Talk:PANDAS/Archive 2

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Editing process proposal

Now, my real question is should we create two subpages: a working draft page. So we have one -- it isn't the "published" article but sort of our working sandbox and a primary/secondary references page (basically our working list treated not as a talk but as an article). This way we can keep it up to date without having to keep to adding to bottom style of talk. I think these two changes will make this process a lot easier. Any objections?

Buster23 (talk) 18:55, 14 September 2009 (UTC)

Eubulides, I'm sorry to keep troubling you, but I just don't have access to a "real" computer while I travel. Would you set up auto archiving here now that we seem to be on a bit more of a normal track? I hope we'll no longer need manual archiving, but Archive 1 is more than full, with 200KB. Talk should work for most experienced editors, and I suspect it won't be hard to develop new text from here on, but setting up your own sandbox might be a shortcut for you to propose new text, Buster23. SandyGeorgia (Talk) 16:08, 18 September 2009 (UTC)
OK, I set up autoarchiving; currently for threads older than 4 weeks (though this can be easily adjusted). Eubulides (talk) 18:53, 18 September 2009 (UTC)

Pichichero 2009 sighted

I can confirm that Pichichero 2009 (PMID 19280860) is indeed in print. I have a copy. Haven't had a chance to read it yet (nor the recent changes here) but it does look quite good. 3 of its pages (in very small print) are citations. Eubulides (talk) 23:41, 14 September 2009 (UTC)

I will try to get a copy once I'm home, but see my comment in the primary sources section, concerned about balance, although I acknowledge I haven't yet read it. SandyGeorgia (Talk) 16:09, 18 September 2009 (UTC)

Sources

Primary sources

  • I left this listed here for a significant reason: anyone who hasn't read it and taken it on board may not have a full enough understanding of PANDAS to help collaboratively on this article. Although it is not a review article, everything that is says can also be sourced to other review articles (Singer, other Kurlan reviews, or other Yale Group reviews), and it is the easiest place to get an overview of the many methodological problems that plague the PANDAS hypothesis and the primary sources. As an example, Perlmutter was listed here earlier as "seminal" research, although it was well refuted by Singer. It seems that many of the researchers focusing on the OCD angle have not always had a solid understanding of the natural course of tic disorders, hence their work has been plagued with methodological problems (the Mell computer registry is another real problem from that angle ... a look at retrospective data from a computer registry simply cannot reflect the full range of TS due to ascertainment issues and most physicians not recognizing TS-only). I strongly recommend that anyone working on this article read and take on board this Kurlan article, as this content will need to be added to the article, and it can all be sourced to reviews. Also, I misstated something the other day ... Pichichero did not work with Kurlan, rather Murphy, so although I haven't yet read that article, it may need to be balanced by other reviews from researchers who may have less of a pro-PANDAS orientation. I've still not gained real internet access due to my travel, and may not be able to catch up on all of these sources for another week, but I urge balancing of Pichichero with Kurlan, Singer or Yale Group sources. SandyGeorgia (Talk) 15:36, 18 September 2009 (UTC)
  • If we list Kurlan2004, we need to list its rebuttal that was published in the same journal. (PMID 15060242). Referencing and using a recent secondary that critically reviewed both viewpoints for merit would be a better choice than relying on interpretation of contradicted primary research. Buster23 (talk) 02:35, 19 September 2009 (UTC)
  • You don't seem to have understood my previous post: listing a journal article on the talk page doesn't mean we will use it as a source for the Wiki article. Everything Kurlan said has also been written about and can be sourced to multiple secondary reviews and is covered by multiple recent reviews; it's just easier for editors working on this article to read it all in one place. SandyGeorgia (Talk) 05:37, 21 September 2009 (UTC)
  • I think I understood perfectly :-), I was just saying that if you want to help editors read good references by pointing them to the 2004, they should read also the rebuttal. Buster23 (talk) 17:18, 21 September 2009 (UTC)
  • Kurlan's text is covered and repeated by many secondary reviews; is Swedo's? Please provide one of our reliably sourced secondary reviews that backs up the Swedo rebuttal-- many secondary reviews report exactly what Kurlan reports. That was the only thing I was saying ... that Kurlan's article covers it well, but many reviews summarize the problems. SandyGeorgia (Talk) 18:45, 21 September 2009 (UTC)
  • Yes, GoogleScholar gives 70 citations to Swedo's commentary, and in our secondary reviews it is discussed in martino_2009, moretti_2008, pavone_2006, shulman_2009, Singer_2005 as well as the Snider2004 paper. Even Kurlan_2008 adjusts his position after the 2004 article as does Kaplan. Buster23 (talk) 21:35, 21 September 2009 (UTC)
Just checking, we're planning on not using these right? Buster23 (talk) 19:10, 15 September 2009 (UTC)
Right. We've got plenty of reviews. Eubulides (talk) 20:39, 15 September 2009 (UTC)
As discussed elsewhere, we will likely use the NIMH PANDAS treatment warning, unless we find mention of it in a review. SandyGeorgia (Talk) 05:46, 16 September 2009 (UTC)
Well, I found this one from the Kalra2009 review, "Because IVIG and plasma exchange both carry a substantial risk of adverse effects, use of these modalities should be reserved for children with particularly severe symptoms and a clear-cut PANDAS presentation."Buster23 (talk) 05:54, 16 September 2009 (UTC)
That wording is troubling, and doesn't say what the warning said. (What is a "clear-cut PANDAS presentation" according to Kalra, btw? All parents think their children's "PANDAS" is severe, so I wonder how this wording, in relation to the original warning, is helpful? ) SandyGeorgia (Talk) 06:07, 16 September 2009 (UTC)
I suppose we could quote Gerber2009 who has the statement from the AHA "Until carefully designed and well-controlled studies have established a causal relationship between PANDAS and GAS infections, the committee does not recommend routine laboratory testing for GAS to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (eg, intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder (Class III, LOE B)." As far as I can find so far, that's as strong as it gets. Buster23 (talk) 06:28, 16 September 2009 (UTC)
Looks like the message is changing a bit since the 2000 notice. Here's from Gordon2009: "Immune therapies, such as corticosteroids [36], intravenous immunoglobulin, and plasma exchange can be considered in selected patients with both Sydenham’s chorea and PANDAS [16], in view of their side effects such as headache and vomiting, not as a routine. Cardoso et al. [25] tried the effect of intravenous methylprednisolone followed by oral prednisolone and reported favourably on the results when given to refractory patients, and Garvey et al. [37] found that the response to treatment was better when immunoglobulin and plasma exchange were used, than with prednisone. Buster23 (talk) 17:51, 16 September 2009 (UTC)
Please see Shprecher listed in our review section: "The Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) hypothesis suggested that chronic, recurrent tics and OCD can arise as an autoimmune sequela of infection with group A beta-hemolytic streptococcus.[111] In our opinion, there is insufficient evidence to conclude that streptococcal infection has a true etiological role in causing tics. We recommend that children with documented streptococcal infections be treated with an appropriate course of antibiotics, but that treatment with chronic antibiotics or immune-modifying therapies like plasma exchange or intravenous immune globulin are not justified based on existing evidence." I am strongly opposed to removing the text of the NIH/TSA message until better evidence for dangerous and unproven therapies emerges or reliable sources endorse it. SandyGeorgia (Talk) 15:46, 18 September 2009 (UTC)
And I'm strongly opposed to its use unless it comes from a proper secondary without interpretation. I'm fine with using the Kalra2009, Shprecher or Gerber2009 quote if you wish but will object to citing an archived website from 2000 with broken links or a press release given all the secondary research. We agreed early on to use secondary articles. Surely given over 30 secondary papers, there's one we can quote. Buster23 (talk) 02:56, 20 September 2009 (UTC)
Since the issue is covered by many secondary reliable reviews, keeping the original text of the original warning from the very authors of the PANDAS hypothesis out of the article would require some strange reasoning. This is precisely when we would prefer to reference the primary source, since secondary reviews cover the issues (as but one example, see Singer, PANDAS, a commentary, there are others, but that is one I have with me on this trip). SandyGeorgia (Talk) 05:37, 21 September 2009 (UTC)
I'm fine with an exact quote (which said to restrict to clinical trials) or to use the latest surveys that add 10 years of reasoned opinion. The original quote was in response to an inrush from the annoucement of the Perlmutter results, 10 years have passed since then. Please make sure that what we quote represents the "current" position and not something from 10 years ago. Buster23 (talk) 17:18, 21 September 2009 (UTC)

Reviews

Excerpts

Swerdlow, in his journal paper as the outgoing chair of the Tourette Syndrome Association Medical Advisory Board, described well the desperation this hypothesis has engendered among Internet-armed parents of children with tics:

... perhaps the most controversial putative TS trigger is exposure to streptococcal infections. The ubiquity of strep throats, the tremendous societal implications of over-treatment (eg, antibiotic resistance or immunosuppressant side effects) versus medical implications of under-treatment (eg, potentially irreversible autoimmune neurologic injury) are serious matters. With the level of desperation among Internet-armed parents, this controversy has sparked contentious disagreements, too often lacking both objectivity and civility. PMID 16131414

SandyGeorgia (Talk) 21:30, 2 December 2008 (UTC)

I'll add some excerpts to highlight some of the basic problems and inherent biases in this article. One of the main problem with uncontrolled studies of PANDAS:

