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Objectives: Previous studies have demonstrated that optic neuritis (ON) affects brain plasticity. However, whether ON affects the spinal cord remains unclear. We aimed to investigate the spinal cord changes in ON and their associations with disability., Methods: A total of 101 ON patients, and 41 healthy controls (HC) were retrospectively recruited. High-resolution imaging was conducted using a Magnetization Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) sequence for T1-weighted images and an echo planar imaging (EPI) sequence for Diffusion Tensor Imaging (DTI) data collection. Additionally, patients' disability and cognitive impairment were evaluated using the Expanded Disability Status Scale (EDSS) and the Paced Auditory Serial Addition Test (PASAT), respectively. The quantitative spinal MRI was employed to examine the cross-sectional area (CSA) and diffusion indicators, with a specific focus on calculating the average values across the C2-C7 cervical spinal cord segments. CSA, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Correlation analyses were performed between CSA, diffusion indicators, and clinical variables., Results: No significant differences were found in CSA between ON patients and HCs. MD (p = 0.007) and RD (p = 0.018) were increased in ON patients compared with HCs, and AD was decreased in ON (p = 0.013). The AD values of the ON patients were significantly positively correlated with PASAT scores (r = 0.37, p < 0.001)., Conclusions: This study provided imaging evidence for DTI abnormalities in patients with ON. Spinal cord DTI can improve our knowledge of the path physiology of ON, and clinical progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective . Chronic motor impairments of arms and hands as the consequence of a cervical spinal cord injury (SCI) have a tremendous impact on activities of daily life. A considerable number of people however retain minimal voluntary motor control in the paralyzed parts of the upper limbs that are measurable by electromyography (EMG) and inertial measurement units (IMUs). An integration into human-machine interfaces (HMIs) holds promise for reliable grasp intent detection and intuitive assistive device control. Approach . We used a multimodal HMI incorporating EMG and IMU data to decode reach-and-grasp movements of groups of persons with cervical SCI (n = 4) and without (control, n = 13). A post-hoc evaluation of control group data aimed to identify optimal parameters for online, co-adaptive closed-loop HMI sessions with persons with cervical SCI. We compared the performance of real-time, Random Forest-based movement versus rest (2 classes) and grasp type predictors (3 classes) with respect to their co-adaptation and evaluated the underlying feature importance maps. Main results . Our multimodal approach enabled grasp decoding significantly better than EMG or IMU data alone (p<0.05). We found the 0.25 s directly prior to the first touch of an object to hold the most discriminative information. Our HMIs correctly predicted 79.3 ± STD 7.4 (102.7 ± STD 2.3 control group) out of 105 trials with grand average movement vs. rest prediction accuracies above 99.64% (100% sensitivity) and grasp prediction accuracies of 75.39 ± STD 13.77% (97.66 ± STD 5.48% control group). Co-adaption led to higher prediction accuracies with time, and we could identify adaptions in feature importances unique to each participant with cervical SCI. Significance . Our findings foster the development of multimodal and adaptive HMIs to allow persons with cervical SCI the intuitive control of assistive devices to improve personal independence., (Creative Commons Attribution license.)

Introduction: Patients presenting with spinal cord injury (SCI) often times have notable deficits or polytrauma and may require urgent decision making for early management. However, their presentation may affect decision-making ability. Although advance care planning (ACP) may help guide spine surgeons as to patient preferences, the rate at which they are available and disparities in ACP completion are still not understood. The objective of this study was to evaluate disparities in the completion of ACP among patients with acute SCI., Methods: All patients presenting with cervical SCI to the emergency department at an urban, tertiary level I trauma center from 2010 to 2021 were identified from a prospective database of all consults evaluated by the spine service. Each patient's medical record was reviewed to assess for the presence of ACP documents such as living will, power of attorney, or advance directive. Community-level socioeconomic status was assessed using the Distressed Communities Index. Bivariable and multivariable analyses were performed., Results: We identified 424 patients: 104 (24.5%) of whom had ACP. Patients with ACP were older (64.8 versus 56.5 years, P = 0.001), more likely White (78.8% versus 71.9%, P = 0.057), and present with ASIA Impairment Scale grade A SCI (21.2% versus 12.8%, P = 0.054), although the latter two did not reach statistical significance. On multivariable logistic regression, patients residing in at-risk communities were significantly less likely to have ACP documents compared with those in prosperous communities (odds ratio [OR]: 0.29, P = 0.03). Although patients living in distressed communities were less likely to complete ACP compared with those in prosperous communities (OR 0.50, P = 0.066), this did not meet statistical significance. Female patients were also less likely to have ACP (OR: 0.43, P = 0.005)., Conclusion: Female patients and those from at-risk communities are markedly less likely to complete ACP. Attention to possible disparities during admission and ACP discussions may help ensure that patients of all backgrounds have treatment goals documented., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Objective: To use the ulnar compound muscle action potential (CMAP) to abductor digiti minimi (ADM) to identify the proportion of individuals with cervical spinal cord injury (SCI) who have lower motor neuron (LMN) abnormalities involving the C8-T1 spinal nerve roots, within 3-6 months, and thus may influence the response to nerve transfer surgery., Design: Retrospective analysis of prospectively collected data. Data were analyzed from European Multicenter Study About SCI database., Setting: Multi-center, academic hospitals., Participants: We included 79 subjects (age=41.4±17.7, range:16-75; 59 men; N=79), who were classified as cervical level injuries 2 weeks after injury and who had manual muscle strength examinations that would warrant consideration for nerve transfer (C5≥4, C8<3)., Interventions: None., Main Outcome Measures: The ulnar nerve CMAP amplitude to ADM was used as a proxy measure for C8-T1 spinal segment health. CMAP amplitude was stratified into very abnormal (<1.0 mV), sub-normal (1.0-5.9 mV), and normal (>6.0 mV). Analysis took place at 3 (n=148 limbs) and 6 months (n=145 limbs)., Results: At 3- and 6-month post-injury, 33.1% and 28.3% of limbs had very abnormal CMAP amplitudes, respectively, while in 54.1% and 51.7%, CMAPs were sub-normal. Median change in amplitude from 3 to 6 months was 0.0 mV for very abnormal and 1.0 mV for subnormal groups. A 3-month ulnar CMAP <1 mV had a positive predictive value of 0.73 (95% CI 0.69-0.76) and 0.78 (95% CI 0.75-0.80) for C8 and T1 muscle strength of 0 vs 1 or 2., Conclusion: A high proportion of individuals have ulnar CMAPs below the lower limit of normal 3- and 6-month post cervical SCI and may also have intercurrent LMN injury. Failure to identify individuals with LMN denervation could result in a lost opportunity to improve hand function through timely nerve transfer surgeries., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Controversy exists whether blood pressure augmentation therapy benefits patients suffering from spinal cord injury (SCI). This retrospective comparative study was designed to assess the impact of two different mean arterial pressure (MAP) targets (85-90 mmHg vs. 65-85 mmHg) on neurological recovery after traumatic cervical SCI., Methods: Fifty-one adult patients with traumatic cervical SCI were retrospectively divided into two groups according to their intensive care unit (ICU) MAP targets: 85-90 mmHg (higher MAP group, n = 32) and 65-85 mmHg (lower MAP group, n = 19). Invasive MAP measurements were stored as 2-min median values for 3-7 days. The severity of SCI (AIS grade and neurological level) was evaluated upon ICU stay and during rehabilitation. Neurological recovery was correlated with individual mean MAP values and with the proportion of MAP values ≥85 mmHg upon the first 3 days (3d-MAP% ≥85 )., Results: The initial AIS grades were A 29.4%, B 17.6%, C 31.4%, and D 21.6%. AIS grade improved in 24 patients (47.1%). During ICU care, 82.0% and 36.8% of the measured MAP values reached ≥85 mmHg in the higher and the lower MAP groups, respectively (p < .001). The medians of individual mean MAP values were different between the groups (90.2 mmHg vs. 81.4 mmHg, p < .001). Similarly, 3d-MAP% ≥85 was higher in the higher MAP group (85.6% vs. 50.0%, p < .001). However, neurological recovery was not different between the groups, nor did it correlate with individual mean MAP values or 3d-MAP% ≥85 ., Conclusion: The currently recommended MAP target of 85-90 mmHg was not associated with improved outcomes compared to a lower target in patients with traumatic cervical SCI in this cohort., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Spinal cord injury is characterized by hemodynamic disruption at the injury epicenter and hypoperfusion in the penumbra, resulting in progressive ischemia and cell death. This degenerative secondary injury process has been well-described, though mostly using ex vivo or depth-limited optical imaging techniques. Intravital contrast-enhanced ultrasound enables longitudinal, quantitative evaluation of anatomical and hemodynamic changes in vivo through the entire spinal parenchyma. Here, we used ultrasound imaging to visualize and quantify subacute injury expansion (through 72 h post-injury) in a rodent cervical contusion model. Significant intraparenchymal hematoma expansion was observed through 72 h post-injury (1.86 ± 0.17-fold change from acute, p < 0.05), while the volume of the ischemic deficit largely increased within 24 h post-injury (2.24 ± 0.27-fold, p < 0.05). Histology corroborated these findings; increased apoptosis, tissue and vessel loss, and sustained tissue hypoxia were observed at 72 h post-injury. Vascular resistance was significantly elevated in the remaining perfused tissue, likely due in part to deformation of the central sulcal artery nearest to the lesion site. In conjunction, substantial hyperemia was observed in all perilesional areas examined except the ipsilesional gray matter. This study demonstrates the utility of longitudinal ultrasound imaging as a quantitative tool for tracking injury progression in vivo., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the changes of spinal vascular blood flow in SD rats after cervical, thoracic and lumbar spinal cord injury (SCI) using super-resolution ultrafast ultrasound technology. Methods: A total of 9 SD rats were used to construct SCI models at different segments using a 50 g aneurysm clip. Super-resolution ultrafast ultrasound technology was used to perform vascular blood flow imaging on the spinal cord of rats before and after injury at 6 hours, obtaining quantitative information such as spinal cord vascular density and blood flow velocity. Results: Ultrasound imaging showed that after SCI, the vascular density in the thoracic segment decreased (18.16%±1.04%) more than in the cervical segment (11.42%±1.39%) and lumbar segment (13.88%±1.43%, both P <0.05). The length of the spinal cord with decreased vascular density in the thoracic segment [(4.80±0.34)mm] was longer than that in the cervical segment [(2.80±0.57)mm] and lumbar segment [(3.10±0.36)mm, both P <0.05]. After injury, the decrease of blood flow in the thoracic segment [(8.87±0.85)ml/min] was higher than that in the cervical segment [(4.88±0.56)ml/min] and lumbar segment [(6.19±0.71)ml/min, both P <0.05]. HE staining and Nissl staining showed that the proportion of cavity area after thoracic SCI (11.53%±0.93%) was higher than that in the cervical segment (4.90%±1.72%) and lumbar segment (7.64%±0.84%, both P <0.05). The number of Nissl bodies in the thoracic segment (18.0±5.3) was also lower than that in the cervical segment (32.3±5.1) and lumbar segment (37.0±5.6) (both P <0.05). Conclusions: There are different changes in vascular blood flow after SCI in different segments of rats. The same injury causes the most severe damage to blood vessels in the thoracic spinal cord, followed by the lumbar spinal cord, and the cervical spinal cord has the least damage.

Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Sarah C. Heilshorn reports financial support was provided by National Institutes of Health. Sarah C. Heilshorn reports financial support was provided by California Institute for Regenerative Medicine. Giles W. Plant reports financial support was provided by Wings for Life Spinal Cord Research Foundation. Giles W. Plant reports financial support was provided by International Spinal Research Trust. Giles W. Plant reports financial support was provided by Dennis Chan Foundation. Giles W. Plant reports financial support was provided by Klein Family Fund. Giles W. Plant reports financial support was provided by Department of Defense. Sarah C. Heilshorn has patent #9,399,068 issued to The Board of Trustees of the Leland Stanford Junior University., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cervical spinal cord injury impacts ventilatory and non-ventilatory functions of the diaphragm muscle (DIAm) and contributes to clinical morbidity and mortality in the afflicted population. Periodically, integrated brainstem neural circuit activity drives the DIAm to generate a markedly augmented effort or sigh-which plays an important role in preventing atelectasis and thus maintaining lung function. Across species, the general pattern of DIAm efforts during a normal sigh is variable in amplitude and the extent of post-sigh "apnea" (i.e., the post-sigh inter-breath interval). This post-sigh inter-breath interval acts as a respiratory reset, following the interruption of regular respiratory rhythm by sigh. We examined the impact of upper cervical (C 2 ) spinal cord hemisection (C 2 SH) on the transdiaphragmatic pressure (P di ) generated during sighs and the post-sigh respiratory reset in rats. Sighs were identified in P di traces by their characteristic biphasic pattern. We found that C 2 SH results in a reduction of P di during both eupnea and sighs, and a decrease in the immediate post-sigh breath interval. These results are consistent with partial removal of descending excitatory synaptic inputs to phrenic motor neurons that results from C 2 SH. Following cervical spinal cord injury, a reduction in the amplitude of P di during sighs may compromise the maintenance of normal lung function., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Cervical spinal injury often disrupts the supraspinal vasomotor pathways projecting to the thoracic sympathetic preganglionic neurons, leading to cardiovascular dysfunction. The current guideline is to maintain the mean arterial blood pressure at 85 to 90 mmHg using a vasopressor during the first week of the injury. Some studies have demonstrated that this treatment might be beneficial to alleviate secondary injury and improve neurological outcomes; however, elevation of blood pressure may exacerbate spinal hemorrhage, extravasation, and edema, exacerbating the initial injury., Purpose: The present study was designed to (1) examine whether vasopressor administration exacerbates spinal hemorrhage and extravasation; (2) evaluate whether spinal decompression surgery relieves vasopressor-induced spinal hemorrhage and extravasation., Study Design: In vivo animal study., Methods: Animals received a saline solution or a vasopressor (phenylephrine hydrochloride, 500 or 1000 μg/kg, 7 mL/kg/h) after mid-cervical contusion with or without spinal decompression (ie, incision of the dura and arachnoid mater). Spinal cord hemorrhage and extravasation were examined by expression of Evans blue within the spinal cord section., Results: The results demonstrated that cervical spinal contusion significantly reduced the mean arterial blood pressure and induced spinal hemorrhage and extravasation. Phenylephrine infusion significantly elevated the mean arterial blood pressure to the preinjury level within 15 to 60 minutes postcontusion; however, spinal hemorrhage and extravasation were more extensive in animals that received phenylephrine than in those that received saline. Notably, spinal decompression mitigated spinal hemorrhage and extravasation in contused rats who received phenylephrine., Conclusions: These data indicate that, although phenylephrine can prevent hypotension after cervical spinal injury, it also causes excess spinal hemorrhage and extravasation., Clinical Significance: Spinal decompressive surgery seemed to minimize the side effect of phenylephrine as vasopressor treatment during acute spinal cord injury., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: One of the most important predictors of clean intermittent catheterization (CIC) adoption after spinal cord injury (SCI) is upper extremity (UE) motor function at discharge from rehabilitation. It is not clear however if post-discharge improvements in UE motor function affect future bladder management decisions., Methods: We assessed persons with cervical SCI in the National Spinal Cord Injury Dataset for the years 2000-2016 who underwent motor examination at discharge from rehabilitation and again at 1-year follow-up. Individuals were stratified based on a previously described algorithm which categorizes the ability to independently perform CIC based upon UE motor scores. Improvements in the predicted ability to self-catheterize over the first year after rehabilitation discharge were evaluated in relation to bladder management., Results: Despite 15% of our SCI cohort improving from "less than able to independently catheterize" to "able to independently catheterize", more patients in the overall cohort dropped out of CIC (175/643 = 27.2%) than adopted CIC (68/548 = 12.4%) (P < .001). We found that in those initially categorized as "less than able to independently catheterize" at the time of rehabilitation discharge, CIC adoption was not significantly different at 1-year follow-up whether or not there was motor improvement to "able to independently catheterize" (12.7% vs 9.2% respectively, P = 0.665). Between these two groups, CIC dropout was also equivalent (34.3% vs 30.0% respectively, P = 0.559)., Conclusions: In the first year after rehabilitation, more overall SCI patients transition away from CIC than convert to CIC. Significant improvements in UE motor function during the first year after rehabilitation discharge do not appear to affect bladder management decisions.

