momto2pandas

This is a really good idea. I don't know, but I'm guessing maybe. When I got into the issue with the immunologist yesterday where he said that insurance would not cover IVIG for my kids without revax, and I then refused to revax, he suggested that we could look at the kids' response to the vaccine in vitro at a research lab and assuming that it was awry, use that information to go forward with the insurance companies to justify coverage without revax. I think he said that there is a lab at UCLA that could do that? Not sure about that part. Anyway, I didn't pursue it because it sounded like a long and complicated and expensive path and I wasn't sure the insurance company would buy it in any case (what would be their motivation to do so?), and I figured that there must be some other way to approach the insurance that someone had already figured out. But obviously there are labs that can look at responses to vaccines (or, for that matter, bacterial challenges directly) and it would be fascinating to see results to such a clear-cut challenge in pre- and post-IVIG blood. If a lab could be found to do it, this would be a fascinating study to do as a piggyback study onto an IVIG study. For reasons you mentioned, though, I think funding that part would be tough. I wonder how much it would cost. Maybe I am getting carried away here, but if we were able to get IVIG supplied for free as part of a clinical study, perhaps parents who could wouldn't mind chipping in for a piggyback study or two. That is exactly what parents are clamoring for!!!!!! If you can get Baxter to acknowledge that there is a substantial group of individuals that are predisposed to adverse reactions, develope a test for it, well, I will host that party that others have talked about! The implications of acknowledging that scenerio tho are huge and none of the Pharma people have wanted to persue it, that I'm aware of. Seems it's much easier to stick with the rare rare event mantra.

I've been in touch with Diana P, not on this specifically, and she actually gave me an introduction to Dr. Leckman. Thanks for the details on the fact that this was Talecris. Given that Leckman et al approached Talecris, I would be surprised if they hadn't also tried Baxter, but I will call him on Monday to try to find out. Having spent most of my career on "the inside", I know that often it is a matter of finding the medical director within the company that has the interest and going directly there - and company priorities change a lot from year to year and with different people in the various medical director positions. Also, sometimes it does boil down to the specific relationships between the company and the doctors that they have or want to have relationships with. I'll try to find out from my immunologist who he's been talking to that claimed strong interest, and then find out from Dr. Leckman what path he's already tread with Baxter.

Good point! Though I guess that if the idea is that you could treat with IVIG before vaccination in a select group of vulnerable individuals for optimal benefit/risk profile, they get two hits in one there. Still, it calls to light the fact that the vaccine can set off a bad reaction. Point was that Baxter stated that they were interested in this area. If there is an opportunity with Baxter, I'd actually rather see if we can get in a real (small) clinical trial, rather than a vaccine pre-treatment thing for me, in any case. I was just saying that this is where the connection started. To be honest, as I mentioned before, I'm not sure that I would do it - I would need to know a lot more than I currently know. For example, what if the IVIG did NOT prevent a reaction to the vaccine? And what if the reaction was worse this time around or harder to stop? Don't think I could take that risk. The last time around was really bad.

Yes, but if we can get PANDAS to "exist," then things move from hard to expedited, given that it is a pediatric, "orphan" (probably not truly - but at least for now the numbers would say so) disease. This is why I think that a very systematic database (perhaps filled at least partly by survey for reasons of practicality) on which one can do cluster analyses etc. to figure out appropriate criteria (and probably wind up removing the P and the S from PANDAS), would be a big step in the right direction. Honestly, I predict that there will be a problem in trying to distinguish PANDAS from "regular" OCD, tic disorders, etc., on some fronts, since I'm guessing that the latter sample is liberally littered with people who belong in the former sample, making differentiation difficult. I wonder if the way to approach a protocol is not to have it be on PANDAS per se but on autoimmune neuropsychiatric conditions of childhood meeting certain criteria (CAM Kinase/autoantibodies, DSM symptomatology, maybe immune irregularities, etc.). I still think getting hung up on the "S" in PANDAS makes the applicability of PANDAS findings more restricted than I think they should be. Mustn't there already also be a code somewhere for autoimmune neurological condition NOS, or something like that, and can't one get treated for it in a way that's appropriate to the clinical findings and available, replicated, peer-reviewed research, and get coverage? Maybe I'm being naive about the insurance situation in the US. I know that in places with more socialized medicine they rely more on research findings and expert opinions. IVIG is already covered for PANDAS in Canada, for example. I also still think it would be important, in advance of putting together a protocol, to get some idea from existing cases of what traits separate those who get the best benefit from IVIG from those who don't, at least with respect to whether there are pre-existing deficiencies. If you get a chance to do a pilot you have to make sure that your inclusion criteria give it the best possible chance of success. I can tell you right now that undoubtedly PANDAS will be the #1 use for IVIG in all of child neurology, and maybe high on the list of all pediatric diseases There are quite a few other diseases in child neurology where IVIG is indicated, but they are rare compared to PANDAS Why would Baxter not want to fund this, at least on a pilot scale ? ... the potential benefits to them could be enormous. By the way, it's hard to get FDA approval and insurance coverage for treatment of a disease that officially "doesn't exist"! That's the first mountain to climb. But I'm very excited by this. Dr. T

