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Hi MomMD,

Can you elaborate on what you said re: the BBB closing at puberty? I have never heard that before--thanks.

Also, on another post you mentioned research at Yale (Dr. Leckman?) re: antibiotic use, can you chat about that too--

thanks so much,

T.Mom

 

"I do think it is reasonable to suspect that IVIG or steroids will be needed periodically to treat "relapses" until puberty when the BBB closes. Carter's ASO had dropped to 950 (from 1750) and his antiDNase B rose to 1360 from 1320 after two plus months of antibiotics. his symptoms improved somewhat but his ANA is positive at +1:640 which just seems to point once again to an autoimmune course of treatment rather than antibiotics alone."

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I spoke to Dr. Leckman on the phone and we discusses the nature of PANDAS. Read the post auto-antibody neuronal cell signaling. It basically sums up what he said. This was started by strep but the antigen antobody complexes have attached to the vasculature in the basal ganglis. Anytime the child is stressed, the BBB opens up and the PANDAS flares. Knowing all this he said treating kids with antibiotics does not make much sense. The antibodies are the issue, not the strep that is why IVIG and plasmaphoresis works. I think these kids with PANDAS are genetically predisposed to get this and then the strep starts the process and a "trigger" (like stress, viral infection, vaccines) spirals the immune system out of control. It overacts to the strep and then you get PANDAS. He also said this data won't be published completely until 2011 but may serve as a basis for understanding autism and ADHD. Fascinating. My thoughts are antibiotics have a place to prevent reoccurance but do not treat true PANDAS.

Hi MomMD,

Can you elaborate on what you said re: the BBB closing at puberty? I have never heard that before--thanks.

Also, on another post you mentioned research at Yale (Dr. Leckman?) re: antibiotic use, can you chat about that too--

thanks so much,

T.Mom

 

"I do think it is reasonable to suspect that IVIG or steroids will be needed periodically to treat "relapses" until puberty when the BBB closes. Carter's ASO had dropped to 950 (from 1750) and his antiDNase B rose to 1360 from 1320 after two plus months of antibiotics. his symptoms improved somewhat but his ANA is positive at +1:640 which just seems to point once again to an autoimmune course of treatment rather than antibiotics alone."

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Hi MomMD,

 

Thanks for posting on your conversation with Dr. Leckmann. I've been tracking his work (or more precisely his student's work on T-cell regulation).

 

Anytime the child is stressed, the BBB opens up and the PANDAS flares. Knowing all this he said treating kids with antibiotics does not make much sense. The antibodies are the issue, not the strep that is why IVIG and plasmaphoresis works.

 

I think that is partially true. The anti-neural antibodies are in the blood stream and if Kirvan is right, they are targeting GlcNAc which is a fairly common carbohydrate in the body and just happens to be on the exterior cell wall of the GABHS. Since the monoclonal antibody doesn't seem to be binding to other sources of GlcNAc but only to Tubulin and neural tissue, there's probably something unusual about the chain itself.

 

In Kirvan's JNI paper, she shows that CaM Kinase II activation is reduced in the case of convalescent PANDAS and SC patients in 15 of the 16 patients. This indicates that by removing the initial antigen (presumably GABHS) the antibodies reduce and the B-cells stop replicating the antibody. If the blood-brain barrier opens in the convalescent state then the concentration is low and unlikely to cause CaM Kinase II activation. This seems to warrant keeping triggers from coming -- just to keep the antibody concentration low.

 

In 4 of the 16 cases, the antibodies were still high in convalesence so that a disruption of the BBB would have then just let the already active antibodies in.

 

So, it seems in both cases, lowering (and keeping low) the anti-neural antibodies would be the goal and hopefully reseting the B-cell to stop making the wrong antibody.

 

Long way of saying, I'd still try to remove the antigen and keep the B-cells from producing antibodies if possible. Part of me is worried that the Neural cells themselves will be considered antigens by these anti-neurall antibodies and thus you don't need the external trigger. However, I'm hopeful that is not the case -- i.e., that the seminal event requires an external infection.

 

But I agree with you that periodic pred or IVIG or PeX might be required. Hoping Leckmann publishes before 2011.

