Temporal dynamics of gait function in acute cervical spinal cord injury.

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Corticospinal inhibition investigated in relation to upper extremity motor function in cervical spinal cord injury.

OBJECTIVE: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI. METHODS: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T). RESULTS: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores. CONCLUSIONS: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP. SIGNIFICANCE: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI.

Lower Motor Neuron Abnormality in Chronic Cervical Spinal Cord Injury: Implications for Nerve Transfer Surgery.

Nerve transfer surgery (NT) constitutes an exciting option to improve upper limb functions in chronic spinal cord injury (SCI), but requires intact sublesional lower motor neuron (LMN) health. The purpose of this study was to characterize patterns of LMN abnormality in nerve-muscle groups that are the potential recipients of NT, using a standardized electrodiagnostic examination, in individuals with chronic SCI (injury duration >2 years, injury levels C4-T1). The LMN abnormality was determined using a semihierarchical approach, combining the amplitude compound muscle action potential (CMAP) and abnormal spontaneous activity on needle electromyography (EMG). Ten participants (46 potential recipient muscles) were included (median age, 42.5 years; six males and four females; median duration from injury, 15.5 years). A high frequency of LMN abnormality was observed (87%), although there was substantial variation within and between individuals. No statistically significant discordance was observed between LMN abnormality on CMAP and EMG (p = 0.24), however, 50% of muscles with normal CMAP demonstrated abnormal spontaneous activity. The high frequency of LMN abnormality in recipient nerve-muscle groups has implications to candidate selection for NT surgery in chronic SCI and supports the important role of the pre-operative electrodiagnostic examination. Our results further support the inclusion of both CMAP and needle EMG parameters for characterization of LMN health. Although the number of nerve-muscle groups with normal LMN health was small (13%), this underscores the neurophysiological potential of some patients with chronic injuries to benefit from NT surgery.

Increased intensity of unintended mirror muscle contractions after cervical spinal cord injury is associated with changes in interhemispheric and corticomuscular coherences.

Mirror contractions refer to unintended contractions of the contralateral homologous muscles during voluntary unilateral contractions or movements. Exaggerated mirror contractions have been found in several neurological diseases and indicate dysfunction or lesion of the cortico-spinal pathway. The present study investigates mirror contractions and the associated interhemispheric and corticomuscular interactions in adults with spinal cord injury (SCI) - who present a lesion of the cortico-spinal tract - compared to able-bodied participants (AB). Eight right-handed adults with chronic cervical SCI and ten age-matched right-handed able-bodied volunteers performed sets of right elbow extensions at 20% of maximal voluntary contraction. Electromyographic activity (EMG) of the right and left elbow extensors, interhemispheric coherence over cerebral sensorimotor regions evaluated by electroencephalography (EEG) and corticomuscular coherence between signals over the cerebral sensorimotor regions and each extensor were quantified. Overall, results revealed that participants with SCI exhibited (1) increased EMG activity of both active and unintended active limbs, suggesting more mirror contractions, (2) reduced corticomuscular coherence between signals over the left sensorimotor region and the right active limb and increased corticomuscular coherence between the right sensorimotor region and the left unintended active limb, (3) decreased interhemispheric coherence between signals over the two sensorimotor regions. The increased corticomuscular communication and decreased interhemispheric communication may reflect a reduced inhibition leading to increased communication with the unintended active limb, possibly resulting to exacerbated mirror contractions in SCI. Finally, mirror contractions could represent changes of neural and neuromuscular communication after SCI.

The Protein Kinase Inhibitor Midostaurin Improves Functional Neurological Recovery and Attenuates Inflammatory Changes Following Traumatic Cervical Spinal Cord Injury.

