Buster

Our dd9 had the oddest handwriting issues when in an exacerbation. She would start her sentences in the middle of the line. It seemed she just couldn't find the left margin. Each sentence would then indent from there. All punctuation would disappear (including capitalization). When the exacerbation ended, her left margin returned. It is really odd and very easy to see. Her handwriting becomes more like a scrawl during an exacberation. In her early exacerbations, we thought she had dysgraphia. It wasn't until she was in remission that we saw what her handwriting could be. Curiously she had a slight tremor in her hand when writing -- this was more noticable after 20 min of writing. Buster

Hi Santi, Prednisone is a corticosteroid that is particularly effective at suppressing the immune system. Adrenal suppression occurs if prednisone is taken for longer than 7 days. This is why if you are on pred longer than 7 days you need to wean off it. The amount of time to wean depends on the amount of time you are on pred. While prednisone is typically quite safe, it is nothing to mess around with. For example, the treatment for severe poison oak or poison ivy is often 1mg/kg of prednisone. In terms of experience, we have used pred twice and have seen good effect from the prednisone. PANDAS is thought to be caused by three things: the creation of an anti-neuronal antibody a failure of the immune system to supress the faulty antibody a breach in the blood-brain barrier that allows the antibody to reach neuronal tissue Prednisone acts in two ways. First, it is highly anti-inflammatory. If the breach in BBB is due to inflammation, then the predinsone can close the BBB. Second, predinsone acts to suppress antibody creation and T-cell activation. As such it affects #2 by supressing the effect of the faulty antibody Each child seems to respond differently to pred. In our case, we had pretty complete remission of symptoms with a child with significant social anxiety feeling comfortable talking with others, a child with separation anxiety feeling comfortable being alone. I think each parent probably has something different, but in our case it was seeing our child again. Regards, Buster

I got some questions what was wrong with the Kurlan study (by analogy) -- several folks said that recent doctors had used the Zebra's and Horses analogy with them and they'd like some ammunition. In the analogy, the flaws in the "Kurlan" study are: Kurlan selected children who were already heavily medicated (and succesfully managed on meds) -- and thus checking for exacerbations is problematic Kurlan broke the blind by informing pediatricians if the strep test was positive. On the assumption that the pediatricians followed the standard protocol they'd put the kids on antibiotics. This means that Kurlan was checking whether treated GABHS caused ARF or SC or PANDAS. But we know from multiple other studies that treating GABHS early enough does not lead to ARF/SC. Kurlan had sampling theory issues. He defined an exacerbation as one that occured within 4 weeks of a "definite" infection. When he relaxed his criteria he found more correlations. However, this was not in his report. His kids had no OCD exacerbations in 2 years (regardless of GABHS) -- that is really unusual and certainly makes these kids different from Swedo's 17 pt changes in CYBOCs. He uses the variety of claimed symptoms to discredit PANDAS but has no pathogenesis for any of the symptoms observed. He claims his failure to confirm creates serious doubt about PANDAS -- but it doesn't. It only raises serious doubts about his methodology since he was running a new experiment and did not have a control from the prior experiment. Hope that is clearer as to what is wrong. Buster

Strangely enough good analogies are hard to create -- Let's try this one. High CaM Kinase II is like a sunburn. When you now take a shower, the shower feels incredibly hot -- you are feeling the same temperature, but your temperature guage is hyper sensitive. Your clothing rubs, the finest piece of sand is agony, everything feels puffy/raw -- everything is now more sensitive. So High CaM Kinase II increases the sensitivity of the bacteria sensors making them create inflammation with the slighted provocation. Hopefully I'll think of a better analogy but that's the one I'm thinking of right now -- and yes, I just got a sunburn :-) Buster

