Buster

Hi Lismom, I've struggled with this too and don't have a great answer but do have another theory to add to the mix... look to the end. On zith suppressing the immune system Yes, azithromycin is immuno-modulating (and hence somewhat immune suppressing) and is also an anti-inflammatory The immuno-modulating effect is that azith tends to move the T helper cells from generating Th2 cells (that lead to more macrophages and antibodies) to Th1 (NK killer cells). This has several effects: the increased NK Killer cells can go after intracellular strep fewer antibodies are getting produced (than without) less inflammatory cytokines are generated -- reducing inflammation Our immunologist believes the big benefit of azith was its anti-inflammatory property and wasn't a big believer that there was any strep left (intracellular or otherwise). On whether GABHS is acting like a virus rather than like a bacteria The results of high-dose augmentin seem to have helped several. This has made me wonder if perhaps there is strep lingering in the body (intracellular) but was left at such a low residual amount that it is not detectable by anything but the faulty immune system. Again, all just a theory, but what if the GABHS acts a bit like a virus -- think of chicken pox for a moment. The virus can live in cells for a very long time with no ill effect until it bursts forth and starts again. So perhaps what is happening is the suceptible child's immune system isn't quite strong enough to get rid of the GABHS that's in a cell (i.e., due to low NK killer cells or an inability to flag that the cell is infected). So every so often one of these cells "bursts" and the GABHS gets back out into the blood stream, runs into a T-cell and more antibodies are formed but some of the GABHS gets into another cell before the bodies found it and removed it. Perhaps what is happening is that with the high-dose augmentin, when the cell bursts, the GABHS runs smack into the antibiotic (which actually is bacteriacidal at that dosage level) and the GABHS can't get back into another cell before it is destroyed. This is sort of how anti-viral's work -- I wonder if that is what is happening here. No science here, just it seems to fit with what we are seeing. I think this waky strain of strep is acting like a virus rather than acting like an extra-cellular bacteria and thus has all the same problems. I really hope one of these doctors does an emm-type on this strain. Anyway, my thoughts, Buster

To the best of my knowledge, the BBB can open to a lot of different things: high stress (increase epinephrine, high blood pressure, infections, ....) Essentially anything that can cause inflammation of the BBB. There may be other transport mechanisms as well, but inflammation seems the most likely. Strep gives off >100 different exotoxins. These exotoxins are pretty much what they sound like -- things the body doesn't like and treats as "foreign stubstances" that the immune system responds to. Stretolysin-O (for example) is one exotoxin produced that the antibody ASO is created to attack. There are also all sorts of super antigens (SpA, SpB, SpC, ... ) that are found to trigger pretty significant inflammation. So yes, a strep invasion (or infection) would trigger inflammation and this inflammation in the susceptible inidividual might open the BBB -- we don't know because I don't think anyone has tested the drift of other material into the central spinal fluid. Kirvan found that 24.3.1 did cross into CSF, but how it got there, they don't know yet. Regards, Buster

Yup, it sure seems their part of the problem/solution. They missed locking up the bad antibody. There's a nice paper by Kessel on his thoughts here: http://www.jimmunol.org/cgi/content/full/179/8/5571 Regards, Buster

There was a nice small study done by Garvey and Snider "Treatment of Sydenham's Chorea with Intravenous Immunoglobulin, Plasma Exchange, or Prednisone." http://jcn.sagepub.com/cgi/content/abstract/20/5/424 This was followed up by a nice double blind study http://www.pedneur.com/article/S0887-8994(...0543-6/abstractfor Sydenham Chorea where the severity of the symptoms dropped dramatically in the pred group where they followed up over a longer time interval. On the theory that PANDAS and Syndenham Chorea are similar, this would make a lot of sense. With PEX you are getting an immediate removal of antibodies. With IVIG you are causing significant anti-inflammatory and removal of some anti-host antibodies, with prednison you are suppressing the creation of new antibodies in response to antigen presentors. So pred would take longer but could have same longer term effect. Most assuredly prophylactic antibiotics seems to help too - however, in our case we seemed to get exacerbations when our PANDAS dd was exposed to strep from her sister. This made it tough to keep the antibodies titers down. It's all still a big experiment though... I totally agree. Buster

