Balance impairment in individuals with Wolfram syndrome

Abstract

Aim: Wolfram syndrome (WFS), a rare neurodegenerative disorder, is characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities. Although previously unreported, we hypothesized that neurological complications may be detectable in relatively early stages of the disease. As the cerebellum and brainstem seem particularly vulnerable in WFS, we focused on balance functions critically dependent on these regions. The primary goal of this investigation was to compare balance in young individuals with WFS, in relatively early stages of the disease, to an age-matched cohort using a clinically applicable test.

Method: Balance was assessed via the mini-BESTest in 13 children, adolescents and young adults with WFS and 30 typically developing age-matched individuals.

Results: A significant difference was observed between groups in balance as well as in three of four subcomponents of the mini-BESTest and in two timed tasks related to balance. Mini-BESTest scores were correlated with age among typically developing individuals. In the WFS group, mini-BESTest scores were related to overall motor dysfunction, but not age.

Interpretation: Impairments in balance in WFS may occur earlier in the disease process than previously recognized and appear to be related to overall neurological progression rather than chronological age. Recognizing balance impairments and understanding which balance systems contribute to balance deficits in those with WFS may allow for development of effective patient-centered treatment paradigms.

Figure 1

Frequency of mini-BESTest (A) and mini-BESTest Subcomponent scores (B–E) for typically developing (left) and WFS (right). (A) mini-BESTest total score; (B) anticipatory transitions (AT) subcomponent scores; (C) postural responses (PR) subcomponent scores; (D) sensory orientation (SO) subcomponent scores and (E) dynamic gait (DG) subcomponent, maximum 10. Individual with WFS scored significantly lower in the overall mini-BESTest and all subcomponents except dynamic gait.

Figure 2

Timed balance tasks for the typically developing (grey) and WFS (white) groups. Times for the step over an obstacle (SOO) and Timed Get Up and Go (TUG) and subsections differed between groups (# = p ≤ 0.001). Cognitive Get Up & Go With Dual Task (DT-TUG) times did not differ between groups (p = 0.38). Within group, comparisons of TUG to DT-TUG showed within group differences at all levels (## = p < 0.05).

Figure 3

Mini-BEST total scores compared to (a) age and (b) PANESS Gaits and Stations reverse z-scores. A) A significant positive correlation between mini-BEST and age was present for typically developing individuals (triangles) but not individuals with WFS (squares). B) A significant positive correlation between mini-BEST and PANESS reverse z-scores was present for the WFS group, but not the typically developing individuals.