Yes, there are such tests for the inflammatory cytokines (for example http://www.aruplab.com/guides/ug/tests/0051394.jsp) I'm not sure under what circumstances doctors order them. There was a very recent paper from Swedon (http://www.americanbiotechnologist.com/blog/wp-content/uploads/2010/02/Up-regulation-of-cytokines-and-chemokines-predate-the-onset-of-rheumatoid-arthritis.pdf ) Where they found that the inflammatory cytokines predated the rheumatoid arthritis. Buster

The article is quite good. It builds on some research from 2005 that Rifkin published around "Toll-like receptors, endogenous ligands, and systemic autoimmune disease" (for those who read such stuff : http://www3.interscience.wiley.com/journal...649336/abstract ) What this new article found was that certain cells that had detectors for bacteria (these detectors are known as TLR2 and TLR4) became super sensitive and produced significant inflammation (inflammatory cytokines and IFN Beta) when in the presense of sustained Cam Kinase II. They found that a particular signalling pathway (known as MyD88) was being enhanced and resulted in significant amounts of pro-inflammatory cytokines (stuff that causes localized inflammation). On the other hand, there's an interesting paper elsewhere that mice who have deficient MyD88 have difficulty clearing gram-positive bacteria (see "MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS" http://brain.oxfordjournals.org/cgi/content/full/127/6/1437). This left me a bit confused. I originally thought that PANDAS kids might be deficient in MyD88 - i.e., unable to clear GABHS on their own. What this new paper indicates is that perhaps the MyD88 is working fine but something is causing sustained Cam Kinase II levels and this is causing a hyper-sensitivity to GABHS. This left me wondering if Kirvan's Auto-antibody 24.3.1 might be the cause of sustained Cam Kinase II activation and then the Cam Kinase II activation is causing MyD88 to become hyper-sensitive producing significant inflammatory cytokines. Perhaps this is the reason that the kids appear to not be able to clear GABHS and then have a hyper sensitivity. There are several good new references I hadn't seen to research around siRNA. The researchers used siRNA -- a relatively recent discovery of how to block specific genes from being copied in cell creation -- to isolate and disable the Cam Kinase II activation. They found that the inflammatory cytokines were stopped when the Calcium fluxuations and Cam Kinase II activation was stopped. This indicated that CaM Kinase II is directly involved in the pro-inflammatory cytokine signalling. This does not mean that CaM Kinase II causes inflammation, but only that it is part of the signalling pathway. Think of it as a light switch -- if the Cam Kinase II switch is on then the "current" can flow through to the motor producing inflammation. Most of the rest of the paper is about figuring out the specific signalling pathway that occurs and trying to confirm, refute or redraw a more accurate signalling pathway to those published by others such as: On the discussion regarding autoimmune diseases and Cam Kinase II activation -- there isn't substantial new evidence there, but rather that they think the current research adds more clarity on what is happening and more research may yield insight into how the ligands (or pieces) of proteins are defeating the host-recognition mechanism and triggering auto-immune responses. That's what I got out of the paper... very glad for the post -- thanks Peglem. Buster

I'll point you here: http://www.latitudes.org/forums/index.php?showtopic=6266 and then answer here as well... Anti-DNAse B starts to rise in response to exotoxins from the GABHS. It takes about 2 weeks from a positive throat culture before the Anti-DNAseB start to show and it will keep rising until a peak at about 6-8 weeks from the initial infection. Often the infection period (i.e., from colonization to infection) is about 3-5 days (some faster, some slower). The fall rate of anti-DNAseB is not well studied. Essentially if the anti-DNAse B is still rising then the infection was typically within the last 6-8 weeks. One quick thing to mention is that anti-biotics do not stop an infection. antibiotics slow an infection once it starts so the immune system can suppress the infection. If you have a compromised immune system, it's very hard to clear an infection. Also, if you were using penicillin, you do have to be super careful to be very consistent in dosing (don't miss a dose) and you also need to ensure you have replaced things like toothbrushes and cleared other people in the house. The rate of re-infection is pretty high and so what might be happening is you are getting ping-ponging between individuals in the house if you have been super dilligent about dosing. Buster Hi Santi, Anti-DNAse will keep rising for 6 weeks. ASO will start to fall at 1-3 weeks. Buster

