The sudden onset of severe behavioral and neuropsychiatric symptoms in children is a frightening and potentially life-changing situation. The pediatric health care providers and clinicians to whom families turn need guidance on how to accurately diagnose and treat new-onset neuropsychiatric symptoms in children. They need expert guidance about whether these symptoms indicate a diagnosis compatible with pediatric acute-onset neuropsychiatric syndrome (PANS). The cause of PANS is unknown, but it is theorized to be triggered, in some cases, by a recent infection and/or autoimmunity issues (similar to Sydenham chorea, autoimmune encephalitis [AE], and Guillain-Barré syndrome). The condition is challenging from a clinical perspective, because it lacks disease-specific biomarkers, strong evidence for pathogenic causes, and consensus on treatment of clinical symptoms. Further, the evidence base for PANS encompasses multiple subspecialties, including child and adolescent psychiatry, pediatric rheumatology, pediatric neurology, pediatric infectious diseases, pediatric immunology, and developmental-behavioral pediatrics.
Given this complexity, there is a clear need for guidance and advice for pediatric clinicians and the families they serve and support. To that end, with the encouragement of the Board of Directors, the American Academy of Pediatrics (AAP) has developed this clinical report. It focuses primarily on PANS, an umbrella condition that encompasses pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Although PANDAS is, by definition, associated with streptococcal infection,1 it is now considered by many to represent a subset of the larger spectrum of infection-induced acute-onset neuropsychiatric symptoms.2,3 This clinical report was developed after a comprehensive literature review and analysis of the findings. Because they are limited by the present level of evidence on the topic, the findings are presented as a report rather than a clinical practice guideline. The contents are intended to aid the pediatric health care provider in evaluating, diagnosing, and treating sudden-onset and severe behavioral changes in children that could indicate potential PANS and in supporting these children and their families.
Comments
PANS- a definitive diagnosis?
It is with great interest that I read the article, “Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report” in the current issue of Pediatrics(1). PANS was unknown in the 1990s when I completed my pediatrics residency training. However, I recently became aware of the entity when a child of a close personal acquaintance experienced acute onset vocal and motor tics, severely restricted food intake with weight loss, extreme emotional lability, aggression, exaggerated separation anxiety, sleep disturbances, hallucinations, nocturnal hyperhidrosis, enuresis, and developmental regression. The parents (both medical professionals) were overcome with emotion; frightened, concerned, and unsure of what was happening to their child. They feared the worst and sought medical attention. All laboratory testing and imaging assessments were unremarkable and his signs and symptoms were dismissed as a tic disorder. Some suggested it could be PANS, however, fell short of offering a treatment plan. The parents felt abandoned by the medical system- the very system that they work in as academic medical professionals.
We came across PANS after scouring the literature and internet for information. The child “checked every box” in the diagnostic criteria(1). However, we quickly learned that PANS was a controversial and hotly debated topic because there is no biomarker, there is a lack of PANS-related research, the pathophysiology in unknown, there are no adequately powered clinical trials, and there is no consensus on treatment. Sadly, there are few, if any, academic centers that systematically manage PANS. Thus, PANS exists within a medical desert and desperate parents are forced to seek solutions on their own (finding “alternative” and holistic providers who only accept cash payment). As medical professionals, the parents in this case were able to navigate the “void” and advocate for their son. They were able to weave together care plans from community PANDAS/PANS experts and progressive academic pediatric neuroimmunologists. However, this is not necessarily the scenario for lay people who quickly become frustrated and feel helpless. Here, the boy responded to a combination of oral ibuprofen, monthly IVIG, and a short course of oral antibiotics with almost complete resolution of symptoms over a 7-month period. As an NIH-funded clinician-scientist, I know that this child’s treatment plan was not evidence-based, formed from the most cutting edge and up-to-date scientific information. But it worked for him. His family now has a plan should he relapse or flare again until he (hopefully) grows out of it; and that helps them all sleep at night.
The Clinical Report is a first step in recognizing PANS as a diagnosis(1). However, language stating that, “…PANS is likely a valid diagnosis…” opens the door for interpretation and doubt and is less than definitive(1). The endorsement from the AAP should be full-throated, without hedging. Nevertheless, I am gratified that the Board has chosen to take this step and I am hopeful the article will be a catalyst for more research and clinical trials. Children with PANS and their families are anxiously waiting for advances in this space.
References:
1. American Academy of Pediatrics Board of Directors. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics. 2024: doi: 10.1542/peds.2024-070334. Epub ahead of print.