Traumatic spinal cord injury (SCI) impairs neuronal function and introduces a complex cascade of secondary pathologies that limit recovery. Despite decades of preclinical and clinical research, there is a shortage of efficacious treatment options to modulate the secondary response to injury. Protein kinases are crucial signaling molecules that mediate the secondary SCI-induced cellular response and present promising therapeutic targets. The objective of this study was to examine the safety and efficacy of midostaurin-a clinically-approved multi-target protein kinase inhibitor-on cervical SCI pathogenesis. High-throughput analyses demonstrated that intraperitoneal midostaurin injection (25 mg/kg) in C6/7 injured Wistar rats altered the local inflammasome and downregulated adhesive and migratory genes at 24 h post-injury. Treated animals also exhibited enhanced recovery and restored coordination between forelimbs and hindlimbs after injury, indicating the synergistic impact of midostaurin and its dimethyl sulfoxide vehicle to improve functional recovery. Furthermore, histological analyses suggested improved tissue preservation and functionality in the treated animals during the chronic phase of injury. This study serves as a proof-of-concept experiment and demonstrates that systemic midostaurin administration is an effective strategy for mitigating cervical secondary SCI damage.

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury.

Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function, with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore the rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity, including a brief examination of sex-related differences in these mechanisms. Finally, we suggest that more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.

Autonomic dysreflexia associated with cervical spinal cord gliofibroma: case report.

BACKGROUND: Autonomic dysreflexia (AD) is an abnormal reflex of the autonomic nervous system normally observed in patients with spinal cord injury from the sixth thoracic vertebra and above. AD causes various symptoms including paroxysmal hypertension due to stimulus. Here, we report a case of recurrent AD associated with cervical spinal cord tumor. CASE PRESENTATION: The patient was a 57-year-old man. Magnetic resonance imaging revealed an intramedullary lesion in the C2, C6, and high Th12 levels. During the course of treatment, sudden loss of consciousness occurred together with abnormal paroxysmal hypertension, marked facial sweating, left upward conjugate gaze deviation, ankylosis of both upper and lower extremities, and mydriasis. Seizures repeatedly occurred, with symptoms disappearing after approximately 30 min. AD associated with cervical spinal cord tumor was diagnosed. Histological examination by tumor biopsy confirmed the diagnosis of gliofibroma. Radiotherapy was performed targeting the entire brain and spinal cord. The patient died approximately 3 months after treatment was started. CONCLUSIONS: AD is rarely associated with spinal cord tumor, and this is the first case associated with cervical spinal cord gliofibroma. AD is important to recognize, since immediate and appropriate response is required.

The Restless Spinal Cord in Degenerative Cervical Myelopathy.

BACKGROUND AND PURPOSE: The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy. MATERIALS AND METHODS: Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P = .368; mean age, 62.2 [SD, 6.5] years; P = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups. RESULTS: In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [n = 18], 0.54 [SD, 0.16] mm; patients [n = 29], monosegmental stenosis [n = 10], 1.86 [SD, 0.92] mm; P < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [n = 18], 0.36 [SD, 0.09] mm; patients [n = 52]; stenosis: C3, n = 21; C4, n = 11; C5, n = 18; C6, n = 2; 0.85 [SD, 0.46] mm; P < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle. CONCLUSIONS: Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions.

Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord.

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.

Effects of aerobic exercise training on muscle plasticity in a mouse model of cervical spinal cord injury.

