Longitudinal change in fine motor skills after brain radiotherapy and in vivo imaging biomarkers associated with decline

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Abstract
We explored fine motor skills (FMS) before and after brain radiotherapy (RT), analyzing associations between longitudinal FMS and imaging biomarkers of cortical and white matter (WM) integrity in motor regions of interest (ROIs). On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric brain MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant Hands [PDH], and Grooved Pegboard Nondominant Hands [PNDH]) at baseline and 3-, 6-, and 12-month post-RT. Motor ROIs autosegmented included: sensorimotor cortices and superficial WM, corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Volume (cc) was measured in all ROIs at each timepoint. Diffusion biomarkers (FA [fractional anisotropy] and MD [mean diffusivity]) were additionally measured in WM ROIs. Linear mixed-effects models assessed biomarkers as predictors of FMS scores. P values were corrected for multiple comparisons. Higher RT dose was associated with right paracentral cortical thinning (β = −2.42 Gy/(month × mm), P = .03) and higher right precentral WM MD (β = 0.69 Gy/(month × µm2/ms), P = .04). Higher left (β = 38.7 points/(month × µm2/ms), P = .004) and right (β = 42.4 points/(month × µm2/ms), P = .01) cerebellar WM MD, left precentral cortical atrophy (β = −8.67 points/(month × mm), P = .02), and reduced right cerebral peduncle FA (β = −0.50 points/month, P = .01) were associated with worse DKEFS-MS performance. Left precentral cortex thinning was associated with worse PDH scores (β = −17.3 points/(month × mm), P = .02). Left (β = −0.87 points/(month × cm3), P = .001) and right (β = −0.64 points/(month × cm3), P = .02) cerebellar cortex, left pons (β = −19.8 points/(month × cm3), P = .02), and right pallidum (β = −10.8 points/(month × cm3), P = .02) atrophy and reduced right internal capsule FA (β = −1.02 points/month, P = .03) were associated with worse PNDH performance. Biomarkers of microstructural injury in motor-associated brain regions were associated with worse FMS. Dose avoidance in these areas may preserve FMS.
Funding Information
  • National Institutes of Health (1TL1TR001444, 1TL1TR001443, F31 NS111883-01, UL1TR001442)
  • CTRI (1KL2TR001444, UL1TR000100, R01 CA238783-01)
  • National Cancer Institute
  • UC San Diego Moores Cancer Center (P30 CA02310029)
  • American Cancer Society (RSG-15-229-01-CCE)

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