Oddly, that is what was happening in our house. If our PANDAS ds was having a flare-up, we'd take her sister in and sure enough her sister would be positive for GABHS. We did run cultures at 3weeks post treatment to see if her sister cleared of GABHS (yes, she cleared). This happened 4 times last year. Our pediatrician kept asking us how we knew. We told her our canary told us :-) Buster

I'm with Peglem here! Jump for Joy with whatever you are doing. I don't think we know, but prophylaxis seems to be working in all our cases and in Swedo's cases. IVIG and PEX had more dramatic near term effect for severe cases. In our case it seemed to be necessary to get her back to a baseline (i.e., we didn't change any other treatment -- we've only changed one variable at a time). I fear that we still have to be religous about prophylaxis for a long time. We're hopeful that IVIG did some other things (such as play with the T-regs) but there's no science there that helps us with any confidence. I expect we'll be on prophylaxis for a long time. We too are just happy for the moment... and recovering. Best regards, Buster I'd jump for joy anyway...if it comes back, there will be time to grieve later! This is where I'm at...a lot of times progress has been stolen back away, so my philosophy is to celebrate whenever I can, no matter how briefly!

Sorry, I'm trying to find the reference, but I think it was only about augmentin/penicillin derivatives. If I find it, I'll post it. The actual study was about testing invitro (i.e., direct contact). Searching now (even in my archives) I can't find the actual paper. Probably should have removed the sentence from the post till I can find the paper. Buster

Sort of. Replace antigens with antibodies. The flare up could come from old antibodies that are still circulating from previous infections. Not exactly. The rapid and the culture are both essentially the same test (whether there is colonized strep on the mucosal lining). The rapid tends to check for a carbohydrate, the culture looks for a tell-tale growth pattern. If the culture doesn't grow it likely means a bad swab. It could also be a false positive on the rapid (less likely). No, it means that your child is getting recolonized. Typically recolonization leads infection. This is why only a throat swab is necessary to recommend antibiotics. Colonization means it's on the mucosal lining but might not be getting into the blood stream. If you are getting an infection and/or the colony isn't clearing, then yes, the antibiotic dose isn't the right one, not strong enough, or you may be IgA deficient. Sort of. Yes, IVIG can help provide missing antibodies but there are several other effects of IVIG. One of them is just the closure of the BBB. IVIG is highly anti-inflammatory. In addition, IVIG is thought to cause a reset to the T-regulator cells thereby causing the T-regulators to suppress the faulty antibody creation. Essentially this is why IVIG is sometimes called internal plasmapherisis because it can suppress the "bad" antibodies and remove them. Best regards, Buster P.S. I modified my earlier posts hoping they are now clearer

Okay, the longer version: So if our PANDAS child is on prophylaxis antibiotics, why did she have an exacerbation? Well, this is a bit tricky but here's how I understand it... Prophylaxis does not prevent strep colonization and may not prevent strep invasion but will likely prevent strep infection. The difference between these stages is that colonization occurs on the skin or mucosal lining and is typically not reached by antibiotics. In healthy people, when strep invades, a wandering Macrophage comes along and finds the strep and presents a flag saying that it found strep -- this is called antigen presentation. The macrophage then runs into a T-cell that puts out a few more macrophages or a B-cell that might create some antibodies to the antigen. If the density of strep is low, then very few macrophages or antibodies are created. The more bacteria, the more macrophages and antibodies find it and the more macrophages/antibodies are created. It's a race to see if the immune system will overwhelm the bacteria growth or the bacteria will grow faster than the macrophages. Antibiotics slow the rate of growth of the bacteria while allowing the immune system to keep going, so antibiotics help the immune system win the race. In almost all dosages, the antibiotics are not bacteriacidal (i.e., don't kill the bacteria) in and of themselves. Even in the case of penicillin, the bacteria is replicating while the penicillin kills some. So, long way of saying, if you have strep in the home, then it can recolonize on your prophylaxis kid. The antibiotic has a hard time getting to it, so in some kids it will invade. The invasion is stopped by the antibiotics (in combination with the immune system), but there will be some immune reaction. If the BBB is open, then the antibodies created to fight off the invasion will cross and we're in exacerbation. Now the good news is that the invasion is likely really short lived and the antibodies aren't too many. But the antibodies hang around for 4-6 weeks, so if your child keeps getting re-exposed, then you'll get a slow build up of antibodies until you've got enough that the next time the BBB opens - boom you're there as if you were in an unprotected state. Remember that PANDAS is thought to be the combination of three events: an immune response to GABHS that creates a faulty antibody a failure of the T-regulatory system to suppress the faulty antibody a breach of the blood brain barrier The antibodies tend to have a half-life of 4-6 weeks and thus if your BBB is closed, the antibodies may still be circulating but not causing any problems. Now if you have a BBB breach (due to stress, blood pressure, infection, ...) then symptoms can occur just from the antibodies "floating around". Antibiotics don't get rid of antibodies, they can help reduce new antibodies. Phew, Buster

