[5] The CANS/PANS hypotheses include different possible mechanisms underlying acute-onset neuropsychiatric conditions, but do not exclude GAS infections as a cause in a subset of individuals.

[12] The children originally described by Susan Swedo et al. (1998)[17] usually had an abrupt onset of symptoms, including motor or vocal tics, obsessions, or compulsions.

[18][19] In addition to an obsessive–compulsive or tic disorder diagnosis, children may have other symptoms associated with exacerbations such as emotional lability, enuresis, anxiety, and deterioration in handwriting.

[10][21][22][23] Pediatric acute-onset neuropsychiatric syndrome (PANS)[12][5] is a hypothesized disorder characterized by the sudden onset of OCD symptoms or eating restrictions, concomitant with acute behavioral deterioration or severe neuropsychiatric symptoms including sleep, emotional and behavioral disturbances, regression in school performance, or motor and sensory issues.

[12][5] PANS eliminated tic disorders as a primary criterion and placed more emphasis on acute-onset OCD, while allowing for causes other than streptococcal infection.

[9][6] The mechanism is hypothesized to be similar to that of rheumatic fever, an autoimmune disorder triggered by streptococcal infections, where antibodies attack the brain and cause neuropsychiatric conditions.

It is thought that similar to Sydenham's, the antibodies cross-react with neuronal brain tissue in the basal ganglia to cause the tics and OCD that characterize PANDAS.

[20] The proposed PANS criteria call for abrupt onset of OCD (severe enough to warrant a DSM diagnosis) or restricted food intake, along with severe and acute neuropsychiatric symptoms from at least two of the following: anxiety, emotional lability or depression, irritability or oppositional behaviors, developmental regression, academic deterioration, sensory or motor difficulties, or sleep or urinary disturbances.

[13] The diagnostic criteria of all the proposed conditions (PANDAS, PITANDs, CANS and PANS) are based on symptoms and presentation, rather than on signs of autoimmunity.

[12][13][c] PANDAS may be overdiagnosed: the diagnostic criteria are unevenly applied and a presumed diagnosis may be conferred in "children in whom immune-mediated symptoms are unlikely",[12] according to Wilbur et al (2019).

[42] When individuals have "persistent or disabling symptoms", Wilbur (2019) et al recommend referral to specialists, treatment of identified acute streptococcal infections according to established guidelines, and immunotherapy only in clinical trials.

[12] There is inconclusive evidence supporting immunomodulatory therapies (intravenous immunoglobulin (IVIG) or therapeutic plasma exchange (TPE)[19]) for PANS and PANDAS; most studies have methodological issues.

[5] Kalra and Swedo wrote in 2009, "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.

Studies of experimental treatments for PANS and PANDAS (IVIG, TPE, antibiotics, tonsillectomy, corticosteroids and NSAIDs) are "few and in general have moderate or high risk of bias", according to a Sigra et al review published in 2018, which states:[5] Nevertheless, there are 3 recent papers proposing guidelines for how to treat PANDAS and PANS using psychiatric and behavioral interventions (Thienemann et al., 2017), immunomodulatory therapies (Frankovich et al., 2017) and antibiotics (Cooperstock et al., 2017).

In addition, it would behoove skeptics and advocates to collaborate in pursuing both good science and sound patient care, while eschewing pseudoscientific approaches and calling out profit-seeking behaviors such as cash-pay clinics, Internet diagnoses, and expert witness testimony.

[46] In April 2021, the British Paediatric Neurology Association (BPNA) issued a consensus statement with the Child and Adolescent Psychiatry Faculty of the Royal College of Psychiatrists stating that there is an absence of evidence for recommending immunomodulatory or prophylactic antibiotic treatments.

[9] Similarly, the April 2021 treatment guidelines for Nordic countries (Denmark, Norway, Sweden and the UK) do not recommend tonsillectomy, antibiotic prophylaxis, or experimental immunomodulatory therapies outside of a specialist setting.

The American Heart Association's 2009 guidelines state that they do "not recommend routine laboratory testing for GAS to diagnose, long-term antistreptococcal prophylaxis to prevent, or immunoregulatory therapy (such as intravenous immunoglobulin, plasma exchange) to treat exacerbations of this disorder".

[16] Murphy, Kurlan and Leckman (2010) discussed the influence of the media and the Internet in a paper that proposed a "way forward" with the "group of disorders collectively described as PANDAS":Of concern, public awareness has outpaced our scientific knowledge base, with multiple magazine and newspaper articles and Internet chat rooms calling this issue to the public's attention.

This gap between public interest in PANDAS and conclusive evidence supporting this link calls for increased scientific attention to the relationship between GAS and OCD/tics, particularly examining basic underlying cellular and immune mechanisms.

[18] A similar clinical picture was proposed for PITANDs (pediatric infection-triggered autoimmune neuropsychiatric disorders) for those who met the Swedo et al criteria for PANDAS, but with symptoms triggered by an infection other than GAS.

For now we have only to offer our standard therapies in treating OCD and tics, but one day we may have evidence that also allows us to add antibiotics or other immune-specific treatments to our armamentarium.

[53] CANS removes the requirement for GAS infection,[5] allowing for multiple causes, which Singer proposed because of the "inconclusive and conflicting scientific support" for PANDAS, including "strong evidence suggesting the absence of an important role for GABHS, a failure to apply published [PANDAS] criteria, and a lack of scientific support for proposed therapies".

[53] By 2012, with limitations of the PANDAS hypothesis published, the broader pediatric acute-onset neuropsychiatric syndrome (PANS) was proposed (also by Swedo and colleagues, following a conference[9]) to create a better defined condition for research purposes.

[12] It describes individuals with eating disorders or rapid onset of OCD along with other neuropsychiatric symptoms,[5] and postulates that the causes can be other than GAS.