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On PANDAS
edit@ScienceFlyer and Bon courage: this was on my user talk page. I have visitors for a week, and will read when I have time. SandyGeorgia (Talk) 16:37, 11 February 2023 (UTC)
ls,
I am writing this rather lengthy message as i do not feel the urge to try and change a wikipedia page by doing my own edits, but rather by asking you as the the main author to rethink your view about about a wikipedia lemma, called PANS/PANDAS.
On reading the English PANDAS/PANS wiki, it seemed to me that the general tone about the diagnosis is somewhat summarized as "the condition as clearly a pseudoscientific, non-existent illness". Reading through the version history, you seem to be the main author of the article, guarding it from misinformation and edits by other wikipedians. But as stated, i think that your opinion on the current status/degree of knowledge of the illness is outdated.
Other than trying to change the wikipedia article, i decided it might be better to point you as the main author to some findings in recent literature, and in the literature used (i guess by you) in the drafting of the PANS/PANDAS article.
While it is true that much about this condition is not well known and not well understood, the debate whether PANS/PANDAS is a real condition has been closed recently, when investigators found clear immunological evidence in human/mice ex vivo studies, implicating a immunological role of PANDAS symptoms. Please read Xu et al., 2021. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity; American Journal of Psychiatry 2021 Vol. 178 Issue 1 Pages 48-64. DOI: 10.1176/appi.ajp.2020.19070698
In my world, if antibodies from PANDAS patients have been found to specifically bind to hypothesized neurons, as compared to controls, neurons of which a deficiency is known to play a role in OCD disorders, and that these neurons show altered activity, the debate whether this is a real condition or not is closed in favor of: it's real.
So, to summarize, i think the scientific debate about PANDAS is currently not about "is PANDAS a real condition", but: how to distinguish between PANDAS / not PANDAS in OCD, Tics/Tourette syndromes, and : how to effectively treat PANDAS.
I do agree that not all OCD/Tourettes/Autism/etc disorders can all be attibuted to auto-immune disease (at least, there is no evidence to assume that this is the case), and i think the major controversies lie here, in parents rather wanting their child to suffer from PANDAS (a severe, but treatable condition) over classical Tourettes/OCD (a condition for life). This is a matter that needs addressed, but it should not lead to an abolisment of the disease as being 'non-existent', and pseudoscientific.
It is also true that there still is much research to be done on the treatment of PANS/PANDAS, but i feel this is at the time mostly due to a lack of large, double blind randomized controlled trial studies than due to a lack of evidence.
Finally, and maybe a bit speculative. May i point to Wilbur et al., 2018: competing interest statement:
Potential Conflicts of Interest
EAY has served on a scientific advisory board for Juno Therapeutics and has provided a one-time consultation to Novartis. Teva provided unrestricted funds to the Hospital for Sick Children Foundation for a symposium she organized. RML serves as a consultant Sobi, Novartis, Eli Lilly, and Sanofi. SK, CW, DL, MS, AB, and WJL have no relevant disclosures to report. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. so, to conlcude, Several authors report funding and links to Novartis, manufacturer of ritalin (i.e. methylphenidate).
The authors report that this drug has been shown to be effective in treating pandas over other modes of therapy: page 3, second column' Approximately half of the responders reported SSRIs (44%) and medications for ADHD (e.g., methylphenidate) (43%) to be effective or somewhat effective (29)'. However, the paper they refer to, compared this with other types of therapy and the authors formulate a different conclusion:
Calaprice D, Tona J, Murphy TK. Treatment of Pediatric Acute-Onset Neuropsychiatric Disorder in a Large Survey Population. J Child Adolesc Psychopharmacol. 2018 Mar;28(2):92-103. doi: 10.1089/cap.2017.0101. Epub 2017 Aug 23. PMID: 28832181; PMCID: PMC5826468.
'Psychotropic medications, most commonly SSRIs (38% reported a trial), were commonly employed, but were often ineffective (e.g., 44% found SSRIs "somewhat" to "very effective").
for other forms of therapy, the same authors conclude: 'Response to antibiotic treatment was best when treatment was relatively aggressive, with broad-spectrum antibiotics and courses of >30 days generally producing the best results (i.e., up to 52% of patients achieving a "very effective" response). For immune-deficient patients (caregiver-reported laboratory studies below normal limits; N = 108), use of broad-spectrum antibiotics appeared to be particularly desirable. Anti-inflammatory therapies, including over-the-counter medications such as ibuprofen, were at least "somewhat effective" for most patients. Intravenous immunoglobulin (IVIG) had been used to treat PANS in 193 (28%) of the patients and was at least "somewhat effective" for 89%, although for 18% of these, the effect was not sustained. The highest rate of sustained response to IVIG treatment was seen in immune-deficient patients who received doses of at least 0.8 g/kg IVIG on a regular basis.'
However; wilbur et al (2018) somehow decided not to include these findings in their review in the respective paragraphs.