Singer PMID 12842229
Although patients with tic disorders generally have a slow, more gradually evolving pattern of tics, abrupt changes are not uncommon. In a study of 80 consecutive unselected children with tic disorders, a structured clinical interview found that 42 of 80 (53%) had the sudden explosive onset or worsening of their tic symptoms. This same study also raised the issue of parent bias being a confounding factor; 78% of informants who described an offspring with abrupt onset of tics induced by a streptococcal infection were knowledgeable about PANDAS, compared with only 21% in the group that denied any association.
Singer [1]
As for the strep-tic link, that may be coincidental. "In any population of children, both tics and strep infections are common. Some will have them both. Are the two related?" asks Singer. "Perhaps. Did one cause the other? We don't know.
"People are drawn to simple explanations for complex neuropsychiatric problems," he says. "In Tourette syndrome, most parents would rather you say that their child's disease is due to infection than to inheritance."
From Swain (Yale Group) PMID 17667475
There is too much to excerpt all of it. One paragraph:
In contrast, unselected TS cases followed longitudinally for 1 year (Luo et al., 2004) indicated no more than a chance association between newly acquired GABHS infections and tic symptom exacerbations. Similarly, in a case-control study Perrin et al. (2004) found little evidence of increased tic or OC symptoms in the aftermath of well-documented (and treated) GABHS infections, casting some doubt on the hypothesis. To date, treatments based on the molecular mimicry hypothesis have been nonspecific, the results have been inconsistent (Hoekstra et al., 2004b; Perlmutter et al., 1999) and the data concerning antibiotic prophylaxis have not been particularly compelling (Garvey et al., 1999; Snider et al., 2005).
Kurlan PMID 15060240
Regarding the Murphy Pichichero results, points out that:
... report suggesting improvement of new-onset of acute exacerbations of symptoms in such children with antibiotics provides inadequate support for such an approach, because treatment was not placebo-controlled and was unblinded. It is well known in treatment studies of TS that there is a substantial placebo effect; the natural course of TS and OCD is such that exacerbatoins are followed by remissions. This latter phenomenon of "reversion to the mean" implies that virtually any intervention at the time of peak symptoms may seem successful. Only a double-blind, placebo-controlled study can identify a true therapeutic effect.
Another reason to feel comfortable with avoiding antibiotic treatment for these patients is that, to date, no cases have been reported to develop any rheumatic carditis as occurs in patients with Sydenham's chorea. This is a very important point to remember, because some have attempted to relate this syndrome to rheumatic fever. It is recognized that as many as one third of patients with Sydenham's chorea ultimately will have evidence of rheumatic valvular heart disease. This issue requires additional investigation, because the lack of heart disease strongly argues against a relationship between PANDAS and Sydenham's chorea or other forsm of rheumatic fever.
The degree of clinical change required for recognizing exacerbations to distinguish a "PANDAS-like process" from the typical course of more established tic and OCDs has not been differentiated or quantitated adequately. For example, one recent study of 80 consecutively examined (unselected) patients in a tic-disorders clinic found that 53% reported sudden, explosive onset of worsening of their tics. These patients were not considered to have met criteria for a diagnosis of PANDAS. Preliminary evaluation of our own ongoing, case-control epidemiologic study of PANDAS indicated that 36% of the carefully selected control subjects (who had no recognized link between symptoms and GABHS infection) also reported an abrupt onset or dramatic exacerbations (R. Kurlan, MD, unpublished data, 2003). Thus, clinical course does not seem particularly useful in distinguishing patients suspected of PANDAS from children with more typical cases of TS or OCD.
From Singer, PMID 15721825
In 1998, Swedo and colleagues90 proposed that a subset of children with tic disorders, OCD, or both had an abrupt exacerbation of symptoms at about the same time as a streptococcal infection. Labelled as paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), the notion of this entity is controversial.91,92 Support for PANDAS is derived from the description of additional cohorts,93 familial studies showing that first-degree relatives of children with PANDAS have higher rates of tic disorders and OCD than do those in the general population,94 and expanded expression of a trait marker for susceptibility in rheumatic fever (the monoclonal antibody D8/17) in individuals with PANDAS.95
Despite these findings, debate about the existence of PANDAS continues.92,96,97 No prospective epidemiological study has confirmed that an antecedent Group A beta haemolytic streptococcal (GABHS) infection is specifically associated with either the onset or exacerbation of tic disorders or OCD. Diagnostic criteria for PANDAS are potentially confounded by the phenotypic variability commonly associated with tic disorders, such as a normal fluctuation in the frequency and severity of symptoms, exacerbation of tics by stress, fatigue, and illness, occurrence of “sudden, abrupt” onset and recurrence of tics in patients without PANDAS,98 and the absence of a precise definition for associated neurological disorders. Additionally, longitudinal laboratory data, rather than studies that use only a throat culture or only a single antistreptolysin O or antideoxyribonuclease B titre, are necessary to confirm the presence of a previous GABHS infection. Two prospective longitudinal studies showed no clear relation between new GABHS infections and the development or exacerbation of tic or OCD symptoms.12,99
According to a model proposed for Sydenham’s chorea, it is hypothesised that the underlying pathology in PANDAS involves an immune-mediated mechanism with molecular mimicry.90 Antibodies produced against GABHS are believed to cross-react with neuronal tissue in specific brain regions (ie, become antineuronal antibodies) and result in tic or behavioural symptoms or both. A single study that examined the response of patients with PANDAS to immunomodulatory therapy supports this hypothesis.100 In this partially double-blind protocol, the severity of obsessive-compulsive symptoms improved after either plasmapheresis or intravenous immunoglobulin treatment, and tics were reduced after plasmapheresis.
Antineuronal antibodies have been assessed in patients with PANDAS with variable results. Pooled data from 40 children with movement disorders associated with streptococcal infections (20 with PANDAS, 16 with Sydenham’s chorea, and four with “idiopathic” movement disorders) suggest that this cohort can be differentiated from various disease controls by ELISA and western immunoblotting.101 In frozen tissue, by use of a colorimetric assay, only a few bands were detected in controls (limited reactivity against any basal ganglia antigens), but substantially more bands (at 60 kDa, 45 kDa, and 40 kDa) were found in patients after streptococcal infection. By contrast, other investigators who have used several different epitopes, including supernatant, pellet, and synaptosomal fractions from homogenised fresh human post-mortem caudate, putamen, and globus pallidus, were unable to distinguish 15 patients with PANDAS from controls.102 Additionally, comparison of serum antineuronal antibodies against supernatant fractions from fresh adult post-mortem caudate, putamen, and prefrontal cortex (Brodmann’s area 10) in 48 children with PANDAS to similar fractions in 46 children with TS did not find differences in ELISA optical density values or bands identified on immunoblotting in any brain region.103 Furthermore, the microinfusion of serum samples from children with PANDAS into rodent striatum does not reliably change the number of observed motor stereotypy behaviours.104,10
Singer PMID 12842229

Conclusion

The originators of the PANDAS diagnosis had the laudable goal of defining a clinical syndrome in which a subset of individuals with diagnoses of tic disorders and/or OCD could be subcategorized based on the induction of symptoms after a GABHS infection. This concept has generated broad interest from divergent groups and caused many physicians to become polarized on opposing sides of the issue. If true, identification of factors that convey susceptibility or render the host less susceptible would be a major advance. Our goal in this manuscript was not to confirm or refute the diagnosis, but rather to discuss the numerous challenges that persist. As noted, despite claims of a distinct clinical syndrome, multiple areas of concern remain, involving the current diagnostic criteria and the presumed mechanism of pathogenesis. We suggest that confirmation will require careful longitudinal studies of sufficient size to establish significance. Additionally, until further clarification is available, treatment should continue to focus on the use of standard approaches to control symptoms. Although there is the risk of delaying potential advances, there is a longstanding rationale to support the concept of "putting the horse before the cart." Along with the scientific community, we anxiously await the result of longitudinal case-controlled studies now in progress.

Introduction

Advocates for the PANDAS disorder emphasize its clinical and laboratory similarities to Sydenham's chorea (SC), a manifestation of rheumatic fever (RF) [2]. In contrast, those who question the existence of this condition cite concerns with its diagnostic criteria and the lack of evidence confirming an association between group A-hemolytic streptococcal (GABHS) infection and tics/OCD [3].
The expanding list of proposed environmental factors that may alter the presentation or exacerbation of tics includes low birth weight, nonspecific maternal emotional stress, severity of maternal nausea and vomiting during pregnancy, pre- or postnatal exposure to drugs or toxins, hyperthermia, allergens, and infections [34]. The recognition that infection, fever, and medications can exacerbate tics has important implications for establishing strict definitional criteria for PANDAS. More specifically, we contend that, until other clinical or laboratory markers are available to distinguish tic disorders from PANDAS, the presence of tics before any infection-related exacerbation should exclude the diagnosis of a primary post-infectious etiology, i.e., PANDAS.

Challenges for PANDAS

The existence of PANDAS is not free of controversy [3]. A variety of diagnostic shortcomings have been identified, as has the lack of other classical features often associated with RF. Despite these limitations, a major deficiency is the absence of a prospective epidemiologic study confirming that an antecedent GABHS infection is associated with either the onset or exacerbation of tic disorders (or OCD). Two NIH-funded multicenter studies, designed to address these critical issues, are currently in progress.
Although patients with tic disorders generally have a slow, more gradually evolving pattern of tics, abrupt changes are not uncommon. In a study of 80 consecutive unselected children with tic disorders, a structured clinical interview found that 42 of 80 (53%) had the sudden explosive onset or worsening of their tic symptoms [56]. This same study also raised the issue of parent bias being a confounding factor; 78% of informants who described an offspring with abrupt onset of tics induced by a streptococcal infection were knowledgeable about PANDAS, compared with only 21% in the group that denied any association.
Additional difficulties in confirming a temporal association with a GABHS infection include a positive throat culture in an asymptomatic carrier and the misinterpretation of a single ASO or antiDNAse-B determination. Too often, clinicians fail to recall the warning of Swedo et al. [1] that "positive antistreptococcal titers obtained at the time of a single exacerbation are not sufficient to prove that a child has PANDAS." Longitudinal laboratory data, rather than just an isolated throat culture or antistreptococcal antibody titer, are necessary to demonstrate that a GABHS infection is associated with PANDAS, i.e., rising titers with symptom exacerbation and falling titers with symptom remission.

Other challenges

Several clinical studies are occasionally cited as supporting evidence for PANDAS, but the data actually have little relevance. For example, based on the postulated role of GABHS in the pathogenesis of PANDAS, researchers have sought to identify whether individuals with a tic disorder have increased levels of streptococcal antibodies.
In each study, however, there was no correlation between levels of antistreptococcal titers and clinical symptoms.

SandyGeorgia (Talk) 00:29, 3 December 2008 (UTC)

I was wondering whether we should perhaps archive this section since it was from 10 months ago and we've now refreshed to new reviews? Seems to be mixing primary and secondary papers. Buster23 (talk) 20:56, 22 September 2009 (UTC)

No. We've got automatic archiving in place now, so unless the page grows unusually large again, there should be no need to manually archive. And I'm still planning to use some of this. SandyGeorgia (Talk) 23:04, 22 September 2009 (UTC)

Classification 3

Here's yet another draft of a Classification section. It assumes a Venn diagram that we'd have to draw, from the info in the source. It's probably too long but I haven't had time to shorten it. Comments are welcome.


