Secondary Logo

Treating pediatric acute-onset neuropsychiatric syndrome

Heavey, Elizabeth, PhD, RN, CNM; Peterson, Kathleen, PhD, RN, PCPNP-BC

doi: 10.1097/01.NPR.0000553400.88847.5d

Abstract: Pediatric acute-onset neuropsychiatric syndrome (PANS) can be caused by infectious and noninfectious triggers. NPs can help children with PANS recover from their symptoms and prevent future recurrences by appropriately screening, recognizing, and diagnosing the clinical presentation of PANS. PANS treatment includes pharmacologic therapies as well as cognitive behavioral therapy.

Pediatric acute-onset neuropsychiatric syndrome (PANS) can be caused by infectious and noninfectious triggers. NPs can help children with PANS recover from their symptoms and prevent future recurrences by appropriately screening, recognizing, and diagnosing the clinical presentation of PANS. PANS treatment includes pharmacologic therapies as well as cognitive behavioral therapy.

Elizabeth Heavey is a professor of nursing and graduate program director at The College at Brockport, Brockport, N.Y. Heavey is also a certified nurse-midwife.

Kathleen Peterson is a professor of nursing and chair of the department of nursing at The College at Brockport, Brockport, N.Y. Peterson is also a certified pediatric NP.

The authors have disclosed no financial relationships related to this article.



In the late 1990s, after clinicians noted children with an abrupt onset of obsessive-compulsive disorder (OCD) and tics associated with recent streptococcal infection, the first reports of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) appeared in the literature.1 By 2012, evidence accrued showing additional potential infectious and noninfectious exposures that trigger this syndrome and that concomitant symptoms may include the presence of tics.2 The diagnostic criteria were adjusted, and the PANS/PANDAS workgroup at the National Institutes of Health (NIH) recommended the terms pediatric acute-onset neuropsychiatric syndrome (PANS) be used going forward.3 PANDAS is now seen within a larger context as one manifestation of PANS. The term PANDAS is still used to describe pediatric patients who present with an identified group A Streptococcal (GAS) infection and subsequent PANS.3 The NIH PANS/PANDAS workgroup released the first treatment guidelines in 2014.4 These guidelines are continually evaluated and updated as additional information becomes available from much-needed randomized controlled trials.5

Back to Top | Article Outline

Clinical presentation

PANS disorders all include an abrupt onset of OCD and/or severe food intake restriction.6 In addition, to being diagnosed with PANS, patients must exhibit simultaneous development of at least two symptoms from the following core categories: anxiety, emotional lability or depression, irritability, aggression and/or severely oppositional behaviors, behavioral/developmental regression, deterioration in school performance, sensory or motor abnormalities, and somatic signs and symptoms that may include generalized pain, sleep disturbances, and/or urination issues.2,3 Although symptoms from only two core categories are required for diagnosis, as many as 93% of children with PANS will exhibit more.2 The syndrome is clearly distinct from the typical gradual presentation of OCD in childhood because of the abrupt onset, two comorbid symptoms, and waxing and waning nature of the symptoms in PANS.7 PANS is a diagnosis of exclusion, meaning other neuropsychiatric conditions must be assessed and ruled out before the diagnosis can be made.4 Symptoms often begin suddenly and may be severe enough to require emergency evaluation.8 Up to 25% of children impacted by PANS require immediate assessment because of reports of hallucinations and depression with self-injurious behavior.7

PANS is also distinct from other childhood tic disorders (TDs). Up to 25% of school-aged children will experience transient tics that generally only include motor tics that resolve in less than a year.9 When PANS-associated tics are present, there may be a simultaneous onset of both motor and vocal tics.8 PANS symptoms usually improve or resolve gradually over several weeks to months; however, relapse of symptoms occurs in about 50% of patients, again followed by gradual resolution.8

OCD is common in childhood; 0.1% to 3.6% of the general pediatric population are impacted by the disorder.10 Prevalence estimates for OCD and TDs include those who may have had an abrupt onset and meet the diagnostic criteria for PANS.10 Although rare, it is estimated that 5% to 10% of OCD/TDs in children may be due to PANS.2,8

