Relationship Between Timed 25-Foot Walk Impairment and Diffusion Tensor Imaging Markers in Multiple Sclerosis: STUDY

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To identify relationships between Timed 25-foot walk (T25FW) and both conventional MRI and diffusion tensor imaging (DTI) in MS patients.

T25FW is commonly used to gauge gait impairment in MS. We have previously shown widely variable response to Ampyra (dalfampridine) using this measure. Objective biological markers that correlate with patients’ disability are needed. DTI, quantifying fiber tract integrity, might provide such information. To undergird our ongoing investigation into imaging predictors of Ampyra response, we analyzed relationships between T25FW and DTI calculations.

Using our previously established cohort of Ampyra-treated subjects with T25FW data, a subset met inclusion criteria for the imaging sub-study. Patients underwent 3T brain and cervical MRI. Conventional metrics included T2 and T1 lesion volume; grey-, white- and normalized brain volume, and cervical cord volume at C2/3. Using restricted FOV (rFOV) RESOLVE DTI, mean diffusivity (MD) and fractional anisotropy (FA) were measured in brain cortico-spinal tracts (CST) and rFOV at C2/3. Hypothesizing that the region of greatest impairment drives loss of function, we analyzed both mean right/left brain CST FA values, as well as the lower of the two values.

Eleven subjects met inclusion criteria. Mean T25FW was 8.2 seconds (range=4.8-12.5); 73[percnt] patients had progressive disease. Mean brain CST FA was 0.53 (SD=0.038), mean CST MD was 0.8x10-3 mm2/sec (SD=0.06). Mean spinal FA was 0.68 (SD=0.04), and mean MD was 1.08x10-3mm2/sec (SD=0.087). Only lowest CST FA (mean=0.54, SD=0.042) significantly inversely correlated with T25FW (r=-0.63), with a trend using linear regression (p=0.174).

Our results suggest modest correlation between CST damage shown by FA with T25FW impairment in this Ampyra-treated cohort. Inability to demonstrate cord imaging predictors may relate to known technical limitations of spinal DTI or small sample size. These results will inform our subsequent analyses of MRI predictors of Ampyra response.

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