PANDAS is hypothesized to be caused by an autoimmune disorder that results in a variable combination of tics, obsessions, compulsions, and other symptoms that may be severe enough to qualify for diagnoses such as chronic tic disorder, OCD, and Tourette's. The cause is thought to be akin to that of Sydenham's chorea, which is known to result from childhood Group A streptococcal (GAS) infection leading to the autoimmune disorder acute rheumatic fever of which Sydenham's is one manifestation. Like Sydenham's, PANDAS is thought to involve autoimmunity to the brain's basal ganglia. Unlike Sydenham's, PANDAS is not associated with other manifestations of acute rheumatic fever, such as inflammation of the heart.[1]

PANDAS has not been validated as a disease classification, for several reasons. Its proposed age of onset and clinical features reflect a particular group of patients chosen for research studies, with no systematic studies of the possible relationship of GAS to other neurologic symptoms. There is controversy over whether its symptom of choreiform movements is distinct from the similar movements of Sydenham's. It is not known whether the pattern of abrupt onset is specific to PANDAS. Finally, there is controversy over whether there is a temporal relationship between GAS infections and PANDAS symptoms.[1]

(end of draft) Eubulides (talk) 08:57, 15 September 2009 (UTC) updated as discussed below 02:23, 18 September 2009 (UTC) / 20:46, 21 September 2009 (UTC) / 04:45, 22 September 2009 (UTC) / 05:58, 22 September 2009 (UTC)'

Eubulides, does the artwork figure I provided provide what you were seeking? I couldn't tell if you were saying that we should draw the diagram from a clinical presentaton (i.e., comorbidity) -- which is how it is drawn? Or from some other perspective. I like the comment about:

  • "OCD and chronic tic disorders intersect but neither is a subset of the other."
  • "Tic-related OCD is their intersection." Shouldn't this be Tics with OCD co-morbidity or OCD with tic comorbidity. I'm not sure which becomes the primary diagnosis here. Probably depends on whether someone visits a neurologist.
  • "PANDAS is a small subset of the union of OCD and tic disorders". Yes.
  • "and is in all three subregions of their union." Yes.

Doesn't Leckman 2009 also indicate exacerbation measured in terms of YGTSS or CYBOCS in his paper. I don't have it infront of me. I know that that's how Kurlan measured it in Kurlan 2008.

So, how do we bring in the Sydenham chorea into the picture, does Leckman adress that too? Did you have any comment on my earlier Classification. I saw SandyGeorgia's but wasn't sure what you thought. Buster23 (talk) 14:43, 15 September 2009 (UTC)

There's a great picture in Miguel et all 2005 (PMID 15611786) -- already in our primary list. That has the basic overlaps. I like this article because it has a series of phenotypes separating out Early-onset OCD phenotype versus tic related OCD phenotypes. It also covers tic related and has a figure with Strep Infection related correlations. Buster23 (talk) 17:10, 15 September 2009 (UTC)

  • Figure 1 in Miguel et al. 2005 (PMID 15611786) is about OCD, and doesn't mention PANDAS. A better figure is Figure 1 of Leckman et al. 2009 (PMID 19432385), which is specifically about PANDAS. The proposal is to redraw that figure, omitting familial non-tic-related OCD removed for simplicity. The style used in the artwork on this talk page is fine, but the content has to be taken directly from a reliable source (in this case Leckman et al.).
  • As far as I can see from a quick scan, Leckman et al. doesn't talk about exacerbation. That source is freely readable on the web, by the way, in the journal's full issue (PDF). Leckman et al. does review Kurlan et al. 2008 (PMID 18519489).
  • The draft above mentions Sydenham's chorea, and cites Pichichero 2009 (PMID 19280860). Leckman et al. don't discuss that topic, as it's mostly about OCD.
Eubulides (talk) 20:39, 15 September 2009 (UTC)

:: I get your point and wasn't disagreeing. I was, however, also trying not to do synthesis in the combination. So in Miguel there is a picture that has strep infections on it -- it doesn't use the expression PANDAS in the image, but does in the text.

I'm not really arguing here, just trying to find a good picture or enough text that we can craft one without "synthesis" -- tough to do :-)

Buster23 (talk) 20:46, 15 September 2009 (UTC)

Just saw Leckmann picture (thank you for the paper reference). Wow! Perfect, exactly what I was trying to convey. The only disagreement I have with the picture is that he highlighted chronic tic disorders rather than just tic disorders. While his diagram is correct, it misses the population of transient tic disorders. Really good though. Thanks.

Buster23 (talk) 22:59, 15 September 2009 (UTC)

Eubulides, I haven't yet been able to gain access to print any of the new articles, have a miserably slow dialup now, and was only able to briefly scan Leckman2009. I am aware of the thinking wrt subsets of tics, OCs and TS, but where in the paper does he say that PANDAS is also thought to be subdivided into those three subtypes? I couldn't find it ... would you pull out that piece for me? Concerned since Singer seems to refute that thinking. I will continue trying to catch up, but connectivity is difficult. I'm troubled that Mell, which was only a computer registry, hence likely missed *most* TS and had numerous easily spotted flaws, is cited, but it is what it is. SandyGeorgia (Talk) 23:23, 16 September 2009 (UTC)
Please see figure 1. That defines 3 subbands: Sporadic OCD-only PANDAS, tic-related OCD PANDAS, and Chronic tic disorder-only PANDAS. This abbreviates to OCD-only PANDAS, tic-related OCD PANDAS and tic-disorder-only PANDAS. Buster23 (talk) 01:49, 17 September 2009 (UTC)
Figure 1 defines subtypes of tic-related OCD, not PANDAS subtypes (which is my question -- I'm aware of the thinking on a subset of OCD being tic-related, but have not seen that applied to PANDAS, and the proposed text seems to go beyond what the source says, although I acknowledge I haven't fully caught up -- but it's giving a credence to PANDAS that I've not yet encountered). The caption also describes OCD, not PANDAS, and is tentative on PANDAS (the article is, after all, the familiar description of tic-related OCD subtypes): "Venn diagram of obsessive-compulsive subtypes. In addition to adult-onset obsessive-compulsive disorder (OCD), there appear to be several subtypes of early-onset OCD. These include cases with a personal or family history of Tourette syndrome or a chronic tic disorder, as well as individuals without tics but with a strong family history of OCD. Other cases are sporadic, and some cases may reflect a postinfectious autoimmune disorder (pediatric autoimmune disorders associated with streptcoccal infections, PANDAS)." The caption does not reflect subtypes of PANDAS; is it elsewhere in the article? OCD subtypes is not the same as PANDAS subtypes, so unless this is mentioned elsewhere, I'm confused. SandyGeorgia (Talk) 02:58, 17 September 2009 (UTC)
Hi SandyGeorgia, I can't tell whether you are having difficulties with how to read a venn diagram or something else. This is a math problem involving intersections and unions. Buster23 (talk) 03:08, 17 September 2009 (UTC)
I assure you, I know how to read a Venn diagram (just ask Jankovic, who printed an erroneous one in the NEJM). Unless there is text describing three proposed sub-types of PANDAS, I suspect you may be overinterpreting the diagram; the caption is clear, and it is subtypes of OCD that has long been proposed by the Yale Group. Is there text somewhere supporting subtypes of PANDAS, as opposed to subtypes of OCD? The PANDAS hypothesis does not yet have enough acceptance to be branching into subtypes, AFAIK. SandyGeorgia (Talk) 03:11, 17 September 2009 (UTC)
I sort of figured you would :-) Which is why I was surprised by your comment. A math problem is not interpretation per WP:SYN. Are you actually arguing this? Buster23 (talk) 03:37, 17 September 2009 (UTC)
I have been reading Jim Leckman's-- and the Yale Group's writings on subtypes of OCD-- for at least 15 years. This is not a math problem. This is a question of whether you are overinterpreting a Venn diagram. It's very simple; do we have some text which indicates that the Yale Group (or anyone) is proposing subtypes of PANDAS? The caption to that Venn diagram does not, and I suspect you are overinterpreting what Leckman is saying. If there is some text to back up your interpretation of the Venn, that will solve that; it certainly won't be the first or last time interpretation or development of a Venn diagram led to misunderstanding (reference the Jankovic Venn in the NEJM, which was decidedly wrong). SandyGeorgia (Talk) 05:03, 17 September 2009 (UTC)
A better figure is Figure 1 of Leckman et al. 2009 (PMID 19432385), which is specifically about PANDAS. Eubulides, it's labeled as being about OCD, not PANDAS, and the caption also is about subtypes of OCD, not PANDAS-- I haven't yet gotten through all the (newer) literature that you have, so you may have something new I haven't seen yet, but I've not ever before encountered this notion of subtypes of PANDAS, so if you have some supportive text indicating researchers are now talking about subtypes of PANDAS, that will help settle my concern that we're overinterpreting Leckman's intent with that diagram. SandyGeorgia (Talk) 05:33, 17 September 2009 (UTC)
SandyGeorgia, I'll wait for Eubulides to weigh in here. I'm missing what is your actual concern. Let me ignore the picture for a moment and go back to the definition. The definition of PANDAS has a first critierion that is "Presence of obsessive–compulsive disorder and/or a tic disorder". The expression and/or is a logical disjuction. A statement of "Presence of A and/or B" means that either A-only is present, B-only is present, or A and B are present. Are you objecting to the word "sub-type" or to the separation of patients with OCD-only, tic-only and tic-related OCD? Buster23 (talk) 00:07, 18 September 2009 (UTC)
In reviewing Leckman et al. I agree that my draft had original research in mentioning a subclassification that is not mentioned in the original. I've rewritten the text to avoid that. The proposed figure could still stay, though, no? as it's better sourced. Eubulides (talk) 02:23, 18 September 2009 (UTC)
Looks good now; we just can't be implying there is an etiological distinction where researchers haven't explicitly stated as such. Which figure do you want to keep? A version of the Leckman Venn? Since it's sourced and not OR, I wouldn't see a problem with that, although I'm so murky on images, I'm not sure how we draw that without violating copyright ... but I'm sure you're up on that. SandyGeorgia (Talk) 05:32, 18 September 2009 (UTC)
Graham and Fvasconcellos are good at diagrams. Graham does PNGs and Fvasconcellos does SVGs. Colin°Talk 17:34, 18 September 2009 (UTC)
The idea was to do the Leckman et al. Venn. I proposed simplifying it a bit, but could easily be talked into doing the whole thing (it's not that complicated). We can't clone the presentation, but we can clone the idea. Eubulides (talk) 18:53, 18 September 2009 (UTC)
Sounds good, thanks for everything, I'm off til Monday now. SandyGeorgia (Talk) 19:00, 18 September 2009 (UTC)