Cervical spinal cord injury (SCI) results in permanent life-altering motor and respiratory deficits. Other than mechanical ventilation for respiratory insufficiency secondary to cervical SCI, effective treatments are lacking and the development of animal models to explore new therapeutic strategies are needed. The aim of this work was to demonstrate the feasibility of using a mouse model of partial cervical spinal hemisection at the second cervical metameric segment (C2) to investigate the impact of 6 weeks training on forced exercise wheel system on locomotor/respiratory plasticity muscles. To measure run capacity locomotor and respiratory functions, incremental exercise tests and diaphragmatic electromyography were done. In addition, muscle fiber type composition and capillary distribution were assessed at 51 days following chronic C2 injury in diaphragm, extensor digitorum communis (EDC), tibialis anterior (TA) and soleus (SOL) muscles. Six-week exercise training increased the running capacity of trained SCI mice. Fiber type composition in EDC, TA and SOL muscles was not modified by our protocol of exercise. The vascularization was increased in all muscle limbs in SCI trained group. No increase in diaphragmatic electromyography amplitude of the diaphragm muscle on the side of SCI was observed, while the contraction duration was significantly decreased in sedentary group compared to trained group. Cross-sectional area of type IIa myofiber in the contralateral diaphragm side of SCI was smaller in trained group. Fiber type distribution between contralateral and ipsilateral diaphragm in SCI sedentary group was affected, while no difference was observed in trained group. In addition, the vascularization of the diaphragm side contralateral to SCI was increased in trained group. All these results suggest an increase in fatigue resistance and a contribution to the running capacity in SCI trained group. Our exercise protocol could be a promising non-invasive strategy to sustain locomotor and respiratory muscle plasticity following SCI.

Serotonergic innervation of respiratory motor nuclei after cervical spinal injury: Impact of intermittent hypoxia.

Although cervical spinal cord injury (cSCI) disrupts bulbo-spinal serotonergic projections, partial recovery of spinal serotonergic innervation below the injury site is observed after incomplete cSCI. Since serotonin contributes to functional recovery post-injury, treatments to restore or accelerate serotonergic reinnervation are of considerable interest. Intermittent hypoxia (IH) was reported to increase serotonin innervation near respiratory motor neurons in spinal intact rats, and to improve function after cSCI. Here, we tested the hypotheses that spontaneous serotonergic reinnervation of key respiratory (phrenic and intercostal) motor nuclei: 1) is partially restored 12 weeks post C2 hemisection (C2Hx); 2) is enhanced by IH; and 3) results from sprouting of spared crossed-spinal serotonergic projections below the site of injury. Serotonin was assessed via immunofluorescence in male Sprague Dawley rats with and without C2Hx (12 wks post-injury); individual groups were exposed to 28 days of: 1) normoxia; 2) daily acute IH (dAIH28: 10, 5 min 10.5% O2 episodes per day; 5 min normoxic intervals); 3) mild chronic IH (IH28-5/5: 5 min 10.5% O2 episodes; 5 min intervals; 8 h/day); or 4) moderate chronic IH (IH28-2/2: 2 min 10.5% O2 episodes; 2 min intervals; 8 h/day), simulating IH experienced during moderate sleep apnea. After C2Hx, the number of ipsilateral serotonergic structures was decreased in both motor nuclei, regardless of IH protocol. However, serotonergic structures were larger after C2Hx in both motor nuclei, and total serotonin immunolabeling area was increased in the phrenic motor nucleus but reduced in the intercostal motor nucleus. Both chronic IH protocols increased serotonin structure size and total area in the phrenic motor nuclei of uninjured rats, but had no detectable effects after C2Hx. Although the functional implications of fewer but larger serotonergic structures are unclear, we confirm that serotonergic reinnervation is substantial following injury, but IH does not affect the extent of reinnervation.

Association Between Magnetic Resonance Imaging-Based Spinal Morphometry and Sensorimotor Behavior in a Hemicontusion Model of Incomplete Cervical Spinal Cord Injury in Rats.