 

Regards,

 

Buster

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We are headed up to D.C. next week to see Dr. Latimer. She has offered prednisone for three months as a start, IVIG, or plasma exchange. Knowing all you know which one would you do? Chronic steroids do not appeal to me due to the side effects. I am trying to go through the literature but it seems plasma exchange may be more effective. What do you think?

Thanks,

Claire

Hi MomMD,

 

Thanks for posting on your conversation with Dr. Leckmann. I've been tracking his work (or more precisely his student's work on T-cell regulation).

 

Anytime the child is stressed, the BBB opens up and the PANDAS flares. Knowing all this he said treating kids with antibiotics does not make much sense. The antibodies are the issue, not the strep that is why IVIG and plasmaphoresis works.

 

I think that is partially true. The anti-neural antibodies are in the blood stream and if Kirvan is right, they are targeting GlcNAc which is a fairly common carbohydrate in the body and just happens to be on the exterior cell wall of the GABHS. Since the monoclonal antibody doesn't seem to be binding to other sources of GlcNAc but only to Tubulin and neural tissue, there's probably something unusual about the chain itself.

 

In Kirvan's JNI paper, she shows that CaM Kinase II activation is reduced in the case of convalescent PANDAS and SC patients in 15 of the 16 patients. This indicates that by removing the initial antigen (presumably GABHS) the antibodies reduce and the B-cells stop replicating the antibody. If the blood-brain barrier opens in the convalescent state then the concentration is low and unlikely to cause CaM Kinase II activation. This seems to warrant keeping triggers from coming -- just to keep the antibody concentration low.

 

In 4 of the 16 cases, the antibodies were still high in convalesence so that a disruption of the BBB would have then just let the already active antibodies in.

 

So, it seems in both cases, lowering (and keeping low) the anti-neural antibodies would be the goal and hopefully reseting the B-cell to stop making the wrong antibody.

 

Long way of saying, I'd still try to remove the antigen and keep the B-cells from producing antibodies if possible. Part of me is worried that the Neural cells themselves will be considered antigens by these anti-neurall antibodies and thus you don't need the external trigger. However, I'm hopeful that is not the case -- i.e., that the seminal event requires an external infection.

 

But I agree with you that periodic pred or IVIG or PeX might be required. Hoping Leckmann publishes before 2011.

 

Regards,

 

Buster

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Claire,

 

I only wish I knew the answer to your question. We're going through the same dilemma ourselves. We haven't pursued any of the treatments yet as dd's symptoms are largely controlled on azith and so we've been in a holding pattern trying to figure out what to do and blessing the momentary calm.

  • IVIG makes me nervous because it is a blood product (i.e., who knows what's in it) and I can't quite get why it should work (see my caveat below, I've got a clue now).
  • Plasmapherisis I understand, but think it is at best a short term fix because the B-cells are still there and can reactivate. I'm also not thrilled about opening a central line.
  • Plasmapherisis + antibiotics makes sense to me (remove the serum antibodies and protect against another B-cell trigger on presumption that strep is the trigger and not some other GlcNAc carbohydrate). Unfortunately there aren't great studies here.
  • Prednisone, I understand (suppress the B-cell activation, reduce inflammatory cytokines). This could be working by stopping leakage across BBB or by suppressing B-cells. There are a lot of side effects and I agree with you that I don't want dd on it for any length of time.

So, with all that said, we're leaning towards IVIG this summer with an initial burst of Prednisone (i.e., essentially following Dr. K's protocol). We're trying to get a local immunologist to do it, but if not, we'll be on a flight to Chicago. What is swaying me to this unknown is:

  1. Dr. K's apparent success with IVIG -- many on this forum have found significant help there
  2. A really interesting paper by Aharon Kessel in 2007 called "Intravenous Immunoglobulin Therapy Affects T Regulatory
    Cells by Increasing Their Suppressive Function".

You can get a copy of the paper at http://www.jimmunol.org/cgi/reprint/179/8/5571 . I'm trying to track down peer reviews of this paper now.

 

What Aharon is showing is that there really may be something to IVIG resetting T regulatory cells. If true, this may provide long term suppression of the B-cell activation by stopping the anti-host antibodies.