Trying to clarify for Buster23 before I go; getting used to writing on Wiki can be a challenge, and this article is a very hard place to start, because it's a difficult, contentious and controversial topic. The subgroups of PANDAS text was clearly original research, and we have to be very careful to stick closely to sources. PANDAS is an unproven hypothesis, not in the DSM. There is widespread medical consensus that OCD is probably not a homogeneous condition, and that there are likely subsets, but neither is that in the DSM, it is also still a hypothesis, albeit one with wide support and good evidence. Adding together subsets of OCD to deduce subsets of PANDAS is *surely* not what Leckman intended, and using only a Venn to deduce that is walking a fine line of original research, particularly in the absence of text stating explicitly that was his intent ... implying etiological differences of one hypothesis on top of another hypothesis is really stretching too thin. It defies me why so many researchers get Venn diagrams wrong, but we surely have evidence of that in the Jankovic Venn diagram published by the NEJM, which blatantly and incorrectly defined TS as occurring at the intersection of tics, OCD, ADHD and behavioral disorders. SandyGeorgia (Talk) 19:10, 18 September 2009 (UTC)

Thanks for the directed note. I thought it curious that you had jump to etiological differences as that seems to be overreading the diagram -- whereas the statement that there are children meeting the criteria with tic-only or OCD-only symptoms is a direct reading of the diagram.
However, let's pull back to definitional terms. Pandas is defined with a first critieria of "Presence of obsessive–compulsive disorder and/or a tic disorder". This can be represented with the simple picture:

Buster23 (talk) 01:34, 20 September 2009 (UTC)

It's better to use an SVG diagram, which I've now done in the draft. Eubulides (talk) 20:46, 21 September 2009 (UTC)
I'm happy to make it a .SVG, but we have to go back to the definition as the concensus is that PANDAS is defined to be a subset of OCD and/or tic disorders (not just chronic tic disorders). Buster23 (talk) 03:14, 22 September 2009 (UTC)

PANDAS has not been validated

I'm copying this comment from User talk:Eubulides #PANDAS, as the comment is about this article and not about me:

Hello, Eubulides, I'm still tracking down a copy of Pichichero2009. It has been somewhat difficult to find (although strangely seems to at a couple of used book stores already :-)). There's a line in the classification section you wrote and I wonder what the original text being cited said. You wrote "PANDAS has not been validated as a classification of diseases, for several reasons." Does Pichichero2009 actually say that? Regards, Buster23 (talk) 03:40, 18 September 2009 (UTC)

Yeah, there are what? 300 copies of that paper in the world? Sheesh, why didn't Pichichero just hide it under his mattress? Anyway, what Pichichero 2009 (PMID 19280860) actually says on page 211 is "PANDAS is not yet a validated nosological construct (Table 4)." My attempt to translate this medical jargon into English is "PANDAS has not been validated as a classification of diseases, for several reasons." Pichichero's Table 4 contains the several reasons. Eubulides (talk) 18:53, 18 September 2009 (UTC)

And there's more to be found in other reviews lest we want to expand. SandyGeorgia (Talk) 19:01, 18 September 2009 (UTC)
On rereading it it's probably better to say "disease classification" instead of "classification of diseases", so I reworded it that way. This draft has been sitting around with only very small changes for quite some time; it sound's like it's ripe to go in. Eubulides (talk) 20:46, 21 September 2009 (UTC)
Looks good enough from here ... if I were home, I'd put up a number of excerpts from which we could further tweak the writing, but what you've offered (including the SVG) looks fine. SandyGeorgia (Talk) 20:53, 21 September 2009 (UTC)
Re-reading now. On the picture, I would have preferred to use the one I provided (although I can convert it to SVG if you prefer) as the image you provided only lists PANDAS as covering chronic tic disorders. non-chronic tic disorders are also covered by PANDAS but that is missing from the picture. I'm probably 4 days away from getting my hands on Pichichero's paper. Can we wait till then? I suppose we can put the text in and then adjust, but I'd sure like to see what Pichichero says. I'm surprised that he did not cite any of the papers that found an association or supported an auto-immune pathogenisis -- but not having the article, I can't confirm. My understanding is that we're trying not to mix reviews here so as to not create original research, so if Pichichero is it, I'd love a one pass over it. Are you translating a particular section or the overall report? Updated Buster23 (talk) 21:50, 21 September 2009 (UTC)
Fig. 1 in the source (Leckman et al. 2009, PMID 19432385) puts PANDAS as a subset of chronic tic disorders (or OCD), which is why I did the diagram that way. I'm reluctant to change the diagram unless we have a recent review that directly supports the revised diagram. Pichichero 2009 (PMID 19280860) spends more than a page on pathogenesis and cites several sources, but that's material for the yet-to-be-written Mechanism section, not for Classification. Naturally we can edit the text later. It is OK for the article to cite multiple reviews; our goal should be to cite the best sources available, and typically a single review won't be the best source for all aspects of a topic. Eubulides (talk) 22:58, 21 September 2009 (UTC)
The figure as it stands is asserting that PANDAS is a subset of OCD and/or chronic tic disorders. I can find no text supporting that position. I can find text supporting that PANDAS is a subset of OCD and/or tic disorders. Again, my recommendation is to not use the article, but the definition from the first critierion of the PANDAS definition. Buster23 (talk) 03:11, 22 September 2009 (UTC)
  • We obviously have a reliable and high-quality source that directly supports the position. Which reliable source disagrees with the position? (A source that merely says "PANDAS is a subset of OCD and/or tic disorders" does not disagree with the position, since chronic tic disorders are a subset of tic disorders.) That is, which reliable source says that PANDAS is also hypothesized to cause the symptoms of someone who has a tic disorder that is not chronic, and who also has neither OCD nor a chronic tic disorder? If so, we could add that disagreement among reliable sources to the caption.
  • In the meantime, is the only objection to the image? If so, we can add Classification without the image for now, and work on the image later.
Eubulides (talk) 03:29, 22 September 2009 (UTC)
Well, wouldn't all the work by Kurlan and Singer which pulled subjects diagnosed with Tourette's syndrome be explicitly a contradiction. They asserted in Kurlan_2008 that the children met the PANDAS critieria. But the children were diagnosed with Tourette's syndrome and not a tic disorder. Chronic tic disorder is considered a separate diagnosis from Tourette's syndrome. Is that enough? Or shall I pull explicit language? (I'm fine doing so). I appreciate the way you are making the argument and will walk though the lines. On the classification, is "dance-like" actually the definition used by Pichichero 2009 for choreiform? That most certainly isn't the typical definition which is usually described as piano playing movements in a stressed stance. Buster23 (talk) 03:55, 22 September 2009 (UTC)
That's no contradiction, because Tourette syndrome is one of the chronic tic disorders. Pichichero doesn't say "dance-like"; that was my quick translation from jargon into English based on etymology, but I agree that it can be improved. I changed it to "involuntary and jerky". Eubulides (talk) 04:45, 22 September 2009 (UTC)
Well, I guess Lombroso2008 says that Tourette's syndrome is a chronic tic disorder, "The prevalence of chronic tic disorders, including TS, is between 2 and 4%". Sorry, I thought Sandy was arguing before that these were distinct diagnosis. Okay, So it would only be transient tics not included. Lombroso2008 also says "(3) a history of a sudden onset of symptoms and/or an episodic course with abrupt symptom exacerbation interspersed with periods of partial or complete remission; " the complete remission would remove a chronic tic diagnosis. Similarly deOliverira2007 says "Patients have an uneventful recovery for weeks or months until a new streptococcal infection causes a new outbreak of tics and OCD, characterizing a clinical course with remissions and relapses." This would not qualify under chronic tic condition. Is that enough? Buster23 (talk) 04:49, 22 September 2009 (UTC)
This is getting uncomfortable; why not just ditch the diagrams? I'm actually wondering ... aloud, since I don't have all of my papers here while I'm traveling ... if we are correct in showing tic-related OCD as the intersection of tics and OCD. I am not certain on this (since I'm traveling and don't have all of my papers), but tic-related OCD is thought by some to be a subset of OCD and others to be a subset of tic disorders ... I'm not certain it's thought by medical consensus to occur at the intersection. Could be wrong there, but this whole business of splitting hairs to draw diagrams is making me uneasy. But, yes, chronic tic disorder is a term defined quite distinctly from TS in the TS jargon ... see tic disorder. SandyGeorgia (Talk) 04:53, 22 September 2009 (UTC)
I agree that Lombroso2008 contradicts Leckman et al. 2009. Rather than insisting on the chronic tic disorder, I have removed the diagram and reworded the lead to be more vague (and I hope more reflective of the consensus among reliable sources). Eubulides (talk) 05:58, 22 September 2009 (UTC)

Eubulides, "involuntary and jerky" are not terms that are usually used with choreiform movements. They tend to be complex (such as the classic piano playing motion in a stressed stance with arms extended and extended tongue). Do you want me to find you a reference for choreiform movements. They really aren't how you describe them. They are also unlike the writhing and non-stereotype full chorea. There several references online that I can track down.Buster23 (talk) 05:08, 22 September 2009 (UTC)

