Paediatric acute-onset neuropsychiatric syndrome

Suspect paediatric acute-onset neuropsychiatric syndrome (PANS) in a child with an abrupt and dramatic onset (<72 hours) of new obsessive-compulsive symptoms or severely restricted food intake, with similarly severe and acute onset of at least two concurrent cognitive, behavioural, or neurological symptoms.

PANS symptoms are thought to result from brain changes secondary to inflammation triggered by infections, metabolic disturbances, other inflammatory reactions, and psychological trauma.

PANS is a diagnosis of exclusion and other causes for the neuropsychiatric symptoms, such as Sydenham's chorea, systemic lupus erythematosus, or autoimmune encephalitis, should be ruled out at initial presentation.

Treatment needs to be individually tailored and may include: education, supportive, and behavioural therapies; psychotropic drugs for neuropsychiatric symptoms; antibiotics for identified infections; and anti-inflammatory or immunomodulatory therapies. Management of the most impairing psychiatric symptoms should be prioritised.

Effectiveness of treatment should be evaluated at frequent intervals and modified accordingly. Treatment can be tapered down or stopped when symptoms resolve. However, treatment may need to be restarted due to the relapsing-remitting nature of symptoms.

Follow-up is recommended at 1, 3, 6, and 12 months if symptoms resolve or stabilise and the immunomodulatory/antibiotic treatment options have been sufficiently tried.

Paediatric acute-onset neuropsychiatric syndrome (PANS) is a condition characterised by an unusually abrupt onset (<72 hours) of obsessive-compulsive symptoms or severely restricted food intake, with similarly severe and acute onset of at least two concurrent cognitive, behavioural, or neurological symptoms.[1]Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;2(2):1000113. https://www.longdom.org/open-access/from-research-subgroup-to-clinical-syndrome-modifying-the-pandas-criteria-to-describe-pans-pediatric-acuteonset-neuropsy-37688.html [2]Pfeiffer HCV, Wickstrom R, Skov L, et al. Clinical guidance for diagnosis and management of suspected pediatric acute-onset neuropsychiatric syndrome in the Nordic countries. Acta Paediatr. 2021 Dec;110(12):3153-60. https://onlinelibrary.wiley.com/doi/10.1111/apa.15875 http://www.ncbi.nlm.nih.gov/pubmed/33848371?tool=bestpractice.com PANS has a pre-pubescent onset and follows a relapsing-remitting course, in which patients experience acute psychiatric symptom flares between periods of relative symptom quiescence.[1]Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;2(2):1000113. https://www.longdom.org/open-access/from-research-subgroup-to-clinical-syndrome-modifying-the-pandas-criteria-to-describe-pans-pediatric-acuteonset-neuropsy-37688.html [3]Frankovich J, Thienemann M, Pearlstein J, et al. Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):38-47. http://www.ncbi.nlm.nih.gov/pubmed/25695943?tool=bestpractice.com Flares are defined as abrupt deteriorations in neuropsychiatric symptoms, lasting an average of 12 weeks.[3]Frankovich J, Thienemann M, Pearlstein J, et al. Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):38-47. http://www.ncbi.nlm.nih.gov/pubmed/25695943?tool=bestpractice.com [4]Gromark C, Harris RA, Wickström R, et al. Establishing a pediatric acute-onset neuropsychiatric syndrome clinic: baseline clinical features of the pediatric acute-onset neuropsychiatric syndrome cohort at Karolinska Institutet. J Child Adolesc Psychopharmacol. 2019 Oct;29(8):625-33. https://www.liebertpub.com/doi/10.1089/cap.2018.0127 http://www.ncbi.nlm.nih.gov/pubmed/31170007?tool=bestpractice.com [5]Gromark C, Hesselmark E, Djupedal IG, et al. A two-to-five year follow-up of a pediatric acute-onset neuropsychiatric syndrome cohort. Child Psychiatry Hum Dev. 2022 Apr;53(2):354-64. https://link.springer.com/article/10.1007/s10578-021-01135-4 http://www.ncbi.nlm.nih.gov/pubmed/33559023?tool=bestpractice.com