PANS may also include an abrupt onset of severe food restriction. It is well documented that food restriction is associated with other autoimmune disorders, such as systemic lupus erythematosus. This symptom occurs when autoantibodies attack the alpha-melanocyte stimulating hormone and impact appetite and behavior.11 PANS anorexia is hypothesized to occur in a similar fashion and can lead to compulsive ways of preparing food, obsessional anxiety about contamination, and extreme fear of swallowing, choking, or vomiting often related to the perceived texture or appearance of the food.11 In its most striking form, the refusal to ingest even liquids places the child at risk for severe dehydration and can be life threatening.11 Many children with PANS anorexia also experience abrupt onset OCD and continue to experience abnormal eating patterns and require interdisciplinary support even after initial triggers are treated and resolved.7

Back to Top | Article Outline

Role of infection and immune response

Although 40% to 77% of PANS cases are linked to GAS infection, non-GAS infections including Mycoplasma pneumoniae (M. pneumoniae), influenza, and other common viruses have also been linked to the development of PANS.12 This suggests nonspecific immune activation mechanisms are involved in the PANS development.12 Interestingly, 71% of patients diagnosed with PANS have one or more first-degree relative with an autoimmune inflammatory disorder.1,2,4 Also, 75% to 80% of children diagnosed with PANS have some documented immune abnormality.4 All these associations support the hypothesis that this syndrome may be related to an autoimmune process and subsequent neuroinflammation.4 However, a conclusive immunologic link has yet to be discovered.5

It is premature to say that GAS infection is a causative agent for PANDAS, but there is clearly an association that warrants investigation. The current hypothesis is that in a susceptible host (particularly those with a family history of autoimmune disorders), GAS infection triggers an inappropriate immune reaction that impacts the central nervous system.8 A similar process can occur with acute rheumatic fever caused by GAS infection. When a patient has rheumatic fever, the antibodies to GAS may misidentify and attack the normal cells in the basal ganglia area of the brain, resulting in Sydenham chorea (SC).13 Patients with SC exhibit random, involuntary writhing movements of the arms, legs, trunk, and face.13 The grimacing, slurred speech, unstable gait, OCD, and emotional lability associated with SC can last 7 to 10 months; in more than a third of patients, symptoms recur even after initially resolving.10 Researchers currently believe that PANDAS mimics SC after a subacute GAS infection and symptoms may exhibit a similar remitting/relapsing pattern.10 In one study, mild GAS infection, leading to pharyngeal erythema with minimal additional symptomology, was documented in 92% (11/12) of children with PANDAS.12 PANDAS is also more commonly diagnosed among patients with a familial history of rheumatic fever.1,2,4

Children with PANDAS and a history of multiple GAS infections have more frequent and more severe relapses of PANDAS symptoms; rising GAS antibody titers are associated with exacerbation of symptoms for many patients with PANDAS.12 Although GAS infection may be associated with the initial appearance of symptoms, most episodes of relapsing symptoms occur with viral triggers, not repeated GAS infection.14

Back to Top | Article Outline

Why is this disorder seen in children?

GAS exposure and infection, as well as repeated infections, are more common in childhood.15 In addition, the immune response mounted by those ages 5 to 12 involves higher levels of antibodies than in those in their teen years and beyond, which may contribute to an increased likelihood of antibodies cross-reacting with normal cells.8

Back to Top | Article Outline

Making the diagnosis

Children who present with rapid onset OCD symptoms should have a throat culture that includes good contact with the tonsils and the posterior pharynx.12 In the event of a negative rapid strep, the culture should still be evaluated to avoid missing the 15% of GAS cases not detected by rapid strep testing.12 GAS infection may be asymptomatic and still generate an immune response, PANDAS symptoms, and even reoccurrence of rheumatic fever.12 Perineal and dermatologic sites should be examined and cultured if GAS infection is a concern.12 Family members should also have a throat culture if children are diagnosed with PANDAS.12

Serology testing for GAS-specific antibodies antistreptolysin O (ASO) and antideoxyribonuclease-B antibody (anti-DNase B) should be conducted when symptoms present and then be repeated at the same lab 2 to 6 weeks later.8,12 Anti-DNase B titers are elevated in 80% of PANDAS cases, and ASO titers are elevated in 20% to 50% of PANDAS cases.16 Any rise of 50% is considered significant, though it is important to note that for many children, even with confirmed GAS infection, rising titers may not be present (38% of new GAS cases and for 57% with acute GAS pharyngitis).12 ASO and anti-DNase B levels may be elevated for several months after an acute infection.8 Although an initial single positive antibody level may be helpful for establishing the correct diagnosis of GAS infection, checking antibody levels one time without a point of comparison or checking titers for the first time multiple weeks after the GAS infection occurred is not useful because false-positive and false-negative results are common.12 Serial testing of ASO and anti-DNase B levels may be considered every 3 to 4 months to assist with diagnosis of subclinical infection or ineffective antibiotic treatment.12