Objective: To describe and analyze a case of acute spinal cord injury after head and neck surgery., Description: One hour after left lobo-isthmectomy under laryngeal neuromonitoring for a 3-cm EU-TIRADS 4 - Bethesda 4 thyroid nodule in a 48-year-old euthyroid male without any known comorbidity, left hemiparesis occurred. Cervical spine MRI showed an anteromedial herniated C6-7 disk with medullary compression. The disk was resected, compression was released and C6-7 fusion was performed via an anterior cervical approach on postoperative day 1. Postoperative course was unremarkable, with complete recovery of motion within 2 days. One month later, neurological clinical examination was normal and interview revealed left cervicalgia with onset a few days prior to lobo-isthmectomy. One year later, at the time of writing, the patient was doing fine., Conclusion: Otorhinolaryngologists and head and neck surgeons must be aware of the risk of acute cervical spinal injury after cervical mobilization in head and neck surgery, and should take all measures to avoid this exceptional but dramatic complication., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The purpose of this study was to compare the acceleration and surface electromyography (EMG) of the lower extremity and trunk muscles during straight-leg raising (SLR) in patients with incomplete cervical cord injury according to their levels of walking independence. Twenty-four patients were measured acceleration and EMG during SLR held for 10 s. Data were analyzed separately for the dominant and nondominant sides and compared between the nonindependent (NI) and independent (ID) groups based on their levels of walking independence. Frequency analysis of the EMG showed that the high-frequency (HF) band of the contralateral biceps femoris (BF) in the ID group and bands below the medium-frequency (MF) of the BF and the HF and MF bands of the rectus abdominis in the NI group were significantly higher during dominant and nondominant SLR. During the nondominant SLR, the low-frequency band of the internal oblique and the MF band of the external oblique were significantly higher in the NI group. The ID group mobilized muscle fiber type 2 of the BF, whereas the NI group mobilized type 1 of the BF and types 2 and 1 of the trunk muscles to stabilize the pelvis. This result was more pronounced during the nondominant SLR., (© 2024. The Author(s).)

Objective: The hand function of individuals with spinal cord injury (SCI) plays a crucial role in their independence and quality of life. Wearable cameras provide an opportunity to analyze hand function in non-clinical environments. Summarizing the video data and documenting dominant hand grasps and their usage frequency would allow clinicians to quickly and precisely analyze hand function., Method: We introduce a new hierarchical model to summarize the grasping strategies of individuals with SCI at home. The first level classifies hand-object interaction using hand-object contact estimation. We developed a new deep model in the second level by incorporating hand postures and hand-object contact points using contextual information., Results: In the first hierarchical level, a mean of 86% ±1.0% was achieved among 17 participants. At the grasp classification level, the mean average accuracy was 66.2 ±12.9%. The grasp classifier's performance was highly dependent on the participants, with accuracy varying from 41% to 78%. The highest grasp classification accuracy was obtained for the model with smoothed grasp classification, using a ResNet50 backbone architecture for the contextual head and a temporal pose head., Discussion: We introduce a novel algorithm that, for the first time, enables clinicians to analyze the quantity and type of hand movements in individuals with spinal cord injury at home. The algorithm can find applications in other research fields, including robotics, and most neurological diseases that affect hand function, notably, stroke and Parkinson's.

Study Design: Cross-sectional study., Objectives: To evaluate unsupported sitting posture impairments and identify postural regulatory strategies in cervical spinal cord injury (cSCI) participants via a head-mounted IMU sensor., Setting: A research lab in the United States of America., Methods: cSCI participants and controls maintained postural stability during unsupported sitting with eyes either open or closed. The head-mounted IMU sensor recorded accelerometer data to calculate cumulative sway motion. The postural regulatory strategy was analyzed by assessing the normalized power spectral density (PSD) in four frequency bands: 0-0.1 Hz (visual regulation), 0.1-0.5 Hz (vestibular regulation), 0.5-1 Hz (cerebellar regulation), and >1 Hz (proprioception and muscle control)., Results: Significant increases in postural sway were observed in cSCI participants compared to controls during unsupported sitting. For cSCI participants, normalized PSD significantly increased in the low-frequency bands (0-0.1 Hz and 0.1-0.5 Hz) but decreased in the high-frequency band (>1 Hz) compared to controls., Conclusions: cSCI participants were more reliant on visual and vestibular systems for sitting balance, while depending less on proprioception and muscle control compared to controls. These findings suggest that the altered postural regulatory strategy is ineffective in maintaining postural stability during unsupported sitting, emphasizing the importance of proprioception and muscle control for seated postural stability in cSCI participants., (© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)

Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Improvements in obstetric care have certainly led to a decrease in the incidence of birth related spinal cord trauma but unfortunately the incidence of hypoxic-ischemic encephalopathy is still very high. The exact incidence of spinal cord trauma is difficult to determine because the spinal cord is not routinely examined in far and few neonatal autopsies done in India. Here, authors present a neonate who received treatment for birth asphyxia and then had extubation failure which made the clock tick towards cervical cord injury. This baby had a hemorrhagic contusion of cervical spinal cord., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background Context: Magnetic stimulation can noninvasively modulate the neuronal excitability through different stimulatory patterns., Purpose: The present study hypothesized that trans-spinal magnetic stimulation with intermittent theta burst stimulatory pattern can modulate respiratory motor outputs in a pre-clinical rat model of cervical spinal cord injury., Study Design: In vivo animal study., Methods: The effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity was assessed in adult rats with unilateral cervical spinal cord contusion at 2 weeks postinjury., Results: The results demonstrated that unilateral cervical spinal cord contusion significantly attenuated the inspiratory activity and motor evoked potential of the diaphragm. Trans-spinal magnetic intermittent theta burst stimulation significantly increased the inspiratory activity of the diaphragm in cervical spinal cord contused rats. Inspiratory bursting was also recruited by trans-spinal magnetic intermittent theta burst stimulation in the rats without diaphragmatic activity after cervical spinal cord injury. In addition, trans-spinal magnetic intermittent theta burst stimulation is associated with increases in oxygen consumption and carbon dioxide production., Conclusions: These results suggest that trans-spinal magnetic intermittent theta burst stimulation can induce respiratory neuroplasticity., Clinical Significance: We propose that trans-spinal theta burst magnetic stimulation may be considered a potential rehabilitative strategy for improving the respiratory activity after cervical spinal cord injury. This will require future clinical study., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation long-term. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426-21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL-ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Spinal cord injury (SCI) is devastating, with limited treatment options and variable outcomes. Most in vivo SCI research has focused on the acute and early post-injury periods, and the promotion of axonal growth, so little is understood about the clinically stable chronic state, axonal growth over time, and what plasticity endures. Here, we followed animals into the chronic phase following SCI, to address this gap. Male macaques received targeted deafferentation, affecting three digits of one hand, and were divided into short (4-6 months) or long-term (11-12 months) groups, based on post-injury survival times. Monkeys were assessed behaviorally, where possible, and all exhibited an initial post-injury deficit in manual dexterity, with gradual functional recovery over 2 months. We previously reported extensive sprouting of somatosensory corticospinal (S1 CST) fibers in the dorsal horn in the first five post-injury months. Here, we show that by 1 year, the S1 CST sprouting is pruned, with the terminal territory resembling control animals. This was reflected in the number of putatively "functional" synapses observed, which increased over the first 4-5 months, and then returned to baseline by 1 year. Microglia density also increased in the affected dorsal horn at 4-6 months and then decreased, but did not return to baseline by 1 year, suggesting refinement continues beyond this time. Overall, there is a long period of reorganization and consolidation of adaptive circuitry in the dorsal horn, extending well beyond the initial behavioral recovery. This provides a potential window to target therapeutic opportunities during the chronic phase., (Copyright © 2024 the authors.)

Transcutaneous spinal stimulation (TSS) is a promising rehabilitative intervention to restore motor function and coordination for individuals with spinal cord injury (SCI). The effects of TSS are most commonly assessed by evaluating muscle response to stimulation using surface electromyography (sEMG). Given the increasing use of robotic devices to deliver therapy and the emerging potential of hybrid rehabilitation interventions that combine neuromodulation with robotic devices, there is an opportunity to leverage the on-board sensors of the robots to measure kinematic and torque changes of joints in the presence of stimulation. This paper explores the potential for robotic assessment of the effects of TSS delivered to the cervical spinal cord. We used a four degree-of-freedom exoskeleton to measure the torque response of upper limb (UL) joints during stimulation, while simultaneously recording sEMG. We analyzed joint torque and electromyography data generated during TSS delivered over individual sites of the cervical spinal cord in neurologically intact participants. We show that site-specific effects of TSS are manifested not only by modulation of the amplitude of spinally evoked motor potentials in UL muscles, but also by changes in torque generated by individual UL joints. We observed preferential resultant action of proximal muscles and joints with stimulation at the rostral site, and of proximal joints with rostral-lateral stimulation. Robotic assessment can be used to measure the effects of TSS, and could be integrated into complex control algorithms that govern the behavior of hybrid neuromodulation-robotic systems.