Hi Santi, Anti-DNAse will keep rising for 6 weeks. ASO will start to fall at 1-3 weeks. Buster

I will undoubtedly regret starting this thread It’s hard not to sound like a critic When studying about beta hemolytic Streptococcus Group A And ELISA assays And research that itself is arthritic

Hold on. You had a positive throat culture -- go treat it. Given the tic symptoms as well, ask your doctor to extend the antibiotic to 30 days. If your child is still culture positive and your doctor wants a paper see if they'll emm type the strain. If you get a chance to nudge your pediatrician on medication, go for Augmentin or Azithromycin -- both shown to be quite clinically effective against GABHS. The titers are not meaningful unless taken at specific time intervals from the colonization of strep. Take a look at the FAQ here: http://www.latitudes.org/forums/index.php?showtopic=6266 Regards, Buster

Well, that's kind of the debate: disease or syndrome. A Syndrome is a collection of signs and symptoms known to frequently appear together but without a known cause. A disease is defined as a disorder in a system or organ that effects the body's function. Most add the requirement that the disease must also have either a recognized cause or a consistent anatomic alteration. Swedo and Kirvan have a proposed cause (an anti-neuronal antibody binding to D2 receptors in the basal ganglia ). Others say that this is correlation but not causality. To show causality you have to show that every time the result occurs, the proposed cause was present and that the result does not occur without the proposed cause. This is a pretty high bar. So in answer to your actual question -- we would say that PANDAS is in remission. Regards, Buster

Clearly I'll have tighten it up a bit :-) But no, he didn't take that into account -- he focused on whether the person with Hives had cat hair on them -- not whether someone else in the house had cat hair on them. Buster

I was trying to explain the difference between the research approach of Swedo and Kurlan and decided to post an analogy here. I hope you get a chuckle from it. Analogies are tricky and break down -- but see if this makes sense... Swedo noticed that when she ran across people who had allergies a number of them had orange cats. Interestingly, that group of people aren't allergic to all cats -- just orange ones. She found that if you kept them away from orange cats, they didn't sneeze as much But if you brought an orange cat near them, they would have very severe reactions until the orange cats were removed. She also found that if you gave Benadyl -- the severity of the sneezes/hives was less Others reported that if someone who had been holding an orange cat came near the individual, the person would have an allergic reaction She didn't think it was the color orange that made people sneeze, but rather perhaps something unusual about the orange cats. Swedo wondered if the issue was a glycoprotein that was in the saliva of cats and found more of the glycoprotein on the hair of orange cats She postulated that people were allergic to the glycoprotein and not specifically to the color of the cat Hmmm Kurlan has been studying allergies for years -- particularly ones that make you break out in hives. He thought that allergies are really common problems and are caused by lots of things He stated that cats are everywhere and it is unlikely that cats are the most likely causes of allergies He designed an experiment where he selected a bunch of people from his hive study group who had allergies (to all sorts of stuff) He asked them if they had ever sneezed or had hives within 1 month of being near a cat Several of them had a cat He then waited a 3 month period and checked if anyone had had hives and seen a cat within the 3 months (not controlling for any other allergens) He then took those who said yes as group A and age matched them with kids who said no He then started monitoring them for 2 years to see if they reported hives (or sneezes) if an orange cat happened to be around Most of the selected children had been taking other medication for controlling hives He didn't control for people who took benadryl or self medicated -- he also allowed people to get treated for hives -- even if they had a cat He calculated that on average each person should meet an orange cat 0.05 times per year He did really clever experiments to detect the proximity of orange cats that involved poking each patient a bunch of times and checking their clothes for cat hair He decided that cat hair alone isn't a good indicator and the person might just be a carrier so he required orange cat hair, hives or sneeze, and someone seeing an orange cat. If you had all 3 then that was a definite orange cat sighting. If you had only 2, it was a probable cat sighting. If you had only 1 it was a possible cat sighting. He found : A small percentage of people who once had hives around a cat are more likely to have hives around a cat That orange cats are not the most common reason that people get hives (especially if they don't meet too many cats, or meet non-orange cats) That his control group didn't happen to meet as many orange cats as he expected That his group of people who got hives didn't seem to have big bouts of sneezing with orange cats [*] He then wrote several papers and gave lectures that his longitudinal study did not confirm that orange cats cause hives seriously calling into question the validity of the allergy to cat hypothesis [*] Finally he raised that the variety of claimed symptoms (some people getting red eyes, some people having scratchy throats, some people sneezing, some having hives, some feeling itchy) seriously undermine the credibility that this all has a similar cause Sneezing = OCD hives = tics cats = strep orange cats dander = GABHS checking clothes for cat hair = throat swab benadryl = antibiotics I'm hoping this sort of casts the two studies in the right light :-) I had some fun with this. Buster