Aim: Structural connectivity in the reorganizing spinal cord after injury dictates functional connectivity and hence the neurological outcome. As magnetic resonance imaging (MRI)-based structural parameters are mostly accessible across spinal cord injury (SCI) patients, we studied MRI-based spinal morphological changes and their relationship to neurological outcome in the rat model of cervical SCI. Introduction: Functional connectivity assessments on patients with SCI rely heavily on MRI-based approaches to investigate the complete neural axis (both spinal cord and brain). Hence, underlying MRI-based structural and morphometric changes in the reorganizing spinal cord and their relationship to neurological outcomes is crucial for meaningful interpretation of functional connectivity changes across the neural axis. Methods: Young adult rats, aged 1.5 months, underwent a precise mechanical impact hemicontusion incomplete cervical SCI at the C4/C5 level, after which sensorimotor behavioral assessments were tracked during the reorganization period of 1-6 weeks, followed by MRI of the cervical spinal cord at 8 weeks after SCI. Results: A significant ipsilesional forelimb motor debilitation was observed from 1 to 6 weeks after injury. Heat sensitivity testing (Hargreaves) showed ipsilesional forelimb hypersensitivity at 5 and 6 weeks after SCI. MRI of the cervical spine showed ipsilateral T1- and T2-weighted lesions across all SCI rats compared with no significant lesions in sham rats. Morphometric assessments of the lesional and nonlesional changes showed the diverse nature of their interindividual variability in the SCI receiving rats. While the various T1 and T2 MRI lesional volumes associated weakly or moderately with neurological outcome, the nonlesional spinal morphometric changes associated much more strongly. The results have important implications for interpreting functional MRI-based functional connectivity after SCI by providing vital underlying structural changes and their relative neurological impact. Impact statement Functional connectivity assessments on patients with SCI relies heavily upon MRI based approaches. Hence, underlying MRI based structural and morphometric changes in the reorganizing spinal cord and its relationship to neurological outcomes is vital for meaningful interpretation of functional connectivity changes across the complete neural axis (both spinal cord and the brain).

Enabling respiratory control after severe chronic tetraplegia: an exploratory case study.

Respiratory dysfunction is one of the most debilitating effects of spinal cord injury (SCI) impacting the quality of life of patients and caregivers. In addition, breathing difficulties impact the rehabilitation routine a patient may potentially undergo. Transcutaneous electrical spinal cord neuromodulation (TESCoN) is a novel approach to reactivate and retrain spinal circuits after paralysis. We demonstrate that acute and chronic TESCoN therapy over the cervical spinal cord positively impacts the breathing and coughing ability in a patient with chronic tetraplegia. ln addition, we show that the improved breathing and coughing ability are not only observed in the presence of TESCoN but persisted for a few days after TESCoN was stopped.NEW & NOTEWORTHY Noninvasive spinal neuromodulation improves breathing and coughing in a patient with severe and complete tetraplegia.

Influence of early extensive posterior decompression on hyponatremia and cardiopulmonary dysfunction after severe traumatic cervical spinal cord injury: A clinical observational study.

Retrospective single institution observational study.The aim of the present study was to analyze the influence of early extensive posterior decompression on complications in patients with severe traumatic cervical spinal cord injury (tcSCI).Cervical SCI is associated with a high prevalence of hyponatremia and cardiopulmonary dysfunction. However, very few studies have focused on this exploration to reduce the incidence of SCI early complications.We reviewed the medical records of consecutive patients undergoing extensive posterior decompression within 24 h for severe tcSCI (American Spinal Injury Association Impairment Scale [AIS] A to C) admitted between January 2009 and January 2018. The data collected retrospectively included age, gender, mechanism, and level of SCI, AIS grade, fracture or dislocation, electrolyte, and cardiopulmonary complications.Of the 97 enrolled patients, the baseline AIS grade was AIS A in 14, AIS B in 31, and AIS C in 52. Improvement of at least two AIS grades was found in 26 (26.8%), and improvement of at least one grade was found in 80.4% of patients at discharge. Twenty-nine (29.9%) patients had mild hyponatremia, 8 (8.2%) had moderate hyponatremia, and 3 (3.1%) had severe hyponatremia during hospitalization. The incidences of hyponatremia, hypotension, and tracheotomy were 41.2%, 13.4%, and 6.2%, respectively. The mean forced vital capacity (FVC) on admission and at discharge was 1.34 ±â€Š0.46 L and 2.21 ±â€Š0.41 L (P < .0001), respectively. Five patients developed pneumonia.Our results suggest that early expansive posterior decompression significantly reduces the incidence of hyponatremia, hypotension, and tracheotomy by promoting recovery of spinal cord function after severe tcSCI.

