7-Tesla Brain MRI as A Biomarker of Disease Onset and Progression in CSF1R Mutation Carriers – Preliminary Report
Zbigniew Wszolek1, Erik Middlebrooks2, Jaroslaw Dulski1
1Department of Neurology, 2Department of Radiology, Mayo Clinic Florida
Objective:
To investigate the potential application of 7-Tesla (T) MRI as a biomarker of disease onset and progression in CSF1R mutation carriers.
Background:
CSF1R-related disorder (CSF1R-RD) is a hereditary neurodegenerative disease with rapid progression and death ensuing within few years from onset. Disease-modifying treatment is already available, and recently, glucocorticoid use as preventive therapy was reported. However, there are no biomarkers available to monitor conversion from asymptomatic to symptomatic stage, as well as disease progression in CSF1R mutation carriers.
Design/Methods:
Three heterozygous carriers (females n=2) of CSF1R pathogenic mutations at a mean age of 41 years (range 26-50 years) and positive family history for the late-onset (≥18 years) form of CSF1R-RD were recruited and assessed with clinical measures and 7T brain MRI at baseline and at 6-month follow-up. Sundal's MRI scale was used to quantify neuroimaging findings.
Results:
The clinical and radiological evaluations were performed at a mean interval of 5 months. During the follow-up period, two individuals remained asymptomatic, whereas one individual progressed in the clinical measures. The Sundal’s MRI scale score remained stable in the two asymptomatic individuals with a mean score of 6 points, whereas it progressed in the symptomatic individual from 8 to 10 points.
Conclusions:
The 7-Tesla MRI findings correlate well with the clinical measures of the CSF1R-RD both at the asymptomatic and symptomatic stages. Further research is warranted to assess the sensitivity and specificity of 7T MRI findings. Identification of biomarkers of CSF1R-RD would help timely application of preventive and disease-modifying therapy.