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Buster

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Posts posted by Buster

  1. Where to donate for PANDAS research?

    in PANS / PANDAS (Lyme included)

    Posted

    There are several great places to donate depending what your focus is. I donate to two groups: pandasppn.org and pandasnetwork.org.

     

    Pandasppn.org focuses on sponsoring clinical research and research grants associated with pans/pandas - it's more focused on medical professionals. Pandasnetwork.org sponsors research, research symposiums, and provides parent support services and outreach.

     

    Buster

  4. What questions are various research papers answering...?

    in PANS / PANDAS (Lyme included)

    Posted

    Hi folks,

     

    I've been going through the various papers and trying to tease out what questions the researchers are actually answering. If you've been reading papers you think are signfiicant can you add to this list or send me a message regarding other questions/papers? I'm not looking for "review" articles, but rather people running experiments that are testing certain hypothesies.

     

     

    Whether sudden onset OCD is correlated with untreated strep infections?

     

    [swedo1997] S Swedo et al, "Identification of Children With Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections by a Marker Associated With Rheumatic Fever", Am J Psychiatry 154:1, January 1997 http://ajp.psychiatryonline.org/cgi/reprint/154/1/110.pdf

    [swedo1998] Swedo SE et al., "Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections: Clinical Description of the First 50 Cases", Am J Psychiatry 155:2, February 1998. http://ajp.psychiatryonline.org/cgi/reprint/155/2/264

    Whether established OCD and/or tic disorders have exacerbations associated with treated strep infections?

     

    [Kurlan 2008] Kurlan R, et al. Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008 Jun;121(6):1188-97.

    [Leckman 2011] Leckman JF, et al. Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2011 Feb;50(2):108-118

    Whether symptoms remit when treated with antibiotics?

     

    [Garvey 1999] Garvey, MA et al. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry. 1999 Jun 15;45(12):1564-71.

     

     

    [snider 2005]. Snider2005, et al, Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry. 2005 Apr 1;57(7):788-92.

    [Murphy2004] Murphy TK, Muhammad S, Soto O, et al. "Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics", Biological Psychiatry, Volume 55, Issue 1, Pages 61-68, January 2004 http://www.journals.elsevierhealth.com/per...0704-2/abstract

    Whether symptoms remit when treated with IVIG/PEX?

     

    [Perlmutter1999]Perlmutter SJ, Leitman SF, Garvey MA, "Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood", Lancet 1999; 354 : 1153 58 http://intramural.nimh.nih.gov/pdn/pubs/pub-5.pdf

    Whether strep colonization alone is sufficient to trigger exacerbations?

     

    [Dileepan 2011] Dileepan T, et al. Robust antigen specific th17 T cell response to group A Streptococcus is dependent on IL-6 and intranasal route of infection. PLoS Pathog. 2011 Sep;7(9)

    [Wang 2010] Wang B, et al. Induction of TGF-beta1 and TGF-beta1-dependent predominant Th17 differentiation by group A streptococcal infection. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5937-42.

    [ Hyland 2009] Hyland KA , et al. The early interferon response of nasal-associated lymphoid tissue to Streptococcus pyogenes infection. FEMS Immunol Med Microbiol. 2009 Apr;55(3):422-31.

    [Constalonga 2009] Costalonga M, et al. Intranasal bacteria induce Th1 but not Treg or Th2. Mucosal Immunol. 2009 Jan;2(1):85-95.

     

    Whether anti-neuronal antibodies are diagnostic for PANDAS?

     

    [singer 2008] Singer, et al. “Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.”, Pediatrics. 2008 Jun;121(6):1198-205.

