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

Abstract

Little is known about the long-term prognosis of children with pediatric acute-onset neuropsychiatric syndrome (PANS). Out of the 46 eligible patients from the Karolinska PANS cohort, 34 consented to participate in a follow-up (median 3.3 years). Participants underwent a thorough clinical evaluation and were classified according to their clinical course. Resulting groups were compared on clinical characteristics and laboratory test results. We observed significant reductions in clinician-rated PANS symptom severity and improved general function. Two patients were classified as remitted, 20 as relapsing–remitting, and 12 as having a chronic-static/progressive course. The latter group had an earlier onset, greater impairment and received more pharmacological and psychological treatments. Although remission was rare, the majority of children with PANS were significantly improved over the follow-up period but a non-negligible minority of patients displayed a chronic-static/progressive course and required additional treatments. The proposed definitions of flare and clinical course may be useful in future clinical trials.

Diagnostic Approach to Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS): A Narrative Review of Literature Data

“…Moreover, evaluation for autoimmune disease through measurements of serum antinuclear antibody (ANA) or others (b2-glycoprotein antibodies, anticardiolipin antibodies, antiphospholipid antibody, and lupus anticoagulant) has yielded conflicting results. Positive ANA titers have been found in 0.5–37.1% of PANDAS/PANS patients ( 17 , 20 , 28 – 30 , 32 – 35 ), while no other autoantibodies were detected ( 17 , 35 ) ( Table 3 ). Furthermore, Murphy et al ( 3 , 23 ) have documented elevated anti-A carbohydrate (anti-A CHO ) antibody levels in PANDAS patients compared to healthy controls, while Frankovich et al ( 28 ) have reported positive histone antibodies in 15% of PANS patients ( Table 3 ).…”

“…However, D8/D17 is no longer used owing to poor specificity for PANDAS diagnosis ( 37 – 39 ). Given its role in the modulation of innate immunity and autoimmunity, vitamin D levels have been investigated in several studies, with detection of low levels in PANDAS ( 19 , 27 ) as well as in PANS patients ( 28 – 30 ) ( Table 3 ). Evidence from a recent study also suggested that lower vitamin D levels may be associated with the presence and severity of comorbid ADHD in children and adolescents with chronic tic disorders ( 40 ).…”

“…Hypoferritinemia was documented in two different pediatric PANS cohorts ( 29 , 31 ), associated in one case with low serum iron levels ( 31 ) ( Table 3 ). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease, have been explored in a few studies ( 17 , 28 – 30 , 32 ). Elevated transglutaminase and antithyroid antibodies have been documented in, respectively, 1.2–11% and 2.46–36% of patients affected with PANDAS or PANS, whereas TSH abnormalities and/or low T4 have been found in 3.8–11% ( 17 , 28 – 30 , 32 ) ( Table 3 ).…”

“…Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease, have been explored in a few studies ( 17 , 28 – 30 , 32 ). Elevated transglutaminase and antithyroid antibodies have been documented in, respectively, 1.2–11% and 2.46–36% of patients affected with PANDAS or PANS, whereas TSH abnormalities and/or low T4 have been found in 3.8–11% ( 17 , 28 – 30 , 32 ) ( Table 3 ). Moreover, evaluation for autoimmune disease through measurements of serum antinuclear antibody (ANA) or others (b2-glycoprotein antibodies, anticardiolipin antibodies, antiphospholipid antibody, and lupus anticoagulant) has yielded conflicting results.…”

Identification of ultra-rare genetic variants in Pediatric Acute Onset Neuropsychiatric Syndrome (PANS) by exome and whole genome sequencing

“…According to the Stanford PANS Clinic, the median Caregiver Burden Inventory (CBI) during a 1st PANS flare is 37, which is higher than the CBI for those caring for someone with Alzheimer disease and similar to that found in Rett syndrome 10 . Although most children with PANS show significant improvement at follow-up, according to a recently published longitudinal study, full remission was rare, and more than one-third were classified as having a chronic course 11 .…”