Experimental and clinical studies suggest that primate species exhibit greater recovery after lateralized compared to symmetrical spinal cord injuries. Although this observation has major implications for designing clinical trials and translational therapies, advantages in recovery of nonhuman primates over other species has not been shown statistically to date, nor have the associated repair mechanisms been identified. We monitored recovery in more than 400 quadriplegic patients and found that that functional gains increased with the laterality of spinal cord damage. Electrophysiological analyses suggested that corticospinal tract reorganization contributes to the greater recovery after lateralized compared with symmetrical injuries. To investigate underlying mechanisms, we modeled lateralized injuries in rats and monkeys using a lateral hemisection, and compared anatomical and functional outcomes with patients who suffered similar lesions. Standardized assessments revealed that monkeys and humans showed greater recovery of locomotion and hand function than rats. Recovery correlated with the formation of corticospinal detour circuits below the injury, which were extensive in monkeys, but nearly absent in rats. Our results uncover pronounced inter-species differences in the nature and extent of spinal cord repair mechanisms, likely resulting from fundamental differences in the anatomical and functional characteristics of the motor systems in primates versus rodents. Although rodents remain essential for advancing regenerative therapies, the unique response of the primate corticospinal tract after injury re-emphasizes the importance of primate models for designing clinically relevant treatments.

Key factors positively influencing rehabilitation and functional recovery after spinal cord injury (SCI) include training variety, intensive movement repetition, and motivating training tasks. Systems supporting these aspects may provide profound gains in rehabilitation, independent of the subject’s treatment location. In the present study, we test the hypotheses that virtual reality (VR)-augmented training at home (i.e., unsupervised) is feasible with subjects with an incomplete SCI (iSCI) and that it improves motor functions such as lower limb muscle strength, balance, and functional mobility. In the study, 12 chronic iSCI subjects used a home-based, mobile version of a lower limb VR training system. The system included motivating training scenarios and combined action observation and execution. Virtual representations of the legs and feet were controlled via movement sensors. The subjects performed home-based training over 4 weeks, with 16–20 sessions of 30–45 min each. The outcome measures assessed were the Lower Extremity Motor Score (LEMS), Berg Balance Scale (BBS), Timed Up and Go (TUG), Spinal Cord Independence Measure mobility, Walking Index for Spinal Cord Injury II, and 10 m and 6 min walking tests. Two pre-treatment assessment time points were chosen for outcome stability: 4 weeks before treatment and immediately before treatment. At post-assessment (i.e., immediately after treatment), high motivation and positive changes were reported by the subjects (adapted Patients’ Global Impression of Change). Significant improvements were shown in lower limb muscle strength (LEMS, P = 0.008), balance (BBS, P = 0.008), and functional mobility (TUG, P = 0.007). At follow-up assessment (i.e., 2–3 months after treatment), functional mobility (TUG) remained significantly improved (P = 0.005) in contrast to the other outcome measures. In summary, unsupervised exercises at home with the VR training system led to beneficial functional training effects in subjects with chronic iSCI, suggesting that it may be useful as a neurorehabilitation tool.Trial registrationCanton of Zurich ethics committee (EK-24/2009, PB_2016-00545), : NCT02149186. Registered 24 April 2014.

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