Wilbur et al., then conclude in their' what's new' highlight with: 'Youth satisfying criteria for PANDAS/PANS should receive treatment with psychotropic medications and can be expected to show improvement rates similar to youth with OCD not satisfying PANDAS/PANS criteria.'
Conclusions
1. Recent studies support the hypothesis of PANS/PANDAS as an auto-immune disorder: antibodies either bind or do not bind to neurons. To me, this is science at its best, well-setup experiments, controlled and verifiable. Next steps are to proceed into living patients, rather than lab-cultures, to develop better ways of diagnosis, and to start large RCTs to investigate best ways to treat.
2. To me, the article about the controversies on PANS/PANDAS treatment itself is rather controversial. This is important, as it is the first citation in the wikipedia article used to support the statement that PANS/PANDAS itself is a controversial diagnosis. Again, this whole second part of my writing is rather speculative, but i do feel that this 'review' article has some major flaws and it should at least be considered to find a better article to support the claim that is made in the first line of the article.
3. I would ask you to consider the suggestion to decide to change the article's tone over these lines: " PANS/PANDAS like conditions are real, but poorly understood and best ways to treat are poorly known", as in my opinion, this is more in agreement with current scientific literature.
Sincerely, Sirdragos Sirdragos (talk) 15:08, 11 February 2023 (UTC)
- PMID 32539528 is a primary mouse study; see Wikipedia's guideline for sourcing medical content. Also see Wikipedia's policy on original research. SandyGeorgia (Talk) 16:43, 11 February 2023 (UTC)
- PMID 32539528 in not a primary mouse study, it is a combined human ex vivo / mouse ex vivo study. 2A02:A46F:3519:1:1E86:311C:C24A:297A (talk) 10:56, 18 February 2023 (UTC)
- It's a primary study. It uses mouse brain tissue. Sample sizes are small. It doesn't meet WP:MEDRS. To round it out, the authors include proponents of the hypothesis. SandyGeorgia (Talk) 11:31, 18 February 2023 (UTC)
- PMID: 35013105 is a more recent review article that complies to the original research policy.
- PMID: 31367805 reviews autoimmune OCD in a broader context, including streptococcal infections and PANS/PANDAS.
- Both conclude that there is sufficient evidence for autoimmune disease as a causal factor in a subset of OCD Sirdragos (talk) 11:32, 18 February 2023 (UTC)
- Proposing a new diagnostic scheme for OCD, to include sub-categories, might warrant one sentence at Obsessive–compulsive disorder#Research. I don't see anything in those articles that changes anything in this article. SandyGeorgia (Talk) 11:41, 18 February 2023 (UTC)
- Took me a long time to decide on a reply, but today, I made a decision:
- Endres et al state:(PMID: 35013105)
- Perspectives: the concept of autoimmune OCD
- The clinical experience with patients with PANDAS/PANS and other autoimmune disorders points to the existence of secondary autoimmune forms of OCD, at least in some patients with atypical clinical manifestations. Several studies on different immunological markers support this hypothesis. Especially in the presence of the “red flag” symptoms mentioned in Box 2, an autoimmune etiology should be considered, and extended diagnostic investigations seem to be warranted. It is not yet clear whether a classical primary presentation of OCD excludes secondary causes, which should be investigated in the future.
- Pathophysiologically, the following subtypes should currently be distinguished:
- 1. OCD with PANDAS/PANS,
- 2. OCD with neuronal antibodies: a. against well-characterized cell surface antigens (such as NMDA-R), b. against well-characterized paraneoplastic, intracellular antigens (such as Ma2), and c. against non-well-characterized and novel neuronal autoantibodies,
- 3. OCD in the context of systemic autoimmune diseases with potential brain involvement (such as systematic lupus erythematosus),
- 4. OCD in the context of established autoimmune CNS disorders (such as multiple sclerosis).
- The conclusion of Endres et al (PMID: 35013105)
- "There is increasing evidence for secondary immune-mediated forms of OCD. The DSM-5 and novel ICD-11 criteria include the category of secondary OCD, without, however, providing guidelines according to which such a diagnosis should be established. In the current paper, the authors have drafted a first proposal of clinical criteria for the definition of secondary autoimmune OCD. Future studies should investigate the prevalence (e.g., by analyzing the rate of neuronal antibodies in patients with OCD), diagnostic regimes (combination and comparison of different diagnostic methods), and optimal therapy of autoimmune OCD, including the development of clear treatment algorithms and clinical guidelines. Recognizing the autoimmune causes of OCD could inform additional therapeutic options for the affected patients to promote treatment response and reduce chronicity."
- please explain to me why you do not think it is necessary to include this article. This review does not dispute the pandas hypothesis at all as problematic/controversial/pseudoscientific. True, it correctly states that there is still a lot to learn about the mechanisms and treatment, but thas is something different than disputing the existence of the condition, which the authors obviously do not, as they clearly include PANS/PANDAS as a subtype of immune-mediated OCD. Not including this review article is IMO a violation of wikipedias neutral point of view content policy.