Because PANS can be triggered by a variety of infections, clinicians should test appropriately for any suspected infections based on the patient's exam, presenting symptoms, and history. M. pneumoniae infection should be considered if upper respiratory tract infection symptoms are present. A nasopharyngeal/pharyngeal swab should be collected and sent for immunoglobulin M (IgM) and immunoglobulin G (IgG) titers as well as polymerase chain reaction (PCR) testing.12 IgG and IgM antibody levels should also be drawn for M. pneumoniae when patients first present and during any flare up of symptoms.12 M. pneumoniae is associated with many neurologic syndromes as well as exacerbations of Tourette syndrome and is a suspected trigger agent for PANS.12

The presence of biomarkers indicating brain inflammation (cerebrospinal fluid pleocytosis, protein, and oligoclonal bands), and abnormalities of electroencephalography, polysomnography, and MRI may be helpful to confirm the neurologic inflammation; however, clinicians should be cautious about the low sensitivity associated with some of these measures, which may lead to false negatives.4

Back to Top | Article Outline


Because PANS and PANDAS are similar syndromes, recommendations and treatment are fairly consistent, with the exception that PANDAS involves diagnosing and treating GAS infection specifically.7 Antibiotics specific to any identified bacterial triggers may significantly improve symptoms or at least make them tolerable and minimize the distress they cause.4 First-line treatment for GAS infection is penicillin or amoxicillin in younger children.12,17 Antibiotic treatment for confirmed GAS infection should be followed by a repeat throat culture 2 to 7 days later to ensure treatment is effective. Retreatment is recommended if the culture remains positive.12 The rate of treatment failure for PANDAS using penicillin and amoxicillin is high because the GAS may be intracellular and intracellular penetration is not provided by these antibiotics.8 Children with PANDAS who were treated previously for GAS infection but who remain symptomatic should be treated again with oral azithromycin.8 Clinicians should be aware that in some areas GAS resistance to azithromycin may be as high as 5% to 10%.12 Azithromycin should also be used cautiously in any patients taking medications that can produce a prolonged QT interval, which includes many selective serotonin reuptake inhibitors and antipsychotic medications.12 As an alternative, cefadroxil, cephalexin, or cefpodoxime may be considered.8,12 Children with PANDAS who are treated with azithromycin or a cephalosporin should see improvement in symptoms within a week, although some clinicians opt to continue antibiotic treatment for up to 3 weeks while waiting resolution of neuropsychiatric symptoms.8,12

Children with PANS for which GAS infection is not identified should still be treated with GAS-appropriate antibiotic regimens to ensure hidden GAS infection is treated appropriately.12 Also, children with rising IgG titers or positive PCR testing for M. pneumoniae should be treated with a macrolide, azithromycin, or tetracycline.12

Children may benefit from oral nonsteroidal anti-inflammatory drugs (NSAIDs) with regular dosing to maintain continuous anti-inflammatory and immunomodulatory action.4 NSAIDs should be stopped every 6 weeks to assess for symptom abatement or exacerbation.4 If long-term use is indicated, clinicians should monitor liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT)], blood urea nitrogen level, creatinine level, complete blood cell count with differential, and urinalysis every 3 to 6 months.4 Oral corticosteroids may also be considered during the early stages of symptom flare-ups but should not be administered concurrently with NSAIDs.4 Corticosteroids should be used cautiously because they may improve symptoms brought on by neuroinflammation, but they also have the potential to exacerbate psychiatric symptoms.4

A comprehensive safety assessment should be made for all children and families with PANS.7 Suicidality, psychosis, severe food restriction, and acute aggression may pose an immediate threat to the child's well-being and should be addressed accordingly.7 In addition, behavioral manifestations of PANS, including severe anxiety or oppositional behaviors can be exhausting for both the child and the family involved. Support including referral to cognitive behavioral therapy (CBT) for the entire family, and respite options should be explored.

Symptom-specific behavioral and pharmacologic treatment should be initiated as soon as the syndrome is recognized to minimize suffering and improve prognosis.7 Standard neuropsychiatric treatment and behavioral interventions should be the first approach to OCD and TD symptoms.4 (See Pharmacotherapy for OCD.) Pharmacotherapy and CBT should be considered for both OCD symptoms and TDs.8 (See CBT approach to TDs.) Children with severe food restriction may require hospitalization or feeding tube placement to maintain adequate hydration and nutrition while the inflammatory trigger is treated.7 Referral to a skilled behavioral health professional is warranted.