Interesting. This is exactly what my ds6's one and only tic is like. He opens his eyes very wide and then rolls his eyeballs up and to the side in one motion. Sometimes he lowers his head a bit at the same time. He does this pretty much in exact proportion (frequency) to how badly he seems to feel. He's not self conscious about it, luckily, but it does look kind of strange. I've asked him what it was about and he just says that his eyes make him do it. He doesn't tic a lot even on his worst day, maybe once per hour or so on average. I've found it kind of funny because it was the exact same tic I had as a teenager and it drove me mad at that time. My Mom always bugged me about it. I always claimed it was my contact lenses bugging me because I didn't want to be thought of as ticcing.

Thinking about this more and my immunologist and I are really not the ones who should be doing this. Neither one of us is a PANDAS expert by any means. If Baxter is really interested in funding this, presumably some of the experts (at least one?) would be interested in submitting a proposed protocol and running a study? Does anyone actually know? I'm not in that circle. There is a lot to running a clinical trial and maybe it's just too much for a busy practice focusing on patient care? Perhaps I could just get the name/contact info of the person who said that Baxter was very interested in this line of research and make an appropriate connection. I would rather pursue it than see the potential opportunity die if no-one else wants to pursue it, but my immunologist and I are definitely not the best ones to take advantage of this by a very long stretch.

We are on the West Coast too. Now I'm intrigued but scared to turn it on later...

What a great connection. One can see how easily this connection can get missed. When you're not thinking in terms of connecting behavior with infections, and when both infections and moodiness can be pretty common in little kids - and especially when you have multiple kids and someone is always sick and/or moody - it's easy not to put the pieces together at the time until things get pretty dramatic.... sometimes even WHEN things get pretty dramatic!

Not to put a damper on, but I guess what I'm trying to say is that I'm not sure how encouraging it is. I just can't believe that this hasn't been tried before (going to Baxter for funding) and failed for some reason. Unless someone tells me that it has failed, though, it's worth at least calling up his contact and assessing the situation more.

I think that without deficiencies, if you want IVIG you have to argue it on the basis of PANDAS or another condition, which as I understand it is an uphill battle. Our insurance specifically excludes covering PANDAS, as do the other policies I looked at. We weren't yet at the point of thinking of doing it for PANDAS in any case, but if we were, we would definitely be thinking cash pay. We could swallow that for one or a few tx but if immundeficiency means they will need it over and over long-term..... gotta try to avoid swallowing that. No idea what high IgG means!

Thanks, are these the same folks you pm'ed me about before? I am willing to travel if it results in something... obviously if they need ongoing care, we would try to find a situation that didn't require our traveling cross-country on a frequent basis. Would also hate to travel just to hear the same thing or to have a repeat test that suddently showed that things inched over the border to normal for some random reason. We haven't done Cunningham since we've never felt so far that we needed verification of the diagnosis. Does insurance look at that? If the test contributes something other than "this is PANDAS" then we could get it, if the lab is back to doing it. I did look at our insurance guidelines (and a couple of others just to see) and there is indeed something in there about needing to revaccinate to "verify" that the immune system doesn't work. Probably just their way of avoiding paying. I just thought that perhaps someone would have experience with insurance companies listening to reason when the vax is contraindicated and when the clinical picture is pretty clear.