     

    [Kirvan2003] Kirvan CA, Swedo SE, Heuser JS, Cunningham MW, "Mimicry and Auto-antibody mediated neuronal Signaling Cells in Sydenham Chorea", Nature Medicine 9, 914 - 920 (2003) http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf

    [Kirvan2006] Kirvan CA, Swedo SE, Kurahara D, Cunningham MW, "Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea". 2006 Autoimmunity 39 (1): 219. http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf

    [Dale 2012] Dale RC, et al. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain. 2012 Nov;135 (Pt 11):3453-68. doi: 10.1093/brain/aws256. Epub 2012 Oct 11.

    [brilot 2011] Brilot F, et al. Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome. Neurology. 2011 Apr 26;76(17):1508-13.

     

    Whether antibodies to GABHS trigger behavioral changes (in mice)?

    [Yaddenapudi 2010] Yaddanapudi K, et al. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry. 2010 Jul;15(7):712-26.

    [Hoffman 2004] Hoffman KL et al, A murine model for neuropsychiatric disorders associated with group A beta-hemolytic streptococcal infection. J Neurosci. 2004 Feb 18;24(7):1780-91.

     

    Whether exacerbations are correlated with otherwise asymptomatic carriage?

    ??? Kurlan?

     

     

    Any others?

     

    Buster

     

  7. Dr. Leckman?

    in PANS / PANDAS (Lyme included)

    Posted

    Hi,

     

    Leckman is an extremely reasonable doctor and has seen now first hand the PANDAS kids. He didn't retract his prior papers (which is a shame, but has said publically that he didn't think he had PANDAS kids in his prior trials and instead had kids with Tourettes who met most (if not all) the PANDAS criteria as interpreted at the time). He frankly thought sudden onset or episodic course was a throw away line as it applied to any tic because they all have sudden onset and wax/wane. It took him seeing a PANDAS kid before, during, and after an exacerbation to understand how different the sawtooth pattern of exacerbation was from the more wave like transitions associated with tics/traditional OCD.

     

    Buster

  12. Swedo clarifies PANS and PANDAS

    in PANS / PANDAS (Lyme included)

    Posted · Edited by Buster

    Hi folks,

     

    I've seen a bunch of traffic about whether PANS replaces PANDAS. It does not. I checked with Dr. Swedo and with Dr. Leckman. PANDAS remains a research criteria and there is considerable scientific support for the association with streptococcal infections as well as support for the broader PITAND criteria due to H1N1, mycoplasma pneumonia, etc.

     

    You might be asking "why if there is good scientific evidence do we have three criteria rather than one". Well....

     

    The reason for creating PANS as a new set of criteria was to enable epidemiology studies. Dr Swedo writes in PANS that the lack of uniformity in applying the PANDAS criteria led to significant differences in the outcome of studies. This is research speak for "if you don't have any ducks in your sample, don't make claims about ducks".

     

    Dr. Swedo comments that "establishing an etiologic role for GAS in the onset of PANDAS is often as difficult as it is for SC". In fact it is probably worse because several researchers failed to understand what a PANDAS case even looks like.

     

    Neurologists seem to think PANDAS is a horse and pediatric psychiatrists/clinicians see PANDAS as a zebra with very distinctive markers. But until neurologists see a zebra -- it's sort of hard to describe the difference.

     

    I'm writing this to ask your help in reminding folks why we have three distinct criteria:

    1. PANS is to help neurologists actually recognize a zebra so we can have multi-site research
    2. PANDAS is to help researchers understand the pathogenesis in one specific infection
    3. PITAND is to be a broader category to remind folks it isn't just GABHS

     

    I know we as parents are very focused on diagnosis and treatment, but please don't lose sight of the big picture. We must get uniformity of subjects in multi-site research -- i.e., so experiments can be replicated. Otherwise we'll continue having neurologists testing horses and psychiatrists testing zebras with controversy on whether the tail is the same (hope the analogy works).

     

     

    Buster

  13. great article in St. Louis Today

    in PANS / PANDAS (Lyme included)

    Posted

    Oh, I assumed it meant he "researched" PANDAS on wikipedia! :wacko:

     

     

    LOL, we all know if its in Wikipedia it must be true!

