Neurological scoring and gait kinematics to assess functional outcome in an ovine model of ischaemic stroke

Annabel J Sorby-Adams; Oana C Marian; Isabella M Bilecki; Levi E Elms; Jonathan Camargo; Kelly Hall; Robert G Crowther; Anna V Leonard; George I Wadsworth; Joshua H Spear; Renée J Turner; Claire F Jones

doi:10.3389/fneur.2023.1071794

Neurological scoring and gait kinematics to assess functional outcome in an ovine model of ischaemic stroke

Front Neurol. 2023 Feb 20:14:1071794. doi: 10.3389/fneur.2023.1071794. eCollection 2023.

Authors

Affiliations

¹ School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
² George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, United States.
³ School of Public Health, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
⁴ Alliance for Research in Exercise, Nutrition and Activity (ARENA), University of South Australia, Adelaide, SA, Australia.
⁵ School of Mechanical Engineering, Faculty of Sciences, Engineering and Technology, The University of Adelaide, Adelaide, SA, Australia.
⁶ Adelaide Spinal Research Group, Centre for Orthopaedics and Trauma Research, The University of Adelaide, North Terrace, SA, Australia.
⁷ Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, SA, Australia.

Abstract

Background: Assessment of functional impairment following ischaemic stroke is essential to determine outcome and efficacy of intervention in both clinical patients and pre-clinical models. Although paradigms are well described for rodents, comparable methods for large animals, such as sheep, remain limited. This study aimed to develop methods to assess function in an ovine model of ischaemic stroke using composite neurological scoring and gait kinematics from motion capture.

Methods: Merino sheep (n = 26) were anaesthetised and subjected to 2 hours middle cerebral artery occlusion. Animals underwent functional assessment at baseline (8-, 5-, and 1-day pre-stroke), and 3 days post-stroke. Neurological scoring was carried out to determine changes in neurological status. Ten infrared cameras measured the trajectories of 42 retro-reflective markers for calculation of gait kinematics. Magnetic resonance imaging (MRI) was performed at 3 days post-stroke to determine infarct volume. Intraclass Correlation Coefficients (ICC's) were used to assess the repeatability of neurological scoring and gait kinematics across baseline trials. The average of all baselines was used to compare changes in neurological scoring and kinematics at 3 days post-stroke. A principal component analysis (PCA) was performed to determine the relationship between neurological score, gait kinematics, and infarct volume post-stroke.

Results: Neurological scoring was moderately repeatable across baseline trials (ICC > 0.50) and detected marked impairment post-stroke (p < 0.05). Baseline gait measures showed moderate to good repeatability for the majority of assessed variables (ICC > 0.50). Following stroke, kinematic measures indicative of stroke deficit were detected including an increase in stance and stride duration (p < 0.05). MRI demonstrated infarction involving the cortex and/or thalamus (median 2.7 cm³, IQR 1.4 to 11.9). PCA produced two components, although association between variables was inconclusive.

Conclusion: This study developed repeatable methods to assess function in sheep using composite scoring and gait kinematics, allowing for the evaluation of deficit 3 days post-stroke. Despite utility of each method independently, there was poor association observed between gait kinematics, composite scoring, and infarct volume on PCA. This suggests that each of these measures has discreet utility for the assessment of stroke deficit, and that multimodal approaches are necessary to comprehensively characterise functional impairment.

Keywords: functional outcome; gait; motion capture; neurological score; sheep; stroke.

Grants and funding

This study was supported by funding from the National Health and Medical Research Council (NHMRC) Australia (Project Grant 1082556; RT) and Brain Foundation, Australia (RT). CJ was partially supported by a National Health and Medical Research Council (Australia) Early Career Fellowship during this study (APP1072387). AS-A was funded by a Research Training Program Scholarship administered by the Australian Federal Government and a Doctoral Scholarship provided by the Peter Couche Foundation.