So.... my immunologist is apparently quite connected at Baxter, maker of Gammagard IVIG, and he had a meeting with them a week or two ago where he approached them about supplying IVIG (for free) for a PANDAS clinical study with himself as Principal Investigator. He actually came up with this idea out of interest in studying me -- after I had that terrible Pneumovax reaction, he said that he would love treat me with IVIG first and then see if I still got the reaction - that it would be a great proof of concept for IVIG for PANDAS since I have the condition (and documented history) but not any significant background "noise" symptomatology to confuse things, so it could be kind of a "'clean" study. Not sure that makes sense (or that I would do it), but it got him talking to his Baxter buddies about PANDAS research, in any case. Anyway, his Baxter connection told him that they were indeed very interested in pursuing this type of research. They suggested high doses (2 g or something like that) and asked him to submit a protocol describing the details of the PANDAS study he wanted to conduct. He told me that he is happy to be PI in the sense that he would deliver the treatment and would not charge a fee for being a research investigator, but he doesn't have the time to work up a protocol and all the other prep/paperwork stuff - and he is no expert in PANDAS, so he would want a neuropsychiatrist/specialist involved in clinical evaluation, etc. When he first mentioned to me that he was planning to approach Baxter about a PANDAS study, I had offered to compile a protocol and do the admin for free if it would help to move things forward (this is my field so I've written and run loads of clinical trial protocols) and I gave him my CV to provide to Baxter in case he/they wanted to take me up on it. I was sure that they would not. I figured that Baxter must have been approached about PANDAS research before without success. But at my kids' appointment today he gave me the forms on which to submit a PANDAS IVIG protocol if I was still willing/interested. Can it be true that no-one has approached Baxter in this way before? I don't mind blocking out time at some point to put a protocol together for my immunologist and Baxter (obviously nearly 100% gathering info from experts, since I am no IVIG expert whatsoever)...but can it really be true that no-one has previously done this and failed? My "real job" is already too busy and I don't want to waste my time if someone has already gone down this path and wound up at a dead end for reasons either scientific or political. I'm also wondering if my immunologist may just be well-connected enough to get this through, since obviously he wouldn't be the very best candidate out there for Investigator and yet still there is interest.

I am really hoping that someone can help me out here. Just got back from the immunologist. Both kids' labs are consistent with immunodeficiency (one of them is actually total IgG deficient, not just IgG subclass 3 deficient as the other one is). They failed the strep pneumoniae titers, as I mentioned before. The immunologist said that, given that we have now finished round 9 of various different strong courses of antibiotics and their sinus infections remain, and given their lab results, they should be treated with IVIG....if the lab tests come out the same way on repeat. The issue is - he wants to re-vaccinate with Prevnar to "prove" that their immune systems are not making a response, prior to repeating the labs. He claims that without this proof, insurance will NOT cover their IVIG, no way, no how. I don't get this - they have already undergone a full vaccination schedule and obviously didn't have the required response - and are showing both by labs and clinically that they can't fight infections...so why do we need to vax again? I refused the revax. They are doing decent with respect to PANDAS despite these infections (which, it turns out, have raised neither ASO nor mycoplasma - but they still have WAY high and messed up lymphocytes), and I don't want to rock the boat with Prevnar/Pneumovax. The immunologist repeat vaccinated me, and while it did appear bring up my immune tests, it was a neurololgical/mental health disaster that needed to be stopped with steroids. Not sure I'm willing to open that Pandora's box with the kids. So where does this leave us? Others on this board must have dealt with this before.... did you just bite the bullet and revax, or can insurance companies be convinced not to make us go through this, given the comorbid PANDAS diagnosis and the fact that we have already vaccinated? I can't afford to be giving 2 kids perhaps monthly IVIG for who knows how long, without support from our insurance. And obviously, I can't afford to let these infections go on and on ... and to keep them waiting as sitting ducks for something worse than a sinus infection to hit. To make matters worse, he wouldn't even continue their antibiotics, which had been helping a lot, though obviously not eliminating the infections entirely. The last course ended Tuesday, and ds6 is already ill again. This was ridiculous to me given that my child (his patient!) was obviously sick when I brought him in, and the immuno said that he could clearly see the green mucus up his nose. He said that he couldn't "just keep them on antibiotics for the rest of their lives." I called the pediatrician afterwards to complain and they called in Omnicef, which we haven't yet tried, saying that there was no way that we should just let a sinus infection rage untreated, particularly in an immunodeficient child.

Not disputing whether it's a good idea or not, just whether it could theoretically be a cure. As I mentioned before, I don't think "cure" is necessary to have a very positive outcome. If life is good and management is minimal, then the difference is largely theoretical.

