Prevalence and Predictors of Pain and Fatigue in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

@misc{miles2026prevalence,
  title = {{Prevalence and Predictors of Pain and Fatigue in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)}},
  author = {K. Miles and N. Schlenk and M. Ma and B. Farahadian and S. Leonard and O. Knight and S. A. Challa and S. Gao and S. H. Gunther and C. Manko and Y. Xie and P. Tran and M. Silverman and K. W. Hoffman and M. Thienemann and J. Frankovich},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.02.26364612},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.02.26364612v1},
  note = {CC BY-NC-ND},
}

TY  - UNPB
TI  - Prevalence and Predictors of Pain and Fatigue in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)
AU  - K. Miles
AU  - N. Schlenk
AU  - M. Ma
AU  - B. Farahadian
AU  - S. Leonard
AU  - O. Knight
AU  - S. A. Challa
AU  - S. Gao
AU  - S. H. Gunther
AU  - C. Manko
AU  - Y. Xie
AU  - P. Tran
AU  - M. Silverman
AU  - K. W. Hoffman
AU  - M. Thienemann
AU  - J. Frankovich
PY  - 2026
DA  - 2026/10/02
PB  - medRxiv
DO  - 10.64898/2026.10.02.26364612
UR  - https://www.medrxiv.org/content/10.64898/2026.10.02.26364612v1
AB  - ObjectivesPatients with pediatric acute-onset neuropsychiatric syndrome (PANS) frequently report pain and fatigue. While some patients experience resolution of pain and fatigue following improvement in psychiatric symptoms, others develop persistent symptoms resembling fibromyalgia. Understanding these trajectories is critical for early identification and intervention in patients at risk for chronic pain or fatigue. In this study we characterize fibromyalgia symptoms in PANS and identify predictors of symptom progression following a PANS flare.  DesignProspective observational cohort study.  SettingStanford University Immune Behavioral Health (IBH) Clinic in Menlo Park, California, USA.  Participants204 consecutive patients with PANS evaluated by the IBH Clinic. The average (SD) age at first neuropsychiatric deterioration was 8.2 (3.3) years.  Main outcome measuresWe prospectively collected data on pain, fatigue, and other fibromyalgia symptoms using the 2016 American College of Rheumatology (ACR) Fibromyalgia Survey Questionnaire (FSQ), which includes the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS). For the reference standard, clinician-documented diagnoses of pain syndromes were ascertained through a retrospective review of participants electronic medical records. We report the prevalence of these symptoms in PANS patients and controls and evaluate factors associated with time to meeting ACR fibromyalgia criteria threshold scores following clinic presentation using a Cox proportional hazards model.  ResultsAmong 204 patients with PANS (110 boys [54%]), eighty-five (42%) met ACR fibromyalgia criteria threshold scores at least once during follow-up (95% CI at 10 years follow-up time: 60.5 [46.7-74.5]). Twenty-eight of these 85 patients (13.7% of total cohort) progressed to meet full ACR fibromyalgia criteria (95% CI at 10 years follow-up time: 24.1 [15.6-36.2]). Compared with controls, patients with PANS reported substantially elevated rates of pain, daytime fatigue, waking unrefreshed, and cognitive symptoms ("brain fog"). Higher scores on the WPI and SSS at presentation were associated with a higher hazard of subsequently meeting ACR fibromyalgia criteria threshold scores.  ConclusionsFibromyalgia symptoms were common in this PANS cohort, with a notable subset developing symptoms meeting full ACR fibromyalgia criteria. These findings suggest that pain and fatigue may represent post-inflammatory sequelae of PANS and may overlap mechanistically with other post-infectious conditions. Recognizing these symptom patterns may inform clinical management, development of outcome measures, and future clinical trials in these patients, as well as support investigation into shared neuroimmune mechanisms underlying post-infectious pain and fatigue syndromes.  Key PointsO_ST_ABSQuestionC_ST_ABSIn youth with pediatric acute-onset neuropsychiatric disorder (PANS), what is the prevalence, severity, and clinical pattern of fibromyalgia and fibromyalgia symptoms (pain, fatigue, brain fog, sleep disturbance, exercise intolerance, sensory amplification, etc.)? Which baseline clinical and demographic factors predict the subsequent fulfillment of diagnostic criteria for fibromyalgia in this population?  FindingsAmong 204 consecutive patients with PANS evaluated at a single center, pain and fatigue were common at presentation and persisted in a subset of patients. Forty-two percent of subjects met American College of Rheumatology (ACR) fibromyalgia criteria threshold scores at least once during follow-up, with fourteen percent ultimately progressing to meet full ACR fibromyalgia criteria.  MeaningPain and fatigue may represent long-term sequelae in PANS, overlapping with other hypothesized post-infectious syndromes like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long coronavirus disease ("Long COVID"). Acknowledging this symptomatic overlap is crucial for stimulating research into shared neuroimmune mechanisms and may reveal a common post-infectious pathophysiology.
ER  -