- https://en.wikipedia.org/wiki/Wikipedia:Neutral_point_of_view Sirdragos (talk) 21:58, 3 February 2024 (UTC)
- Proposing a new diagnostic scheme for OCD, to include sub-categories, might warrant one sentence at Obsessive–compulsive disorder#Research. I don't see anything in those articles that changes anything in this article. SandyGeorgia (Talk) 11:41, 18 February 2023 (UTC)
- PMID 32539528 in not a primary mouse study, it is a combined human ex vivo / mouse ex vivo study. 2A02:A46F:3519:1:1E86:311C:C24A:297A (talk) 10:56, 18 February 2023 (UTC)
Scientific update needed -- Article not neutral
editOne reads this article with the impression that there is absolutely no good reason to entertain that PANDAS exists. It speaks to the controversial nature of the subject matter but fails to be neutral. It's obvious the main author thinks the condition is a blanket diagnosis that is overused and has little merit.
The article ends with: "As of 2020, the NIH information pages (which Swedo helped write) do not mention the studies that do not support the PANDAS hypothesis." This line verbatim is used in Dr. Swedo's wikipedia page.
I think the same charge could be leveled at the principal keeper of this article.
Using the phrase, "As of 2021, the autoimmune hypothesis of PANDAS is not supported by evidence" Is not an accurate statement. Perhaps, the evidence is not to the level that is needed for definitive proof, or to martial a broad scientific consensus but to imply that there is no evidence or any evidence in general that could suggest a connection to an autoimmune response is flat out wrong and shows the level of bias in this article.
Here is one recent review that gives a more neutral overview of scholarly conversations, studies , investigations being had:
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease
PMID: 37894207
PMCID: PMC10609001
DOI: 10.3390/microorganisms11102549
Yes, there are conflicting findings, and the studies are of various kinds, but speak to the conflicting evidence. Don't say, "no evidence." Factfinder2024 (talk) 20:33, 7 February 2024 (UTC)
Additional PANS/PANDAS reviews (i.e. non primary), 2023 update
editPMID 37742615 Vreeland, A., D. Calaprice, N. Or-Geva, R. E. Frye, D. Agalliu, H. M. Lachman, C. Pittenger, S. Pallanti, K. Williams, M. Ma, M. Thienemann, A. Gagliano, E. Mellins & J. Frankovich (2023). Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder. Developmental Neuroscience 45(6), 361-374. DOI: 10.1159/000534261.
PMID 37251418 Gagliano, A., A. Carta, M. G. Tanca & S. Sotgiu (2023). Pediatric Acute-Onset Neuropsychiatric Syndrome: Current Perspectives. Neuropsychiatric Disease and Treatment 19, 1221-1250. DOI: 10.2147/NDT.S362202.
WoS 001058295600001 Franklin, M. E., S. Eken & E. Osterlund (2023). Current Research Updates on PANDAS and PANS. Current Developmental Disorders Reports 10(4), 264-273. DOI: 10.1007/s40474-023-00280-w.
Time for a re-write of this wiki page. Sirdragos (talk) 10:41, 7 March 2024 (UTC)
I suggest incorporating material from the American Academy of Pediatrics Committee on Infectious Diseases, which wrote in its 2021-2024 Red Book the following:
An association between GAS infection and sudden onset of obsessive-compulsive behavior, tic disorders, or other unexplained acute neurologic changes—pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), as a subset of pediatric acute-onset neuropsychiatric syndrome (PANS)—has been proposed. Data for an association with GAS infection and either PANDAS or PANS rely on a number of small and as yet unduplicated studies. In the absence of acute clinical symptoms and signs of pharyngitis, GAS testing (by culture, antigen detection, or serology) is not recommended for such patients (see Indications for GAS Testing). There also is insufficient evidence to support antibiotic treatment or prophylaxis, Immune Globulin, or plasmapheresis for children suspected to have PANDAS or PANS. Management is best directed by specialists with experience with the presenting symptoms and signs, such as child psychiatrists, behavioral and developmental pediatricians, or child neurologists.
— American Academy of Pediatrics Committee on Infectious Diseases, 2021
Inaccurate
editThe reference to “controversial” is outdated and misleading.
https://adc.bmj.com/content/109/Suppl_1/A92.1 BeccaW1986 (talk) 22:54, 5 August 2024 (UTC)
- That's a primary source; see WP:MEDRS. SandyGeorgia (Talk) 00:16, 6 August 2024 (UTC)
- It's a conference abstract that has not been peer reviewed. It's not a good idea to judge studies based on just the abstract. Also the abstract does not say anything about whether or not PANDAS is controversial. ScienceFlyer (talk) 02:23, 6 August 2024 (UTC)