Mismatch of MRI White Matter Hyperintensities and Gait Function in Patients With Cerebral Small Vessel Disease

Background: Cerebral small vessel disease (CSVD) is closely related to gait disorders. Previous studies have found a negative correlation between the severity of MRI white matter hyperintensities (WMH) and gait speed. However, not every individual with WMH experiences a gait disorder.Purpose: To investigate the mechanisms underlying the mismatch between the severity of MRI WMH and gait impairment, in particular in subjects with severe WMH (Fazekas 3, scale 0-3) resulting from vascular disease.Study Type: Cohort.Population: 54 subjects with severe WMH and gait disorder (WMH-GD; 29 males) and 114 subjects with severe WMH with no gait disorder (WMH-nGD; 60 males).Field Strength/Sequence: 3T/diffusion tensor imaging (DTI), and T1-weighted, T2-weighted, FLAIR, DWI, SWI.Assessment: Trace-based spatial statistics analysis (TBSS) approach (fractional anisotropy, FA; mean diffusivity; radial diffusivity; axial diffusivity); Cognitive assessment; Conventional MRI markers of CSVD (WMH, enlarged perivascular spaces, lacunae, and cerebral microbleeds); Gait parameters (gait speed; cadence; stride length; gait cycle duration; step duration; time-up-and-go test, TUG). Gait disorder was defined as a TUG time exceeding 12 sec.Statistical Tests: The t-tests, Mann-Whitney U tests, Chi-square tests, and partial correlation analysis (Pearson or Spearman) were used. P < 0.05 with threshold-free cluster enhancement corrected was considered statistically significant for TBSS.Results: After adjusting for age, sex, height, and other conventional MRI markers of CSVD, the WMH-nGD group showed significantly decreased FA values in the corpus callosum, bilateral superior longitudinal fasciculus, left corona radiata, and left posterior thalamic radiation. There was a significant association between FA values and TUG time, gait speed, and stride length in multiple WM tracts, independent of other conventional CSVD markers.Data Conclusion: This study provides evidence for microstructural damage of specific fibers in WMH-GD subjects compared to WMH-nGD subjects. This may explain the mismatch between WMH and gait impairment in subjects with severe WMH.