Association of PANS With Microstructural Brain Differences on Diffusion MRI
Study: Zheng J, Frankovich J, McKenna ES, et al. Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging. JAMA Network Open. 2020;3(5):e204063. doi:10.1001/jamanetworkopen.2020.4063
📘 Deeper Dive: Brain MRI Findings in PANS (2020 Study)
We take a closer look at a 2020 case-control neuroimaging study that goes beyond abstract-level summaries to explore what diffusion-weighted MRI findings may reveal about Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). In this study, 34 children with PANS were compared with 64 pediatric control participants, and diffusion-weighted MRI showed statistically significantly increased diffusivity across all examined brain regions in the PANS group, with the most pronounced differences in deep gray matter structures including the thalamus, basal ganglia, and amygdala. These regions are closely involved in obsessive-compulsive symptoms, emotional regulation, and sleep, aligning with the core clinical features of PANS. Notably, the study did not find significant differences in overall brain volume and showed limited differences in cerebral blood flow, suggesting the findings reflect microstructural changes rather than gross structural abnormalities. The authors interpret these diffusion abnormalities as consistent with the symptom domains that define PANS and conclude that diffusion MRI may provide useful quantitative information to support the diagnostic workup, while emphasizing that further prospective research is needed before imaging can be applied routinely in clinical practice.
Why this study matters
PANS is defined by sudden onset obsessive-compulsive symptoms (and/or restricted eating) plus additional abrupt neuropsychiatric symptoms. Clinically, the presentation can look “psychiatric-only” on the surface, yet many researchers and clinicians suspect an inflammatory process involving the brain, particularly circuits connected to the basal ganglia.
This study asks a practical, high-stakes question: Do children with PANS show measurable differences on brain MRI differences that could support the diagnostic workup with objective data?
What the researchers examined
The team compared diffusion-weighted MRI findings between:
- 34 patients with PANS (before immunomodulatory treatment)
- 64 pediatric control participants
They used atlas-based analysis to measure:
- Diffusion (reported as ADC / mean diffusivity) across multiple brain regions
- Brain volume
- Cerebral blood flow (available in a subset)
A key concept here: diffusion/ADC reflects how water molecules move through brain tissue. In the paper’s framework, increased diffusivity can be consistent with tissue microstructural differences in a context of neuroinflammation.
What they found
1) Diffusion was higher across all assessed brain regions in PANS
The central finding is straightforward:
All assessed brain regions had statistically significantly increased median diffusivity in patients with PANS compared with controls.
2) The biggest differences were in deep gray matter
The authors highlight the most pronounced increases in diffusion in deep gray matter structures, including:
- Thalamus
- Basal ganglia (caudate, putamen, pallidum)
- Amygdala
They interpret these regions as clinically relevant because they align with hallmark PANS symptoms—obsessions/compulsions, emotional dysregulation, and sleep disturbance—which are explicitly named in the Key Points and Results narrative.
3) Volume and cerebral blood flow were not clearly different
In contrast to diffusion findings:
- No statistically significant differences were found in brain volume measures between groups.
- Cerebral blood flow showed limited differences; in the analysis that included CBF, the paper reports only limited group differences, with broader variability among patients.
What this could mean for PANS evaluation
The authors’ “Meaning” statement is important because it stays in a clinically cautious lane:
Diffusion-weighted MRI may offer valuable quantitative information to assist with the diagnostic workup of PANS.
That’s not the same as saying “MRI can diagnose PANS.” What it does suggest is that—at least in this clinic-based sample—measurable brain microstructural differences were detectable using diffusion imaging, especially in circuits that plausibly map onto core symptom domains.
A note on clinical context inside the paper
The study includes a characterization of the PANS group at the time of MRI, showing substantial symptom burden and impairment. For example, the table excerpted in the article reports high rates of obsessions/compulsions and frequent anxiety, emotional dysregulation, and sleep disturbance, among other symptoms.
This matters because the paper is not describing mild, transient stress-related symptoms; it’s describing a cohort with significant clinical impact at presentation to a specialty clinic.
Limitations (as framed by the authors)
This was a retrospective case-control study from a single center clinic, and MRI timing varied across the illness course. The authors explicitly note that imaging was obtained at different points relative to symptom onset/flare and that patient heterogeneity in disease timing can influence findings.
They also emphasize that more work is needed—particularly prospective studies and clinical trials to determine how MRI diffusion measures might be used as a quantitative tool in evaluation and monitoring.
Gabriella True
