Gait Analysis at Multiple Speeds Reveals Differential Functional and Structural Outcomes in Response to Graded Spinal Cord Injury

Abstract

Open-field behavioral scoring is widely used to assess spinal cord injury (SCI) outcomes, but has limited usefulness in describing subtle changes important for posture and locomotion. Additional quantitative methods are needed to increase the resolution of locomotor outcome assessment. This study used gait analysis at multiple speeds (GAMS) across a range of mild-to-severe intensities of thoracic SCI in the rat. Overall, Basso, Beattie, and Bresnahan (BBB) scores and subscores were assessed, and detailed automated gait analysis was performed at three fixed walking speeds (3.5, 6.0, and 8.5 cm/sec). Variability in hindpaw brake, propel, and stance times were analyzed further by integrating across the stance phase of stepping cycles. Myelin staining of spinal cord sections was used to quantify white matter loss at the injury site. Varied SCI intensity produced graded deficits in BBB score, BBB subscores, and spinal cord white matter and total volume loss. GAMS measures of posture revealed decreased paw area, increased limb extension, altered stance width, and decreased values for integrated brake, propel, and stance. Measures of coordination revealed increased stride frequency concomitant with decreased stride length, resulting in deviation from consistent forelimb/hindlimb coordination. Alterations in posture and coordination were correlated to impact severity. GAMS results correlated highly with functional and histological measures and revealed differential relationships between sets of GAMS dynamics and cord total volume loss versus epicenter myelin loss. Automated gait analysis at multiple speeds is therefore a useful tool for quantifying nuanced changes in gait as an extension of histological and observational methods in assessing SCI outcomes.

A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments

“…Interlimb coordination was also diminished after blast SCI, as evidenced by an increase in diagonal phase dispersion. Similar, albeit greater, decreases in interlimb coordination have been reported after both unilateral hemisection and contusive injuries (Jin et al, 2014; Krizsan-Agbas et al, 2014; Redondo-Castro et al, 2013), and attributed to damage to the propriospinal tracts linking fore-limb and hindlimb central pattern generators (Jin et al, 2014). …”

“…The mice subjected to blast did not show consistent changes in any of their gait parameters over this time period, nor were there consistent differences between the blasted and sham mice. Whether the absence of persistent deficits indicated recovery of normal gait and/or if it reflected the increased variability in gait that other investigators have described when over-training rodents on treadmill systems (Beare et al, 2009; Krizsan-Agbas et al, 2014) is not clear. We did, however, observe a striking loss in the ability of many blasted mice to maintain their position on the treadmill over the 4-week long test period (Figs.…”

“…Each mouse was tested at two speeds, 20 cm/s and 30 cm/s. As recently noted by Krizsan-Agbas et al (2014), variability was greater at the lower speed, and so we focused our analysis on 30 cm/s. We tested 34 blast and 27 sham mice before blast and again at 2 days post-blast.…”

Ground reaction forces are more sensitive gait measures than temporal parameters in rodents following rotator cuff injury

“…Second, it is noted that non-force couple gait analysis systems can calculate temporal metrics other than stance, propulsion, and braking duration. However, these parameters were selected for the current study as they are commonly reported, easy to interpret, and have been previously associated with the interval available for force generation (Allen et al, 2009; Angeby-Moller et al, 2008; Hampton et al, 2011; Krizsan-Agbas et al, 2014). Despite these limitations, our results clearly demonstrate that ground reaction forces are more sensitive than kinetic parameters to differences in gait in a rat model of rotator cuff injury.…”

“…Interpretation of the clinical relevance of tissue-level animal studies can be aided with quantitative measures of limb/joint function (Fu et al, 2015; Reuther et al, 2014b). Gait analysis is a highly sensitive, non-invasive technique used to study the pathophysiology of various orthopaedic diseases (Clarke et al, 1997; Krizsan-Agbas et al, 2014; Mora-Macias et al, 2015). For example, abnormalities in kinetic gait parameters during locomotion have been observed in rat models of osteoarthritis, spinal cord injury recovery, and rotator cuff disease (Johnson et al, 2012; Reuther et al, 2015; Roemhildt et al, 2010).…”