There is evidence that vitamin D mitigates damaging autoimmune responses and enhances the body's ability to fight off infections.12 Levels of Serum 25-hydroxy vitamin D should be kept above 30 ng/mL (75 nmol/L) in children impacted by PANS.12 The recommended dosing regimen includes a daily children's multivitamin as well as age-based dosing of vitamin D 3 supplementation.12 Serum 25-hydroxy vitamin D levels should be monitored every 3 to 12 months to ensure adequate supplementation. Adjustments may need to be made during winter months, in obese children, and for those who are Hispanic, Asian, or Black.12

Because of the remitting/relapsing pattern of symptoms, treatment may need to be adjusted to adapt to new symptoms or address those that emerge as more distressing over time.7 However, clinicians should be cautious about changing course too quickly because some symptoms may be temporary and remit on their own.7 Management should focus on ameliorating current symptoms and preventing future recurrences similar to treatment for other episodic disorders, such as multiple sclerosis and asthma.4 Most children who are treated appropriately will improve within 1 to 12 months; however, relapses may still occur years later and may be associated with an identifiable infection or even stress.12

During any periods of relapse, the patient, family members, and close contacts with pharyngitis should have throat cultures completed and treatment should be initiated if any are positive for GAS.12 Exposure to siblings with GAS infection without acute infection themselves has also been associated with relapsing symptoms in children with PANDAS.12 It is also important to closely monitor siblings of children with PANS as they may be at a higher risk of developing the condition themselves.12 GAS antibody levels should be reevaluated, and a PCR test for M. pneumoniae may also be appropriate.12

Patients presenting with severe symptoms that do not improve with standard treatment should be referred to a pediatric rheumatologist/immunologist for further evaluation. They may benefit from intensive immunomodulatory interventions using an individually tailored approach.4,12

PANS may resolve spontaneously or repeated stimulation of the autoantibodies can lead to chronic episodic symptoms.8

Back to Top | Article Outline


Currently, there is no reliable means to prevent the development of PANS. It is postulated that prompt diagnosis and treatment of GAS may help prevent some cases from developing and may limit relapsing episodes. Prophylactic antibiotics have been proposed; however, the actual pathogenesis of PANS is not fully understood and the adverse impact of long-term antibiotic use has been clearly established. This remains a controversial issue, and experts have failed to reach consensus. If prophylactic antibiotics are considered, they should be administered for 6 months to 1 year, including during the winter when risk for GAS infection is the highest.8 Amoxicillin or azithromycin for children with a penicillin allergy has been proposed.8 The NIH PANS/PANDAS workgroup only recommends administering long-term prophylactic antibiotics for children with PANDAS and very severe symptoms associated with multiple GAS-associated relapses.12 It is important to remember that most symptom flares are actually associated with viral triggers, which do not respond to antibiotic treatment.4

Influenza has been associated with PANS, so an annual influenza vaccination is recommended for all individuals with PANS and their close contacts.12 Good hygiene practices are also recommended to prevent future infections of any kind that may exacerbate neuronal inflammation and produce relapsing symptoms. When close contacts of children with PANS are diagnosed with influenza, consideration should be given to providing antiviral treatment to the close contacts, preferably within 48 hours of onset of symptoms.12 Children with PANS should follow the recommended childhood vaccine schedule. Symptom flare-ups associated with vaccines are rare, temporary, and respond to anti-inflammatory treatment.12

Back to Top | Article Outline


PANS is a syndrome that can be associated with severe manifestations. It is important for primary care advanced practice registered nurses, to recognize the symptoms described and to screen for safety, initiate treatment for infection, and ensure adequate pharmacologic and nonpharmacologic management of the disorder. Collaboration with other healthcare professionals is a key aspect to making the correct diagnosis and treating the whole family unit. Patient education includes ensuring families know how to properly administer treatment, monitor for, and manage the symptoms of PANS, as well as coordinate necessary follow-up care. Monitoring the work of the PANS/PANDAS workgroup at the NIH will assist providers in keeping abreast of changes resulting from new research.