I'll answer with a short answer first, and then add a longer answer.... The short answer is you can get a positive GABHS culture even if on antibiotics. The reason is that cultures check for colonizaton and not for infection. A strep infection occurs in 4 stages: Adhesion -- attaching, Colonization -- which is what a swab/culture checks. Invasion -- which is largely undetectable. Infection -- which is what ASO, AntiDNAseB, ... checks. Antibiotics can slow/stop an infection. Antibiotics don't stop an invasion (typically) but can prevent an invasion from becoming a severe infection. Many sntibiotics can't affect colonization (whether on skin or in mucosal lining). There's just not enough concentration in mucus or penetration through the epithilial cells for the antibiotic to get to the colony. So child1 can recolonize child2 despite child2 being on antibiotics. I'll try to post something about why can you get exacerbations from colonization only and why antibodies can go up (even though you are on prophylaxis). Buster P.S. Edited above to remove reference to suspended antibiotics until I can find the reference.

We had very odd activation on Klonipin. Of course there was lots of other stuff going on at the time, so hard to know if it was the Klonipin or other stuff. They tried Ativan and Klonipin at the hospital and if anything it had the opposite effect -- i.e., made her more anxious and more demanding... not sure what to say. In our case, reading a book aloud was the most calming effect. Regards, Buster

Hi Ellie, Thanks for the note and numbers. What was on my mind is whether the dopamine levels would be inhibited by fluoxetine levels in the blood serum. I've sent a note off to Cunningham's lab to ask. I was curious -- nothing more than that. It's still not known what all the numbers mean and what you have to control for. I was wondering if perhaps she'll have to control for SSRIs. In addition, I was curious how many others had maintained their kids on SSRIs or were using CBT or ERP for treatment of OCD. There have been studies indicating that PANDAS kids are more sensitive to SSRIs and I'm wondering if that is because of the combined impact of the SSRI with the anti-D1 or anti-D2. So at this point, this is just me being curious -- nothing more. Our own daughter became activated (akathesia) on higher doses of another SSRI but due to a latent social anxiety we haven't taken her off the SSRI entirely. Best regards, Buster

If your child was on SSRIs (such as Prozac) when the Cunningham test was run, can you IM me your anti-D1 and anti-D2 numbers? Thanks, Buster

We're thinking of you too.

Buster, You lost me there! Are you talking about my PANDAS child, or the other children in the house? Yes. If you were going to get ASO then please get throat culture first (at least a rapid but preferably the 72 hour kind). ASO is only useful if you really think there was a strep infection, you missed the window for a throat culture but are likely within 4 weeks of the event. You actually need to culture others in the family because GABHS can ping-pong between family members. So if one is positive, they just tend to re-infect the others. This is why carrier status is not benign for others in the household and is possibly not benign for the carrier themselves. Regards, Buster

