This study has me excited

[Buster]

Problems with the Singer Study

 

 

Hi Kim,

 

You asked a bunch of interesting questions in your post.

 

Moreover, researchers found no evidence of strep antibodies – the antibodies produced by the immune system against the streptococcus bacterium – binding to or interacting with brain tissue, a finding that makes an immune origin of PANDAS unlikely, investigators say.

I haven't been abe to get my mind around the fact that they found nothing in these 12 children, but IF it's only a certain strep for a certain child that causes a problem, would they catch it using only 12 kids over 2 years? I wonder how many confirmed strep infections each child had during the 2 year period.

 

Your point is really good. The underlying paper is a paper by Singer et al. in the June issue of Pediatrics:

http://pediatrics.aappublications.org/cgi/...ract/121/6/1198

 

I think the paper is fundamentally flawed and I have 5 major issues with this paper.

1. This study is about long-term tic disorders in older kids (11-12) and not about sudden onset PANDAS (mean age 7.5).
   This is study about children with long term chronic tics who had onset over 3 years prior. 75% of the subjects in the proported PANDAS group were diagnosed with TS (i.e., had symptoms for > 1 year and no remission for > 3 months). The sample is pulled from the longitudinal study by Kurlan reported in the same issue of Pediatrics.

   
    
   

2. The diagnostic criteria used by Kurlan for his proported PANDAS group is not the same as used by Swedo or Snider.
   
   Kurlan used a "clinical course characterized by the abrupt onset of symptoms
   or
   by a pattern of dramatic recurrent symptom exacerbations and remission". Swedo used an "Episodic course characterized by acute, severe onset
   and
   dramatic symptom exacerbations." (emphasis added) While these sound similar, they are not. Indeed the episodic nature is the key distinguishing element in Swedo's studies as is the severity of the symptoms. Swedo wrote in her May 2003 response to Kurlan, "The episodic, relapasing-remitting course of the PANDAS subgroup is distinctly different from the undulating, waxing-waning course seen in other patients with OCD or tic disorders." In addition, Singer discloses that the average onset was over 4 years prior to his study. Kurlan discloses that the onset was not from documentation, but rather obtained through interviews thus being very prone to recall bias. So it is unclear whether the proported PANDAS subjects met the Episodic course, the severe onset, and the dramatic symptom exacerbations of the Swedo critieria.
   
   

   
   

3. The subjects exhibited no OCD behavioral changes and are different from Swedo's/Snider's subjects
   
   The subjects attributed to be PANDAS subgroup in the Kurlan and Singer studies had a CY-BOCS score that changed only 1.6 [-0.4 to 3.6] (i.e., no change) with controls changing 1.0 [-1.1 to 3.1] (i.e., no change). This is hardly episodic given the baseline CY-BOCS scores and certainly does not indicate remission within the 2 year period but rather the small waxing and waning of OCD symptoms and the limited objective accuracy of the CY-BOCS measure. Swedo subjects often exhibited > 15 points of change in CY-BOCS score. Granted, I have some issues with these studies as well, but this 10 fold difference in CY-BOCS measured exacerbations definitely makes one wonder if these are the same subgroups.

   
    
   

4. The subjects have high tic exacerbations but not OCD exacerbations.
   
   It is true that the subjects in the Kurlan/Singer studies had YGTSS-tic exacerbations of 11 pts [4.2-17.9] and certainly this is significant, but most of the other papers on PANDAS focus on the OCD element and less on the tics. So this begs the question about whether the study was more about Tourette's and association with streptococcal pyogenes rather than PANDAS. It also begs the question whether Swedo's criteria should include tic-only exacerbations. It also begs the question whether chronic tics are fundamentally different than onset.

   
    
   

5. The subjects were all on numerous anti-psychotic, alpha-agonists, and mood stabilizers.
   
   it is totally unclear what these effects had on the subjects and how these variables were controlled

   
   

So the key question is how many of the kids in Kurlan's and Singer's studies actually had PANDAS as opposed to being kids with severe Tourettes with the unfortunate waxing/waning of tics associated with Tourette symptoms.

 

This is a long way of saying that I don't see how they can reach any conclusion regarding PANDAS given that their kids don't seem to be PANDAS subjects but rather Tourette's subjects.

 

in re-reading this post, I realize I should soften my criticism by saying how very impressed I was to see the size of the Kurlan study and Singer study and that the data set they collected is undoubtedly very helpful. Think of it, 40 kids being bleed every 4 weeks for 2 years with no immediate benefit. The study is impressive in scope, the data undoubtedly valuable, but the claims are definitely questionable.

