Construct Validity of the 10-meter Walk/Run Test to Assess Motor Impairment in Patients with Alexander Disease
Aaron Yarlas1, Ann Harrington2, Tracy Kornafel2, Elizabeth Ballance2, Kimberly Kopin2, Samuel R. Pierce2, Joshua Joung2, Kathryn Gallison2, Geraldine W Liu2, Walter Faig2, Abigail Collins1, Amy T. Waldman2
1IONIS Pharmaceuticals, 2Children’s Hospital of Philadelphia
Objective:
To evaluate construct validity of the 10-meter walk/run test (10MWRT) to capture motor impairments in patients with Alexander disease (AxD).
Background:
There are no validated outcome measures to capture motor impairments in patients with AxD, a rare progressive astrocytopathy.
Design/Methods:
Patients with clinical and radiographic features of AxD, confirmed by a pathologic variant in GFAP, were enrolled in a natural history study with data collected by physical and occupational therapists using standardized testing. Clinical outcome assessments included 10MWRT, Gross Motor Function Measure-88 (GMFM-88), Peabody Developmental Motor Scales-2 (PDMS-2), Berg Balance Scale (BBS), Pediatric Balance Scale (PBS), Gross Motor Function Classification System Expanded and Revised (GMFCS-ER), and Manual Ability Classification System (MACS). For 10MWRT (but not GMFM-88), orthoses or assistive devices were allowed. For 10MWRT, patients were instructed to walk or run as fast as possible from start line to finish line. Time was recorded for three trials. Construct validity was evaluated by strength of associations between the fastest of three 10MWRT trials and concurrent GMFM-88 (walking domain and total score), PDMS-2 Gross Motor Score, PBS, and BBS (convergent validity), and GMFCS-ER and MACS (known-groups validity). Pearson correlations (convergent validity) and numeric mean differences (known-groups validity) assessed associations among measures at first visit with 10MWRT completed.
Results:
Thirty patients (13 females; mean [SD] age 16.5 [15.3] years, range 2.2-54.8) completed 10MWRT. Fastest 10MWRT time correlated strongly with GMFM-88 (Domain E: r=-0.68, Total: r=-0.76), PDMS-2 Gross Motor Score (<6 years old only, n=5, r=-0.94), and BBS (>13 years, n=14, r=-0.82) or PBS (<13 years, n=12, r=-0.90). Stepwise numeric increases in mean 10MWRT rates were observed with greater impairments on GMFCS and MACS. Sensitivity analyses using all available 10MWRT assessments to date supported primary analyses.
Conclusions:
Data support 10MWRT as a construct valid measure to capture motor function in patients with AxD.