Commentary on gait analysis in Duchenne muscular dystrophy: integrating contracture, strength, and kinematic perspectives

INTRODUCTION

Duchenne Muscular Dystrophy (DMD) remains one of the most extensively studied neuromuscular disorders due to its profound implications for motor function and quality of life. As a progressive X-linked disease caused by mutations in the dystrophin gene, DMD manifests as chronic muscle fiber necrosis, weakness, and eventual loss of ambulation^[1,2]. Among the diverse phenotypic presentations of DMD, gait abnormalities stand as clinically significant biomarkers for disease progression and therapeutic efficacy. The recent longitudinal work by Bagley et al.^[3] on the use of gait-based biomarkers provides valuable insights into the multifactorial determinants of gait deterioration in ambulatory boys with DMD, focusing on the interplay between contractures, muscle strength, and gait kinematics.

RESULTS

Bagley et al.^[3] identified ankle plantar flexion contractures and decreased dorsiflexion as the earliest and most pronounced musculoskeletal limitation, often appearing as early as four years of age, consistent with earlier work^[4]. The longitudinal design of the study supports previous cross-sectional findings that contractures, though progressive, are not uniformly distributed across joints. Hip flexion contractures and adductor tightness appear later and remain comparatively mild, whereas ankle contractures exhibit both early onset and steep progression. This distribution reflects the proximal-to-distal gradient of muscle involvement, where distal contractures develop as compensatory adaptations to proximal weakness^[5,6].

The association between contracture development and gait spatiotemporal parameters, including speed, stride length, and cadence, underscores the dynamic nature of ambulatory decline in DMD. Bagley et al.^[3] demonstrated that hip flexor contracture and reduced hip extensor and ankle plantar flexor strength were significant predictors of gait speed decline. This relationship aligns with Perry’s seminal framework on gait biomechanics, which positions the hip extensors and ankle plantar flexors as primary torque generators for forward propulsion^[7]. As these muscle groups weaken, compensatory strategies - such as increased lumbar lordosis and anterior pelvic tilt - emerge to maintain upright posture^[8]. However, these adaptations are metabolically costly and exacerbate gait inefficiency over time.

Importantly, the study also highlights the value of quantitative gait metrics as sensitive indicators of disease progression. While traditional clinical assessments - such as manual muscle testing and passive range of motion - offer qualitative information, gait variable scores (GVS) provide objective, reproducible measures of kinematic deviations. In particular, pelvic tilt and obliquity GVS were significantly associated with declines in gait speed and cadence, respectively, suggesting that alterations in pelvic control may serve as early markers of functional regression. This finding complements the work of Heberer et al.^[9] who identified hip kinetics as a sensitive correlate of early muscle weakness.

A major strength of the study by Bagley et al.^[3] lies in its integration of biomechanical modeling and nonlinear mixed-effects analysis, which captures individual variability in disease progression. Such approaches, increasingly advocated in longitudinal neuromuscular research^[10], enable differentiation between within-subject trajectories and between-subject heterogeneity. This is particularly relevant in DMD, where genotype-phenotype correlations and treatment responsiveness introduce considerable variability^[11]. The modeling framework thus facilitates the identification of subtle biomechanical inflection points that may precede clinical loss of ambulation.

The broader literature reinforces the clinical value of gait analysis in DMD management since consistent reductions in walking speed and stride length in DMD cohorts relative to typically developing peers are widely recognized^[12,13]. These parameters decline in parallel with deteriorations in lower-limb muscle strength and joint range of motion, supporting the view that gait analysis offers a non-invasive biomarker for therapeutic monitoring. Moreover, Sienko et al.^[14] and Buckon et al.^[15] have recently shown that Gait Profile Scores (GPS) and quantitative strength measures correlate strongly with timed function tests such as the 6-Minute Walk Test. Integrating these objective gait measures into clinical trials could thus enhance sensitivity in detecting early therapeutic effects, particularly for emerging gene addition, exon-skipping therapies and more recently emerging genome-editing therapies^[16].

Nonetheless, the study’s findings also invite methodological reflection. The exclusion of non-ambulatory participants limits generalizability to later disease stages. Furthermore, although the use of the Thomas test provides standardization for hip contracture measurement, it may underestimate true hip extension limitations^[17]. Also, the authors note that the sample size for muscle strength analysis was limited, as only 57 of 75 subjects were able to complete these assessments.

Clinically, the evidence supports early and sustained interventions targeting contracture prevention and strength preservation. Nighttime ankle-foot orthoses, regular stretching protocols, and corticosteroid therapy remain standard measures for prolonging ambulation^[18]. Novel therapeutic directions, including utrophin upregulation, antisense oligonucleotide therapies, adeno-associated virus (AAV) mediated microdystrophin delivery, and more recently gene-editing^[19], may further stabilize gait parameters by mitigating primary muscle pathology. However, the study by Bagley et al.^[3] underscores the dual challenge of DMD: biology and biomechanics. While genetic therapies aim to correct the root defect, clinical teams must still address secondary complications - contractures, pelvic instability, and the fear of falling - that erode independence. Nighttime ankle orthoses, stretching protocols, and proactive strength maintenance remain vital complements to emerging molecular therapies.

In parallel, rehabilitation programs should emphasize proximal strengthening and balance training to maintain pelvic stability, given its predictive value for gait efficiency and fall risk. Indeed, the pathomechanics described by Bagley et al.^[3] echo the progressive loss of pelvic and lower-limb muscle control characteristic of DMD. Early gait deviations, such as increased anterior pelvic tilt, reduced knee flexion during stance, and excessive foot drop during swing, reflect compensatory efforts to maintain forward propulsion despite proximal weakness^[8,9,20]. These maladaptations progressively compromise gait efficiency and may accelerate fatigue and energy expenditure^[12], as recently shown by the progressive increase in the energy cost of walking in boys with DMD, closely linked to declining gait kinematics^[21]. Thus, interventions that preserve pelvic alignment and ankle mobility may yield disproportionate benefits in functional endurance.

CONCLUSION

The study by Begley et al.^[3] could have placed a greater emphasis on the clinical application of the outcome parameters such as gait profile score. Also, the study could have justified more how and why the monitored parameters could be more sensitive than traditional outcomes such as timed function tests and manual motor testing. Nevertheless, the study offers a significant contribution to the understanding of longitudinal gait changes in DMD. Its findings confirm that gait spatiotemporal parameters, particularly speed, stride length, and cadence, serve as sensitive markers of disease progression, closely linked to specific biomechanical impairments. The study advances a multidimensional model of DMD gait pathology, in which contractures, muscle weakness, and kinematic deviations interact dynamically. Going forward, the integration of quantitative gait metrics into both clinical and research frameworks will be essential for optimizing patient monitoring and evaluating emerging therapeutics. Such approaches will ensure that the evolving landscape of DMD management remains firmly grounded in objective, functional patient-reported outcome measures (PROMs). In summary, integrating quantitative gait metrics into clinical practice shows potential to support early identification of disease progression. This, in turn, could facilitate timely interventions using both traditional and advanced therapies, such as exon skipping and gene editing. Additionally, such metrics could be important in patient selection for emerging treatments in the clinical trial setting.