The prediction of intraoperative cervical cord function changes by different motor evoked potentials phenotypes in cervical myelopathy patients.

BACKGROUND: Surgery is usually the treatment of choice for patients with cervical compressive myelopathy (CCM). Motor evoked potential (MEP) has proved to be helpful tool in evaluating intraoperative cervical spinal cord function change of those patients. This study aims to describe and evaluate different MEP baseline phenotypes for predicting MEP changes during CCM surgery. METHODS: A total of 105 consecutive CCM patients underwent posterior cervical spine decompression were prospectively collected between December 2012 and November 2016. All intraoperative MEP baselines recorded before spinal cord decompression were classified into 5 types (I to V) that were carefully designed according to the different MEP parameters. The postoperative neurologic status of each patient was assessed immediately after surgery. RESULTS: The mean intraoperative MEP changes range were 10.2% ± 5.8, 14.7% ± 9.2, 54.8% ± 31.9, 74.1% ± 24.3, and 110% ± 40 in Type I, II, III, IV, and V, respectively. There was a significant correlation of the intraoperative MEP change rate with different MEP baseline phenotypes (r = 0.84, P < 0.01). Postoperative transient new spinal deficits were found 0/31 case in Type I, 0/21 in Type II, 1/14 in Type III, 2/24 in Type IV, and 4/15 in Type V. No permanent neurological injury was found in our cases series. CONCLUSIONS: The MEP baselines categories for predicting intraoperative cervical cord function change is proposed through this work. The more serious the MEP baseline abnormality, the higher the probability of intraoperative MEP changes, which is beneficial to early warning for the cervical cord injury.

Effects of Rubber Hand Illusion and Excitatory Theta Burst Stimulation on Tactile Sensation: A Pilot Study.

Synchronous visuotactile stimulation on the own hidden hand and a visible fake limb can alter bodily self-perception and influence spontaneous neuroplasticity. The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually occluded hand. The aim of this cross-over, placebo-controlled, single-blind study was to assess whether RHI, in combination with high-frequency repetitive transcranial magnetic stimulation (rTMS) given as intermittent (excitatory) theta burst stimulation (iTBS) applied over the hand area of the primary sensory region (S1) can enhance tactile sensation in a group of 21 healthy subjects and one patient with cervical spinal cord injury. Four sessions covered all combinations of real and sham stimulations of the RHI and the TBS: real TBS and real RHI, real TBS and sham RHI, sham TBS and real RHI, and both conditions sham. The condition sham TBS and real RHI shows the greatest effect on the proprioceptive drift (median 2.3 cm, IQR 2) and on the score of RHI questionnaires (median 3, IQR 2) in the control group as well as in the real-real condition (median 2, IQR 2). The sham TBS and real RHI condition also shows the best results in the electrical perception test of the patient (median 1.9 mA). Conversely, the upregulation of the cortical excitability of S1 via TBS seems to impair the effect of the RHI. This might be due to a strengthening of the top-down connection between the central nervous system and the periphery, diminishing the RHI. This finding helps in understanding the mechanisms of top-down and bottom-up mechanisms in healthy subjects and patients with spinal cord injury. The RHI paradigm could represent an interesting therapeutic approach in improving tactile sensation and rTMS techniques could modulate these effects. Yet, further studies are needed, to examine the direction of the interaction effect of TMS and RH.

Effects of spinal immobilization at 20° on end-tidal carbon dioxide.