Really hard to say. Augmentin helps slow the growth of gram positive bacteria. It usually doesn't do very much for mycoplasma pneumonia -- but perhaps you cleared that out with the clarith. Hard to say why you got a good effect but glad you did. Buster

These are slightly different posts with similar components. If we take PANDAS, the current theory is one of interference with Dopamine 2 receptors -- not having too much or too little but rather that the dopamine becomes unregulated. Dopamine works with a rather funny thing called a feedback cycle. A way to think about it is like listening to a show and then a commercial comes on really loud so you turn down the TV then your show comes back on and now you can't hear it. Now have that happen all the time. That's what is thought to be going on in PANDAS. It isn't having too much or too little volume it's that the volume is changing or not regulated correctly. The antibodies are like the very loud commercials interferring with the volume setting. Poor analogy but close. Now what was interesting about the narcolepsy paper was that they were finding some other breach of the blood-brain barrier and another interference pattern. It's very possible that the narcolepsy is an interference with Dopamine receptor 1 whereas PANDAS is an interference with dopamine receptor 2 -- we don't really know -- Actually that's probably way more than you wanted to know too :-) The point I should have said was that the narcolepsy paper was interesting because it was finding a genetic predisposition to slow ASO recovery and found an apparent BBB breach. The genetic marker was also one found in ARF/SC and in MS patients. The hypothesis is beyond the findings, but it was interesting. Buster But isn't OCD thought to be related to too much or unregulated dopamine in the brain? "Hyperfunction" of dopamine is the term I keep seeing in the literature. So how could a person like my DS display both OCD and narcoleptic-like behaviors?!?! Color me confused!

Just as a followon comment. PANDAS isn't a reaction to ASO or Anti-DNAse B. The high rates just indicate that he had a prior infection. For a healthy immune system it takes about 4 weeks for the ASO level to return to "normal" and about 8 weeks for Anti-DNAseB to return -- but in many children, and they don't know why, the fall is much much slower. Rejoice in the improvement, don't worry too much about the numbers. Buster

Wow. I can only imagine how frightening this must have been. How aware is your 5 year old of his actions? Does he remember it? Can you talk about it or does he get strongly defiant? It is really possible it is a byproduct of the "rolling back pages" and the intense irritability and headaches that can happen post IVIG. However, safety (for you and your other child) is really, really important. Any chance to have a family member with you or take care of one of them for the next week? Thinking of you, Buster

Yes, an elevated platelet count could mean an infection. In children, an infection often causes an elevation in platelets. You wrote HGV but I presume you meant MCV. Elevated Platelets with elevated hemoglobin with elevated mean corposcular volume might have meaning if really elevated but you won't know what exactly it is from. You have to use other tests for that. CBC basically tells you something is out of wack -- not what is wrong. Buster Is it possible then that there is no elevation in WBC's and there is strep? Have you heard anything about elevation in platelets? My son's is elevated plus his HGB or HGV? A

