A retrospective cohort study found a high prevalence of neurological soft signs in children and adolescents with pediatric acute-onset neuropsychiatric syndrome.
Researchers conducted the study, recently published in JAMA Network Open, at the Stanford Children's Immune Behavioral Health Clinic and examined 119 patients, 95 (79.8%) of whom exhibited at least one neurological soft sign (NSS), which suggested basal ganglia dysfunction. NSSs that may be associated with ganglia dysfunction were common in the study's patient population, the researchers noted: 59.7% of patients presented with overflow movements, 52.1% with choreiform movements, 31.1% with abnormal tongue movements, 30.2% with milkmaid’s grip, 30.2% with milkmaid’s grip, and 17.6% with spooning. Patients with four or more NSSs had significantly higher Global Impairment Scores (mean = 56 vs 40.6; P = .05) and more pediatric acute-onset neuropsychiatric syndrome (PANS) symptoms (mean = 15.1 vs 11.5; P = .008) than those without NSSs.
Regression analysis showed that each additional NSS correlated with a 2.86-point increase in Global Impairment Score (95% confidence interval [CI] = 0.09-5.62; P = .04) and a 5% increase in symptom count (95% CI = 1.02-1.08; P = .002). NSS presence did not correlate with age or illness duration.
"Children and young adults presenting with PANS commonly had multiple NSSs associated with basal ganglia dysfunction on physical examination, with more NSSs associated with greater impairment," wrote Jane E. Zebrack, BA, of the Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics at Stanford University School of Medicine, with colleagues.
The researchers further explained, "distinction [between NSS and 'hard neurological signs'] on examination is not always clear; choreiform movements may be a mild form of chorea, and motor overflow may be a mild form of dystonia. This has clinical implications. For example, in a child with acquired chorea without genetic findings, Sydenham chorea is the probable diagnosis. However, if the chorea is more subtle ('choreiform'), the child is more likely to have PANS, assuming PANS criteria are met. Moreover, research classification and enrollment in trials are challenging in borderline cases."
They concluded that "targeted neurological examinations may support PANS diagnosis."
These findings align with imaging studies that have implicated basal ganglia involvement in PANS and suggest NSSs as potential clinical markers of disease severity. The researchers suggested further research into PANS pathophysiology and proposed standardized neurological exams as a valuable clinical assessment tool, given the absence of a reliable biomarker.
Study limitations included variability in neurological exams, despite a standardized protocol. Not all patients received comprehensive neurological screenings (including neurological soft signs [NSSs]) at their first visit, and some evaluations were performed during remission or resolution of disease flares, which may not have reflected peak symptom severity. Underestimation of findings was also possible: 14 patients (11.8%) had their first NSS evaluation while not in a disease flare, and patients with severe behavioral or mental health issues may have been unable to fully cooperate with the neurological exams.
No conflicts of interest were reported.
