Paediatrics, what is PANDAS? Causes, characteristics, diagnosis and treatment

The term ‘PANDAS’ is an acronym that stands for ‘paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections’


PANDAS is a hypothetical and controversial diagnosis to date

The term applies to a nosological hypothesis that supports the existence of a subset of children with rapid onset of obsessive-compulsive disorder (OCD) and/or tics related to group A haemolytic streptococcus β infection.

The proposed connection between the infection and such psychic disorders is based on the theory that there may be an initial autoimmune reaction triggered by the presence of the bacterium, with the production of ‘self’ antibodies (i.e. directed abnormally towards the body’s own tissues) that, interfering with the basal ganglia, are responsible for the clinical picture.

The PANDAS hypothesis, first described in 1998, was based on observations in clinical case studies by Susan Swedo and colleagues at the US National Institutes of Health and subsequent clinical studies that seemed to demonstrate dramatic and sudden exacerbations of OCD and tics following infections.

There is clinical evidence of a correlation between streptococcal infection and the onset of some cases of OCD and tics, but the results are not conclusive.

There has been much controversy surrounding this hypothesis; there is debate as to whether it should be considered a separate nosological entity from other cases of Tourette’s syndrome and OCD.

PANDAS does not currently correspond to an officially recognised disease: it is not contained in the DSM (Diagnostic and Statistical Manual of Mental Disorders)

PANDAS is mentioned in the World Health Organisation’s ICD-11, effective in 2022, under autoimmune disorders of the central nervous system, but the diagnostic criteria are not defined and no specific code for PANS or PANDAS is given. The 2021 European Clinical Guidelines developed by the European Society for the Study of Tourette Syndrome (ESSTS) do not support the additions made to ICD-11.

As the PANDAS hypothesis was unconfirmed and unsupported by data, in 2012 Swedo and colleagues proposed a new definition, paediatric acute-onset neuropsychiatric syndrome (PANS), to describe the acute onset of obsessive-compulsive disorder related not only to past infections, but in general to apparent environmental precipitating factors or immune dysfunction.

In addition to PANS, two other categories have been proposed:

  • childhood acute neuropsychiatric symptoms (childhood acute neuropsychiatric symptoms hence the acronym CANS);
  • paediatric infection-triggered autoimmune neuropsychiatric disorders (paediatric infection-triggered autoimmune neuropsychiatric disorders hence the acronym PITAND).

The CANS/PANS hypotheses include several possible mechanisms underlying acute-onset neuropsychiatric conditions, but do not exclude group A haemolytic streptococcus β infections as a cause in a subset of individuals.

PANDAS, PANS and CANS are the focus of clinical and laboratory research, but remain unproven

There is no diagnostic test to accurately confirm PANDAS; diagnostic criteria are unevenly applied and conditions may be overdiagnosed.

Treatment for children suspected of PANDAS is generally the same as standard treatments for Tourette syndrome and OCD.

There is insufficient evidence or consensus to support the treatment, although experimental treatments are sometimes used and adverse effects from unproven treatments are expected.

The debate surrounding the PANDAS hypothesis has social implications: the media and the Internet have played a role in the PANDAS controversy.

The media report the difficulties of families who believe their children have PANDAS or PANS.

Attempts to influence public policy have been made by networks such as the US-based PANDAS Network and the Canadian PANDASHELP.

Characteristics of the PANDAS model

The children originally described by Susan Swedo et al. (1998) usually presented with a sudden onset of symptoms, including motor or vocal tics, obsessions or compulsions.

In addition to a diagnosis of obsessive-compulsive disorder or tics, children may have other symptoms associated with exacerbations such as emotional lability, enuresis, anxiety and deterioration of handwriting.

There may be periods of remission.

In PANDAS, this sudden onset is thought to be preceded by a streptococcal infection.

Since the clinical spectrum of PANDAS appears to resemble that of Tourette syndrome, some researchers have speculated that PANDAS and Tourette syndrome may be associated; this idea is being challenged and a focus for research.

Acute-onset paediatric neuropsychiatric syndrome (PANS) is a hypothesised disorder characterised by the sudden onset of OCD symptoms or feeding restrictions, concomitant with acute behavioural deterioration or neuropsychiatric symptoms.

PANS eliminated tic disorders as the main criterion and placed more emphasis on acute-onset OCD, while taking into account causes other than streptococcal infection.


It is also hypothesised that PANS, CANS and PITAND are autoimmune diseases, but this is controversial and unconfirmed.

It is speculated that the mechanism is similar to that of rheumatic fever, an autoimmune disease triggered by infections with group A β-haemolytic streptococcus (streptococcus pyogenes), in which antibodies attack the brain and cause neuropsychiatric conditions.

The cause is thought to be similar to Sydenham’s chorea (SC), which is known to be the result of childhood group A streptococcal infection leading to the autoimmune disorder and rheumatic fever of which SC is a manifestation.

