Researchers gain insight into PANS etiology using diffusion-weighted MRI

Children with pediatric acute-onset neuropsychiatric syndrome, or PANS, exhibited cerebral microstructural differences in multiple brain structures, according to results of a case-control study published in JAMA Network Open.

Researchers noted that diffusion-weighted MRI may provide valuable quantitative data to assist with the diagnostic workup of PANS.

“Some studies have reported poor predictive value (17%-40% for positive predictive value and 44%-74% for negative predictive value) and low test performance (15%-60% sensitivity and 28%-92% specificity) for standard PANS diagnostic evaluations, including inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein and antibody titers,” Jimmy Zheng, BS, of Stanford University School of Medicine, and colleagues wrote. “There remains a pressing need for reliable biomarkers to improve diagnostic accuracy and validate the underlying pathophysiology of PANS.”

According to the researchers, epidemiological studies have indicated an association between obsessive-compulsive disorder and infections, particularly streptococcal pharyngitis. They noted that often after an infectious trigger, PANS occurs suddenly with obsessions, compulsions and other behavioral disturbances. A unifying inflammatory process that involves the central nervous system, particularly the basal ganglia, may contribute to this association, according to the current working model.

Zheng and colleagues sought to determine whether diffusion-weighted MRI detected microstructural abnormalities across the brain regions of children with PANS. They retrospectively reviewed for inclusion 60 patients who underwent 3 Tesla MRI before immunomodulation from Sept. 3, 2012, to March 30, 2018 at a multidisciplinary clinic in the United States that focuses on the evaluation and treatment of this patient population. Blinded investigators excluded six patients because of imaging or motion artifacts, three for major pathologies and 17 for suboptimal atlas image registration. The researchers compared the remaining 34 patients with PANS before initiation of treatment with 64 pediatric controls. They used atlas-based MRI analysis to measure regional brain volume, diffusion and cerebral blood flow in numerous brain regions, as well as an age- and sex-controlled multivariable analysis of covariance to compare patients with controls.

Multivariable analysis revealed a statistically significant difference in MRI parameters between patients with PANS and controls (P < .001). The researchers reported statistically significantly increased median diffusivity among all assessed brain regions compared with controls. The deep gray matter, including the thalamus, basal ganglia and amygdala, demonstrated the most significant increases in diffusivity consistent with the cardinal clinical symptoms of obsessions, compulsions, sleep disturbances and emotional dysregulation. Zheng and colleagues found no statistically significant differences regarding volume and cerebral blood flow.

“The hypothesis that neuroinflammation is the underlying cause of acute-onset OCD in PANS may explain the MRI diffusion differences in multiple brain structures observed herein, particularly the deep gray matter structures, such as the thalamus, basal ganglia and amygdala,” they wrote. “Further study of MRI is warranted in prospective clinical trials as a potential tool to quantitatively assess pediatric patients who are under evaluation for PANS.” – by Joe Gramigna

Disclosures: One study author reports research support from the PANDAS Physician Network and the NIMH, Pediatrics and Developmental Neuroscience Branch, as well as funding for CME activities through The Foundation for Children with Neuroimmune Disorders. The other authors report no relevant financial disclosures.