    I should mention that I spent months trying to move the Wikipedia article (basically because of a single "editor").

     

    On controversial topics, there are apparently some "rules" for the editors:

    • You need to cite review articles and not original research -- apparently to prevent incorrect interpretation
    • You need to cite review articles that have been out for a while -- otherwise it's too recent
    • You can't connect material from different articles -- this is considered original research

     

    You can imagine with PANDAS that this is a bit tough since the editorials are largely written by John Hopkins authors.

  14. Positive strep normal ASO?

    in PANS / PANDAS (Lyme included)

    Posted · Edited by Buster

    Thanks!

     

    Have any changes happened since Jan 2011?

    There was a paper Feb 2010 by Leckman and Kaplan titled "The Human Immune Response to Streptococcal

    Extracellular Antigens: Clinical, Diagnostic, and Potential Pathogenetic Implications." (see http://cid.oxfordjournals.org/content/50/4/481.full)

     

    that also found a considerable failure of ASO to rise in documented and controlled experiments.

     

    The big statement is:

    "Of the previously mentioned 58 new GAS acquisitions, 36 (62.1%) were associated with a significant increase in ASO and/or ADB titer. However, only 28 of these acquisitions were associated with an increase in ASO and 28 with an increase in ADB."

     

    This means ASO rose in only 48% of cases.

     

    So a rise in ASO is confirmatory of a prior strep infection. A failure to rise doesn't seem to be meaningful (i.e., it doesn't happen in 52% of the time in the above cases of confirmed infections).

     

    Is that recent enough?

     

    This is remarkably similar to Shet's numbers -- so really a rediscovery but very recent.

     

    Buster

  16. urination frequency

    in PANS / PANDAS (Lyme included)

    Posted

    There are really two different items raised by Dr Swedo. Daytime urinary frequency and then nightime enurisis. In the last IOCDF conference two of the researchers commented that the dopamine D2 receptor is also on the outer sphincter -- and so if you are having something that interacts with the D2 receptor in the blood, it tends to also affect bladder control and the feeling of needing to pee.

     

    Regardless, it is worth getting the urine checked to see if there is another trigger.

     

    Buster

  17. Moving From PANDAS to CANS?

    in PANS / PANDAS (Lyme included)

    Posted

    Thank you!!!

     

    Do you think this is enough to demand a retraction of the article?

     

    Do you have any idea how to even start such a process?

     

    I don't. But do wonder if someone on this distribution might. Here's how I see the paper:

    • it is a minority position paper -- the 5 named neurologists apparently agreed with the NIH conference about the creation of a broader category, but disagreed with the criteria of the conference.
    • the paper does not fit the critiera for publication -- It is neither a report of "latest advancements" nor a presentation of "logical conclusions and recommendations" (see www.jpeds.com/authorinfo)
    • the paper has factual inaccuracies -- (such as the statement that GABHS carriers can have protractedly elevated titers).
    • the paper misrepresents findings of other papers -- it cites other articles as supporting positions when those citations hold contrary positions to the statement being made. This is either poor research or knowing misrepresentation.
    • the paper is exceedingly self-citing -- the bibliography has over 50% of the papers being by the same author
    • the paper fails to present evidence counter to their position -- The paper is missing papers and evidence contrary to the authors position such as Kirvan's Nature paper or the great work by Hornig.
    • the authors make dangerous treatment recommendations in a field in which they are not experts. -- The authors state that "recommended treatments for OCD are selective serotonin reuptake inhibitors". This is a treatment, but not the recommended treatment -- especially for pre-pubescent children. ERP and CBT is the recommended therapy with SSRIs being used under extremely close monitoring due to black-label risk of suicide. Multiple reports (including the work by Murphy and Storch) cite extreme sensitivity in kids meeting PANDAS criteria to anti-dopaminergic drugs.