Here's a nice summary on choreiform [2] Buster23 (talk) 05:22, 22 September 2009 (UTC)
If "involuntary and jerky" isn't a good phrase, then what would be a good phrase? This section is not the place to go into a lengthy discussion on choreiform movements. On the contrary, when the article is written, I expect that Classification will simply defer to Signs and symptoms for details about choreiform movements. In the meantime, as this appears to be a point of contention, I have simply removed the definition. About the controversy in this area, Pichichero writes in his Table 4 summarizing the controversy: "Patients in original cohort with 'choreiform' movements may have actually been cases of Sydenham's chorea." as the criticism, and "Choreiform movements in PANDAS children are fine piano-playing movements of fingers, not the writing adventitious movements seen in Sydenham's chorea." as the supportive statement. Eubulides (talk) 05:58, 22 September 2009 (UTC)
I'd be fine leaving the actual term rather than interpreting it. Pichichero is making a good point that perhaps a lot of the PANDAS cases are actually poorly diagnosed chorea. I started searching for when is something chorea and when isn't it. I'm not finding a clear definition. Are you okay with just leaving what you had and putting in choreiform movements and then defining that term later in signs/symptoms?
I might also be missing what goes in a classification section. Shouldn't we be distinguishing it from other diseases such as ADEM, SC, and Tourettes? For ADEM, there are not the white lesions and demylination, for SC, there isn't the chorea or ARF, for Tourettes there is remission and a sawtooth pattern. Don't these things also belong in classification section?Buster23 (talk) 06:15, 22 September 2009 (UTC)
Yes, my thought was to just say "choreiform" without defining it, as is done in the current draft. Pichichero did not discuss the relationship between PANDAS and ADEM, so the draft doesn't either. (The draft also does not discuss autism, separation anxiety disorder, and other disorders that have been speculated to be variants of PANDAS, for the same reason.) Pichichero did discuss SC and Tourette's, so the draft discusses that. The Classification section is not intended to cover differential diagnosis; that's for Diagnosis. Eubulides (talk) 06:37, 22 September 2009 (UTC)
Sorry, our edits crossed so I didn't see yours before my comment. So in classification, are we trying to classify by symptoms, by proposed pathogenesis, or by parentage (i.e., tics and/or OCD diagnosis). Also, you said controversy in your interpretation of Pichichero (I've got to get my hands on it), does it actually say that there is controversy on whether the choreiform movements are undiagnosed chorea or is it saying that it is unknown whether a misdiagnosis occurred. Controversy requires (typically) proof on both sides. Was there offered proof? I think I'm fine with the text pending getting a copy of Pichichero. I just want to check that we're representing what he's actually saying. Buster23 (talk) 06:46, 22 September 2009 (UTC)
Classification can be done by any of the schemes your comment mentioned. The draft tries to do it the way Pichichero does it. PANDAS lacks a well-defined classification, so there's not a lot one can say reliably. Yes, Pichichero does say there's a controversy: the quotes are from his Table 4, which is captioned "The PANDAS controversy". I've quoted everything that table has to day about choreiform movements. The (entire) table cites Kurlan & Kaplan 2004 and Swedo 2004. Eubulides (talk) 06:58, 22 September 2009 (UTC)
I have just gotten a copy of "The PANDAS Syndrome" by Pichichero_2009. It appears he classifies multiple ways -- by Pathogenesis and by Clinical diagnosis. Seems we can use that for classification. You are right about his write up in "Perspective on the PANDAS construct". I need to read that a couple more times. Buster23 (talk) 20:15, 22 September 2009 (UTC)
Pichichero's patheogenesis section contains material that's appropriate for our to-be-written Mechanism section, and his clinical diagnosis section contains material that's appropriate for our to-be-written Diagnosis section. His perspective section, which leads with a comment on nosology, contains the material that is most appropriate for our Classification section. Eubulides (talk) 21:45, 22 September 2009 (UTC)

Classification image caption

OCD and chronic tic disorders intersect but neither is a subset of the other. Tic-related OCD is their intersection. PANDAS is a small subset of the union of OCD and tic disorders, and is in all three subregions of their union.
A possible relationship between PANDAS and other early-onset conditions.[2] Other sources note periods of remission[3] and extend PANDAS to other diagnoses such as ADHD.[1]

At this point the text looks fairly ready to go in, so I was bold and installed it. One thought about that image: how about addressing the issues raised above by adding material to the caption? Something like the image to the right, perhaps? Eubulides (talk) 17:46, 22 September 2009 (UTC)

I just caught up, and since the Leckman diagram does show tic-related OCD at the intersection of OCD and tics, I'm OK with the diagram now. SandyGeorgia (Talk) 18:25, 22 September 2009 (UTC)

Management

Beginning to gather excerpts for eventual Management (or Treatment, whatever we decide to call it) section.

  • ref name= Shprecher2009: "The Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) hypothesis suggested that chronic, recurrent tics and OCD can arise as an autoimmune sequela of infection with group A beta-hemolytic streptococcus.[111] In our opinion, there is insufficient evidence to conclude that streptococcal infection has a true etiological role in causing tics. We recommend that children with documented streptococcal infections be treated with an appropriate course of antibiotics, but that treatment with chronic antibiotics or immune-modifying therapies like plasma exchange or intravenous immune globulin are not justified based on existing evidence."
  • ref name = King2006: "Because of the uncertainties surrounding immunomodulatory treatments in children with apparent PANDAS, these interventions should be used only in the context of properly reviewed research protocols. The NIMH Intramural Program study of these treatments is no longer active, and the author of this chapter is unaware of any active clinical trials of these treatments."
  • ref name = Singer2003: Referring to the original Perlmutter article on immunomodulatory therapies, Singer outlines the methodological problems. " ... methodological concerns were raised, including the highly selective recruitment process, the small number of subjects, the lack of tic severity matching within treatment groups, limited comparisons with controls, continued use of psychotropic medications, reduced beneficial response to PEX in individuals initially treated wtih sham IVIG, and side effects that occurred in about two thirds of individuals receiving active therapy. Additionally, several biological questions remained unanswered including: an inconsistency between therapeutic response and rate of antibody removal, the effect of peripheral changes on events across the blood–brain barrier, and the mechanism by which immune therapy produces its beneficial response. Consequently, the NIH has recommended that immunotherapy be reserved for patients participating in controlled double-blind protocols."
  • ref name=NIHPANDAS: "However, there were a number of side-effects associated with the treatments, including nausea, vomiting, headaches and dizziness. In addition, there is a risk of infection with any invasive procedure, such as these. Thus, the treatments should be reserved for severely ill patients, and administered by a qualified team of health care professionals. The NIH is not currently conducting any trials with immunomodulatory therapies, and so is not able to offer either or the treatments. Of note, a separate study was conducted to evaluate the effectiveness of plasma exchange in the treatment of chronic OCD (Nicolson et al: An Open Trial of Plasma Exchange in Childhood Onset Obsessive-compulsive Disorder Without Poststreptococcal Exacerbations. "J Am Acad Child Adolesc Psychiatry 2000," 39[10]: 1313-1315. None of those children benefited, suggesting that plasma exchange or IVIG is not helpful for children who do not have strep. triggered OCD or tics."

That's all I have time for now, not on my own computer. SandyGeorgia (Talk) 17:15, 22 September 2009 (UTC)

Thanks, this is quite helpful. Could I suggest that we work on the Signs and symptoms (a.k.a. Characteristics) section first, though? Wikipedia:Manual of Style (medicine-related articles) #Diseases/disorders/syndromes suggests that Signs and symptoms should be the next section after Classification. This new section would replace the existing Identification section. Eubulides (talk) 17:46, 22 September 2009 (UTC)
Agree ... was just gathering what I could in a free moment. Next free moment, I'll focus on Characteristics or Signs and symptoms ... what are we going to call it ? SandyGeorgia (Talk) 18:14, 22 September 2009 (UTC)

Extracts from our cited secondary reviews

As we have agreed to go to the secondary reviews rather than back to primaries, here's some extracts on both sides from the reviews:

  • ref name = daRocha2008 : "It has been demonstrated that monoclonal antibodies derived from human hybridomas from a patient with acute Sydenham chorea present cross-reactivity between streptococcal and human neuronal antigens. Interestingly one of these antibodies reacted with the surface of neuronal cells, inducing calcium/ calmodulin dependent protein kinase II (CaM Kinase II) activity. This enzyme is involved in signal transduction mechanisms, leading, for instance, to dopamine release that could be responsible for choreic involuntary movements and behavioral symptoms (Kirvan et al., 2003, 2006). The authors argued that their findings constituted the first evidence for a direct pathogenic effect of anti-basal ganglia antibodies. Interestingly, sera from PANDAS patients induced more activation of CaM kinase II than healthy controls but less than Sydenham chorea. A higher threshold level of CaM Kinase II activity would be necessary to trigger choreic movements, while lower levels could lead to behavioral changes, such as obsessive–compulsive symptoms.”
  • ref name = daRocha2008 : "Perlmutter et al. (1999) demonstrated that plasma exchange and the administering of intravenous immunoglobulin were both effective in reducing neuropsychiatric symptoms (40% and 55% reductions, respectively) in a group of children with severe PANDAS. Although the mechanism of action is incompletely understood, both treatments affect a number of components within the immune system, including clearance of cross-reactive antibodies (Kirvan et al., 2003)."
  • Methodological problems in Perlmutter pointed out by Singer and others in several places, see review above. SandyGeorgia (Talk) 23:11, 22 September 2009 (UTC)
I read Singer2003 that references Singer1999 commentary. It would be great to find out if any other reliable review picked up on Singer's arguments here. I see that he argued for additional study and outlined the parameters of a better study; however, such a study has not been conducted. So you want to refer to his commentary when we refer to the Perlmutter study? Buster23 (talk) 02:59, 23 September 2009 (UTC)
If we refer to the Perlmutter article, we should reference its methodological flaws and the controversy surrounding it (just as secondary reviews do). SandyGeorgia (Talk) 03:20, 23 September 2009 (UTC)
That's fine. Which secondary review do you think we should use? Perlmutter is cited in almost all of the reliable secondary reviews we've got above. Only Singer2003 seems to cite Singer's 1999. Is there another? Buster23 (talk) 05:40, 23 September 2009 (UTC)
  • ref name = Gerber2009 : "The PANDAS hypothesis has stimulated considerable research, as well as considerable controversy. The current state of knowledge dictates that the concept of PANDAS should be considered only as a yet-unproven hypothesis.78,79 Until carefully designed and well-controlled studies have established a causal relationship between PANDAS and GAS infections, the committee does not recommend routine laboratory testing for GAS to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (eg, intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder (Class III, LOE B)"
  • Should this not go in the Management section above? Unclear what section you are targetting with this combo of excerpts ... SandyGeorgia (Talk) 23:11, 22 September 2009 (UTC)
  • ref name = Gordon2009 : "Immune therapies, such as corticosteroids [36], intravenous immunoglobulin, and plasma exchange can be considered in selected patients with both Sydenham’s chorea and PANDAS [16], in view of their side effects such as headache and vomiting, not as a routine. Cardoso et al. [25] tried the effect of intravenous methylprednisolone followed by oral prednisolone and reported favourably on the results when given to refractory patients, and Garvey et al. [37] found that the response to treatment was better when immunoglobulin and plasma exchange were used, than with prednisone. The drug of choice is most probably the dopaminergic blocker, pimozide, which has fewer side effects than haloperidol [38]."
  • Should this go in Management ? SandyGeorgia (Talk) 23:11, 22 September 2009 (UTC)
  • ref name = Kalra2009 : "The pathogenesis of obsessive-compulsive symptoms in the PANDAS subgroup of childhood-onset OCD is hypothesized to result from basal ganglia dysfunction produced by antibodies cross-reactive between GABHS epitopes and the human caudate (109). These antibodies are thought to induce calcium/calmodulin-dependent protein kinase II activity, increasing tyrosine hydroxylase activity and thereby dopamine release, which could result in neuropsychiatric symptoms (110). Systematic investigations suggest that obsessive-compulsive symptoms in the PANDAS subgroup of childhood-onset OCD result from a combination of regional and systemic immunological abnormalities (111). The occurrence of regional autoimmune reactions is suggested by the demonstration that monoclonal antibodies specific for mammalian lysoganglioside and N-acetyl-β-d-glucosamine (GlcNAc) (a dominant epitope of group A streptococci [GAS], including GABHS, carbohydrate) can be derived from the serum of patients with PANDAS (110). These monoclonal antibodies cross-react with neurons of the caudate, putamen, and globus pallidus (109, 110)."
  • ref name = Kirvan2006 : "Sydenham’s chorea and PANDAS share similar neuropsychiatric symptoms and a common infectious etiology has been proposed for both disorders [68,69]. Anti-neuronal antibodies have also been demonstrated in PANDAS raising the possibility that development of clinical manifestations in Sydenham’s chorea and PANDAS may be mediated through a similar antibody-directed mechanism of pathogenesis [70,71]. Recently, we have shown that PANDAS serum IgG reacted with the GlcNAc epitope of the streptococcal GAC and lysoganglioside GM1 as in Sydenham’s chorea [72]. PANDAS sera induced CaM kinase II activity in SKN- SH human neuroblastoma cells similar to that seen in Sydenham’s chorea with significant increases in CaM kinase II activity found for PANDAS sera during acute disease, but not in convalescent sera. "
  • ref name = Leckman2009 : "Kurlan et al also recently reported equivocal findings from a 2-year prospective longitudinal study. 69 Of note however, this study did report a significantly higher rate of GABHS infections in the PANDAS cases. Finally, a report based on a more complete data set from the earlier study by Luo et al67 has recently been published that describes a study in which consecutive monthly ratings of OC, tic, and depressive symptom severity were obtained for 45 cases and 41 matched healthy control subjects over a 2-year period.70 Cases and controls were prospectively monitored for the onset of new GABHS infections and the level of psychosocial stress."
  • ref name = Martino2009 : "Kirvan et al. found cross-reactivity of autoantibodies between streptococcal N-acetyl-glucosamine and brain lysoganglioside83; antibodies against lysoganglioside were elevated in SC and PANDAS. Furthermore, these auto-antibodies appeared to cause alteration in calcium-calmodulin kinase-II activation and possibly up-regulation of tyrosine hydroxylase (and therefore dopamine synthesis), which could theoretically result in SC or TS symptoms.73,84 This eloquent work utilized a hybridoma cell line produced from a single patient with SC, and requires replication."
  • Requires replication, should we report ? SandyGeorgia (Talk) 23:11, 22 September 2009 (UTC)
  • ref name = Martino2009 : "Hoekstra found no benefit of IVIg in TS adult patients,96 whereas Perlmutter et al. demonstrated 1-month and a 1-year benefit of plasma exchange and IVIg compared to placebo in children and adolescent patients with PANDAS.97 However, in the absence of more robust and consistent evidence, current recommendations do not support the use of these agents in TS."