 

Okay, now onto the second part of the study -- about antibody interaction with nuronal tissue.

 

Let me paraphrase, they took blood from this group of kids who I don't think have any PANDAS kids. They then injected this into cadaver brains (i.e., dead tissue) to see if the anti-bodies in the blood or the T-cells in the blood would attack the dead brain's of non-PANDAS kids, and they didn't find anything. Okay, so what conclusion can you draw from that. Most certainly not the conclusion that seems to be drawn from folks not reading the actual paper. This stuff gets me soooo irritated.

 

Finally, onto your last question about M-proteins. This is also very interesting.

 

Dr. Ed Kaplan has been studying this for the past 20 years. There's a citation in a recent book, "Streptococcal Pharangytis: Optimal Management", http://books.google.com/books?id=YiYY86j9A...a+streptococcal

 

Where Kaplan indicates that M-protein production was surpressed in children with carrier state streptococcal infections. That is a really interesting result and something that has me wondering. I'll post more about this separately as this post is already pretty long.

 

 

Best regards,

 

Buster

[EAMom]

Yes, I also have a hard time believing that Kurlan/Singer's Tourette's kids really had PANDAS. He had a subset of chronically tic-ky/tourettey kids who reacted to strep (among other things...), perhaps more of a PITAND? I think most (if not all) of his supposed "PANDAS" kids would still have tourettes if GABHS did not exist.

 

If they did have PANDAS, they sure didn't have PANDAS like my daughter did...the debilitating OCD (not eating, not sleeping, missing school, psychotic, "possessed by evil demons" for months on end) kind of PANDAS. No sane parent with debilitating OCD PANDAS would be willing to monkey around with a study where prophylactic antibiotics aren't allowed and there is no possible benefit to the child (how fun, getting your blood drawn all the time). It's not like these kids got anything cool out of the study like IVIG or Azithromycin (as in Swedo's studies). The folks with severe OCD PANDAS are heading to people that really "get PANDAS" like Dr. K. or a good child psychiatrist....not some neurologist (Kurlan) who studies Tourettes.

[kim]

Buster,

 

Sorry for the delay in a huge "thank you" for that response. It would have taken me hours and hours to come up with anything close to that.

 

I'm hoping you will put some of your info on PANDAS on one thread, so we can ask Cheri to pin or sticky it at the top of the forum.

 

In light of this discussion, I want to bring up something that I have touched on here before. http://www.newscientist.com/article.ns?id=mg19426074.500

 

This article is is talking about N-acetylglucosamine (GlcNAc). This substance, in my mind, is almost certainly involved (an inability to synthesize properly) in my boys condition, which is not primarily PANDAS although we have had many problems involving strep and staph. Would love to discuss it in more detail, if anyone has the time or inclination. I should probably update some of what I'm talking about on a different thread here. It involves research relating to a bony tumor that my oldest son has and I've recently come across an article connecting GlcNac deficiency and hyperpigmentation which my oldest son also developed in an area on his back where he had a mole removed and developed staph.

 

I'm hoping that someone (with an awesome Dr.) will ask about this article in possible treatment for PANDAS kids. Interesting that they specifically talk about TH1 and T cells. I believe Crohn's is primarily thought to have problems in overactivation involving the TH1 arm also?

 

EAMom

 

This is something I ran across (saved) as I was looking for the glucosamine article. Since you mention your daughter not eating and anorexia was brought up recently by another poster, this just looks interesting.

 

http://lib.bioinfo.pl/pmid:17823502

 

Neuroendocrinology. 2007 Sep 7; : 17823502 (P,S,E, Regulation of Food Intake by Inflammatory Cytokines in the Brain.

 

Jessica B Buchanan, Rodney W Johnson

A number of inflammatory cytokines are synthesized and released after activation of the immune system. In addition to other biological effects, these cytokines can potently inhibit food intake. Cytokine-mediated inhibition of food intake is of particular importance because excessive production of peripheral inflammatory cytokines is often associated with the cachexia-anorexia syndrome seen in some chronic diseases. The weight loss in cachexia is associated with an increase in morbidity and mortality. Understanding how cytokines regulate food intake may be crucial in enhancing quality of life and facilitating recovery in patients exhibiting cachexia. This review describes the main inflammatory cytokines that influence food intake and explores how peripheral cytokines communicate with hypothalamic nuclei to influence feeding. Copyright © 2007 S. Karger AG, Basel.