The research, led by Giulia Casu and Massimiliano Pau of the University of Cagliari together with colleagues at the Regional Multiple Sclerosis Center of Sardinia, set out to answer a deceptively simple question: what actually happens to the quality of walking as fatigue accumulates over six minutes of continuous walking? While clinicians routinely use the six-minute walk test to gauge exercise capacity, the fine-grained temporal and spatial coordination of gait during this endurance challenge had been explored only through a single metric, leaving much of the picture unexamined.

To capture that picture, the team recruited 65 people with MS who could walk unaided for at least 200 meters, along with 43 age- and sex-matched unaffected individuals. Each participant wore eight miniaturized inertial measurement units sampling at 200 hertz, positioned on the lower spine, sacrum, thighs, tibiae, and forefeet. These wearable sensors tracked accelerations and angular velocities throughout the walk, allowing the researchers to reconstruct heel-strike events and joint-angle trajectories for hip and knee flexion-extension as well as ankle dorsi-plantarflexion. The 180-degree turns between consecutive 30-meter walking segments were carefully identified from pelvic yaw signals and excluded, ensuring that only steady-state straight-line walking entered the analysis.

On average, people with MS covered 477.95 meters over six minutes, significantly less than the 626.94 meters managed by unaffected participants, and both groups slowed progressively. But the most revealing findings came from the coordination metrics. The researchers computed the Phase Coordination Index, or PCI, a temporal measure that captures how accurately and consistently the left and right legs maintain ideal anti-phased stepping at 180 degrees. Healthy individuals typically score between 2 and 4 percent; lower values indicate better bilateral coordination. In this study, the MS group showed significantly higher PCI values than controls across the entire test, with a significant positive linear trend across the six minutes for both groups.

Strikingly, by the end of the test PCI had risen by about 53 percent in unaffected individuals but only 32 percent in people with MS. This counterintuitive pattern — the group with the disease deteriorating less — suggests a ceiling effect. People with MS started from a baseline of already-impaired coordination, constrained by reduced interhemispheric communication between the primary motor cortices, microstructural spinal cord damage, and degraded integrity of corticospinal, cerebellar, and brainstem pathways. With less adaptive capacity remaining, there was simply less room for further fatigue-driven decline. Their consistently slower walking speed may also have limited the range of available coordination strategies, restricting how much further measurable change was possible.

The study’s key methodological innovation was pairing this temporal metric with spatial measures derived from cyclograms — angle-angle diagrams that plot one joint’s motion against another across the gait cycle. From these closed curves, the team extracted geometric features including area, orientation, perimeter, and a dimensionless shape ratio. A perfectly symmetrical gait would collapse the inter-limb cyclogram onto a 45-degree line with zero area; larger areas and orientations deviating from that line signal asymmetry. For inter-joint analysis, hip-knee and knee-ankle cyclograms revealed how conjointly the adjacent joints modulate their movements through each stride.

The spatial data confirmed significant group differences at nearly every point measured. People with MS showed larger inter-limb cyclogram areas, orientations, and trend symmetry values at the hip and knee, indicating reduced symmetry, while their inter-joint cyclogram areas and perimeters for the hip-knee and knee-ankle couples were consistently reduced, reflecting a diminished dynamic range of motion and a reduced ability to modulate joint interactions across the phases of the gait cycle. Correlation analysis added clinical weight: within the MS group, PCI at minute one showed a moderate positive correlation with the MSWS-12 patient-reported walking scale, while hip-knee and knee-ankle cyclogram areas showed moderate-to-large negative correlations, linking laboratory measures of coordination directly to patients’ own perception of walking disability.

The temporal evolution of inter-joint coordination proved particularly instructive at the knee-ankle couple. In unaffected individuals, cyclogram area dropped significantly from the second minute onward; in people with MS, the reduction began a minute later. By the end of the test, however, the overall magnitude of change was similar in both groups. The authors interpret this as a possible convergence toward a shared, fatigue-driven motor strategy that prioritizes stability over flexibility at the distal joints. The ankle, central to propulsion and foot clearance, appears especially vulnerable to fatigue-related impairments such as reduced plantarflexion at push-off, which tightens its coupling with the knee. In contrast, the knee joint alone showed significant fatigue-related worsening only in unaffected individuals, possibly because compensatory strategies common in MS — increased reliance on proximal joints and muscular co-contraction to enhance stability — mask further deterioration at that level.

The authors acknowledge limitations, including a group size too small for stratified analyses of disability level, sex, or fatigability, and the fact that gait speed was not experimentally controlled, which means coordination changes over time cannot be fully disentangled from concurrent speed changes. The repeated turns demanded by the six-minute protocol may also have added sensorimotor load not directly quantified. Even so, the consistency of the baseline coordination deficits across both temporal and spatial domains, and their agreement quantitatively with values reported in earlier independent studies, underscores the robustness of the approach.

The clinical implications reach well beyond the laboratory. Because baseline coordination deficits and fatigue-related changes followed dissociable patterns, rehabilitation strategies for MS may need to target coordination quality and adaptability explicitly, not merely walking endurance. The sensitivity of cyclogram-based measures to knee-ankle coupling suggests that distal coordination is a promising target for interventions aiming to improve propulsion efficiency and stability during prolonged walking. And because temporal and spatial metrics captured joint- and domain-specific behaviors that a single index missed, the multimodal framework developed here offers clinicians a more complete toolkit for tailoring rehabilitation, monitoring therapeutic response, and identifying patients who rely on compensation rather than genuine adaptive motor control — a step toward better walking performance, reduced fatigability, and greater independence in daily life for people living with MS.

Subject of Research: Temporal and spatial gait coordination changes during the six-minute walk test in people with multiple sclerosis, measured with wearable inertial sensors.

Article Title: Changes in temporal and spatial gait coordination during the six‑minute walk test in people with multiple sclerosis

Article References: Casu, G., Lostia di Santa Sofia, E., Leban, B., Inglese, C., Coghe, G., Frau, J., Cocco, E., & Pau, M. (2026). Changes in temporal and spatial gait coordination during the six‑minute walk test in people with multiple sclerosis. Medical & Biological Engineering & Computing. https://doi.org/10.1007/s11517-026-03678-x

Image Credits: AI Generated

DOI: 10.1007/s11517-026-03678-x

Keywords: multiple sclerosis, gait coordination, six-minute walk test, phase coordination index, cyclograms, inertial measurement units, gait analysis, fatigue, rehabilitation, biomechanics, mobility, neurology