OBJECTIVE: The aim was to determine the effect on end-tidal carbon dioxide (ETCO2) of spinal immobilization (SI) at a conventional 0° angle and to investigate the usefulness of immobilization at a 20° angle for preventing possible hypoventilation. METHODS: The study included 80 healthy volunteers, randomly divided into two groups. Spinal backboards and cervical collars were applied in Group 1 using a 0° angle and in Group 2 using a 20° angle, with the head up. SI was continued for 1 h, and ETCO2 values were measured at the 0th, 30th and 60th minute. RESULTS: There were no significant differences between the groups in 0th and 30th minute ETCO2. However, after 60th minute, results showed a statistically significant increase in ETCO2 in Group 1 (35.5 mmHg [IQR 25-75:35-38]) compared to Group 2 (34 mmHg [IQR 25-75:33-36]) (p < 0.001). During SI, there was a statistically significant increase in ETCO2 in Group 1 (35 mmHg [IQR 25-75:34-36], 35.5 mmHg [IQR 25-75:34-37] and 36 mmHg [IQR 25-75:35-38] respectively at the 0th, 30th and 60th minute after SI) (p < 0.001) and no change in Group 2. Also, we found statistically significant differences between ΔETCO2 levels in Groups 1 and 2 at all 3 time intervals. CONCLUSION: Conventional SI with an angle of 0° led to an increase in ETCO2 while subjects immobilization at a 20° angle maintained their initial ETCO2 values. Immobilization at 20° may prevent decompensation in patients who have thoracic trauma or lung diseases or those who are elderly, pregnant, or obese.

A Cervical Spinal Cord Hemi-Contusion Injury Model Based on Displacement Control in Non-Human Primates (Macaca fascicularis).

Non-human primate (NHP) spinal cord injury (SCI) models can be informative in the evaluation of treatments that show promise in rodent models prior to translation to humans. In the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology, and magnetic resonance imaging. Twelve adult NHPs were divided into an SCI group (n = 8, 24 and 48 weeks) and a control group (n = 4). An impactor (Φ = 4 mm) was driven to compress the left C5 cord at 800 mm/sec. The contusion displacement and peak force was 4.08 ± 0.17 mm and 19.8 ± 4.6 N. The behavioral assessment showed a consistent dysfunction below the wrist and spontaneous recovery of limb function after injury. Lesion length and lesion area at the epicenter based on T2 hyperintensity were 5.68 ± 0.47 mm and 5.99 ± 0.24 mm2 at 24 weeks post-injury (wpi), and 5.29 ± 0.17 mm and 5.95 ± 0.24 mm2 at 48 wpi. The spared spinal cord area immuno-positive for glial fibrillary acidic protein was significantly reduced, while the staining intensity increased at 24 wpi and 48 wpi, compared with the sham group. Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared with pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the dorsal root ganglia (DRG) was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.

Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools.

Closed-loop vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a strategy to enhance recovery after neurological injury. Previous studies demonstrate that brief bursts of closed-loop VNS paired with rehabilitative training substantially improve recovery of forelimb motor function in models of unilateral and bilateral contusive spinal cord injury (SCI) at spinal level C5/6. While these findings provide initial evidence of the utility of VNS for SCI, the injury model used in these studies spares the majority of alpha motor neurons originating in C7-T1 that innervate distal forelimb muscles. Because the clinical manifestation of SCI in many patients involves damage at these levels, it is important to define whether damage to the distal forelimb motor neuron pools limits VNS-dependent recovery. In this study, we assessed recovery of forelimb function in rats that received a bilateral incomplete contusive SCI at C7/8 and underwent extensive rehabilitative training with or without paired VNS. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection ( https://osf.io/ysvgf/ ). VNS paired with rehabilitative training significantly improved recovery of volitional forelimb strength compared to equivalent rehabilitative training without VNS. Additionally, VNS-dependent enhancement of recovery generalized to 2 similar, but untrained, forelimb tasks. These findings indicate that damage to alpha motor neurons does not prevent VNS-dependent enhancement of recovery and provides additional evidence to support the evaluation of closed-loop VNS paired with rehabilitation in patients with incomplete cervical SCI.