More than half of all spinal cord injuries (SCIs) occur at the cervical level and often lead to life-threatening breathing motor dysfunction. The C2 hemisection (C2Hx) and high cervical contusion mouse and rat models of SCI are widely utilized both to understand the pathological effects of SCI and to develop potential therapies. Despite rigorous research effort, pre-clinical therapeutics studied in those animal models of SCI sometimes fail when evaluated in the clinical setting. Differences between standard-of-care treatment for acute SCI administered to clinical populations and experimental animal models of SCI could influence the heterogeneity of outcome between pre-clinical and clinical studies. In this review, we have summarized both the standard clinical interventions used to treat patients with cervical SCI and the various veterinary aftercare protocols used to care for rats and mice after experimentally induced C2Hx and high cervical contusion models of SCI. Through this analysis, we have identified areas of marked dissimilarity between clinical and veterinary protocols and suggest the modification of pre-clinical animal care particularly with respect to analgesia, anticoagulative measures, and stress ulcer prophylaxis. In our discussion, we intend to inspire consideration of potential changes to aftercare for animal subjects of experimental SCI that may help to bridge the translational "Valley of Death" and ultimately contribute more effectively to finding treatments capable of restoring independent breathing function to persons with cervical SCI.

Background Context: A traumatic spinal cord injury (SCI) can cause temporary or permanent motor and sensory impairment, leading to serious short and long-term consequences that can result in significant morbidity and mortality. The cervical spine is the most commonly affected area, accounting for about 60% of all traumatic SCI cases., Purpose: This study aims to employ machine learning (ML) algorithms to predict various outcomes, such as in-hospital mortality, nonhome discharges, extended length of stay (LOS), extended length of intensive care unit stay (ICU-LOS), and major complications in patients diagnosed with cervical SCI (cSCI)., Study Design: Our study was a retrospective machine learning classification study aiming to predict the outcomes of interest, which were binary categorical variables, in patients diagnosed with cSCI., Patient Sample: The data for this study were obtained from the American College of Surgeons (ACS) Trauma Quality Program (TQP) database, which was queried to identify patients who suffered from cSCI between 2019 and 2021., Outcome Measures: The outcomes of interest of our study were in-hospital mortality, nonhome discharges, prolonged LOS, prolonged ICU-LOS, and major complications. The study evaluated the models' performance using both graphical and numerical methods. The receiver operating characteristic (ROC) and precision-recall curves (PRC) were used to assess model performance graphically. Numerical evaluation metrics included AUROC, balanced accuracy, weighted area under PRC (AUPRC), weighted precision, and weighted recall., Methods: The study employed data from the American College of Surgeons (ACS) Trauma Quality Program (TQP) database to identify patients with cSCI. Four ML algorithms, namely XGBoost, LightGBM, CatBoost, and Random Forest, were utilized to develop predictive models. The most effective models were then incorporated into a publicly available web application designed to forecast the outcomes of interest., Results: There were 71,661 patients included in the analysis for the outcome mortality, 67,331 for the outcome nonhome discharges, 76,782 for the outcome prolonged LOS, 26,615 for the outcome prolonged ICU-LOS, and 72,132 for the outcome major complications. The algorithms exhibited an AUROC value range of 0.78 to 0.839 for in-hospital mortality, 0.806 to 0.815 for nonhome discharges, 0.679 to 0.742 for prolonged LOS, 0.666 to 0.682 for prolonged ICU-LOS, and 0.637 to 0.704 for major complications. An open access web application was developed as part of the study, which can generate predictions for individual patients based on their characteristics., Conclusions: Our study suggests that ML models can be valuable in assessing risk for patients with cervical cSCI and may have considerable potential for predicting outcomes during hospitalization. ML models demonstrated good predictive ability for in-hospital mortality and nonhome discharges, fair predictive ability for prolonged LOS, but poor predictive ability for prolonged ICU-LOS and major complications. Along with these promising results, the development of a user-friendly web application that facilitates the integration of these models into clinical practice is a significant contribution of this study. The product of this study may have significant implications in clinical settings to personalize care, anticipate outcomes, facilitate shared decision making and informed consent processes for cSCI patients., Competing Interests: Declarations of Competing Interests One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: It is believed that early tracheostomy in patients with traumatic cervical spinal cord injury (SCI) may lessen the risk of developing complications and reduce the duration of mechanical ventilation and critical care stay. This study aims to assess whether early tracheostomy is beneficial in patients with traumatic cervical SCI., Methods: We conducted a retrospective cohort study using data from the American College of Surgeons Trauma Quality Improvement Program database from 2010 to 2018. Adult patients with a diagnosis of acute complete (ASIA A) traumatic cervical SCI who underwent surgery and tracheostomy were included. Patients were stratified into those receiving early (at or before 7 days) and delayed tracheostomy. Propensity score matching was used to assess the association between delayed tracheostomy and the risk of in-hospital adverse events. Risk-adjusted variability in tracheostomy timing across trauma centers was investigated using mixed-effects regression., Results: The study included 2001 patients from 374 North American trauma centers. The median time to tracheostomy was 9.2 days (IQR: 6.1-13.1 days), with 654 patients (32.7%) undergoing early tracheostomy. After matching, the odds of a major complication were significantly lower for early tracheostomy patients (OR: .90; 95% CI: .88-.98). Patients were also significantly less likely to experience an immobility-related complication (OR: .90; 95% CI: .88-.98). Patients in the early group spent 8.2 fewer days in the critical care unit (95% CI: -10.2 to -6.61) and 6.7 fewer days ventilated (95% CI: -9.44 to -5.23). There was significant variability in tracheostomy timeliness between trauma centers with a median odds ratio of 12.2 (95% CI: 9.7-13.7), which was not explained by case-mix and hospital-level characteristics., Conclusion: A 7-day threshold to implement tracheostomy seems to be associated with reduced in-hospital complications, time in the critical care unit, and time on mechanical ventilation., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Introduction: Intrathecal baclofen (ITB) therapy is an effective method of treating spasticity in persons with spasticity due to spinal cord injury (SCI), but complications are not rare and can include spinal fluid leaks, infection, and catheter/pump malfunction., Case Presentation: This study presents information related to an adult male patient with traumatic SCI and a history of two prior ITB pump pocket infections that required removal due to pump infection. The patient then developed skin erosion over the third pump, and the fluid around the pump grew methicillin-sensitive Staphylococcus aureus, diphtheroids, and Candida parapsilosis. The patient was initially treated with antibiotics and anti-fungal medication without removal of the ITB pump. The ITB pump was eventually removed 27 months later, and the fourth pump was implanted 10 months later., Discussion: ITB pumps can be an effective treatment modality for spasticity in people with SCI; however, complications, including infection, can occur and require pump removal. This case illustrates a case of possible Candida colonization of the ITB pump, which was eventually removed., (© 2023. The Author(s).)

Background: Traumatic spinal cord injury (SCI) leads to profound neurologic sequelae, and the provision of life-supporting treatment serves great importance among this patient population. The decision for withdrawal of life-supporting treatment (WLST) in complete traumatic SCI is complex with the lack of guidelines and limited understanding of practice patterns. We aimed to evaluate the individual and contextual factors associated with the decision for WLST and assess between-center differences in practice patterns across North American trauma centers for patients with complete cervical SCI., Methods: This retrospective multicenter observational cohort study utilized data derived from the American College of Surgeons Trauma Quality Improvement Program database between 2017 and 2020. The study included adult patients (> 16 years) with complete cervical SCI. We constructed a multilevel mixed effect logistic regression model to adjust for patient, injury and hospital factors influencing WLST. Factors associated with WLST were estimated through odds ratios with 95% confidence intervals. Hospital variability was characterized using the median odds ratio. Unexplained residual variability was assessed through the proportional change in variation between models., Results: We identified 5070 patients with complete cervical SCI treated across 477 hospitals, of which 960 (18.9%) had WLST. Patient-level factors associated with significantly increased likelihood of WLST were advanced age, male sex, white race, prior dementia, low presenting Glasgow Coma Scale score, having a pre-hospital cardiac arrest, SCI level of C3 or above, and concurrent severe injury to the head or thorax. Patient-level factors associated with significantly decreased likelihood of WLST included being racially Black or Asian. There was significant variability across hospitals in the likelihood for WLST while accounting for case-mix, hospital size, and teaching status (MOR 1.51 95% CI 1.22-1.75)., Conclusions: A notable proportion of patients with complete cervical SCI undergo WLST during their in-hospital admission. We have highlighted several factors associated with this decision and identified considerable variability between hospitals. Further work to standardize WLST guidelines may improve equity of care provided to this patient population., (© 2023. The Author(s).)