 

I'd be super interested in your (and others) opinion on the paper and I wonder if Dr. Latimer would comment on it?

 

So bottom line, I don't have a recommendation. In our personal situation our dd's symptoms are drastically reduced on azith (we think for the immunomodulating (Th2->Th1 shift) and antiinflammatory (BBB) properties. At the moment, we have the luxury of time, but every time we get a flare up we worry that her baseline isn't resetting. We also worry that her struggle with math and handwritting is tied to CaM Kinase II activation and that we should do something more... Take it that we're stressing about this too.

 

Best regards,

 

Buster

 

We are headed up to D.C. next week to see Dr. Latimer. She has offered prednisone for three months as a start, IVIG, or plasma exchange. Knowing all you know which one would you do? Chronic steroids do not appeal to me due to the side effects. I am trying to go through the literature but it seems plasma exchange may be more effective. What do you think?

Thanks,

Claire

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Buster, thanks for your great post as always. You break it down for us average medical readers. Interstingly, my son also struggles Math and spelling and writing/handwriting. Do you think my son's symptoms would be less controled on Omnicef? He is about your daughters size 50lb so how much Azith would he need and how often? I also want to get him treatment this summer. However I am torn because a Dr. and parent of a daughter with PANDAS for 11 years feels the best treatment that worked for her daughter was a pulse corticosteroid treatment given over several days at high amounts. She had IVIG and a predisone treatment longterm and neither of them helped as much. Have you researched the pusle corticosteroids? Here is hr history she is now 22.

 

This is from her mom who is a Dr.:

 

To make a very long story short, she developed PANDAS, both, ocd and tics following a strep infection at the age of 10. She also developed a post strep arthritis and now has mitral valve prolapse, so I wonder sometimes if it was PANDAS or Sydenham's, but regardless, she was completely debilitated. We finally found help at New York Hospital. Dr. Rosario Trifiletti a peds neurologist gave her the first treatment which was a five week course of methylprednisolone. Steroids long term, cause big health problems, but short term sort of stun the immune system into compliance. This helped, but did not bring her to where she is today. During that period, she developed the arthritis and we were sent to a peds rheumatologist who did the IVIG. This is collected blood from around the world that has been cleaned. It helped,but I wouldn't recommend it as I don't trust it's safety and I don't think NIMH does it anymore either. Again not satisfied, we sort a third pediatric rheumatologist who got it right. She treated her with 30mg/kg of methylprednisolone for three days straight. This is huge dose of 900mg each day. Gradually across the next four months, she improved and we found we could wean her from the Luvox. She stays on 500mg of zithro twice weekly and has not had a break through strep infection in 9 years. I think zithro and prayer are what worked here. I hold all vaccinations as my own feelings are they stimulate the immune system and will cause problems. She used to take vitamin E,C,CoQ 10 and a probiotic along with a multivit. Now she just takes a multi-vit and probiotic with zithro. She is well, but not cured. Her symptoms do flare right around menses,but she is doing very well.

Sadly she did have a flareup of tics and OCD this winter with a sinus infection and had sinus surgery. This time she responded to Levaquin. Here is her mom's suggestion:

I would if I were you opt for the pulse corticosteroids, it's clean (IVIG has risks)and the results come fairly quickly whereas IVIG caused a massive exacerbation of symptions and the results were not as good. We use zithro as it is a broad spectrum antibiotic and works the best.

 

What do you think? Would any Dr's treat with the high dose pulse corticosteroids? Please let us know what research is telling you because I am following your lead.

 

Michele

 

 

Claire,

 

I only wish I knew the answer to your question. We're going through the same dilemma ourselves. We haven't pursued any of the treatments yet as dd's symptoms are largely controlled on azith and so we've been in a holding pattern trying to figure out what to do and blessing the momentary calm.

  • IVIG makes me nervous because it is a blood product (i.e., who knows what's in it) and I can't quite get why it should work (see my caveat below, I've got a clue now).
  • Plasmapherisis I understand, but think it is at best a short term fix because the B-cells are still there and can reactivate. I'm also not thrilled about opening a central line.
  • Plasmapherisis + antibiotics makes sense to me (remove the serum antibodies and protect against another B-cell trigger on presumption that strep is the trigger and not some other GlcNAc carbohydrate). Unfortunately there aren't great studies here.
  • Prednisone, I understand (suppress the B-cell activation, reduce inflammatory cytokines). This could be working by stopping leakage across BBB or by suppressing B-cells. There are a lot of side effects and I agree with you that I don't want dd on it for any length of time.