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is an overlapping criteria with PANS, defined by an acute onset of tics or obsessive-compulsive symptoms and specific neuropsychiatric symptoms with a temporal association with group A streptococcus (GAS) infection.[6]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 Feb;155(2):264-71. https://ajp.psychiatryonline.org/doi/10.1176/ajp.155.2.264 http://www.ncbi.nlm.nih.gov/pubmed/9464208?tool=bestpractice.com However, the PANDAS diagnostic criteria are used only as a research tool.[6]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 Feb;155(2):264-71. https://ajp.psychiatryonline.org/doi/10.1176/ajp.155.2.264 http://www.ncbi.nlm.nih.gov/pubmed/9464208?tool=bestpractice.com

Both PANS and PANDAS are characterised by abrupt-onset obsessive-compulsive symptoms in addition to other abrupt-onset neuropsychiatric symptoms (sleep disruption, urinary changes, cognitive function loss, behaviour deterioration, emotional lability, irritability, and in some cases rage and violence) causing significant distress to the patient and their family, and carer burden.[3]Frankovich J, Thienemann M, Pearlstein J, et al. Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):38-47. http://www.ncbi.nlm.nih.gov/pubmed/25695943?tool=bestpractice.com [6]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 Feb;155(2):264-71. https://ajp.psychiatryonline.org/doi/10.1176/ajp.155.2.264 http://www.ncbi.nlm.nih.gov/pubmed/9464208?tool=bestpractice.com [7]Murphy TK, Patel PD, McGuire JF, et al. Characterization of the pediatric acute-onset neuropsychiatric syndrome phenotype. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):14-25. http://www.ncbi.nlm.nih.gov/pubmed/25314221?tool=bestpractice.com [8]Swedo SE, Seidlitz J, Kovacevic M, et al. Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings. J Child Adolesc Psychopharmacol. 2015 Feb;25(1):26-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340334 http://www.ncbi.nlm.nih.gov/pubmed/25695941?tool=bestpractice.com [9]Johnson M, Fernell E, Preda I, et al. Paediatric acute-onset neuropsychiatric syndrome in children and adolescents: an observational cohort study. Lancet Child Adolesc Health. 2019 Mar;3(3):175-80. http://www.ncbi.nlm.nih.gov/pubmed/30704875?tool=bestpractice.com [10]Frankovich J, Leibold CM, Farmer C, et al. The burden of caring for a child or adolescent with pediatric acute-onset neuropsychiatric syndrome (PANS): an observational longitudinal study. J Clin Psychiatry. 2018 Dec 11;80(1):17m12091. http://www.ncbi.nlm.nih.gov/pubmed/30549499?tool=bestpractice.com [11]Farmer C, Thienemann M, Leibold C, et al. Psychometric evaluation of the caregiver burden inventory in children and adolescents with PANS. J Pediatr Psychol. 2018 Aug 1;43(7):749-57. https://academic.oup.com/jpepsy/article/43/7/749/4935094 http://www.ncbi.nlm.nih.gov/pubmed/29547961?tool=bestpractice.com

PANS is a complex and controversial condition with ongoing debates surrounding its diagnosis, aetiology, and treatment strategies. There is progressing research in this field, and experts continue to refine their understanding of the condition. An in-depth discussion about the areas of controversy in PANS is out of the scope of this topic. However, some of the key controversies are outlined below.

Controversy exists over the lack of well-defined and widely accepted diagnostic criteria for diagnosing PANS. Some experts argue that the diagnostic criteria may be too broad and that the symptoms can overlap with other psychiatric disorders, such as obsessive-compulsive disorder (OCD), Tourette's syndrome, or generalised anxiety disorder, which may lead to overdiagnosis and unnecessary treatments. Other experts argue that PANS is not a diagnosis but rather a constellation of symptoms for which the underlying causes need to be addressed.

There is ongoing debate about the role of various triggers, including infections, environmental factors, and autoimmune reactions. Research continues to investigate potential underlying mechanisms. One leading theory is that PANS may involve an autoimmune response triggered by infections, leading to brain inflammation. However, some researchers question the strength of the evidence supporting this connection.

Some clinicians advocate for the use of antibiotics and immunomodulatory therapies, while others are more cautious and prefer conventional psychiatric treatments, such as cognitive behavioural therapy and psychotropic medication. The lack of large-scale clinical trials and standardised treatment protocols contributes to this debate.

This topic covers PANS in children.