Objective: To identify and evaluate 3 training variables of motor training programmes involving people with a cervical spinal cord injury: i.e. motor training strategies, therapy dosage, and persons' motivation for arm-hand functioning in subacute and chronic phases., Methods: PubMed, Cochrane, CINAHL, EMBASE, and DARE databases were searched for active arm-hand motor training programmes. Two independent reviewers assessed methodological quality. Pre-post effect sizes were calculated using Hedge's g, and mean effect sizes were calculated to compare outcomes on the International Classification of Functioning, Disability, and Health levels of function and activity., Results: Twelve training programmes integrated mainly skill training alone or combined with strength and/or endurance training. Task-oriented training components included: multiple movement planes, functional movements, clear functional goals, and bimanual practice. Training duration of 8 weeks was common. Quantitative analyses of 8 training programmes showed an overall small effect (0.34) on function level and an overall moderate effect (0.55) on activity level. In depth-analysis of activity level showed moderate effects of skill training only (0.55) or combined with strength and endurance training (0.53). Moderate effects (0.53-0.60) were found for integrating functional movements, clear functional goals, real-life object manipulation, multiple movement planes, total skill practice, context-specific environment, exercise variety, and bimanual practice. Training of minimum 8 weeks showed a moderate effect (0.60-0.69)., Conclusion: Based on limited studies, arm-hand functioning aiming to improve activity level can be improved using skill training with at least 8 task-oriented training components, additional strength and endurance training, with a minimum training duration of 8 weeks.

Background: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients., Methods: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings., Results: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up., Conclusions: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

A man in his 50s with an incomplete cervical spinal cord injury underwent a 3-week occupational therapy programme using a computer-assisted robotic device for the upper limbs (Diego) in an acute care spinal injury unit. The patient and their partner reported their experience. Range of motion (ROM), muscle strength, pain, fatigue, independence and occupational performance are reported. Improvements occurred in upper limb ROM (shoulder and elbow), muscle strength (right elbow extensors), fatigue and functional status. Whether the results in this patient with the Diego were the same or better than standard care could not be determined. Preliminary findings suggest that the Diego was feasible for rehabilitation in an acute setting in our patient. However, it may not be suitable for all patients and a large comparative study with other therapies is needed. A limitation in the use of the Diego relates to the initial cost of the device ($A150 000)., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This prospective pilot study investigated the influence of body position on peak cough flow (PCF) during mechanical insufflation-exsufflation (MI-E) treatment in people with tetraplegia. Fifteen participants with cervical spinal cord injury (C-SCI) were randomized into two groups, which differed in the starting position, that is, the patients were either supine or reclined. Four sessions of MI-E in alternating positions with each session comprising three different maneuvers: five voluntary coughs, five MI-E-assisted coughs, and five MI-E-assisted with manual thrusts were performed with continuous airflow measurement reporting PCF from every cough. PCF was associated with the application maneuvers, total insufflation volume (TIV), and interaction between position and maneuvers but not with the application position. The estimated mean PCF was 1.808, 3.529, and 3.925 L/s when supine and 1.672, 3.598, and 3.909 L/s when reclined from voluntary cough, MI-E, and MI-E with manual thrust, respectively. The estimated PCF change compared to voluntary cough was 1.721 (95% CI, 1.603-1.838) L/s from the combined MI-E and 2.116 (95% CI, 2.005-2.228) L/s from the MI-E with manual thrust, calculated from the linear mixed-model analysis. PCF moderately correlated with TIV (R 2  = 0.64). Therefore, either position can be used for C-SCI patients as long as MI-E can be performed with manual thrust and sufficient TIV is provided., (© 2023. Springer Nature Limited.)

Traumatic spinal cord injury (SCI) results in the loss of neurons, oligodendrocytes, and astrocytes. Present interventions for SCI include decompressive surgery, anti-inflammatory therapies, and rehabilitation programs. Nonetheless, these approaches do not offer regenerative solutions to replace the lost cells, fiber tracts, and circuits. Neural stem/progenitor cell (NPC) transplantation is a promising strategy that aims to encourage regeneration. However, NPC differentiation remains inconsistent, thus, contributing to suboptimal functional recovery. As such, we have previously engineered oligodendrogenically biased NPCs (oNPCs) and demonstrated their efficacy in a thoracic model of SCI. Since the majority of patients with SCI experience cervical injuries, our objective in the current study was to generate human induced pluripotent stem cell-derived oNPCs (hiPSC-oNPCs) and to characterize these cells in vitro and in vivo, utilizing a clinically relevant rodent model of cervical SCI. Following transplantation, the oNPCs engrafted, migrated to the rostral and caudal regions of the lesion, and demonstrated preferential differentiation toward oligodendrocytes. Histopathological evaluations revealed that oNPC transplantation facilitated tissue preservation while diminishing astrogliosis. Moreover, oNPC transplantation fostered remyelination of the spared tissue. Functional analyses indicated improved forelimb grip strength, gait, and locomotor function in the oNPC-transplanted rats. Importantly, oNPC transplantation did not exacerbate neuropathic pain or induce tumor formation. In conclusion, these findings underscore the therapeutic potential of oNPCs in promoting functional recovery and histopathological improvements in cervical SCI. This evidence warrants further investigation to optimize and advance this promising cell-based therapeutic approach., (© The Author(s) 2023. Published by Oxford University Press.)

Objective. Spinal cord injury (SCI) leads to debilitating sensorimotor deficits that greatly limit quality of life. This work aims to develop a mechanistic understanding of how to best promote functional recovery following SCI. Electrical spinal stimulation is one promising approach that is effective in both animal models and humans with SCI. Optogenetic stimulation is an alternative method of stimulating the spinal cord that allows for cell-type-specific stimulation. The present work investigates the effects of preferentially stimulating neurons within the spinal cord and not glial cells, termed 'neuron-specific' optogenetic spinal stimulation. We examined forelimb recovery, axonal growth, and vasculature after optogenetic or sham stimulation in rats with cervical SCI. Approach. Adult female rats received a moderate cervical hemicontusion followed by the injection of a neuron-specific optogenetic viral vector ipsilateral and caudal to the lesion site. Animals then began rehabilitation on the skilled forelimb reaching task. At four weeks post-injury, rats received a micro-light emitting diode (µLED) implant to optogenetically stimulate the caudal spinal cord. Stimulation began at six weeks post-injury and occurred in conjunction with activities to promote use of the forelimbs. Following six weeks of stimulation, rats were perfused, and tissue stained for GAP-43, laminin, Nissl bodies and myelin. Location of viral transduction and transduced cell types were also assessed. Main Results. Our results demonstrate that neuron-specific optogenetic spinal stimulation significantly enhances recovery of skilled forelimb reaching. We also found significantly more GAP-43 and laminin labeling in the optogenetically stimulated groups indicating stimulation promotes axonal growth and angiogenesis. Significance. These findings indicate that optogenetic stimulation is a robust neuromodulator that could enable future therapies and investigations into the role of specific cell types, pathways, and neuronal populations in supporting recovery after SCI., (Creative Commons Attribution license.)

Background: Functional use of the upper extremities (UEs) is a top recovery priority for individuals with cervical spinal cord injury (cSCI), but the inability to monitor recovery at home and limitations in hand function outcome measures impede optimal recovery., Objectives: We developed a framework using wearable cameras to monitor hand use at home and aimed to identify the best way to report information to clinicians., Methods: A dashboard was iteratively developed with clinician ( n = 7) input through focus groups and interviews, creating low-fidelity prototypes based on recurring feedback until no new information emerged. Affinity diagramming was used to identify themes and subthemes from interview data. User stories were developed and mapped to specific features to create a high-fidelity prototype., Results: Useful elements identified for a dashboard reporting hand performance included summaries to interpret graphs, a breakdown of hand posture and activity to provide context, video snippets to qualitatively view hand use at home, patient notes to understand patient satisfaction or struggles, and time series graphing of metrics to measure trends over time., Conclusion: Involving end-users in the design process and breaking down user requirements into user stories helped identify necessary interface elements for reporting hand performance metrics to clinicians. Clinicians recognized the dashboard's potential to monitor rehabilitation progress, provide feedback on hand use, and track progress over time. Concerns were raised about the implementation into clinical practice, therefore further inquiry is needed to determine the tool's feasibility and usefulness in clinical practice for individuals with UE impairments., Competing Interests: Conflicts of Interest The authors declare no conflicts of interest., (© 2023 American Spinal Injury Association.)