     

    I could go on and on. I hate bad science and worse these pseudo science papers that set things back because they move from a focus on etiology and pathogenesis to creating categories of symptoms as if that is meaningful. Great so we know there are kids with acute OCD and Tics -- the point is whether we can treat the condition, not whether we can name it. Grrr...

  18. Moving From PANDAS to CANS?

    in PANS / PANDAS (Lyme included)

    Posted

    I just read through the very thoughtful posts here regarding the "PANDAS to CANS" paper. You all are much better at being neutral here and seeing the paper as being a first step by Dr. S towards recognizing a new illness.

     

    What probably bothers me the most is the misquoting of papers.

     

    In the new paper, the neurologists say "Nevertheless, there is strong evidence suggesting the absence of an important role for GABHS" citing reference 13 (Kurlan2008) and 14(Leckman2011). So I dutifully go off to see if these references support this statement. Nope.

     

    The Kurlan2008 article states "The overall findings from our study suggest that children with PANDAS represent a subgroup of patients with TS or OCD who may be susceptible to GABHS infection as a precipitant of their symptoms.” And “The number of hits expected by chance alone fell slightly outside of the 95% confidence interval for the true mean number of hits, suggesting that, in PANDAS case subjects, exacerbations were significantly associated with antecedent infection (4 weeks after an infection).”

     

    Okay so what do you do with an article that cites as foundation for an argument a report that finds the opposite finding?

     

    How about just plain false statement? In the new article, it states "GABHS carriers can have protractedly elevated anti-streptococcal antibody titers”

     

    Um, absolutely not. Quoting from Pichechero, "Kaplan and associates have defined the streptococcal carrier as a patient with a positive throat culture who shows neither symptoms nor a demonstrable rise in streptococcal antibody titers." Just being very clear, this is not ASO or AntiDNAseB-- but no antibody titers. So the rise in Anti-LysoGangliosides or Anti-Tubulin or ... would also preclude the statement of carriage.

     

    Then the next section "a case-control investigation of a large primary care database (255 cases and 4519 control subjects), comparing the rate of possible streptococcal infection in patients ages 2 to 25 years with OCD, TS and tic disorders, showed no overall increased risk of earlier GABHS infection as compared with matched control subjects." citing Shrag 2009.

     

    Okay, off I go to check the source of this quote. So many problem with this paper. First, the children in the study did not meet th diagnostic criteria for PANDAS. Sigh. Second, the study did not actually look at GABHS -- the study used > 70 diagnostic codes from impetigo to purulent dermatitis with some "sore throat" thrown in. Most of these codes would have triggered for Staph infection .... My point is you can't use this paper for support because the paper didn't study GABHS infections relative to controls. It studied an ocean of other illnesses.

     

    I just am so frustrated that both the scientist publishing their articles and apparently the editors reviewing the articles prior to publication are apparently reading the outrageous abstracts rather than the actual paper.

     

    I do appreciate that folks on this thread are saying that the new paper shows that Singer and Kurlan are moving, but guys, revisionist history, poor quoting and knowingly false statements just shouldn't make it into scientific publications (okay, I appreciate I'm not being realistic given the politics here, but come on...). I keep thinking about how the Le Roy neurologists are quoting this "PANDAS to CANS" paper as the reason that they've excluded PANS or PANDAS. Eghads. How can this horrible article be cited as evidence instead of the random misstatements and misrepresentation of science that it is. Can you believe it doesn't even reference Hornig's work on the mouse validation of the antibody transfers? Or Kirvan's work on the antibody isolation? Unbelievable.

     

    Buster

  19. questions about lab results

    in PANS / PANDAS (Lyme included)

    Posted

    The first was his ASO continues to be high. It has decreased since his last test over a year ago, but it is still above normal at 224 with the lab reference range of <150. His first test was 336 in 9/10, then by 12/10 it had dropped to 285 and now down to 224. So we’re moving in the right direction. Is it possible that 224 is actually relatively normal for DS, or is it a suggestion that his antibodies are still raging?

