Exploring the Roles of Central and Peripheral Nervous System Function in Gait Stability: Preliminary Insights from Cancer Survivors

Abstract

Background: Impairments in central and/or peripheral nervous systems are known to be associated with altered gait; however, the interplay between cognitive function, peripheral sensation, and orbital gait stability remains largely unclear. Elucidating these relationships is expected to provide a clearer understanding of potential fall risk factors across various populations and targets for novel interventions. Many patients diagnosed with cancer are treated with chemotherapy agents known to be neurotoxic to the central and/or peripheral nervous systems that can contribute to movement deficiencies, making this population a novel model to investigate these relationships.

Research question: The purpose of this exploratory study was to investigate how central and peripheral nervous system impairments associate with orbital stability during single- and dual-task gait.

Methods: Twenty cancer survivors were enrolled and separated into three groups: no prior chemotherapy exposure (CON, n = 6), and prior treatment with chemotherapy and having no/mild chemotherapy-induced peripheral neuropathy (CIPN) symptoms (-CIPN, n = 8) or moderate/severe CIPN symptoms (+CIPN, n = 6). Testing included single- and dual-task (i.e., serial sevens) treadmill walking as well as a computerized test of executive function. Maximum Floquet multipliers were calculated to assess orbital stability during gait.

Results: Worse executive function was associated with decreased orbital stability during the dual-task condition in the +CIPN group (Spearman's ρ = 0.94, P = 0.017). Additionally, decreased orbital stability during dual-task gait was observed for the -CIPN group compared to the CON group (ES = 1.96, P = 0.019).

Significance: Executive dysfunction was associated with decreased gait stability during challenging dual-task gait in survivors with sensory symptoms of CIPN. The association between combined central and peripheral nervous system impairments and decreased gait stability in cancer survivors provides a novel demonstration of potential compensatory strategies that accompany deficiencies in these functions. Future work is needed to confirm these relationships and whether they hold in other populations.

Keywords: Dual-task gait; Executive function; Neuropathy; Orbital stability.

Figure 1.

Schematic representation of the relationships of interest. a) How does altered peripheral sensation (i.e., sensory symptoms of CIPN) associate with gait stability? b) Are estimates of cognitive function (executive function) correlated with gait stability? c) How does altered peripheral sensation influence the potential relationships between cognitive function and gait stability?

Figure 2.

Maximum Floquet multiplier (maxFM) across the gait cycle during single-task (left) and dual-task (right) gait. Lines represent group means and shaded region corresponds to ± 1SD for the CON group. The most pronounced differences between groups are that the -CIPN group had higher maxFM estimates early in the gait cycle for the dual-task condition, indicating lower orbital stability.

Figure 3.

Proposed theoretical framework to interpret the increased dual-task cost for orbital stability in participants with CIPN sensory symptoms and poorer executive function. A. Peripheral nervous system impairments are commonly associated with CIPN. These impairments may result in a compensatory increase in cognitive attention devoted to gait to accommodate degraded afferent sensory information. Greater concentration on gait may correspond to maintained or increased attenuation of perturbations during gait, which would represent a potential increase in orbital stability. B. Experimental data showing increased orbital stability in +CIPN participants (solid markers and line; ρ = −0.94 (95% CI: −1.05, −0.77)) with worse executive function during single-task gait. C. When a simultaneous cognitive task is introduced (i.e., a dual task), the ability to compensate for degraded afferent information via increased attention is hindered. Individuals with cognitive impairments may be preferentially impacted. A consequence of the degraded afferent information along with divided attention may be a decrease in orbital stability for individuals with combined peripheral and central nervous system impairments. D. Experimental data showing increased dual-task cost (% change from single- to dual-task gait) in orbital stability for +CIPN participants with worse executive function (ρ = 0.94 (95% CI: 0.78, 1.05)). The aforementioned relationships were not detected in the CON or -CIPN groups (hollow markers and dashed lines), which is consistent with an attentionally-demanding compensatory strategy in +CIPN group being associated with the presence of sensory symptoms of CIPN. As everyday activities are performed in the presence of a number of potential concurrent demands and distractions, dual-task assessments may provide insight into physiologically-relevant demands and behavior that exist outside of the laboratory.