Characterization and long-term follow-up of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS)

Abstract

Background: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a cluster of psychiatric and somatic symptoms of proposed autoimmune etiology. It remains a descriptive entity, still of unclear validity and uncertain clinical utility. Further characterizing this patient group, describing its long-term prognosis and reaching a consensus regarding how to best measure its complex phenomenology are therefore important steps towards more efficient assessment, and management of this emerging patient group.

Aims: We aimed to: establish a Swedish cohort of well-characterized patients with PANS and to follow them up longitudinally; propose definitions for different clinical aspects of the syndrome, such as flare and disease course; investigate the suitability of standard clinical measures for following up PANS as well as assessing agreement between informants for these measures. Furthermore, and due to the ongoing COVID-19 pandemic, we wanted to investigate how the pandemic had affected patients with PANS.

Methods: This thesis comprises four studies. Study I was a descriptive study based on the establishment of the PANS cohort (n=45), including detailed clinical assessments, comprehensive laboratory tests and family history of autoimmune disease. Studies II and III were based on the same data collection, from the naturalistic two-to-five year follow-up of patients included in the PANS cohort (n=34). Study IV was a global survey investigating challenges for PANS patients during the ongoing COVID-19 pandemic (n=154).

Results: In study I we showed that PANS was a clinical entity with high variability in psychiatric and somatic symptom presentation and in level of impairment at onset. We also noted a strong association with autoimmunity in the cohort. The results of study II showed that although remission was rare, a majority of patients with PANS was significantly improved two-to-five years after inclusion in the cohort. Approximately one third of the patients had developed a chronic disease course requiring further treatments. These chronic patients had an earlier disease onset and a higher level of impairment at onset. Proposed definitions of flare and disease course seemed to meaningfully distinguish patients regarding impairment and subsequent need of healthcare resources. In study III we showed that ratings on symptomspecific measures varied largely between participants, due to the wide spectrum of PANS symptom presentations. Agreement between informants was excellent on functional scales, fair-to-moderate on global symptom severity scales, and mixed on the symptom-specific scales. Clinician-rated global and functional measures had stronger inter-correlations with parent- and child-rated functional measures than with symptom-specific ones. According to the survey results in study IV, a third of the parents responded that their child was currently receiving the care they need for their PANS symptoms during the pandemic, while a third perceived a worsening of their children’s psychiatric and somatic symptoms and high stress levels.

Conclusion: The PANS clinical presentation can vary widely between patients, and the symptoms can range from mild to severe and disabling. The combination of psychiatric and somatic symptoms and the association with autoimmune disorders warrants a multi-specialist approach with access to a child and adolescent psychiatrist, psychologist, pediatric neurologist and rheumatologist. While a majority of patients improve significantly over time, a group of patients develop a chronic disease course requiring further treatments and interventions. When assessing and following up patients with PANS, the multi-dimensional clinical presentation of the syndrome should be taken into consideration. Global rather than symptom-specific measures are better suited at a group level, but these should be complemented with an efficient protocol of rating scales assessing core symptoms, such as OCD, anxiety, depression and tics. PANS patients and their families have been affected by the ongoing COVID-19 pandemic. Lack of regular healthcare contacts, school closures, and social distancing, resulting in lack of everyday support systems, have put strain on these families. Future research should focus on further defining the boundaries of the syndrome, prognostic factors, much-needed treatment trials and biomarkers in larger samples with adequate control groups.