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

Abstract

This case-control study investigates whether diffusion-weighted imaging shows microstructural abnormalities across the brain regions of children with pediatric acute-onset neuropsychiatric syndrome.

Key Points

Question

How does diffusion-weighted magnetic resonance imaging differ between patients with pediatric acute-onset 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, basal ganglia, and amygdala), had statistically significantly increased mean diffusivity compared with 64 control participants. These diffusion abnormalities are consistent with the cardinal clinical symptoms of these patients, including obsessions, compulsions, emotional dysregulation, and sleep disturbances.

Meaning

Diffusion-weighted magnetic resonance imaging may offer valuable quantitative information to assist with the diagnostic workup of pediatric acute-onset neuropsychiatric syndrome.

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 Measures

Using 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.

Results

This 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.

Conclusions and Relevance

This study identifies cerebral microstructural differences in children with PANS in multiple brain structures, including the deep gray matter structures (eg, the thalamus, basal ganglia, and amygdala). Further study of MRI is warranted in prospective, clinical trials as a potential quantitative method for assessing patients under evaluation for PANS.