To date, no drug therapy has shown significant efficacy in improving functional outcomes in patients with acute spinal cord injury (SCI). Riluzole is an approved benzothiazole sodium channel blocker to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) and is of interest for neuroprotection in SCI. In a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT00876889), riluzole was well tolerated with a 2-week treatment at the dose level approved for ALS and exhibited potential efficacy in patients with SCI. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes alter the pharmacokinetics (PK) of therapeutics. In the PK sub-study of the multi-center, randomized, placebo-controlled, double-blinded Riluzole in Spinal Cord Injury Study (RISCIS) Phase II/III trial (ClinicalTrials.gov Identifier: NCT01597518), a total of 32 SCI patients were enrolled, and most of our patients were middle-age Caucasian males with head and neck injuries. We studied the PK and pharmacodynamics (PD) of riluzole on motor recovery, measured by International Standards for Neurological Classification of SCI (ISNCSCI) Motor Score at injury and at 3-month and 6-month follow-ups, along with levels of the axonal injury biomarker phosphorylated neurofilament heavy chain (pNF-H), during the 2-week treatment. PK modeling, PK/PD correlations were developed to identify the potential effective exposure of riluzole for intended PD outcomes. The longitudinal impacts of SCI on the PK of riluzole are characterized. A time-varying population PK model of riluzole is established, incorporating time-varying clearance and volume of distribution from combined data of Phase I and Phase II/III trials. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification to preserve the required therapeutic exposure of riluzole. The PD of riluzole and the relationship between PK and neurological outcomes of the treatment were established. The time course of efficacy in total motor score improvement (ΔTMS) and pNF-H were monitored. A three-dimensional (3D) PK/PD correlation was established for ΔTMS at 6 months with overall riluzole exposure area under the curve for Day 0-Day14 (AUC D0-D14 ) and baseline TMS for individual patients. Patients with baseline TMS between 1 and 36 benefited from the optimal exposure range of 16-48 mg*h/mL. The PD models of pNF-H revealed the riluzole efficacy, as treated subjects exhibited a diminished increase in progression of pNF-H, indicative of reduced axonal breakdown. The independent parameter of area between effective curves (ABEC) between the time profiles of pNF-H in placebo and treatment groups was statistically identified as a significant predictor for the treatment effect on the biomarker. A mechanistic clinical outcomes (CO)/PD (pNF-H) model was established, and the proposed structure demonstrated the feasibility of PK/PD/CO correlation model. No appreciable hepatic toxicity was observed with the current riluzole treatment regimen. The development of effective treatment for SCI is challenging. However, the future model-informed and PK-guided drug development and regimen modification can be rationally executed with the optimal dosing regimen design based on the developed 3D PK/PD model. The PK/PD/CO model can serve as a rational guide for future drug development, PKPD model refinement, and extension to other studies in SCI settings.

Purpose: To determine existing trends concerning in-hospital mortality in patients with traumatic subaxial cervical spinal cord injury (SCI) over the last four decades., Methods: We searched MEDLINE and EMBASE to assess the role of the following factors on in-hospital mortality over the last four decades: neurological deficit, age, surgical decompression, use of computed tomography (CT) and magnetic resonance imaging (MRI), use of methylprednisolone in the acute post-injury period, and study location (developing versus developed countries)., Results: Among 3333 papers after deduplication, 21 studies met the eligibility criteria. The mortality rate was 17.88% [95% confidence interval (CI): 12.9-22.87%]. No significant trend in mortality rate was observed over the 42-year period (meta-regression coefficient = 0.317; p = 0.372). Subgroup analysis revealed no significant association between acute subaxial cervical SCI-related mortality when stratified by use of surgery, administration of methylprednisolone, use of MRI and CT imaging, study design (prospective versus retrospective study), and study location. The mortality rate was significantly higher in complete SCI (20.66%, p = 0.002) and American Spinal Injury Association impairment scale (AIS) A (20.57%) and B (9.28%) (p = 0.028)., Conclusion: A very low level of evidence showed that in-hospital mortality in patients with traumatic subaxial cervical SCI did not decrease over the last four decades despite diagnostic and therapeutic advancements. The overall acute mortality rate following subaxial cervical SCI is 17.88%. We recommend reporting a stratified mortality rate according to key factors such as treatment paradigms, age, and severity of injury in future studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: The aim of this study was to investigate the efficacy of surgical treatment and conservative treatment for cervical spinal cord injury without fracture and dislocation (CSCIWFD) in adults by meta-analysis., Methods: With a time span from 2010 to 2022, PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for all clinical randomized controlled trials on the comparison of surgical treatment and conservative treatment for CSCIWFD in adults. The Cochrane quality assessment tool was used as the standard. Stata 16.0 statistical software was used for meta-analysis., Results: A total of 870 articles were retrieved, and 12 studies were finally included for meta-analysis. Among them, there were 451 patients in the observation group (surgical treatment) and 346 patients in the control group (conservative treatment). The results of meta-analysis showed that the observation group was superior to the control group in the effective rate (OR = 4.737, 95% CI [2.613, 8.586], P < .001), Japanese Orthopedic Association (JOA) score at 3 months after treatment (SMD = 1.038, 95% CI [0.417, 1.659], P = .001), 6 months after treatment (SMD = 3.135, 95% CI [2.120, 4.151], P < .001) and 12 months after treatment (SMD = 2.808, 95% CI [1.880, 3.737], P < .001). In addition, the JOA scores of patients at 12 months after surgical treatment (SMD = 6.397, 95% CI [4.654, 8.14], P < .001) and conservative treatment (SMD = 3.197, 95% CI [2.144, 4.24], P < .001) were significantly higher than those before treatment., Conclusions: Surgical treatment can improve the effective rate and JOA score of adult patients with CSCIWFD compared to conservative treatment. This suggests that surgical treatment can significantly improve the patient's spinal cord function., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone., Methods: This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results)., Discussion: We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care., Trial Registration: IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Traumatic injuries are among the leading causes of death and disability worldwide. Major trauma presentations have seen a demographic shift recently from the young to the elderly, with significant associated neurological deficit., Aims: To review the presentation and outcome of elderly patients presenting with cervical spinal injuries and associated neurological deficit that underwent surgical intervention in order to optimise treatment strategies., Methods: A retrospective review was conducted at a national tertiary referral centre to analyse admission trends from June 2016 to July 2020 for outcomes of elderly patients (≥ 65) presenting with traumatic cervical spine injuries associated with spinal cord injuries (SCI). Demographic, clinical, and radiological characteristics were collected and analysed., Results: Forty-two patients met the inclusion criteria. The most common mechanisms of injury (MOIs) were falls from standing (38.1%) and falls from height (≥ 2 m) (33.3%). Complete SCIs had increased mean LOS (57.6 vs 21.6 days; p = 0.013), postoperative complications (100% vs 60.6%; p = 0.022), life-threatening complications (57.1% vs 9.1%; p = 0.001), and 90-day mortality (37.5% vs 5.9%; p = 0.007) compared to incomplete SCIs., Conclusion: Elderly patients with complete SCIs have poorer outcomes and mortality than those with less extensive SCIs. They require more resources, have greater risk of complications, and have higher mortality than those with incomplete SCIs, with subsequent implications on optimal treatment strategies. More robust studies are needed to derive improved risk stratification tools for geriatric patients with spinal injuries., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Spinal cord injury (SCI) causes neural disconnection and persistent neurological deficits, so axon sprouting and plasticity might promote recovery. Soluble Nogo-Receptor-Fc decoy (AXER-204) blocks inhibitors of axon growth and promotes recovery of motor function after SCI in animals. This first-in-human and randomised trial sought to determine primarily the safety and pharmacokinetics of AXER-204 in individuals with chronic SCI, and secondarily its effect on recovery., Methods: We conducted a two-part study in adults (aged 18-65 years) with chronic (>1 year) cervical traumatic SCI at six rehabilitation centres in the USA. In part 1, AXER-204 was delivered open label as single intrathecal doses of 3 mg, 30 mg, 90 mg, or 200 mg, with primary outcomes of safety and pharmacokinetics. Part 2 was a randomised, parallel, double-blind comparison of six intrathecal doses of 200 mg AXER-204 over 104 days versus placebo. Participants were randomly allocated (1:1) by investigators using a central electronic system, stratified in blocks of four by American Spinal Injury Association Impairment Scale grade and receipt of AXER-204 in part 1. All investigators and patients were masked to treatment allocation until at least day 169. The part 2 primary objectives were safety and pharmacokinetics, with a key secondary objective to assess change in International Standards for Neurological Classification of SCI (ISNCSCI) Upper Extremity Motor Score (UEMS) at day 169 for all enrolled participants. This trial is registered with ClinicalTrials.gov, NCT03989440, and is completed., Findings: We treated 24 participants in part 1 (six per dose; 18 men, six women), and 27 participants in part 2 (13 placebo, 14 AXER-204; 23 men, four women), between June 20, 2019, and June 21, 2022. There were no deaths and no discontinuations from the study due to an adverse event in part 1 and 2. In part 2, treatment-related adverse events were of similar incidence in AXER-204 and placebo groups (ten [71%] vs nine [69%]). Headache was the most common treatment-related adverse event (five [21%] in part 1, 11 [41%] in part 2). In part 1, AXER-204 reached mean maximal CSF concentration 1 day after dosing with 200 mg of 412 000 ng/mL (SD 129 000), exceeding those concentrations that were efficacious in animal studies. In part 2, mean changes from baseline to day 169 in ISNCSCI UEMS were 1·5 (SD 3·3) for AXER-204 and 0·9 (2·3) for placebo (mean difference 0·54, 95% CI -1·48 to 2·55; p=0·59)., Interpretation: This study delivers the first, to our knowledge, clinical trial of a rationally designed pharmacological treatment intended to promote neural repair in chronic SCI. AXER-204 appeared safe and reached target CSF concentrations; exploratory biomarker results were consistent with target engagement and synaptic stabilisation. Post-hoc subgroup analyses suggest that future trials could investigate efficacy in patients with moderately severe SCI without prior AXER-204 exposure., Funding: Wings for Life Foundation, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Drug Abuse, and ReNetX Bio., Competing Interests: Declaration of interests GM, CA, CH, GB, and ES are employees of ReNetX Bio, which holds rights to develop AXER-204. SMS is a founder of, is a consultant for, and holds equity interest in ReNetX Bio, as well as being an inventor on NgR1 intellectual property licensed from Yale to ReNetX Bio. AEF is a principal investigator for Medical Imaging and Data Resource Center and serves on the Board of Radiological Society of North America. RZ serves on boards of Myomo, Onecare.ai, NanoDiagnostics, J Neurotrauma, and Frontiers in Neurology. JS, DPL, DC, CL, RM, XW, JL, WW, and TL declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: To explore the factors affecting the quality of accelerated rehabilitation for patients with cervical spinal cord injury, therefore, to propose targeted improvement strategies and provide reference for promoting the quality of nursing care for accelerated rehabilitation., Design: This descriptive qualitative inquiry followed the COREQ guidelines., Methods: From December 2020 to April 2021, 16 subjects including orthopaedic nurses, nursing management experts, orthopaedic surgeons, anaesthesiologists and physical therapists experienced in accelerated rehabilitation were selected by objective sampling method to conduct semi-structured interviews. Thematic analysis was used to analyse the interview content., Results: Through analysis and summary of the interview data, the following two themes and nine sub-themes were finally extracted. Factors related to the quality of accelerated rehabilitation structure include: construction of multidisciplinary teams, thorough system guarantee and adequate staffing. Factors related to the quality of accelerated rehabilitation process include: inadequate training and assessment, lack of medical staff's awareness, incapability of the accelerated rehabilitation team members, poor multidisciplinary communication and collaboration, lack of patient's awareness, and ineffective health education., Conclusion: Quality of implementation of accelerated rehabilitation can be improved by maximizing the role of multidisciplinary team, establishing a flawless accelerated rehabilitation system, increasing allocation of nursing resources, enhancing knowledge of medical staff, improving their awareness of accelerated rehabilitation, establishing personalized clinical pathways of accelerated rehabilitation, increasing communication and collaboration among multidisciplinary disciplines, and improving health education of patients., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Benign paroxysmal positional vertigo (BPPV) is characterized by short, sudden episodes of vertigo when the head moves in specific positions. The treatment is particle repositioning maneuvers. BPPV usually is underdiagnosed, unreported and therefore not adequately treated. We present the case of a patient with spinal cord injury and BPPV. A 72-year-old patient who suffered a C5 fracture with spinal cord injury C5 AIS C that required surgical fixation. In the spinal cord injury unit BPPV of the left lateral semicircular canal was documented and treated using specific repositioning maneuvers, the patient progressively improved and was able to complete the rehabilitation treatment. The spinal cord injury unit with access to vestibular rehabilitation units can carry out the diagnosis and specific treatment of BPPV, minimizing the risks for the patient., (Copyright © 2023 Sociedad Española de Rehabilitación y Medicina Física. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Following a spinal cord injury, regaining hand function is a top priority. Current hand assessments are conducted in clinics, which may not fully represent real-world hand function. Grasp strategies used in the home environment are an important consideration when examining the impact of rehabilitation interventions., Objective: The main objective of this study is to investigate the relationship between grasp use at home and clinical scores., Method: We used a previously collected dataset in which 21 individuals with spinal cord injuries (SCI) recorded egocentric video while performing activities of daily living in their homes. We manually annotated 4432 hand-object interactions into power, precision, intermediate, and non-prehensile grasps. We examined the distributions of grasp types used and their relationships with clinical assessments., Results: Moderate to strong correlations were obtained between reliance on power grasp and the Spinal Cord Independence Measure III (SCIM; P  < .05), the upper extremity motor score (UEMS; P  < .01), and the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) Prehension ( P  < .01) and Strength ( P  < .01). Negative correlations were observed between the proportion of non-prehensile grasping and SCIM ( P  < .05), UEMS ( P  < .05), and GRASSP Prehension ( P  < .01) and Strength ( P  < .01)., Conclusion: The types of grasp types used in naturalistic activities at home are related to upper limb impairment after cervical SCI. This study provides the first direct demonstration of the importance of hand grasp analysis in the home environment.

