Abstract
BackgroundClassically characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities, Wolfram syndrome (WFS) is also associated with atypical brainstem and cerebellar findings in the first decade of life. As such, we hypothesized that gait differences between individuals with WFS and typically developing (TD) individuals may be detectable across the course of the disease.MethodsGait was assessed for 13 individuals with WFS (min 6.4 yrs, max 25.8 yrs) and 29 age-matched, typically developing individuals (min 5.6 yrs, max 28.5 yrs) using a GAITRite ® walkway system. Velocity, cadence, step length, base of support and double support time were compared between groups.ResultsAcross all tasks, individuals with WFS walked slower (p = 0.03), took shorter (p ≤ 0.001) and wider (p ≤ 0.001) steps and spent a greater proportion of the gait cycle in double support (p = 0.03) compared to TD individuals. Cadence did not differ between groups (p = 0.62). Across all tasks, age was significantly correlated with cadence and double support time in the TD group but only double support time was correlated with age in the WFS group and only during preferred pace forward (rs= 0.564, p = 0.045) and dual task forward walking (rs= 0.720, p = 0.006) tasks. Individuals with WFS also had a greater number of missteps during tandem walking (p ≤ 0.001). Within the WFS group, spatiotemporal measures of gait did not correlate with measures of visual acuity. Balance measures negatively correlated with normalized gait velocity during fast forward walking (rs = −0.59, p = 0.03) and percent of gait cycle in double support during backward walking (rs = −0.64, p = 0.03).ConclusionsQuantifiable gait impairments can be detected in individuals with WFS earlier than previous clinical observations suggested. These impairments are not fully accounted for by the visual or balance deficits associated with WFS, and may be a reflection of early cerebellar and/or brainstem abnormalities. Effective patient-centered treatment paradigms could benefit from a more complete understanding of the progression of motor and other neurological symptom presentation in individuals with WFS.
Highlights
Characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities, Wolfram syndrome (WFS) is associated with atypical brainstem and cerebellar findings in the first decade of life
Developing individuals were examined for neurological soft signs via the Physical and Neurological Examination for Subtle Signs (PANESS) [24], and were excluded if they presented more than two standard deviations below the mean for their age group
The average number of verbal responses generated during dual task walking trials for typically developing (TD) and WFS did not differ significantly (F = 0.408, p = 0.53) between groups
Summary
Characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities, Wolfram syndrome (WFS) is associated with atypical brainstem and cerebellar findings in the first decade of life. Clinical evaluation of magnetic resonance images (MRIs) in a small sample of young individuals (mean age 17.5 years) with WFS revealed atrophy in the brainstem [14]. This finding was confirmed and extended by a recent, objectively quantified analysis of a larger and younger sample of people with WFS, which found reduced gray and white matter volumes and reduced white matter microstructural integrity within the brainstem and cerebellum as compared to age and gender comparable healthy and type 1 diabetic control groups [15]. Until recently gait and balance abnormalities in WFS have only been vaguely and qualitatively described
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