So, with all that said, we're leaning towards IVIG this summer with an initial burst of Prednisone (i.e., essentially following Dr. K's protocol). We're trying to get a local immunologist to do it, but if not, we'll be on a flight to Chicago. What is swaying me to this unknown is:

  1. Dr. K's apparent success with IVIG -- many on this forum have found significant help there
  2. A really interesting paper by Aharon Kessel in 2007 called "Intravenous Immunoglobulin Therapy Affects T Regulatory
    Cells by Increasing Their Suppressive Function".

You can get a copy of the paper at http://www.jimmunol.org/cgi/reprint/179/8/5571 . I'm trying to track down peer reviews of this paper now.

 

What Aharon is showing is that there really may be something to IVIG resetting T regulatory cells. If true, this may provide long term suppression of the B-cell activation by stopping the anti-host antibodies.

 

I'd be super interested in your (and others) opinion on the paper and I wonder if Dr. Latimer would comment on it?

 

So bottom line, I don't have a recommendation. In our personal situation our dd's symptoms are drastically reduced on azith (we think for the immunomodulating (Th2->Th1 shift) and antiinflammatory (BBB) properties. At the moment, we have the luxury of time, but every time we get a flare up we worry that her baseline isn't resetting. We also worry that her struggle with math and handwritting is tied to CaM Kinase II activation and that we should do something more... Take it that we're stressing about this too.

 

Best regards,

 

Buster

 

We are headed up to D.C. next week to see Dr. Latimer. She has offered prednisone for three months as a start, IVIG, or plasma exchange. Knowing all you know which one would you do? Chronic steroids do not appeal to me due to the side effects. I am trying to go through the literature but it seems plasma exchange may be more effective. What do you think?

Thanks,

Claire

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Hi Michele,

what an interesting post!

my random thoughts...

 

1) I understand that IVIG is much safer today than it was 12 years ago (stricter regulations were put into place years ago).

 

2) if this girl had a PANDAS/SC variant (or was closer to SC vs. PANDAS) I would see how her dz would be more difficult to treat than a typical PANDAS child. Kids with SC have even higher CaM kinase II levels (and I think also anti-neural antibodies??) than PANDAS kids.

 

3) I wonder if the high dose of steroids would have been as effective if no IVIG was ever done? THe IVIG may have been more beneficial than this mom realizes since all the effects of IVIG do not happen immediately (for example, in the Swedo 1999 IVIG/pex study kids actually had lower symptoms 1 year post IVIG vs. 1 mo. post IVIG).

 

4) that said, we also don't know if this girl would have also benefited from a 2nd round of IVIG. I believe this is what Dr. K recommends if the 1st IVIG doesn't cure.

 

5) our dd is on 250mg/day of azith...apparently that is not enough to make it so she can spell and remember math facts ! (if PANDAS is the cause of these problems). Interestingly, she has had pretty thorough neuropsych. tests b/c of her learning issues. Her IQ is high and her memory is supposed to be fine...so it is a bit of a puzzle why she cannot remember that 8+8=16. Her reading comprehension is excellent (99% percentile) and she does fine with word problems as long as she doesn't get the basic arthimatic/multiplication/division etc. wrong.

 

 

Buster,

 

but one wouldn't do just IVIG...you would do IVIG and then continue with prophylactic abs to prevent future strep infections to prevent another "sentinal" strep infection which could potentially re-trigger the PANDAS...right? In the Swedo 1999 lancet study, their were a few kids that needed repeat IVIG/pex after getting a strep infection. so, it does appear, at least for most kids, you want to still keep them on the abs.

 

I wonder if the ideal course would be to do steroids for a couple of weeks (to suppress the B-cells) and then do IVIG, maintaining your antibiotic prophylaxis the whole time... in other words, I wonder if you are more apt to be successful with a multi-prong approach vs. just doing the IVIG.