Buster23 (talk) 20:47, 22 September 2009 (UTC)

PANDAS is not a DSM or ICD diagnosis

I reverted the previous edit; perhaps an explanation of what was intended would help? DSM-IV-TR was not written in 1994; it was revised in 2000 specifically to address tic disorders. At any rate, PANDAS is not a recognized diagnosis by either the DSM or the ICD, so it's not clear what the edit intended. SandyGeorgia (Talk) 04:36, 22 September 2009 (UTC)

Sorry about that, I didn't think that would be objectionable. The revision in 2000 was a revision of the text of Tourette syndrome but was not a creation of any new diseases. At that time, it was still too new. The purpose of the edit was that PANDAS is actually classifiable under DSM as either a tic disorder (including tic NOS) or under OCD. Much like hoarding is classifiable under OCD. So technically PANDAS has more criteria than the requirement in DSM. This is why I chose the more precise statement that it is not separable. Can you clarify what is the purpose of the line and what reliable source has stated it? Oh, one last thing, DSM IV was a 1994 copyright. It was DSM-IV-TR that was a 2000 revision. Perhaps you meant to quote DSM-IV-TR? (edited) Buster23 (talk) 04:58, 22 September 2009 (UTC)

So to hold the edit here. What was there before said: "PANDAS is currently not listed as a diagnosis by the International Statistical Classification of Diseases and Related Health Problems (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM)." I adjusted this to say "The PANDAS subgroup is not distinguished from tic disorders or OCD in the current International Statistical Classification of Diseases and Related Health Problems (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM)." Have any of the other reviews stated that it's not in the DSM-IV or is this something you feel must be in this article? Buster23 (talk) 05:16, 22 September 2009 (UTC)

I'm still unclear what you are arguing. PANDAS is not a recognized diagnosis; saying it's not "distinguished" from recognized diagnoses is misleading. We don't need a review to state a fact (that PANDAS is not in the DSM or ICD), and of course, almost all reviews indicate the controversy surrounding the hypothesis. When we have recent reviews making statements like "In our opinion, there is insufficient evidence to conclude that streptococcal infection has a true etiological role in causing tics", we can't leave implications that PANDAS is or will ever become a DSM-recognized diagnosis. SandyGeorgia (Talk) 17:15, 22 September 2009 (UTC)
I agree that the "not distinguished" wording is misleading, as it implies that PANDAS is in or near the DSM. That being said, we do currently have a problem with the article, as the lead talks about PANDAS not being in the DSM, but the body does not. Since we've drafted (and I just installed) the Classification section, which would ordinarily be the place that talks about DSM classification, we need to either modify that sentence in the lead to summarize the body, or modify the Classification section to talk about the DSM, or both. Any suggestions? By the way, the usual gossipy sources say that it's highly unlikely that PANDAS will be added to DSM-V; I'm not sure this is worth adding to the article, though. Eubulides (talk) 17:46, 22 September 2009 (UTC)
I'm not too worried about the lead being temporarily out of sync with the body of the article (we're too used to working on FAs, while most articles have undeveloped text, with the lead out of sync :). Eventually we need to develop the entire body of the article, and that will be there when we do. I suppose it should be added to the Classification section, since it is worthy of mention in the lead. Yes, we need to work on signs and symptoms next, but without good access, I can't be of much help for at least another week, so I'm gathering what I can whenever I have a free moment. I don't think we need even gossipy sources to know that it's highly unlikely that PANDAS will be added to DSM-V ... the evidence has always been remarkably lacking, yet the hypothesis has endured IMO because of a combo of desperate internet-armed parents in pursuit of a "cure" for genetic conditions and NIMH backing. I agree that we don't need to add that info until we eventually get a reliable source putting it to rest ... but the article must make clear that this remains an unproven hypothesis, without implying it will ever be any more than that. SandyGeorgia (Talk) 18:12, 22 September 2009 (UTC)
Oh goodness, I'm not sure what formed your opinion, but I hope you'll be a bit more open-minded in reading the articles than presenting this as a "combo of desparate internet-armed parents in pursuit of a "cure" for genertic conditions and NIMH backing." This helps me understand your objections now if you really see it that way. So if PANDAS becomes a subset of Sydenham Chorea (as per the review of Pichichero_2009 and the anti-lysogangliosides in Kirvan_2006 and reported in Moretti_2008 and Pichichero_2009) would that soften your criticism? Buster23 (talk) 20:11, 22 September 2009 (UTC)
You need not concern yourself with my opinions, since I edit according to Wiki policy and form my opinions from reliably sourced text; Wiki articles reflect reliable sources, and if PANDAS becomes a subset of SC, that's what Wiki will report. SandyGeorgia (Talk) 23:06, 22 September 2009 (UTC)

I have read this discussion with great interest, until I reached this point. Surely since we are looking for verifiable sources, we can leave phrases such as "desperate parents" out of the record? Surely that is beyond the point, as any parent whose child become disfuntional overnight is quite obviously desperate. I will simply say that (as one of those parents) that we are desperate not for a "cure for genetic conditions", but for hope and help for our children. As a mom of one of those "unproven miracles", I simply hope that you will present a balanced picture, and that the research will continue in the hopes of "Saving more Sammy's". In the meantime, keep in mind that the next decade will quite likely be a time of exciting research into genetic vulnerability to environmental triggers such as strep. At least leave the door instead of having pre-conceived notions as to the motivation of "desperate parents". I hope will all my heart that you do not learn the true meaning of that phrase. —Preceding unsigned comment added by 74.162.55.159 (talk • contribs) 18:19, September 24, 2009

Please read the excerpts above; the wording about the desperation of internet-armed parents, and parental bias being a confounding factor in PANDAS, comes from reliable sources, not personal opinion. Also please refrain from personalizing discussions on this page; you do not know what any poster to this page has already learned about the true meaning of the phrase, or what any other parent has been through, and those discussions have no place on this page. The desperation of internet-armed parents and how that has confounded the issues comes from journal-published reliable sources, not personal opinion: the excerpts are provided above. SandyGeorgia (Talk) 18:32, 24 September 2009 (UTC)
Sandy, in fairness to our anonymous poster and Buster23, you did say "IMO because of ..." so both are quite right to conclude this is your personal opinion, and that in offering your personal opinion, you've opened the door to "personalizing discussions on this page". Our anon is right that we must keep an open mind and that we must be very careful with inflammatory language, even if it echoes certain expert opinions. Colin°Talk 18:48, 24 September 2009 (UTC)
Yes, it would have been clearer if I had stated that, IMO, the reviews and diligent researchers have it right, and my opinions are formed from their reports. SandyGeorgia (Talk) 19:41, 24 September 2009 (UTC)

Restarting this thread after 6 months. In a separate section Talk:PANDAS#US Insurance companies recognized PANDAS as proven, I highlight that United Healthcare has revised its coverage stating that Immuno globulin is proven for PANDAS. This can be coded in ICD-9 as 293.84 Anxiety disorder due to general medical condition (if OCD symptom is primary) or 307.20 Tic Disorder NOS (Not Otherwise Specified) if tic symptoms are primary. According to the recent draft of the DSM-V, the category "Tic Disorder due to general medical condition" will be added to create parallelism to the Anxiety representation.