Please, please, please do a throat culture. If you're going to do the ASO do a throat culture. There's all sorts of reasons here: 1. You can have one child with colonized strep that affects the other child 2. ASO only shows up 1-2 week post infection and even then does not rise in > 46% of kids 3. AntiDnaseB only shows up 6-8 weeks post infection and even then does not rise in > 55% of kids 4. There is an absence of rise in either ASO and AntiDnase B in > 37% of kids 5. The fall rate of ASO and AntiDNAse B is unknown As you know ASO and AntiDNAseB do *not* cause PANDAS -- rather it is another antibody that seems to react to GABHS. In our house, one of the kids gets strep and is not affected by it (i.e., is a likely carrier) but the low grade strep goes across to the other kid who reacts. Please get a throat culture as long as you are doing the other work. Regards, Buster

Hi Michael, Just want to check: You're on Omnicef (a Cephalosporin) which is generally effective on gram positive bacteria. As far as I can tell, it is not studied for long term us and has LOTs of warnings especially for any child with stomach or intenstinal disorders. Are you taking the treatment dosage of 7mg/kg. So 183 mg 2x/day (i.e., 366mg/day). Have you been on it for a while? Also it sounds like you are 16 days post IVIG at .65 gm/kg. I'm amazed that they aren't offering prophylaxis post-IVIG having gone forward with IVIG. Is he also on risperdal and clonopin? Some on this forum (noticably WorriedDad) has noticed that Clonopin had an opposite effect for PANDAS kids -- has it had a positive effect in your son's case? Given the dangers associated with Omnicef, I wonder if your ped would support you on a different narrower band antibiotic. Omnicef's a big hammer. In our case (pre-IVIG) we weren't effective with cephalasporins but were effective on azith. Wishing you the very best and sad to hear you've not had a turn. Regards, Buster

Happy to add the PEX/IVIG. I pulled the chart together primarily to avoid asking folks about stuff they've already posted -- and then thought it might be helpful to keep up to date. My only real hesitations on posting (versus IM'ing and emailing) are that the table feature on this forum is REALLY terrible it may come across to some as more scientific than it is... I may have inaccuracies in the table . it's just a bunch of anecdotal info about what each of us have tried and what we're doing now -- but it really can't be treated as more than anecdotal. Regards, Buster

Hi folks, What do you think about posting a consolidated chart of symptoms/test results. I've got a spreadsheet going of everyone's posting thus far and with a little encouragement, I'll put it up here. I've pulled the numbers from prior posts -- my only hesitation is that we're all going to be trying to find patterns in it, when truly the research isn't done and we still don't know (nor do the researchers know) what the numbers mean. Especially for new folks, it could make this seem more concrete than the stage of "exploration" we're all in. Regards, Buster So far, I have chart data for: Buster EAMom WorriedDad michele mom_md peglem betty04 iowamom sf-mom dut acdrobert ellen DCMOM colleenrn Bronxmom2 monarchcat pixiesmommy meg's mom KeithandElizabeth Kayanne mama2alex The format would look like: username | m/f | age | onset | primary | report | antibiotic | SSRI (mg) | CKII | anti-lyso | anti-tubulin | anti-d1 | anti-d2 | comment Buster 1 f 9 ? OCD 4/6 250 azith 10 Prozac 183 1280 1000 8000 16000 no-ex [/codeBOX] Regards, Buster

I was more commenting that you were pursuing a direction I hadn't paid any attention to (i.e., the impact of breast milk on immune response). I was following the chain: "A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation." http://www.ncbi.nlm.nih.gov/pmc/articles/P...69/?tool=pubmed That then took me over to the article "The δ isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload" http://www.pnas.org/content/106/7/2342.full I'm now going back to the papers you referenced. No idea if this will lead to something, but it was an unusual direction. Thanks, Buster

Now that's a direction I never thought to pursue... masked/suppressed by breast milk ... I wonder if there's anything to that... really interesting thought.