Back to Top | Article Outline

Pharmacotherapy for OCD18

First-line monotherapy:

  • selective serotonin reuptake inhibitor (SSRI), such as fluoxetine, sertraline
    • – based on previous response, comorbidity, tolerability, adverse reactions, costs
    • – usually higher dose than used for depression

Second-line monotherapy:

  • selective serotonin and norepinephrine reuptake inhibitor (SNRI), such as venlafaxine (off-label use)

Treatment strategy for nonresponders to first-line treatment

  • switching to another medication (another SSRI)
  • augmenting with CBT or behavioral therapy
  • augmenting with another medication
    • – atypical antipsychotics, such as risperidone, aripiprazole
Back to Top | Article Outline

CBT approach to TDs19

The most efficacious CBT is habit-reversal therapy, of which there are two components:

  • tic-awareness training: identify tic, identify premonitory urge associated with tic
  • competing response training: perform a voluntary movement incompatible with tic

Challenge: identifying pediatric clinical psychologists, psychiatric nurse practitioners, and psychotherapists trained in cognitive-behavioral based treatment of tic disorders.

Back to Top | Article Outline


1. Swedo SE, Leonard HL, Garvey M, et al Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155(2):264–271.
2. Jaspers-Fayer F, Han SHJ, Chan E, et al Prevalence of acute-onset subtypes in pediatric obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2017;27(4):332–341.
3. Williams KA, Swedo SE. Post-infectious autoimmune disorders: Sydenham's chorea, PANDAS and beyond. Brain Res. 2015;1617:144–154.
4. Frankovich J, Swedo S, Murphy T, et al Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part II—use of immunomodulatory therapies. J Child Adolesc Psychopharmacol. 2017;27(7):574–593.
5. Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: a systematic review. Neurosci Biobehav Rev. 2018;86:51–65.
6. Orefici G, Cardona F, Cox CJ, Cunningham MW. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). In: Ferretti JJ, Stevens DL, Fischetti VA, eds. Streptococcus Pyogenes: Basic Biology to Clinical Manifestations. Oklahoma City, OK: University of Oklahoma Health Sciences Center; 2016.
7. Thienemann M, Murphy T, Leckman J, et al Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part I—psychiatric and behavioral interventions. J Child Adolesc Psychopharmacol. 2017;27(7):566–573.
8. Pichichero M. PANDAS: pediatric autoimmune neurophychiatric disorder associated with group A streptococci. UpToDate. 2018.
9. Ogundele MO, Ayyash HF. Review of the evidence for the management of co-morbid Tic disorders in children and adolescents with attention deficit hyperactivity disorder. World J Clin Pediatr. 2018;7(1):36–42.
10. Leon J, Hommer R, Grant P, et al Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). Eur Child Adolesc Psychiatry. 2018;27(5):637–643.
11. Toufexis MD, Hommer R, Gerardi DM, et al Disordered eating and food restrictions in children with PANDAS/PANS. J Child Adolesc Psychopharmacol. 2015;25(1):48–56.
12. Cooperstock MS, Swedo SE, Pasternack MS, Murphy TK. Clinical management of pediatric acute-onset neuropsychiatric syndrome: Part III—treatment and prevention of infections. J Child Adolesc Psychopharmacol. 2017;27(7):594–606.
13. National Institute of Neurological Disorders and Strokes. Syndenham Chorea Information Page. 2018.
14. Leckman JF, King RA, Gilbert DL, et al Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2011;50(2):108–118.e3.
15. Centers for Disease Control and Prevention. Group A Streptococcal (GAS) disease. 2018.
16. Murphy ML, Pichichero ME. Prospective identification and treatment of children with pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS). Arch Pediatr Adolesc Med. 2002;156(4):356–361.
17. Shulman ST, Bisno AL, Clegg HW, et al IDSA guidelines for GAS pharyngitis: clinical practice guideline for the diagnosis and management of group a streptococcal pharyngitis: 2012 update by the infectious disease society of America. Clin Infect Dis. 2012;55(10):1279–1282.
18. Janardhan Reddy YC, Sundar AS, Narayanaswamy JC, Math SB. Clinical practice guidelines for obsessive-compulsive disorder. Indian J Psychiatry. 2017;59(suppl 1):S74–S90.
19. Blackburn JS. Tic disorders and PANDAS. Semin Pediatr Neurol. 2018;25:25–33.

group A Streptococcal infection; obsessive-compulsive disorder (OCD); PANS anorexia; pediatric acute-onset neuropsychiatric syndrome (PANS); pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS); Sydenham chorea; tic disorders

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.