It was unclear to me what the purpose of the current text is as it stands alone in the opening without support in the body. Is this the same discussion as whether "hoarding" is a separate diagnosis in DSM-IV (which it isn't) or grouped into OCD (which it is). PANDAS similarly can be classified as being part of the OCD spectrum disorder or a separate diagnosis. Perhaps the author of the original statement could offer what is the purpose of the statement and whether their intent is to say the disease can't be coded or that it is not currently separated. Buster23 (talk) 07:54, 26 April 2010 (UTC)

Minor phrasing issue

A single study of PANDAS patients showed some efficacy of immunomodulatory therapy to symptoms; however, according to the NIMH and the Advisory Board of the Tourette Syndrome Association, this diagnosis has engendered the use of dangerous and unproven treatment methodologies for individuals with tics and OCD, such as intravenous immunoglobulin (IVIG) and plasma exchange.

I get what this means, but IMO that last bit is only a hair's breadth away from describing IVIG and plasmapheresis as "dangerous and unproven treatment methodologies", full stop. Am I splitting hairs too finely? Maralia (talk) 19:05, 3 December 2009 (UTC)

The first cited source says the two treatments are "considered serious medical interventions that carry a potential for significant adverse reactions" and "that there is no evidence of their efficacy in children with TS or OCD and not even any definitive evidence that it is efficacious for children with PANDAS". The second source says "no evidence of benefits" and "serious medical interventions that carry a potential for significant adverse reactions that is not fully understood in children with either TS or OCD". So I would say that the phrasing should talk only about these two treatments, rather than about treatments in general, and installed a change. Does that address the issue? Eubulides (talk) 20:56, 3 December 2009 (UTC)
That's closer, thanks, but we're still describing them as 'experimental treatment methodologies'. How's this?
A single study by the NIMH showed some efficacy of immunomodulatory therapy for PANDAS patients. This trial spurred some parents to seek IVIG or plasmapheresis treatment for children with PANDAS, Tourette's, or OCD. In 2000 the NIMH and the Tourette's Syndrome Association issued a warning cautioning against treating these conditions with IVIG or plasmapheresis outside of clinical research protocols, as they are serious medical interventions and their efficacy in treating PANDAS, Tourette's and OCD has not been proven.
Wordier, but clearer, I think. And now that I've written that...argh. A glance at the current PANDAS FAQ at NIMH (bottom of this page) makes this sound outdated. It looks like they're confirming that IVIG and plasmapheresis were both beneficial (albeit with moderate risk and side-effects) in treating severely ill patients with strep-induced PANDAS. There's also mention of a trial that found no benefit for plasmapheresis in treating OCD. Can you take a look at that? Maralia (talk) 22:40, 3 December 2009 (UTC)
Dangerous and unproven should stay in; the NIMH is not an unbiased source, since the PANDAS theory was put forward by Susan Swedo of the NIMH. Secondary sources should prevail. Also, I think the wording at the bottom of the NIMH page doesn't contradict the secondary sources. SandyGeorgia (Talk) 23:07, 3 December 2009 (UTC)
My rewrite above was an attempt at (1) avoiding ambiguity (IVIG and plasmapheresis are not themselves dangerous and unproven, but are 'serious medical interventions and their efficacy in treating PANDAS, Tourette's and OCD has not been proven') and (2) explaining more clearly that the NIMH warning was spurred by parents seeking experimental treatment outside clinical studies.
RE secondary vs primary: it's just that I found it strange that we note NIMH's position 9 years ago but not their current position. I can see that perhaps NIMH's old warning is noted specifically because a secondary source (TSA) supported it.
"The PANDAS theory was put forward by Susan Swedo of the NIMH." Woah. Maybe I am the most dense person in the world, but I did not get that from reading the article itself. Throws a whole new light on things. Surely the NIMH origin should be explicitly stated? Should it not also be mentioned that the two studies wrt prophylactic antibiotics were also by the NIMH? Maralia (talk) 04:38, 4 December 2009 (UTC)

(outdenting to restart thread) I went back to re-read the citations regarding "unproven and dangerous". Both appear to be woefully out of date and the underlying links removed by the original authors. The warning from NIMH has been removed and the NIMH website was updated in 2008 modifying the recommendation. The first article cited is not from a peer reviewed source but rather a web page. The links on the web site are broken and the original warning is unavailable. The second reference is invalid and a broken link.

It looks like the material is 10 years out of date. In Canada at least, IVIG therapy is considered to have sufficient evidence of efficacy to be a recommended treatment in severe cases PANDAS. Please see "Guidelines on the use of intravenous immune globulin for neurologic conditions. http://www.tmreviews.com/article/S0887-7963(07)00003-X/abstract.

The current NIMH website says " treatments should be reserved for severely ill patients, and administered by a qualified team of health care professionals"

The Guidelines from the expert panel says "IVIG is recommended as an option for treatment of patients with PANDAS. Based on consensus by the expert panel, diagnosis of PANDAS requires expert consultation." This sentence therefore needs revision to reflect the current expert opinion rather than websites from over a decade ago. Buster23 (talk) 20:00, 25 April 2010 (UTC)

The paper you linked says:
  • "Recommendations for use of IVIG were made for 14 conditions, including ... pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections ...
The PMID 17397768 abstract you cite does not specify what those recommendations were, and I'm not sure why we should rely on a single Canadian source. "Severely ill" and a "team of experts" indicates that the current text is still applicable. SandyGeorgia (Talk) 20:59, 25 April 2010 (UTC)
Hi, I posted the actual text from the paper above "IVIG is recommended as an option for treatment of patients with PANDAS. Based on consensus by the expert panel, diagnosis of PANDAS requires expert consultation." After you read the paper, I'm happy to respond to your other comment. The expert panel is the taskforce of the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products for Canada.
I disagree that the current text represents current consensus opinion. I'm providing a reliable source from a national medical review board who is evidence-based. Please provide your reliable source for the alternate position and we can state both in the article.
My recommendation for the rephrasing would be "The Canadian Blood services, the national advisory commitee on blood and blood products for Canada and the National Institute for Mental Health in the US recommends that immunomodulating therapies be reserved for severely ill patients after consultation with PANDAS experts." Buster23 (talk) 04:39, 26 April 2010 (UTC)
In theory, that wording is fine, but I don't have access to the full journal text, so a larger excerpt would be appreciated before we institute this change-- surely they had more to say on the topic than one sentence. SandyGeorgia (Talk) 05:44, 26 April 2010 (UTC)
You should be able to get a copy a number of ways. Here's some more text from the paper: "Interpretation and Consensus Although the evidence is limited to one small placebo-controlled trial, the results are compelling. In the opinion of the expert panel, it is reasonable to consider IVIG among the options for treatment of PANDAS. The panel emphasized that this syndrome is not well understood, and diagnosis of PANDAS requires expert consultation. The optimum dose and duration of IVIG for treatment of PANDAS is uncertain. The randomized trial used 1 g/kg daily for 2 days and there was agreement that this is a reasonable option. Recommendations Intravenous immune globulin is recommended as an option for treatment of patients with PANDAS. Based on consensus by the expert panel, diagnosis of PANDAS requires expert consultation. " Buster23 (talk) 07:29, 26 April 2010 (UTC)
I expected there would be more disclaimers: perhaps you can work some of these disclaimers into your proposed text. (The section below this one merely duplicates this info.) SandyGeorgia (Talk) 07:39, 26 April 2010 (UTC)
I appreciate that the section below might seem similar (i.e., piling on), but actually it is intended to offer a second massive reliable source (namely a US Insurance company) that recognizes the condition as proven. This goes to the heart of concensus position. I'll be using the next section to address coding and DSM-IV and DSM-V discussions. Buster23 (talk) 08:00, 26 April 2010 (UTC)
The problem that we had the last time you attempted to work on this article was that 1) I was traveling, and 2) you didn't appear to have digested WP:MEDRS, or that Wiki articles do not rely on primary sources when we have secondary reviews. PMID 19913659, the most recent review I can find, says in the abstract: " Finally, despite their empirical use in community settings, we still lack conclusive, evidence-based data regarding the usefulness of antibiotic and immunomodulatory treatments in children with PANDAS. Given the relevance of this topic for general pediatric health, additional research efforts to solve all the pending issues and the hottest points of debate are warranted." I recommend writing the article from secondary reviews, rather than insurance company websites or primary studies. SandyGeorgia (Talk) 22:02, 26 April 2010 (UTC)
Medical and scientific organizations are supported within WP:MEDRS. The advisory commitee on blood and blood products for Canada and the National Institute for Mental Health are recognized medical and scientific organizations.
With respect to your quote, I'm fine with including Martino2009 PMID 19913659 provided we also recognize the other findings in the report.
As you know one of the complaints with the current Wikipedia PANDAS page is that it is out-of-date, needs to be rewritten and is not following the guidelines you refer to. Is there a way to tag the current article as under construction, not following WP:MEDRS, and in need of rewrite? Buster23 (talk) 01:23, 27 April 2010 (UTC)

US Insurance companies recognized PANDAS as proven

The current text stating that IVIG treatment for PANDAS is unproven and dangerous is not supported by recent changes in concensus position.

United HealthCare (one of the US's largest healthcare provider who relies on evidence based research) states in their 2009 revised coverage rationale that "Immune globulin is proven for the following: ... Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (streptococcal infections induce exacerbation of symptoms in some children with obsessive-compulsive and tic disorders)." (see page 13 of September 2009 bulletin https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/Tools%20and%20Resources/Network%20Bulletin/NetworkBulletin_Sept_2009.pdf ). Buster23 (talk) 07:35, 26 April 2010 (UTC)

Minor edits around existing citations

I updated the citation to the out-of-date 2000 Family News article with a reference to Scahill2006. The quote from Scahill is "Experimental treatments based on the autoimmune theory, such as plasma exchange, immunoglobulin therapy, or prophylactic antibiotic treatment, should not be undertaken outside of formal clinical trials."