One thing I'd really like to see regarding the results of IVIG treatment is a simple separation of results in kids who had some sort of immune deficiency (not just low-ish levels, but really what an immunologist would call an immune deficiency) vs. kids who did not. Are the kids who are improving dramatically with IVIG treatment the ones who were immunodeficient to begin with and who needed IVIG just based on their immunology results and infection history, regardless of PANDAS? Or is it the reverse? Or neither? And those whose situation was made worse after IVIG, were they immunodeficient orignally, or not? There is some evidence that the state of being immunodeficient creates excessive levels of inflammation. At least in HIV, when the immunodeficiency comes into play, levels of inflammatory cytokines go way up, higher than in "normals". It's like given that the body isn't fighting infection well, it tries harder to stimulate the ole' immune system -- leading to an inflammatory state (and breached BBB.) So I can see a case where the root problem is immunodeficiency (could be primary, could be secondary due to damage from an early infection), which then causes problems both with ongoing infections and with excessive inflammation in response to infections. If the root problem is immunodeficiency and everything else is downstream of that, then it would make sense that treatment of the immunodeficiency would go a long way to a "cure," assuming that once the ID is treated the body figures out that it doesn't have to go so crazy with the cytokines any more. However, though I'm no expert on immunodeficiencies, I haven't seen anything to suggest that early treatment of immunodeficiencies actually "fixes" them. Some kids grow out of them, some require lifelong treatment...but barring stem cells or some such, I haven't seen anything to suggest that immunodeficiencies can be "cured" by treatment, without ongoing treatment. Perhaps the IVIG can take care of it until the kids grow out of it on their own? Or if the immune damage was just residual from an early infection (secondary immune deficiency), maybe it can fix that and then it doesn't come back again, assuming that the kids have matured enough in the mean time not to suffer the same damage again? And if the immune system is healthy to begin with, what is the IVIG doing to help that we could expect to be permanent?

I did that poll on IVIG outcomes a little while back and I don't recall anyone saying that they had gotten a 100% result on IVIG. Most mentioned quite some improvement, but no-one claimed cure if I remember correctly.

Glad you both are seeing gains from adjusting your EPA:DHA ratios!

I agree with you about remission. I pray that there are indeed cures for children that retrain the immune system and make it completely go away, but having had remissions of nearly 10 years myself only to have had a sudden episode or two before going back into remission -- and having seen my grandmother go back to having true anorexia nervosa in her 80's after a 70-year remission -- I am skeptical about "cure" until we have watched people for a lifetime. That having been said, "remission" is not so bad -- having an episode every 10-70 years isn't perfect but few people experience perfect health or psychological histories over such lengths of time. As Sammy even said on his TV interview, yeah he gets symptoms againw when he gets sick, but he takes abx and they go away. So what. I also agree with your other piece about bias in his patient group. I'll bet there are a whole bunch out there who go quite long stretches, if not indefinitely, doing well enough on antibiotics, antidepressants, or whatnot that they it doesn't make sense to travel, pay out of pocket, etc. to seek specialty care unless they're starting to see things really go downhill and suspect they may need something more aggressive.

Thanks for the tips on L-lysine. Any tips on whether one brand is better than another, and on how much you give to kids/adults? My kids are 36 pounds (ds3) and around 48 pounds (ds6). Glad you like the omegabrites - I can't tell you how many times people have come back thanking me for that recommendation. momto2, I would definitely give a trial to L-lysine given what you wrote above! It gets some good press in the fibromyalgia world where EBV is prevalent. I always have it in my house and at the first sign of anything viral, I ramp it up. I have a 94 year old client who says as a child she and her siblings were made to take it all winter long. btw, thanks a million for the lead on omegabrite! We started on 2/21 after a horrific backslide that forced us to give up Biaxin for myco p. Some days are still way less than optimal but he's tolerating the omegabrites (3 per day) well and I believe they are having a good effect as he's showing improvement and that was our only new addition until yesterday when we started Enhansa for more inflammation control. Gat's mom

This is something I've started to wonder about again lately. As I mentioned in a previous post, I had documented issues associated with EBV infection 20 years ago or so. Now I'm getting sore throats, etc. every month and I've been assuming that it's strep or some other bacteria I'm not kicking, but I'm wondering if it's EBV coming back to haunt me. I was doing some research on IgG Subclass 3 deficiencies after I got my kids' results (and mine, which are also low but in the normal range for this). Apparently, there is evidence that EBV can cause such immunodeficiencies. IgG3 apparently deals a lot with viruses. My kids haven't been tested for EBV. They've definitely had bacterial infections based on the green nose slime and (at least temporary) response to antibiotics (though this could just be their antiinflammatory effect), but with the persistent high lymphocytes even after antibiotic tx and with the IgG3 deficiency, I'm thinking that there could be something viral going on too. From what I can see, that creates a very difficult boat to be in - virus creating an immunodeficiency that makes you unable to fight the virus or other infections. Then what do you do? Literature suggests some evidence for utility of IVIG. I'm going to look at Chemar's suggestions.