Like SC, PANDAS is thought to involve autoimmunity to the basal ganglia of the brain. To establish that a disorder is an autoimmune disorder,

Witebsky’s criteria require:

  • that there is an autoreactive antibody,
  • that a particular target for the antibody (autoantigen) is identified
  • that the disorder can be caused in animals
  • that the transfer of antibodies from one animal to another causes the disorder (passive transfer).

The results of studies investigating an autoimmune cause that fulfil Witebsky’s criteria are inconsistent, controversial and subject to methodological limitations.

In order to prove that a micro-organism causes a disorder, Koch’s postulates would require a demonstration that the organism is present in all cases of the disorder, that the organism can be extracted from those with the disorder and be cultured, that transferring the organism into healthy subjects causes the disorder and the organism can be isolated again from the infected part.

Giavanonni notes that Koch’s postulates are not helpful in proving that PANDAS is a post-infectious disorder because the organism may no longer be present when symptoms emerge, multiple organisms may cause the symptoms, and the symptoms may be a rare reaction to a common pathogen.

Some studies support acute exacerbations associated with streptococcal infections among clinically defined PANDAS subjects; other studies have found no association between sudden onset or exacerbation with infection.

The PANS hypothesis, therefore, expands the causes beyond streptococcal infection and postulates that the cause may be genetic, metabolic or infectious.

Among children with PANS or PANDAS, studies are inconsistent and the hypothesis that antibodies trigger symptoms is not proven; some studies have shown antibodies in children with PANS/PANDAS, but those results have not been replicated in other studies.

A large multicentre study (EMTICS – European Multicentre Tics in Children Studies) showed no evidence in children with chronic tic disorders of streptococcal infections leading to tic exacerbation or specific antibodies in children with tics, and a study on the cerebrospinal fluid of adults with Tourette’s syndrome similarly found no specific antibodies.

The antibodies that were found by one group were collectively called the ‘Cunningham Panel’; subsequent independent tests showed that this antibody panel did not distinguish between children with and without PANS and its reliability was not proven.

A consensus statement by the British Paediatric Neurology Association (BPNA), states that “a causative infection (rather than random infection) or inflammatory or autoimmune pathogenesis” has not been confirmed and that “no consistent biomarkers have been identified that accurately diagnose PANDAS or are reliably associated with brain inflammation”.


Swedo et al in their 1998 article proposed five diagnostic criteria for PANDAS.

According to Lombroso and Scahill (2008), these criteria were:

  • the presence of a DSM-IV compatible tic disorder and/or OCD;
  • prepubertal onset of neuropsychiatric symptoms;
  • a history of onset of symptoms and/or an episodic course with a sudden exacerbation of symptoms interspersed with periods of partial or complete remission;
  • evidence of a temporal association between the onset or exacerbation of symptoms and a previous streptococcal infection;
  • adventitious movements (e.g. motor hyperactivity and choreiform movements) during symptom exacerbation.

The proposed PANS criteria require a sudden onset of OCD (severe enough to warrant a DSM diagnosis) or impaired food intake, together with severe and acute neuropsychiatric symptoms from at least two of the following: anxiety, emotional lability or depression, irritability or oppositional behaviour, developmental regression, school deterioration, sensory or motor difficulties or sleep or urinary disorders.

The symptoms should not be better explained by another disorder, such as Syndenham’s chorea or Tourette’s syndrome.

The authors stated that all other causes must be excluded (exclusion diagnosis) for PANS to be considered.

There is no diagnostic test to accurately confirm PANDAS

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

An instrument known as the ‘Cunningham Panel’ and marketed by Moleculera Labs, intended to diagnose PANDAS and PANS on the basis of antibody assays, did not distinguish between children with and without PANS when tested independently.

PANDAS may be overdiagnosed: diagnostic criteria are unevenly applied and a presumptive diagnosis may be conferred on ‘children in whom immune-mediated symptoms are unlikely’, according to Wilbur et al (2019).

The majority of patients diagnosed with PANDAS by community physicians did not meet the criteria when examined by specialists, suggesting that the diagnosis of PANDAS was conferred by community physicians without conclusive evidence.

Differential Diagnosis

Because the symptoms overlap with many other psychiatric conditions, differential diagnosis is difficult.

There are several difficulties in distinguishing PANDAS from TS. The two have a similar onset and an increasing and decreasing course, and the onset or sudden exacerbation of tics hypothesised in PANDAS are not uncommon in TS.

There is a higher rate of OCD and TS among relatives of children with PANDAS, and those children often have tics that precede a diagnosis of PANDAS or may be predisposed to tic disorders; what appears to be a dramatic onset due to GAS infection “could be the natural course of tic disorders”, according to Ueda and Black (2021).[10]


Treatment for children suspected of PANDAS is generally the same as standard treatments for Tourette’s syndrome and obsessive compulsive disorder.

These include cognitive behavioural therapy and medication for the treatment of OCD, such as selective serotonin reuptake inhibitors (SSRIs) and conventional tic therapy.

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

The use of psychotropic drugs for PANS/PANDAS is widespread, although controlled studies were lacking in 2019.

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