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All wonderful thoughts. I am compiling my list of questions to take to Dr. Latimer in DC next week. I will report back. I am also compiling a list of articles to pull from the hospital library. I understand your concerns about blood products but the risks are very slim. The blood product regulations are very strict and the specimen's are checked twice I think 6 months apart. Also, I think as with anything else you have to way risks vs. benefit. In my mind the risk of a longterm untreated encephalopathy outwiegh the blood product risk. Also, I know the central line is creepy but it is also a common thing in infusion/ICU settings and the risks are minimal. I thinks you just want to make sure you are doing it in a controlled setting with someone who knows what they are doing. I am happy to get any data (actual IVIG product risks) etc from my hospital's blood bank if you want more specifics. Carter is also doing better for now but I see signs every day his disease is still there and looking at his lab values freak me out. I also think that whether or not tics are present can influence the IVIG vs PEX choice. I am also going to see if I can track down an immunologist here and get a "curbside consult". We don't have any pediatric ones here but maybe he can help. I also put an e-mail into Eliana Perrin who did some of the initial research with Swedo and she is at UNC. She wanted me to contact her if we got to this crossroad to help us out. I am waiting for her reply but I will also let you know if she has any helpful advice.

Claire

P.S. You always seem to have late posts...please get some sleep.

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I had an interesting call today from a mom of a Pandas child who first had Guillain Barre at age 6. It was treated with IVIG. Then a few months later he comes down with PANDAS where symptoms came on overnight dramaticly after strep. So she is not believing that IVIG can cure the PANDAS because why would her son have gotten it after the IVIG? Just thought I'd bring it up. Also her second child age 5 is now being diagnosed with Pandas and he has always been a bit different and needed early intervention. There has to be a hereditary linK to this stuff. I just wish we knew which was the best way to go plasma, steroids, or IVIG?

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Often autoimmune diseases tend to run together and in families and to see GB, have IVIG, and then get PANDAS does not seem unreasonable. Very unlucky, but not unreasonable. His immune system had a tendency to "overreact" and the IVIG only cleared the GB antibodies. The IVIG does not prevent future autoimmune diseases. I think they all work (PEX and IVIG) but need to be compared by speed of recovery and symptoms at one year. I found an article but I need to locate it which was not a large study but had some comparisons. Steroids in my mind have a place but not for real treatment. Chronic steroids are not a good option for kids. Too many side effects. I think it would be reasonable after IVIG to treat a "flare "with a short course before commiting to IVIG again. I also thing steroids has a place as far as seeing if your child will have a response to IVIG. Some kids with Tourette's and OCD may look like PANDAS but they will not get better on steroids, in fact they may get worse. I am seeing the specialist in two weeks so I will report back.

Claire

I had an interesting call today from a mom of a Pandas child who first had Guillain Barre at age 6. It was treated with IVIG. Then a few months later he comes down with PANDAS where symptoms came on overnight dramaticly after strep. So she is not believing that IVIG can cure the PANDAS because why would her son have gotten it after the IVIG? Just thought I'd bring it up. Also her second child age 5 is now being diagnosed with Pandas and he has always been a bit different and needed early intervention. There has to be a hereditary linK to this stuff. I just wish we knew which was the best way to go plasma, steroids, or IVIG?
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but one wouldn't do just IVIG...you would do IVIG and then continue with prophylactic abs to prevent future strep infections to prevent another "sentinal" strep infection which could potentially re-trigger the PANDAS...right?

 

Yup. I certainly would try to prevent another sentinal event.

 

In the ideal world, I'd:

  1. give the prednisone
  2. check that the anti-neural antibodies are declining
  3. get the IVIG
  4. keep her on narrow-band antibiotics
  5. verify that the anti-neural antibodies are still low 6 months out (or even better check after a sibling gets strep)

If I saw no exacerbations and the anti-neural antibodies remained low despite potential reculture I might really start to think it was a long term cure :-)

 

Best,

 

Buster

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the problem with narrow spectrum abs post IVIG is that pen (narrow spectrum) has such a short 1/2 life...so if you miss a dose you are essentially unprotected for several days. Kind of risky since in our household we have been known to mess up and miss a dose of meds here and there...which fortunately isn't really an issue with azith. and it's long 1/2 life (plus we're on it daily ).

