Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging

Abstract

IMPORTANCE Epidemiological studies indicate a link between obsessive-compulsive disorder and infections, particularly streptococcal pharyngitis. Pediatric acute-onset neuropsychiatric syndrome (PANS) manifests suddenly with obsessions, compulsions, and other behavioral disturbances, often after an infectious trigger. The current working model suggests a unifying inflammatory process involving the central nervous system, particularly the basal ganglia. OBJECTIVE To investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects microstructural abnormalities across the brain regions of children with PANS. DESIGN, SETTING, AND PARTICIPANTS Case-control study performed at a single-center, multidisciplinary clinic in the United States focusing on the evaluation and treatment of children with PANS. Sixty consecutive patients who underwent 3 Tesla (T) magnetic resonance imaging (MRI) before immunomodulation from September 3, 2012, to March 30, 2018, were retrospectively reviewed for study inclusion. Six patients were excluded by blinded investigators because of imaging or motion artifacts, 3 patients for major pathologies, and 17 patients for suboptimal atlas image registration. In total, 34 patients with PANS before initiation of treatment were compared with 64 pediatric control participants. MAIN OUTCOMES AND MEASURESUsing atlas-based MRI analysis, regional brain volume, diffusion, and cerebral blood flow were measured in the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem.An age and sex-controlled multivariable analysis of covariance was used to compare patients with control participants. RESULTSThis study compared 34 patients with PANS (median age, 154 months; age range, 55-251 months; 17 girls and 17 boys) and 64 pediatric control participants (median age, 139 months; age range, 48-213 months); 41 girls and 23 boys). Multivariable analysis demonstrated a statistically significant difference in MRI parameters between patients with PANS and control participants (F 21,74 = 6.91; P < .001; partial η 2 = 0.662). All assessed brain regions had statistically significantly increased median diffusivity compared with 64 control participants. Specifically, the deep gray matter (eg, the thalamus, basal ganglia, and amygdala) demonstrated the most profound increases in diffusivity consistent with the cardinal clinical symptoms of obsessions, compulsions, emotional dysregulation, and sleep disturbances. No statistically significant differences were found regarding volume and cerebral blood flow. (continued) Key Points Question How does diffusion-weighted magnetic resonance imaging differ between patients with pediatric acuteonset neuropsychiatric syndrome and pediatric control participants? Findings In this case-control study of 34 consecutive patients with pediatric acute-onset neuropsychiatric syndrome who had 3 Tesla magnetic resonance imaging, all assessed brain regions, particularly the deep gray matter (eg, the thalamus, b...

Metabolomic Characterization of Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

“…In particular, an enlarged striatal volume (Giedd et al, 2000;Elia et al, 2005) and an inflammatory state of the striatum, confirmed by positron emission tomography using a marker of microglial activation (Kumar et al, 2015), has been reported in PANDAS. A recent diffusion-weighted magnetic resonance imaging study identified cerebral microstructural differences in children with PANS in multiple brain structures (including deep gray matter structures such as the thalamus, basal ganglia, and amygdala) putatively related to a neuroinflammatory state (Zheng et al, 2020). In cohorts of rigorously selected subjects with PANS, evidence of post-infectious autoimmune processes and/or a condition of neuroinflammation was observed in over 80% of cases (Swedo et al, 2017).…”

Artificial Neural Networks Analysis of polysomnographic and clinical features in Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): from sleep alteration to “Brain Fog”

“…Recent neuroimaging studies indicate that microstructural differences (ie, apparent diffusion coefficient, but not regional brain volume nor cerebral blood flow) may be observed in the basal ganglia, thalamus, and amygdala of children and adolescents with PANS. 4 Interestingly, recent evidence indicates that also thalamus and amygdala play an important role in sleep regulation. 68 Considering the complex microstructure of the basal ganglia, 69 PANS neuro-inflammation may heterogeneously impact specific sub regions modulated by midbrain dopaminergic pathways, leading to apparently opposite symptoms (ie tics and PLMD).…”

“…Taken together, altered sleep has been linked to abnormalities in basal ganglia and neuroinflammatory diseases (ie, narcolepsy), and seeing that a recent study shows microstructural changes to the deep grey matter in patients with PANS, 4 it is not surprising that this PANS cohort has sleep disturbances.…”

“… 3 Recently, a neuroimaging MRI investigation showed cerebral microstructural abnormalities in multiple brain structures, including basal ganglia, thalamus, and amygdala in children with PANS in comparison with healthy children. 4 …”

Medal: a patient similarity metric using medication prescribing patterns

“…Current evidence suggests that PANS has an inflammatory or autoimmune etiology that is associated with an infection [11-15]. A recent MRI study in children with PANS showed an increased median diffusivity in multiple brain structures including basal ganglia, thalamus and amygdala compared to controls, suggesting neuroinflammation in these regions.…”