Unique Pattern of Intracranial Calcification: Neuroimaging Signature Distinguishing CSF1R-related Disorder from Autoimmune Encephalopathy
Jai Kumar Rajavoor Muniswamy1, Sidharth Suresh2, Max Herman2, Vanessa Marin Collazo2, Zbigniew Wszolek4, Karthik Muthusamy3
1Clinical Genomics, 2Neurology, 3Clinical Genomics and Neurology, Mayo Clinic, 4Neurology, Mayo Clinic- Jacksonville
Objective:
To define the neuroimaging (MRI+CT) signature of CSF1R-related disorder, to establish imaging discriminators that should prompt early genetic evaluation.
Background:
CSF1R-related disorder usually presents with adult-onset rapidly progressive white matter disease, seizures, and cognitive decline, a phenotype that usually triggers initial autoimmune workup and empiric immunotherapy in clinical practice. Key discriminating imaging features, including parenchymal calcifications and diffusion changes, remain underutilized in autoimmune neurology workflows, contributing to diagnostic delay.
Design/Methods:
A 37-year-old male presented with a four-year history of progressive neurologic disorder characterized by seizures, asymmetric weakness of extremities, dysarthria, urinary urgency, cognitive decline, and behavioral changes. Physical exam demonstrated asymmetric spasticity and extrapyramidal involvement with rigidity and dystonia.
Results:
Interval MRI brain demonstrated progressive T2 hyperintensities in periventricular and subcortical white matter involving frontal and parietal regions along with the corpus callosum and brain stem. Spine imaging demonstrated longitudinally extensive signal changes in the lateral and dorsal columns. Comprehensive autoimmune evaluation, including MOG-IgG, AQP4-IgG, and CSF analysis was unrevealing. Empiric trial of intravenous methylprednisolone administered elsewhere resulted in no clinical response.
Review of DWI images demonstrated scattered areas of restricted diffusion within involved white matter. Non-contrast CT revealed callosal calcifications in a characteristic ‘stepping-stone’ pattern. This constellation of imaging finding is incompatible with autoimmune/inflammatory leukoencephalopathy, and is considered characteristic of CSF1R-related disorder. Trio whole genome sequencing confirmed a heterozygous paternally inherited CSF1R variant (p.Ala780Thr, tyrosine kinase domain). Management options were then directed toward hematopoietic stem cell transplantation evaluation alongside spasticity management and multidisciplinary rehabilitation.
Conclusions:
CSF1R-related disorder has clinical and radiological overlap with autoimmune/inflammatory white matter disorders. Variability in the clinical spectrum and reduced penetrance with the absence of family history often leads to delay in suspicion and diagnostic evaluation. Identification of the radiologic hallmarks is paramount in prompting early genetic referral and consideration of potential treatment options including hematopoietic stem cell transplantation.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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