I reread the Shulman 2009 reference that is in the opening. The current article says "Consequently, the PANDAS model is a complex and rapidly-moving area of medical research, with a 2009 review stating that the link between autoimmunity and tic disorders has remained unclear, despite a great deal of work in the area.[4]" This is not exactly what Shulman says. Shulman says "That there is an OCD/tic disorder patient group with an autoimmune pathogenesis specific to GAS infection has not been proved and seems increasingly unlikely." While we might make the leap that he is talking generally about autoimmunity, that's not what the reference actually states. I recommend rewriting this to say "the association between streptococcal infection and OCD/tic disorders has remained elusive" which is his summary in the abstract. Buster23 (talk) 01:04, 30 April 2010 (UTC)

I think it would be better to reflect consensus across all sources, which is quite strong and in favor of the current wording-- other sources could be added there, but that's pretty much the consensus view. Also, have a look at WP:FN regarding spacing and footnote placement. SandyGeorgia (Talk) 01:08, 30 April 2010 (UTC)
The difficulty is the statement as provided is not supported by the article. The statement as it stands represents original research. I can tag the current statement as [failed verification] or we can replace the reference with a concensus position in a reliable secondary source. Oh, and thanks for catching the space issue. It's a bit hard to see the extra space. Buster23 (talk) 01:18, 30 April 2010 (UTC)
I've reworded the statement to refer specifically to streptococcal infections, rather than autoimmunity. Tim Vickers (talk) 16:09, 30 April 2010 (UTC)
Thanks Tim. I was going to do the same change. We may need to broaden it to OCD and tics but we can do that after we get body material that supports the lead.Buster23 (talk) 23:13, 30 April 2010 (UTC)

I started working from the bottom of the article up and am noticing that several of the citations do not seem to be verifiable (i.e., the text or construct is not explcit in the cited paper. I'll start by flagging them and then updating them to secondary references that support the construct. Buster23 (talk) 22:19, 2 May 2010 (UTC)

Folks, I'd like to ensure that I have verifiability right per wikipedia policy. We aren't saying whether the statement is true or not, or whether we agree or not, but rather whether there is a reliable secondary source who says the statement. It would be original research to combine material across sources. Therefore we're looking for a good secondary source who presents the construct being presented. I just went through a statement that was purported to have 5 citations backing it and all failed verification. Buster23 (talk) 22:58, 2 May 2010 (UTC)

YOu improperly tagged numerous sources that the diagnosis is controversial. Please be more careful. I've removed them; if you have a problem with the prophylaxis statements, that is quite surprising since it's common knowledge and quite easily sourced (the multiple sources are to the fact that the diagnosis is controversial); perhaps splitting the sentence rather than damaging the article would be a better way to go. Since you appear to working from a particular POV-- unsupported by medical consesnsus-- it might also be more expedient for you to propose wording changes and gain consensus on talk rather than tagging the article. SandyGeorgia (Talk) 23:03, 2 May 2010 (UTC)
I'm fine with splitting the sentence and then using the appropriate reference. I disagree with your modification of removing the tag of failed verification without correcting the sentence. The sentence as it stands fails verification. If you think otherwise, please provide the paragraph or line in any of the references that provides the statement that the controversy is the reason prophylaxis is not recommended. I realize I am splitting hairs here, but this isn't a POV this is merely checking sources. Buster23 (talk) 23:14, 2 May 2010 (UTC)
I have gone ahead and split the sentence and added the citations. I also went back to reread WP:OOA and WP:NPA and hope others will too. Buster23 (talk) 06:10, 3 May 2010 (UTC)
I'm glad you found how simple this was without defacing the article (although there was nothing wrong with the way it was before). SandyGeorgia (Talk) 18:04, 3 May 2010 (UTC)
There was something wrong with the way it was before. The citations only supported half the sentence. WP:NOR specifically deals with the condition where two parts of a sentence may be true and independently supported but the combination is not covered by the sources cited. The example used in WP:NOR is "The UN's stated objective is to maintain international peace and security, but since its creation there have been 160 wars throughout the world." The prior text was "As both the PANDAS diagnosis and the hypothesis that symptoms in this subgroup of patients are caused by infection are controversial, prophylactic antibiotic treatments for tics and OCD are experimental.[8][19][20][21][22]". Each part is independently supported but the combination is not and therefore would be original research.Buster23 (talk) 05:00, 4 May 2010 (UTC)

Verifiability and use of failed verification

In the current article, it states: "As both the PANDAS diagnosis and the hypothesis that symptoms in this subgroup of patients are caused by infection are controversial, prophylactic antibiotic treatments for tics and OCD are experimental.[8][19][20][21][22]"

Reading each of the citations, none make this statement. This could be split into: "The PANDAS diagnosis and the hypothesis that symptoms in this subgroup of patients are caused by infection are controversial.[8][19][20][21][22] Prophylactic antibiotic treatments for tics and OCD are experimental."

Most likely we could cite Shulman2009 who says "Unless more convincing data supportive of a direct link to GAS emerge, the use of long-term prophylaxis (as currently used to prevent recurrent ARF) should be discouraged". Buster23 (talk) 23:34, 2 May 2010 (UTC)

The Controversy

It seems as if we actually are going to need a section on the Controversy. We can use Pichichero_2009 as the reliable secondary source as he's done a fair job in characterizing the debate. Perhaps something like:

The Controversy

The controversy in PANDAS is not whether children have OCD and/or tic symptoms but rather

  1. whether the etiology is due to a GABHS infection
  2. whether the symptoms are a result of auto-immunity
  3. whether improvement is the natural waning of symptoms or placebo effect rather than due to treatment
  4. whether the patients with choreiform movements actually had sydenham's chorea
  5. whether the definition of the PANDAS subgroup is sufficiently distinct

It then seems like putting in material from Witebsky's around the requirement for auto-immunity and outline whether these have been met. Here we can use Giavanonni_2005 regarding the assessment of Witebsky critieria.

Any comments here before I start a draft of this section?Buster23 (talk) 05:56, 3 May 2010 (UTC)

First, controversy sections are discouraged. Second, the entire hypothesis is controversial. Third, a separate section on Controversy would give undue weight, since the entire hypothesis is controversial. The article should be written neutrally, which would give equal weight to the controversy in all sections, rather than segregating it to a separate section, which would imply other pieces of the hypothesis were not controversial. SandyGeorgia (Talk) 18:05, 3 May 2010 (UTC)
Hmm, can you help me find the editing guidelines that indicate explicity dealing with the topics of controversy are discouraged especially as we have a good reliable secondary source who provides explicit discussion of the controversy? I don't see how addressing a controversy causes undo weight since each of the other sections would continue to have the balance of reliable secondary sources. I'm perfectly willing to work within any editing guidelines, but it's hard to know how to deal with preemptive strikes on text not yet written. Perhaps we should debate text after it is submitted. Let's get some positive motion going forward, what area of the current article do you feel are incomplete and would value input on. Presumably signs, symptoms, etiology, pathogenesis would be the next areas of focus. Buster23 (talk) 20:54, 3 May 2010 (UTC)
See WP:STRUCTURE. SandyGeorgia (Talk) 21:23, 3 May 2010 (UTC)
I've gone and read WP:STRUCTURE which says "A more neutral approach can result from folding debates into the narrative, rather than distilling them into separate sections that ignore each other." I was not advocating splitting the text into separate sections that ignore each other but rather going direct at what is the controversy which is documented in a reliable secondary source. However, I'll continue with the current approach of adjacent debated points. It does become difficult in the current paper to see whether there is anything that is agreed on (such as that these children do have OCD and/or tics). Buster23 (talk) 04:46, 4 May 2010 (UTC)
So are there areas of the current article you feel are incomplete and would value input on? Buster23 (talk) 04:46, 4 May 2010 (UTC)
Multiple journal articles detail how the entire hypothesis is controversial: there is no area of it that is not controversial, which is why a separate controversy section won't work. The entire article is incomplete, but in the absence of neutral expert editors to complete the article, I'm confining my input to making sure biased and inaccurate info is not added. PANDAS is a difficult, controversial topic, and I don't believe the article can be written without expert input from neutral informed editors, and the best I can do is to keep inaccurate biased info out of the article. SandyGeorgia (Talk) 11:55, 4 May 2010 (UTC)
I appreciate the sentiment expressed. I too wish the article to be as balanced as possible. I hope we will stick to WP:verifiability rather than each editor's perspective on the truth of sentences. It may require recruiting a neutral knowledgable third editor to assist so that disagreements can be about the verifiability. I'll start proposing text based on the reliable secondary sources we have already agreed on. Buster23 (talk) 23:55, 4 May 2010 (UTC)
It is probably best to discuss the controversy in each section. So in the Identification/diagnosis section we already discuss the reasons why classifying these autistic children as suffering from PANDAS is controversial, we don't need to discuss why this is controversial again in a separate section. At most you could add few sentences at the beginning summarising the two points of view and then expand further in the rest of the paragraph by outlining the various pieces of contradictory data. Tim Vickers (talk) 21:17, 3 May 2010 (UTC)
Fine by me. Seems we need the outline of the sections we want to fill in. Buster23 (talk) 04:46, 4 May 2010 (UTC)
See WP:MEDMOS. SandyGeorgia (Talk) 11:57, 4 May 2010 (UTC)

Adding a third external link

I would like to see a third link added. It is a link to WebPediatrics.com PANDAS page which gives detailed information on PANDAS, its diagnosis and treatment. You may view the suggested page at <http://www.webpediatrics.com/pandas.html>. The page is one maintained by Dr. Miroslav Kovacevic, a pediatrician and professor at the University of Chicago Medical School. He has treated hundreds of children with P.A.N.D.A.S., my son being one of them. In our research on P.A.N.D.A.S., this website was very helpful in helping us to understand the disease, its diagnosis and its treatment.

I added the website as an external link, but Dr. Tom Vickers removed it. I cannot even be sure that he read the information contained on the web page. I would like to see this third link added to the page as it is straight forward, gets to the point and has beneficial information for parents looking for a way to help their child.

Again the site I would like added is The WebPediatrics.com PANDAS page found at <http://www.webpediatrics.com/pandas.html>

Thank you! Wandersenaea11 (talk) 16:30, 11 June 2010 (UTC)

The main problem is that this is a commercial website promoting the practice of the doctors who wrote it, adding the link would therefore be a form of advertising. We much prefer links to expert and disinterested professional or scientific organisations, such as the NIH, NLM or AMA, over the homepages of individual doctors. Tim Vickers (talk) 17:03, 11 June 2010 (UTC)
  1. ^ a b c Cite error: The named reference Pichichero2009 was invoked but never defined (see the help page).
  2. ^ Cite error: The named reference Leckman2009 was invoked but never defined (see the help page).
  3. ^ Cite error: The named reference Lombroso2008 was invoked but never defined (see the help page).
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