Abstract
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. To investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects microstructural abnormalities across the brain regions of children with PANS. 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. 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. 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 (F21,74 = 6.91; P < .001; partial η2 = 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. 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.
Highlights
The diagnostic considerations of childhood-onset obsessive-compulsive disorder (OCD) have evolved substantially since the late 1980s
Further study of magnetic resonance imaging (MRI) is warranted in prospective, clinical trials as a potential quantitative method for assessing patients under evaluation for pediatric acuteonset neuropsychiatric syndrome (PANS)
Research on Sydenham chorea, a neurological sequela of group A streptococcal infection, found that 50% to 70% of affected children experienced obsessions and compulsions before, during, or after onset of chorea.[3,4,5]. These findings led to the hypothesis that Sydenham chorea might share a common pathophysiology with acute-onset OCD even when chorea is absent,[5] forming the basis of a new diagnostic entity, namely, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
Summary
The diagnostic considerations of childhood-onset obsessive-compulsive disorder (OCD) have evolved substantially since the late 1980s. Prospective studies[1,2] of children with OCD revealed that a subgroup experienced an unusually abrupt onset (
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