Wow, fascinating study. There are several great comments in the paper. The authors list 3 basic hypothesies: that streptococcal infections (or their exotoxins) cause superantigen interactions Tcell receptors and lead to the destruction of hypocretin neurons or perhaps the exotoxins open the BBB allowing other specific blood factors to trigger narcolepsy or perhaps the bacteria/exotoxins just reactivate the immune system nonspecifically causing inflammation triggering narcolepsy What was also fascinating was the incredible correlation found to long-lived ASO titers. They noted "In uncomplicated infections, antistreptococcal antibodies are reported to increase after 2 weeks, to peak at 2–4 months, and decrease thereafter.19 The long-lasting antibody response in narcolepsy may thus reflect the special genetic background of these subjects and/or a sustained narcolepsy- related immune reaction." They further go on to quote Machado's 2001 paper where "A similar pattern of slow ASO titer decrease lasting several years, with moderately increased titers up to 3 years from diagnosis, was found in acute rheumatic fever." Finally, they noted a difference in the HLA-DQB1*0602 which is an allele (or specific gene transformation) that has been found in 90% of nacolepsy patients and interestingly in many patients suffering from migraines and interestingly in MS patients. This might (might) be a marker for a BBB susceptibility. There's a nice paper on this here http://www.jimmunol.org/cgi/content/abstract/183/5/3531 Nacrolepsy is thought to be an insufficiency of dopamine (or a blocking/interference with dopamine receptors) so curiously these all might be related. Great paper.

I wasn't sure whether to respond to this post or not... as this is a pretty tricky topic. Even when I saw amazing results and got my child back ( sigh - hard to even think of 2 years ago) -- there remained this weird doubt of whether this was just a placebo effect, was this just the waxing and waning of OCD, .... I know my wife will post and say "are you crazy, the hallucinations, contamination fears, weight loss are not a waxing/waning of OCD." I know, I know, but it bugs me like crazy that we still don't really know exactly what happened at a fundamental level. It must drive folks with Tourettes Syndrome a bit nuts that despite many decades of research there's no better understanding of what causes Tourettes Syndrome. For PANDAS, we've got good experiments and great anecdotal evidence of the effectiveness of antibiotics and IVIG, but it is still relatively weak evidence -- way more studies are needed. What it all comes down to is risk/benefit analysis. As parents we're trying to make the best informed decisions regarding our kids. We elected that long-term azithromycin was the right thing for our child based on studying relative risks and the perceived benefit. We also elected to do IVIG based on the severity of our daughter's symptoms and on reading nearly 200 research papers and finding the benefits (for our daughter's condition) outweighed the perceived risk. I think in our case if we hadn't had the sudden onset, we probably never would have found PANDAS, never had disputed the doctors who told us she'd need long term psychiatric care, and given in to some very nasty (frankly poorly studied) anti-psychotic drugs. What leads to the focus on sudden onset is a really small research study that Swedo did in 2000 where she tested the effectiveness of Plasma Exchange for non-sudden onset childhood OCD http://www.ncbi.nlm.nih.gov/pubmed/11026187. This is an extremely limited trial (5 kids) but it led rightly or wrongly to Swedo's hypothesis that some forms of OCD have auto-immune pathogenesis and others do not. A parallel study was supposed to have been done by Hoekstra in 2004 on IVIG for tic disorders; however, he focused on adolescents/adults (mean age 28) http://www.ncbi.nlm.nih.gov/pubmed/15119917 -- so who knows if this applies to childhood onset. As far as I know there hasn't been a study on effectiveness of IVIG on non-sudden onset OCD in children. This means there isn't a lot of research to help here to give us even a modest compass direction. Personally, knowing what I know now, and listening to Dr. K's talk about being able to treat some misdiagnosed Autism, I would totally try several rounds of antibiotics. I might even try IVIG if my child were in a severe enough case because in our case the potential benefit would outweigh the perceived risk. I just don't know how to evaluate the risk of anti-psychotic drugs and their influence on a child's development versus the risks of IVIG. This is a really personal decision and so I can't really offer any advice here except to say I understand why sudden onset is highlighted because the available research increases the likelihood that a child with this symptom is more likely treatable with anti-biotics/anti-inflammatories/immuno-modulation. Non sudden onset may be auto-immune too -- we just don't have good research to know. Buster