Spinal cord hemisection at C 2 (C 2 SH), sparing the dorsal column is widely used to investigate the effects of reduced phrenic motor neuron (PhMN) activation on diaphragm muscle (DIAm) function, with reduced DIAm activity on the injured side during eupnoea. Following C 2 SH, recovery of DIAm EMG activity may occur spontaneously over subsequent days/weeks. Various strategies have been effective at improving the incidence and magnitude of DIAm recovery during eupnoea, but little is known about the effects of C 2 SH on transdiaphragmatic pressure (P di ) during other ventilatory and non-ventilatory behaviours. We employ SPG302, a novel type of pegylated benzothiazole derivative, to assess whether enhancing synaptogenesis (i.e., enhancing spared local connections) will improve the incidence and the magnitude of recovery of DIAm EMG activity and P di function 14 days post-C 2 SH. In anaesthetised Sprague-Dawley rats, DIAm EMG and P di were assessed during eupnoea, hypoxia/hypercapnia and airway occlusion prior to surgery (C 2 SH or sham), immediately post-surgery and at 14 days post-surgery. In C 2 SH rats, 14 days of DMSO (vehicle) or SPG302 treatments (i.p. injection) occurred. At the terminal experiment, maximum P di was evoked by bilateral phrenic nerve stimulation. We show that significant EMG and P di deficits are apparent in C 2 SH compared with sham rats immediately after surgery. In C 2 SH rats treated with SPG302, recovery of eupneic, hypoxia/hypercapnia and occlusion DIAm EMG was enhanced compared with vehicle rats after 14 days. Treatment with SPG302 also ameliorated P di deficits following C 2 SH. In summary, SPG302 is an exciting new therapy to explore for use in spinal cord injuries. KEY POINTS: Despite advances in our understanding of the effects of cervical hemisection (C 2 SH) on diaphragm muscle (DIAm) EMG activity, very little is understood about the impact of C 2 SH on the gamut of ventilatory and non-ventilatory transdiaphragmatic pressures (P di ). Recovery of DIAm activity following C 2 SH is improved using a variety of approaches, but very few pharmaceuticals have been shown to be effective. One way of improving DIAm recovery is to enhance the amount of latent local spared connections onto phrenic motor neurons. A novel pegylated benzothiazole derivative enhances synaptogenesis in a variety of neurodegenerative conditions. Here, using a novel therapeutic SPG302, we show that 14 days of treatment with SPG302 ameliorated DIAm EMG and P di deficits compared with vehicle controls. Our results show that SPG302 is a compound with very promising potential for use in improving functional outcomes post-spinal cord injury., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