     

    Yes, it could be quite normal for your DS to have a 224 for the ASO. The fall of antibodies is not well studied. There is a correlation seen in many patients of the rise of ASO within 0-4 weeks of an infection; however, the fall rate is not well studied.

     

    In one study, 5% of kids (in the 5-10 age group) with no symptoms or preconditions had an ASO level > 196.

     

    You might find this thread interesting: http://www.latitudes.org/forums/index.php?showtopic=3756&st=0&p=25312entry25312

     

    Bottom line if you are not seeing symptoms, I wouldn't worry too much about the ASO rate as it really isn't an indicator of anything at this point.

     

    The other test that was high was his lymphocytes. They were 42.3 and the normal range is 25 to 33.3.

    Increased lymphocytes means that the T-cells are activated. They're working on something, could be sort of anything. Hard to say what else is going on. The good news is your kid's immune system is working. What it's working on isn't known. My personal advice is to treat this as a baseline and when/if you have a strong behavioral change take another look at the blood work. Sounds like you've got a decent doc.

     

    Buster

  20. Comments on CANS

    in PANS / PANDAS (Lyme included)

    Posted

    I keep thinking about all the flaws in the Kurlan and Singer papers and how much damage has been done with abstracts and titles that don't correspond to the findings of the paper.

     

    As just one example, in the 2011 CANS paper, Kurlan and Singer make the classic fatal research error of assuming a failure to confirm is equivalent to disproving a hypothesis. Arrgh, did they even take statistics?

     

    Their actual quote was "there is strong evidence suggesting the absence of an important role for GABHS [in tic and OCD disorders]" where they self-cite their 2008 longitudinal paper. Contrary to this assertion, the actual referenced paper showed that a purported PANDAS group had significantly more cases of GABHS than the controls. Sigh.

     

    Perhaps they meant to say "there is strong evidence suggesting the absence of an important role for GABHS [in exacerbations of tic and OCD symptoms]", well the cited paper doesn't provide that evidence either. The paper failed to reach a P-value (probability of event) that was of any significance. In research, this means the experiment did not help reach a conclusion.

     

    This whole element is part of what is known as the NULL hypothesis in research. You cannot prove the correctness or falseness of the NULL hypothesis, you can only say that the results of the experiment are consistent or inconsistent with the hypothesis.

     

    Even for a hypothesis like "all swans are white", you might think that if you found a black one this would disprove the hypothesis. But you have to then consider the probability that the black one isn't even a swan. So, what is the probability that Kurlan/Singer purported PANDAS children actually match the criteria of PANDAS? In the CANS paper, they state that they didn't use Swedo's criteria -- so why are they calling it PANDAS?

     

    They compared a group of kids with TS who have had GABHS infections with a group of TS kids who didn't have GABHS infections. This is not the same as comparing those who match the PANDAS criteria with controls. Arggh.

     

    Buster

  21. Comments on CANS

    in PANS / PANDAS (Lyme included)

    Posted

    I had a chance to read through the Singer's new article about "Moving from PANDAS to CANS".

     

    I can't believe he's recommending Lumbar punctures and MRIs and not recommending a throat culture or MycoPlasma test.

     

    On the silver lining side, it is apparent that the authors have finally read Dr. Swedo's 2004 paper and are now using a different criteria of "sudden 'explosive' onset of symptoms and course of recurrent sudden exacerbations and remissions".

     

    This is quite different from Kurlan's 2008 paper where he used "clinical course characterized by the abrupt onset of symptoms or by a pattern of dramatic recurrent symptom exacerbations and remission".

     

    What's wacky is that having just realized they didn't follow the right criteria in 2008, they then reference their paper with the wrong criteria for purported PANDAS saying "there is strong evidence suggesting the absence of an important role for GABHS”. Unbelievable. Did they even read their own study? Did they look at their P-values?

