic acid.  Scared to take Remicade.  Rheumatologist says brain lesions are a separate symptom from Ankylosing Spondylitis.  Neurologist cannot figure out causes for brain lesions and doesn't feel it is Multiple Sclerosis.  Do you know of a diagnosis or cause for multiple small foci of bright FLAIR in the subcortical white matter of both hemispheres in relatively symmetric distribution.  My neurologist says they are located in white matter -along small blood vessels, are not "leaking", and remain active with new lesions each year accumulating.  He has exhausted autoimmune causes.  The brain lesions also effect my vision with optic neuritis and yellow areas of lines and spots in my vision, and a white cloudy glare.  The eye problems are coming from the brain--opthamologist found nothing wrong with the front of my eye.  My other symptoms are mentioned in my original question to you.  These symptoms have been going on since 2002.  I do not have high blood pressure and I am not obese.  I have started recently to go through symptoms like hypoglycemia.  It remains a problem too.  Thank you for your help.

[que03]

I don't know why but I was re-reading your post.  When you were asking about your bright spots that don't go away on MRI.  I have tried to find out why this happens b/c of similiar issue.  I found that chronic hypocalcemia can cause this particularly in basal ganglia.  Hypocalcemia in an acute reaction is easy to pick up but in chronic problem more difficult.  Apparently, serum calcium will not show problems.  Ionized ca has to be done.  Why would you be hypocalcemic?---diuretic use(maybe even some otc drugs), kidney damage, other hormone problems that regulate calcium metabolism-  did anything come of the hypoglycemia check?  On another note, I have heard about treatment with rituxan.  Have you?  Not Remicade.

[dittledittle]

I was receiving treatment for MS until this past spring.  Just had my yearly MRI of brain and my neurologist says definitely not MS.  The radiological terms are “non-specific micro-vascular change” or “leukoaraiosis”.  I do not have hypertension, diabetes, B12 deficiency, Alzheimers, no stroke or TIAs.  What other illnesses can there be. Thank you.

[Joanna Fong, MD]

Your symptoms listed above are typical of multiple sclerosis.  However, without a full neurological examination and MRI films to review, it is difficult to answer your concerns with 100% certainty.  Here are the thoughts:

0) Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS).  
1)  Multiple sclerosis has many different types.  Some are progressive, some are relapsing-remitting course.  If your symptoms have been progressively worsen or with no improvements, this is likely a primary progressive.  Primary progressive MS (PPMS) represents only about 10 percent of cases at onset and is characterized by a steady decline in function from onset with no acute attacks.  Another progressive types are: "Progressive relapsing" — Progressive/relapsing MS (PRMS) begins with a progressive course, with occasional attacks superimposed upon the steadily progressive course.  "Secondary progressive" — Secondary progressive MS (SPMS) begins as relapsing-remitting disease (RRMS), but it later changes so that the course becomes characterized by a steady deterioration in function, unrelated to acute attacks. Typically, the attack rate is also reduced when the secondary progressive stage is reached. This type of MS, which ultimately develops in approximately 80 percent of RRMS patients, causes the greatest amount of neurologic disability.
2)  Number of brain lesions usually correlates with progression of disease (i.e. more symptoms).
3)  I understand that you had tried Betaseron, Solumedrol, Novantrone.  Treatment directed at the progressive phase of MS is typically more difficult than treatment of relapsing forms of MS.  Immunosuppressive therapies such as total lymphoid radiation (TLI), cyclosporine, methotrexate, 2-chlorodeoxyadenosine (2-CdA), cyclophosphamide, mitoxantrone, azathioprine, interferon, steroids, intravenous immune globulin (IVIG), and plasma exchange have shown at least some positive clinical effects in progressive disease.
4)  However, all of these nonspecific immunosuppressants suffer from the same basic defect; they may temporarily halt a rapidly progressive downhill course, but it is difficult or dangerous to employ them for more than a few months to a year or two. Thus, since MS is an illness of decades, not months, immunosuppressive therapy is only a temporary solution at best.
5)  It's a good idea to see a MS specialist.  We have Mellen Center here in the Cleveland Clinic (Cleveland, OH).  They'll be able to help you out more.
6)  Physical therapy is very important, especially you have weakness.
7)  Remicade is a Tumor Necrosis Factor (TNF) Blocking Agent - a disease modifying agent/immunosuppressive agent.  It is sometimes used in crohn's disease and Ankylosing spondylitis.  There are case reports of demyelinating disease of the central nervous system linked to anti-tumor necrosis factor alpha therapy such as Remicade.  It is also in the warning label for Remicade: "Warning: Concerns related to adverse effects:  Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop."

I hope they're helpful and answer some of your concerns.  It is still a good idea to see a MS specialist.  

Good luck.