Monarchcat, there are so many things it could be. Since it is itchy and pimply (and ds has been on a pretty high dose of prednisone), it is unlikely contact dermatitis and sounds more like a viral rash. Definitely worth going in to see a dermatologist. Has the rash spread? Buster

Michael, I'm sorry to hear that things are worse now 3 weeks post-IVIG. What's your son's weight and what dosing of IVIG did you use? In an earlier post, you indicated that your son was on very low-dose antibiotics. Are you confident that your son hasn't been exposed to strep and didn't have an active infection pre-IVIG? At a minimum, it's worth getting a throat culture for your son and other members of household. I'd certainly recommend reading the posts by others here regarding higher antibiotic propholaxis (even post-IVIG). Something to remember is that the antibodies in IVIG seem to last only 4-6 weeks. So while IVIG likely closes open blood-brain barrier (due to significant anti-inflammatory effects) and may remove anti-host antibodies... your son would still be vulnerable to another attack post IVIG -- i.e., IVIG just has the potential of reducing the anti-neuronal antibodies, not removing them. If my kid, I'd recommend upping the antibiotics to a therapeutic dose for 30 days. Hoping to hear better news, Buster

We're now at 13 weeks post-IVIG Hi Folks, We're now 12 weeks post-IVIG. Overall we're good. We do have some slight defiance and bossiness coming back it. It's sort of there and then gone. Hoping it is nothing... ----------- Week 1: significant escalation of symptoms, movement disorders, tremor, contamination fears, vocal tic, very irritable Week 2: continued escalation of symptoms. Very intense but short lived. Interestingly like watching last 6 months on fast reverse. Angry, lashing out, eating issues, handwriting issues. Week 3: school starts. She's interested in school and handwriting has improved. Margins are much better. School teacher indicates dd9 is somewhat defiant in class. Week 4: lots of itchiness. slight food restriction. dramatic fall off of symptoms. concerns about wearing glasses in public, measurement compulsions disappear Week 5: calm, quiet -- some social anxiety when at a large family party Week 6: more calm -- no rages for a week Week 7: calm -- willingly does homework -- is remembering math facts, spelling is eratic, getting along well with sister Week 8: calm, happy -- able to brush teeth alone -- first time in 2 years. Week 9: calm, happy -- enjoys school, likes trumpet, some handwriting issues still, very slight verbal tic Week 10: playing with sister -- laughing, willingly does homework, handwriting improves Week 11: overall happy. Some intermittent handwritting changes Week 12: some slight hand tremor hoping it is nothing. Some slight defiance. Overall good though Week 13: more defiance and some bossiness. Not sure what's happening On the CaM Kinase, we ran a mini-longitudinal study here. Our dd9 was at: 183% not in exacerbation (April), 253% during exacerbation (June), and at 170.5% on post prednisone burst (Aug). and 119% at 6 weeks postIVIG (Sept) For those tracking anti-Lysogangliosides, anti-Tubulin, anti-D1, anti-D2.... At 6 weeks postIVIG (Sept): Cam Kinase II was down to 119% Anti-lysogangliosides at 1280 -- still really high Anti-Tubulin at 8000 -- elevated Anti-D1 at 16000 -- really high Anti-D2 at 16000 So while Cam Kinase II was down, no change on other measures.... Not at all sure what this means. It may mean that antibody 24.3.1 was removed, but the other anti-lysogangliosides are still in the blood. Also might mean that what we are seeing post-IVIG is the BBB was closed. Buster

I totally know what you mean about eggshells.... In our case, the first 2 weeks were worse after IVIG. Old symptoms all came back. It was on the 16th days post IVIG that a sudden calm entered our house. No other word for it. Our dd9 got out her social studies book and started doing her homework. It was unbelievable. This is such an everyday event, but she just clicked into "normal." Handwriting improved noticably week 3-4. Attitude improved dramatically in week 5. She started playing with her sister in week 6 (several hours of it). Her sister was sooo delighted because frankly she's been missing someone to play with. She was able to go to her room by herself and read.... We're now at week 13 post IVIG, things are still very good. We do notice a tiny vocal tic and some pushback/defiance. But it is really nothing but we're hyper alert. We're keeping her on 250mg azith and she's also on an SSRI (Prozac) at very low dose. We've decided not to change any variables for 4 months. Hoping you have similar results... Buster