     

    So many things wrong with the paper...

     

    Buster

  22. 504 vs IEP

    in PANS / PANDAS (Lyme included)

    Posted

    To have an IEP, the child must have either mental retardation, hearing impairments, speech or language impairments, visual impairments, serious emotional disturbance, orthopedic impairments, autism, traumatic brain injury, or other health impairments, or specific learning disabilities (in one of 8 areas); and by reason thereof requires special education and related services.

     

    It is this “requirement of special education” that is the difference between the 504 and the IEP. If the child has a disability but doesn’t require special education/instruction, the child isn’t eligible for an IEP.

     

    Some children with tics or OCD or Tourettes are on an IEP with Other Health Impairment. An OHI specification requires two things [34 CFR 300.8 (9)]:

    1. A limited alertness with respect to the educational environment (i.e., distracted due to fear or tics or …)
    2. and Adversely affects the child’s educational performance

    The schools seem to choose that “adversely affects” means is greater than 1 standard deviation below the bottom of the average of all kids in the US. I could go on and on here, but that’s typically the fight. Again, if there isn’t special education required, then the child isn’t eligible for an IEP.

     

    There’s lots we could discuss about eligibility. But what you might be asking is “suppose my child is eligible, is there a good reason to stay with a 504 vs an IEP?”

     

    The usual bias is about the procedural safeguards. The IEP puts in place certain procedural safeguards that prevent certain disciplinary actions (like expulsion) without due process. These safeguards are not in place for the 504.

     

    The 504 is about “access to the curriculum” through accommodations. It does not have provisions that the child gets special education or that the education is making “meaningful progress.”

     

    One of the painful realities we’ve learned is that the school board seems to have a very low objective of teaching children with special education. In our conversations, they almost always quote the Rowley federal case as being why they only have to show “progress” and not actually help close the gap between ability and production (what is referred to as a severe discrepancy in the specific learning disability rules). I could say a ton here, but it seems like the teachers and the schools where we live are more suited to helping kids with 504 plans than they are at helping kids who have specific learning disabilities. I wish this weren’t true, but it seems that they “hand” kids with special education off to others rather than taking effort to adjust their curriculums to help the child approach the material.

     

    Finally, good or bad, there is a stigma associated with Special Education. In one of our IEP meetings the coordinator said “well, she is likely going to be embarrassed to be pulled out” (which is true) and I asked what program they had in place to help reduce this stigma (I got blank looks), but the reality is being different is just tough at this age group.

     

    Bottom line, if you need special education, then you need an IEP. If you only need accomodations then either could work and in our case, the 504 became more appropriate as we got escalations under control.

     

    Best regards,

     

    Buster

  23. Poll: What did symptoms look like

    in PANS / PANDAS (Lyme included)

    Posted

    Hi T.mom,

     

    Actually I wasn't dealing with the treatment in this version -- so if you used antibiotics or steroids or ... all of those are fine. I was trying to get a sense of the shape of the curve.

     

    Probably what I need to do is have people try to describe their graph pre-treatment and post-treatment and pre-re-treatment (if any) and post-re-treatment (if any).

     

    The t1, t2, ... is for something else where these are time indexes that I was going to use to ask about how long it was from t1 to t2 and from t2 to t3 etc.

     

    Buster

     

     

    Hi Buster--

     

    The way that I read both graphs is that you are showing a "presumed" natural drop in symptoms (with no treatment at all it appears.) Am I reading the graphs correctly???

     

    What do the t1, t2, t3 represent?

     

    Neither of our girls have shown this type of improvement on their own--I with they had! :)

     

    We have only seen a drop in symptoms after treatment of one type or another--and THEN we could say we saw a saw-tooth recover multiple times (ABX, Steroids, IVIG...)

    I like to think that baseline has been low again, but I am not so sure yet--

    Hope that helps--

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