There are two types of lymphocytes - T cells and B cells. Almost any type of infection (bacterial or viral) can cause an elevation of lymphocytes. However, the elevation is non-specific and you can't really tell the cause. A strep infection may show up as an elevation in lymphocytes, but usually shows up as an elevation in neutrophils. However, there is tremendous variability here which is why other tests are typically used for GABHS. Buster

There's a really interesting paper on Acute Rheumatic Fever called Some of the People, Some of the Time Susceptibility to Acute Rheumatic Fever in the Feb 2009 issue of Circulation (see http://circ.ahajournals.org/cgi/reprint/119/5/742.pdf. They found that even with ourbreaks of the GABHS strain that is known to cause ARF, the incidence of ARF is limited to 3-6%. This is a constant regardless of geography and ethnicity indicating a very strong genetic component to susceptibility. There's a good discussion of genetic predisposition and a good figure that tries to explain the incorrect activation of T-cells from molecular mimicry. Nothing earth shattering in the write up, but good solid research and paper that is helpful as a baseline paper when talking with doctors about PANDAS having similar pathogenesis. Combining this paper with the T-cell crossing the BBB helps strengthen the PANDAS argument. Buster

I just ran across the following paper in European Eating Disorders Review, Volume 18, Issue 2 (p 116-123) March 2010: PANDAS and anorexia nervosa--a spotters' guide: suggestions for medical assessment by Vincenzi B, O'Toole J, Lask B. There's not a lot new in the paper but it does resurface some of Mae Sokol's work. The main conclusion of the paper is to consider PANDAS-AN when AN presents and there was a recent upper respiratory infection. One should then look at: A throat swab with a specific request for examination for GABHS infection ESR, CRP and routine blood tests e.g. white cell counts GABHS antibodies, either ASO or antiDNAseB, but preferably both AnAb (anti-neuronal antibodies) and, if at all possible, D8/17. Although this latter is probably the least available of all the relevant investigation it is likely to be the most useful I was a little surprised by #4 as I thought the D8/17 test was not available. The Anti-neuronal antibodies they are referring to are Church and Dale's AnAB tests. There wasn't any reference to Kirvan or Cunninham's work. Nothing super special in the paper, but it's recent and a good summary of the literature todate. Buster

The list is what is known as the JONES critieria for Acute Rheumatic Fever. Tjhe quickest link is probably the mayo clinic web page at: http://www.mayoclinic.org/rheumatic-fever/diagnosis.html That is typically a reference from your pediatrician -- they'll know folks who specialize in Acute Rheumatic Fever -- typically a rheumatologist. Buster

Amy, because of the positive culture and the "hives" you should also get an echocardiogram. The major symptoms of ARF are: Migratory polyarthritis: a temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards. Carditis: inflammation of the heart muscle which can manifest as congestive heart failure with shortness of breath, pericarditis with a rub, or a new heart murmur. Subcutaneous nodules: painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees. Erythema marginatum: a long lasting rash that begins on the trunk or arms as macules and spreads outward to form a snake like ring while clearing in the middle. This rash never starts on the face and it is made worse with heat. Sydenham's chorea (St. Vitus' dance): a characteristic series of rapid movements without purpose of the face and arms. This can occur very late in the disease. if any two of these are true, that is sufficient for a diagnosis of ARF. It did not look like the "hives" are the subcutaneous nodules but worth checking with an ARF specialist. Best regards, Buster