 

Also, do you think that these kids would still benefit from the anti-inflammatory/immune modulating properties of azith post IVIG?

 

My thought would be to continue the azith at 250mg/daily for at least 6 (or 12 mo.) post IVIG...then if all is well consider dropping to a lower dose (say

500mg/week).

 

I suppose I'm just in love with Azith...

:wub:

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  • 2 months later...

Hi Folks,

 

Just a quick note that we went ahead with IVIG this past week for dd9.

 

We decided to do IVIG because exacerbations were continuing despite propholaxis azith and dd9's baseline seemed to be rising significantly over past year. We decided on IVIG over PEX in hope that there is something to IVIG resetting T regulatory cells (per article below by Aharon). We're really hoping it is curative versus just reducing the antibodies. Unfortunately, we won't know for a while.

 

dd9 did great and had no apparent adverse effects from the IVIG. We were concerned because of high dose and moderate flow rate (52 ml/hr). It took a long time (7 hours/day for 2 days).

 

We're 2 days post IVIG. dd9 had a slight fever (100 degree) and a slight headache, but oddly is in a good mood and headache is addressable with tylenol. We'll post as we learn more. For those tracking, dd9's CaM Kinase II was 183% iin April without exacerbation and 253% in July during exacerbation.

 

We did a prednisone burst in July. We saw a positive change 10 days post pred. It lasted about a week (same as length of burst).

 

 

Buster

 

 

Claire,

 

I only wish I knew the answer to your question. We're going through the same dilemma ourselves. We haven't pursued any of the treatments yet as dd's symptoms are largely controlled on azith and so we've been in a holding pattern trying to figure out what to do and blessing the momentary calm.

  • IVIG makes me nervous because it is a blood product (i.e., who knows what's in it) and I can't quite get why it should work (see my caveat below, I've got a clue now).
  • Plasmapherisis I understand, but think it is at best a short term fix because the B-cells are still there and can reactivate. I'm also not thrilled about opening a central line.
  • Plasmapherisis + antibiotics makes sense to me (remove the serum antibodies and protect against another B-cell trigger on presumption that strep is the trigger and not some other GlcNAc carbohydrate). Unfortunately there aren't great studies here.
  • Prednisone, I understand (suppress the B-cell activation, reduce inflammatory cytokines). This could be working by stopping leakage across BBB or by suppressing B-cells. There are a lot of side effects and I agree with you that I don't want dd on it for any length of time.

So, with all that said, we're leaning towards IVIG this summer with an initial burst of Prednisone (i.e., essentially following Dr. K's protocol). We're trying to get a local immunologist to do it, but if not, we'll be on a flight to Chicago. What is swaying me to this unknown is:

  1. Dr. K's apparent success with IVIG -- many on this forum have found significant help there
  2. A really interesting paper by Aharon Kessel in 2007 called "Intravenous Immunoglobulin Therapy Affects T Regulatory
    Cells by Increasing Their Suppressive Function".

You can get a copy of the paper at http://www.jimmunol.org/cgi/reprint/179/8/5571 . I'm trying to track down peer reviews of this paper now.

 

What Aharon is showing is that there really may be something to IVIG resetting T regulatory cells. If true, this may provide long term suppression of the B-cell activation by stopping the anti-host antibodies.

 

I'd be super interested in your (and others) opinion on the paper and I wonder if Dr. Latimer would comment on it?

 

So bottom line, I don't have a recommendation. In our personal situation our dd's symptoms are drastically reduced on azith (we think for the immunomodulating (Th2->Th1 shift) and antiinflammatory (BBB) properties. At the moment, we have the luxury of time, but every time we get a flare up we worry that her baseline isn't resetting. We also worry that her struggle with math and handwritting is tied to CaM Kinase II activation and that we should do something more... Take it that we're stressing about this too.

 

Best regards,

 

Buster

 

We are headed up to D.C. next week to see Dr. Latimer. She has offered prednisone for three months as a start, IVIG, or plasma exchange. Knowing all you know which one would you do? Chronic steroids do not appeal to me due to the side effects. I am trying to go through the literature but it seems plasma exchange may be more effective. What do you think?

Thanks,

Claire

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