I will be very curious to hear if anyone has insight on this, too. My ds3 has had this problem for years, and I never thought much of it. He's the one who also has the bright red lips (and often spontaneously bleeding) and cheeks, and the labs that match SF Mom's Kawasaki's kid. We have always joked in our family that he must be some sort of genetic kick-back with his rosy cheeks and lips, since most of us are rather olive. Now I'm wondering if it's no joke at all.

I had exactly the same issue during my teen episodes. Also during that drug-induced lupus episode I had in my 20's. But nothing abnormal in between, before, or after all of that. Dr. T, During his middle school exacerbation, Gat failed to have a solid BM for over a year. It coincided precisely with his PANDAS (or, in retrospect, likely PITAND) episode. He was never diagnosed as Crohn's, the DAN! doc attributed it to leaky gut, yeast and inflammation. As he healed, emotionally, his gut healed right along with him. During his 18 month reprieve before this exacerbation, he had no gut or bowel issues at all. The beginning of our current exacerbation brought about the same gut and bowel issues again though they, like everything else, have stabilized in the past couple weeks. We have MS, trigeminal neuralgia and vocal tics in the family tree (maternal grandfather for TN & tics and his brother had MS). We can definitely link Gat's bowel issues to PANDAS/PITAND episodes. Gayle

Dr. T, I saw this case when it was first published last year, and that's part of what got me thinking about infliximab and adalimumab (and other biologics). When the infliximab stopped working for this child's Crohn's, probably because of antibody development (our nemesis with these biologics), his OCD flared as well. When he switched to adalumumab, both the Crohn's and the OCD remitted quickly. It says in the article "the stress of diminished response to infliximab may have triggered the OCD." I feel that it's equally possible, if not more so, that the diminished efficacy of infliximab itself was responsible for the flare of OCD. In other words, the infliximab, probably due to antibodies that his body had created to it, came to fail in suppression of TNF-alpha, leading, down different pathways, to both a flare of OCD and a flare of Crohn's. Switching meds to one that effectively suppressed TNF-alpha again for this child resolved both conditions. There is a bunch of research out there that shows a similar effect in other conditions, e.g. psoriasis, RA. When these patients go on biologic medications that inhibit inflammatory cytokines (either those directed at TNF-alpha or IL-1), their psychiatric conditions often improve quite dramatically.

p.s. I should mention that the "interested parties" with which the data would be shared would be restricted to medical/scientific professionals, and the analysis would have to go through an analysis specialist, else the potential for poor analytical techniques leading to wrong conclusions or for the data to be used in the wrong kinds of ways.

Much of what you describe in the beginning is why I left academia! It's a painfully slow process, and you didn't even mention the parts about politics or the fact that what's vogue in any particular era is what gets funded....or the fact that research findings can be suspect due to publication biases, etc. Pharma moves more quickly and easily (and with more regulation), but of course mostly purues profit-oriented questions. I would like to expand further on the "new" model. I think it would be great to take a formal survey approach - allowed any patients with verfied diagnoses to "opt in" to email mailing lists, and then each time a new question arises (by the scientific managers) or new data is created (by the patients), a survey expert formulats appropriate questions and patients can follow a link to enter their information into a well-designed survey/data collection instrument. Someone expert in data analysis then mines the data at appropriate intervals to look for patterns and generate/test hypotheses and shares this information -- of course with lots of caveats about biases, not "scientifically collected", etc., with interested parties. They can then make what they wish out of it or use it as supportive information to get pilot funding for confirmatory research. There are sources of bias and it's not perfect (and not interventional), but I think it would be an observational model from which we could learn a TON particularly about orphan diseases with highly motivated patients. Like having everyone's stories organized as data to be able to search patterns, etc. I have actually already approached a well known clinical research survey company about setting this up as a model for orphan diseases, and have very strong interest. I think I also have funding through personal connections (royal family - not kidding), at least for a pilot, maybe more. But need to choose the pilot disease, finalize the initial data collection instrument with help of experts (have a general one drafted already), organize the medical and patient community around it, and figure out the ethics parts re. consultation with an IRB (e.g. code assignment for surveys to ensure anonymity). I actually think this could be such a promising approach to learning and sharing information about orphan diseases (and maybe ultimately other diseases) that I'm thinking about cutting back my consulting hours to pursue it more freely. We should really talk.