Objective: Spinal cord injury (SCI) is classified as complete or incomplete depending on the extent of sensorimotor preservation below the injury level. However, individuals with complete SCIs can voluntarily activate paralyzed lower limb muscles alone or by engaging non-paralyzed muscles during neurophysiological assessments, indicating presence of residual pathways across the injury. However, similar phenomena have not been explored for the upper extremity (UE) muscles following cervical SCIs., Methods: Eighteen individuals with motor complete cervical SCI (AIS A or B) and five age-matched non-injured (NI) individuals performed various UE events against manual resistance during functional neurophysiological assessment (FNPA), and electromyographic (EMG) activity was recorded from UE muscles., Results: Our findings demonstrated i) voluntary activation of clinically paralyzed muscles as evident from EMG readouts, ii) increased activity in these muscles during events engaging muscles above the injury level, iii) reduced spectral properties of paralyzed muscles in SCI compared to NI participants., Conclusions: Functional EMG activity in clinically paralyzed muscles indicate presence of residual pathways across the injury establishing supralesional control over the sublesional neural circuitry., Significance: The findings may help explain the neurophysiological basis for UE recovery and can be exploited in designing rehabilitation techniques to facilitate UE recovery following cervical SCIs., Competing Interests: Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Traumatic cervical spinal cord injury can cause significant neurologic disability. A cervical spine injury impacts not only the neurologic system but also numerous other organ systems of the body. This complex injury requires a systematic approach to assessment and care aimed at preventing, recognizing, and treating potentially devastating secondary spinal cord injury and multisystem complications. This article focuses on the pathophysiology, initial presentation, and treatment of cervical spinal cord injury by body system., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Peripheral nerve transfer (PNT) to improve upper limb function following cervical spinal cord injury (SCI) involves the transfer of supralesional donor nerves under voluntary control to intralesional or sublesional lower motor neurons not under voluntary control. Appropriate selection of donor and recipient nerves and surgical timing affect functional outcomes. Although the gold standard of nerve selection is intraoperative nerve stimulation, preoperative electrodiagnostic (EDX) evaluation may help guide surgical planning. Currently there is no standardized preoperative EDX protocol. This study reviews the EDX workup preceding PNT surgery in cervical SCI and proposes an informed EDX protocol to assist with surgical planning. The PICO (Population, Intervention, Comparison, Outcome) framework was used to formulate relevant Medical Subject Headings (MeSH) terms and identify published cases of PNT in cervical SCI in Medline, Embase, CINAHL, and Emcare databases in the last 10 years. The EDX techniques evaluating putative donor nerves, recipient nerve branches, time sensitivity of nerve transfer and other electrophysiological parameters were summarized to guide creation of a preoperative EDX protocol. Needle electromyography (EMG) was the most commonly used EDX technique to identify healthy donor nerves. Although needle EMG has also been used on recipient nerves, compound muscle action potential amplitudes may provide a more accurate determination of recipient nerve health and time sensitivity for nerve transfer. Although there has been progress in presurgical EDX evaluation, EMG and nerve conduction study approaches are variable, and each has limitations in their utility for preoperative planning. There is need for standardization in the EDX evaluation preceding PNT surgery to assist with donor and recipient nerve selection, surgical timing and to optimize outcomes. Based on results of this review, herein we propose the PreSCIse (PRotocol for Electrodiagnosis in SCI Surgery of the upper Extremity) preoperative EDX panel to achieve said goals through an interdisciplinary and patient-centered approach., (© 2022 American Academy of Physical Medicine and Rehabilitation.)

Objective: High cervical spinal cord injury (SCI) results in complete loss of upper-limb function, resulting in debilitating tetraplegia and permanent disability. Spontaneous motor recovery occurs to varying degrees in some patients, particularly in the 1st year postinjury. However, the impact of this upper-limb motor recovery on long-term functional outcomes remains unknown. The objective of this study was to characterize the impact of upper-limb motor recovery on the degree of long-term functional outcomes in order to inform priorities for research interventions that restore upper-limb function in patients with high cervical SCI., Methods: A prospective cohort of high cervical SCI (C1-4) patients with American Spinal Injury Association Impairment Scale (AIS) grade A-D injury and enrolled in the Spinal Cord Injury Model Systems Database was included. Baseline neurological examinations and functional independence measures (FIMs) in feeding, bladder management, and transfers (bed/wheelchair/chair) were evaluated. Independence was defined as score ≥ 4 in each of the FIM domains at 1-year follow-up. At 1-year follow-up, functional independence was compared among patients who gained recovery (motor grade ≥ 3) in elbow flexors (C5), wrist extensors (C6), elbow extensors (C7), and finger flexors (C8). Multivariable logistic regression evaluated the impact of motor recovery on functional independence in feeding, bladder management, and transfers., Results: Between 1992 and 2016, 405 high cervical SCI patients were included. At baseline, 97% of patients had impaired upper-limb function with total dependence in eating, bladder management, and transfers. At 1 year of follow-up, the largest proportion of patients who gained independence in eating, bladder management, and transfers had recovery in finger flexion (C8) and wrist extension (C6). Elbow flexion (C5) recovery had the lowest translation to functional independence. Patients who achieved elbow extension (C7) were able to transfer independently. On multivariable analysis, patients who gained elbow extension (C7) and finger flexion (C8) were 11 times more likely to gain functional independence (OR 11, 95% CI 2.8-47, p < 0.001) and patients who gained wrist extension (C6) were 7 times more likely to gain functional independence (OR 7.1, 95% CI 1.2-56, p = 0.04). Older age (≥ 60 years) and motor complete SCI (AIS grade A-B) reduced the likelihood of gaining independence., Conclusions: After high cervical SCI, patients who gained elbow extension (C7) and finger flexion (C8) had significantly greater independence in feeding, bladder management, and transfers than those with recovery in elbow flexion (C5) and wrist extension (C6). Recovery of elbow extension (C7) also increased the capability for independent transfers. This information can be used to set patient expectations and prioritize interventions that restore these upper-limb functions in patients with high cervical SCI.

Frailty, as measured by the modified frailty index-5 (mFI-5), and older age are associated with increased mortality in the setting of spinal cord injury (SCI). However, there is limited evidence demonstrating an incremental prognostic value derived from patient mFI-5. We conducted a retrospective cohort study to evaluate in-hospital mortality among adult complete cervical SCI patients at participating centers of the Trauma Quality Improvement Program from 2010 to 2018. Logistic regression was used to model in-hospital mortality, and the area under the receiver operating characteristic curve (AUROC) of regression models with age, mFI-5, or age with mFI-5 was used to compare the prognostic value of each model. 4733 patients were eligible. We found that both age (80 y versus 60 y: OR 3.59 95% CI [2.82 4.56], P < 0.001) and mFI-5 (score ≥ 2 versus < 2: OR 1.53 95% CI [1.19 1.97], P < 0.001) had statistically significant associations with in-hospital mortality. There was no significant difference in the AUROC of a model including age and mFI-5 when compared to a model including age without mFI-5 (95% CI Δ AUROC [- 8.72 × 10 -4 0.82], P = 0.199). Both models were superior to a model including mFI-5 without age (95% CI Δ AUROC [0.06 0.09], P < 0.001). Our findings suggest that mFI-5 provides minimal incremental prognostic value over age with respect to in-hospital mortality for patients complete cervical SCI., (© 2023. The Author(s).)

Comprehensive characterizations of hand grasping behaviors after cervical spinal cord injuries are fundamental for developing rehabilitation strategies to promote recovery in spinal-cord-injured primates. We used the machine-learning-based video analysis software, DeepLabCut, to sensitively quantify kinematic aspects of grasping behavioral deficits in squirrel monkeys with C5-level spinal cord injuries. Three squirrel monkeys were trained to grasp sugar pellets from wells of varying depths before and after a left unilateral lesion of the cervical dorsal column. Using DeepLabCut, we identified post-lesion deficits in kinematic grasping behavior that included changes in digit orientation, increased variance in vertical and horizontal digit movement, and longer time to complete the task. While video-based analyses of grasping behavior demonstrated deficits in fine-scale digit function that persisted through at least 14 weeks post-injury, traditional end-point behavioral analyses showed a recovery of global hand function as evidenced by recovery of the proportion of successful retrievals by approximately 14 weeks post-injury. The combination of traditional end-point and video-based kinematic analyses provides a more comprehensive characterization of grasping behavior and highlights that global grasping performance may recover despite persistent fine-scale kinematic deficits in digit function. Machine-learning-based video analysis of kinematic digit function, in conjunction with traditional end-point behavioral analyses of grasping behavior, provide sensitive and specific indices for monitoring recovery of fine-grained hand sensorimotor behavior after spinal cord injury that can aid future studies that seek to develop targeted therapeutic interventions for improving behavioral outcomes., Competing Interests: Conflict of interests The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)