Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet

Abstract

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a descriptive clinical entity defined by the abrupt onset of psychiatric and somatic symptoms leading to significant loss of function. Data on well-characterized PANS patients are limited, biomarkers have yet to be identified, and a solid evidence base to guide treatment is lacking. In this study, we present our experience of a systematic evaluation of the first 45 patients included in a Swedish cohort.Methods: During the period 2014–2018, our clinic received 100 referrals regarding suspected PANS. All patients underwent a standardized psychiatric/medical evaluation by a child/adolescent psychiatrist and a clinical psychologist or a nurse. Those with severe symptoms were also assessed by a pediatric neurologist and a pediatric rheumatologist. Laboratory tests were obtained at different time points in an attempt to capture an active disease state.Results: Of the 100 referrals, 45 met strict PANS criteria and consented to participate in a long-term follow-up study. The median age at intake was 7.2 years (range 3.0–13.1) and 56% were male. Ninety-three percent fulfilled both criteria for acute/atypical onset of PANS symptoms and having had an infection in relation to onset. Sixteen percent had an onset of an autoimmune or inflammatory disorder in temporal relation to the onset of PANS-related symptoms. The most common onset symptoms were obsessive-compulsive disorder (89%), anxiety (78%), and emotional lability (71%). Twenty-four percent had a preexisting autoimmune disease (AD) and 18% a preexisting psychiatric/neuropsychiatric diagnosis. Sixty-four percent of biological relatives had at least one psychiatric disorder and 76% at least one AD or inflammatory disorder. Complement activation (37%), leukopenia (20%), positive antinuclear antibodies (17%), and elevated thyroid antibodies (11%) were the most common laboratory findings.Conclusions: In our PANS cohort, there was a strong indication of an association with AD. Further work is needed to establish whether any of the potential biomarkers identified will be clinically useful. Long-term follow-up of these patients using the Swedish national registers will enable a deeper understanding of the course of this patient group.

A Two-to-Five Year Follow-Up of a Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort

“…All study participants were recruited from a specialist OCD and related disorders outpatient clinic in Stockholm, Sweden, and had previously been included in the PANS cohort at Karolinska Institutet [ 3 ]. The clinic primarily receives referrals from Child and Adolescent Psychiatry Services (CAMHS) and pediatric services in the Stockholm region, but also from other parts of Sweden and the Nordic countries.…”

“…Baseline data on age at symptom onset, comorbidity at onset, Children’s Global Assessment Scale (CGAS) and Clinical Global Impressions-Severity scale (CGI-S) scores were extracted from the baseline clinical assessment, published in the original description of the cohort [ 3 ].…”

“…In the acute phase, the symptoms are often severe and may lead to significant loss of function [ 2 ]. Psychiatric comorbidities are common and may need to be treated in parallel to the PANS-related symptoms [ 3 , 4 ]. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) constitutes a sub-group of patients within the broader PANS construct, which requires the verified presence of a streptococcal infection temporally associated with the onset of symptoms [ 5 ].…”

“…While the psychiatric and somatic status of patients with PANS/PANDAS has been reasonably well described in cross-sectional studies, including high rates of pre-existing neuropsychiatric disorders and a strong association with autoimmune disease in both patients and first degree relatives, there is a shortage of long-term follow-up data of PANS/PANDAS cohorts [ 2 , 3 ]. The available longitudinal data primarily originates from a handful of case reports and chart reviews, methods that not well suited for assessing the fraction of participants who may be remitting [ 6 ].…”

“…Given the paucity of available follow-up data on this patient group, we aimed to conduct a naturalistic follow-up of the patients included in a well-characterized Swedish cohort [ 3 ]. To minimize the risk of selectively following-up chronic patients in need of medical attention, we aimed to re-contact families regardless of whether they were still active in our clinic or not.…”