Multi-system benefits of non-invasive spinal cord stimulation following cervical spinal cord injury: a case study

Translational Advances in the Management of Acute Spinal Cord Injury

PurposeTo explore differences based on level of pediatric spinal cord injury (SCI), we compared cervical and thoracic SCI in pediatric trauma patients (PTPs), hypothesizing higher mortality and length of stay (LOS) for cervical SCI.MethodsThe 2017–2021 Trauma Quality Improvement Program was queried for all PTPs ≤ 17 years-old with cervical or thoracic SCI. Bivariate analyses compared the two groups. The primary outcome was mortality and secondary outcomes included hospital LOS and injury severity scores (ISS). Logistic regression models were used to determine independent risk factors for death and prolonged ventilation.ResultsOf 5280 PTPs, 2538 (65.9%) had cervical SCI and 1316 (34.1%) had thoracic SCI. Motor vehicle collisions were the most common cause of both cervical and thoracic SCI (37.8 and 41.9%). PTPs with thoracic SCI had higher rates of positive drug screen as compared to cervical SCI (39.2 vs 29.8%, p = 0.001). PTPs with thoracic SCI had higher median ISS (25 vs 16, p < 0.001), while cervical SCI had higher mortality (13 vs 6.1%, p < 0.001) but decreased hospital LOS (median 9 vs 5 days, p < 0.001. Cervical SCI were associated with a nearly fourfold increase in the risk of death (95% CI 2.750–5.799, p < 0.001) and a 1.6-fold increase in the risk of prolonged ventilator requirement (95% CI 1.228–2.068, p < 0.001).ConclusionsPTPs with cervical SCI have higher mortality while those with thoracic SCI have higher ISS and hospital LOS. Cervical SCI were associated with a fourfold higher risk of death. MVC was the most common cause of injury, and both groups had high rates of positive drug screens. Understanding differing outcomes may assist providers with prognostication and injury prevention.

Bilateral cervical contusion spinal cord injury: A mouse model to evaluate sensorimotor function

Breaking Down Silos to Protect the Spinal Cord

Introduction to the Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries

Nerve Grafting for Spinal Cord Injury in Cats: Are We Close to Translational Research?

The prognosis for patients with a complete traumatic spinal cord injury (SCI) is generally poor. It is unclear whether some subgroups of patients with a complete traumatic SCI could benefit from early surgical decompression of the spinal cord. The objectives of this study were: (1) to compare the effect of early and late surgical decompression on neurological recovery in complete traumatic SCI and (2) to assess whether the impact of surgical timing is different in patients with cervical or thoracolumbar SCI. A prospective cohort study was followed in a single Level 1 Trauma Center specializing in SCI care. All consecutive patients who sustained a traumatic SCI and were referred between 2010 and 2013 were screened for eligibility. Neurological status was assessed systematically using the American Spinal Injury Association impairment scale (AIS) at arrival to the trauma center and at rehabilitation discharge. Patients operated within 24 h of the trauma were compared with patients operated later than 24 h after the trauma. Potential confounders such as age, Injury Severity Score (ISS), smoking history, body mass index (BMI), Glasgow Coma Scale (GCS) score, and duration of follow-up were recorded. Fifty-three patients with complete SCI were included in the study: 33 thoracolumbar and 20 cervical SCIs. The 38 patients operated <24 h were generally younger than the 15 patients operated ≥ 24 h (p = 0.049). Overall, 28% (15/53) of complete SCI had improvement in AIS: 34% (13/38) who were operated <24 h and 13% (2/15) who were operated ≥ 24 h (p = 0.182). Sixty-four percent (9/14) of cervical complete SCI operated <24 h had improvement in AIS as opposed to none in the subgroup of six complete cervical SCI operated ≥ 24 h (p = 0.008). Surgical decompression within 24 h in complete SCI may optimize neurological recovery, especially in patients with cervical SCI.

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps.SIGNIFICANCE STATEMENT Although a number of individuals with cervical incomplete spinal cord injury show limited functional recovery of elbow extensors compared with elbow flexor muscles, to date, the neural mechanisms underlying this asymmetrical recovery remain unknown. Here, we provide for the first time evidence for increased reticulospinal inputs to biceps but not triceps brachii and loss of corticospinal drive to triceps brachii in humans with tetraplegia. We propose that this reorganization in descending control contributes to the asymmetrical recovery between elbow flexor and extensor muscles after cervical spinal cord injury.

Motor Recovery after Spinal Cord Injury Enhanced by Strengthening Corticospinal Synaptic Transmission

Low current stimulation of the dorsal surface of the spinal cord (epidural stimulation) has been shown to restore volitional control of various functions after spinal cord injury (SCI) but has not been clinically translated to breathing. Our lab uses closed-loop epidural stimulation to restore breathing after cervical SCI, using diaphragm EMG activity to trigger short trains of stimulation only during respiratory effort (e.g. closed-loop). We have previously demonstrated that this approach restores some ipsilesional diaphragm EMG activity in rats with C2 hemisection (C2HS) (Mickle et al., 2024); however, it is unknown what neural populations are activated by stimulation to achieve this motor output. This study investigates stimulation and injury-induced changes in neuronal activity within respiratory motor networks, assessed through FOS expression, to see if stimulation activates particular neurons in the spinal diaphragm and intercostal motor pools. Here, we investigate FOS expression at the spinal segments C4, the location of the stimulus electrodes and likely greatest effect of stimulation, and at T4, a distal respiratory motor pool isolated from direct stimulation. Male Sprague-Dawley rats (3–5 months old) were urethane anesthetized and mechanically ventilated. Stimulation electrodes were sutured to the dorsal surface of C4 and recording EMG electrodes sutured to the diaphragm. Rats were then either C2 hemisected or left intact before undergoing two bouts of contralesional EMG-triggered stimulation (in-phase and out-of-phase) separated by 20 minutes or a sham period. Rats were perfused 60 minutes after the end of stimulation and T4 and C4 spinal tissue sectioned at 15 µm and stained for FOS mRNA via RNAScope (sham intact C4: n = 4, T4: n =3; sham C2HS C4: n = 4, T4: n = 4; stim intact C4: n = 8, T4: n = 3; stim C2HS C4: n = 8, T4: n = 4). Cell nuclei were stained with DAPI and identified using StarDist. FOS positivity was detected using a channel intensity threshold classifier. At C4, there was no significant effect of injury or stimulation on the total percentage of all cells positive for FOS. However, stimulation resulted in more gray matter FOS positivity in both injured and intact rats (proportion of total FOS positivity in gray matter mean +/- SD: stim intact 64 +/- 13%, stim C2HS 68 +/- 16%, sham intact 38 +/- 11%, sham C2HS 35 +/- 14%; main effect of stimulation, p = 0.0001). Work is ongoing to colocalize FOS positive cells with various neural markers to identify a population of neurons necessary for stimulation-induced increases in diaphragm EMG. In contrast, at T4, C2HS resulted in elevated FOS positivity in gray matter compared to intact rats (% cells FOS+ in gray matter intact vs C2HS: 0.58 +/- 0.11% vs 0.95 +/- 0.10%, p = 0.025), suggesting injury increases neuronal firing at the intercostal motor pool, potentially as a compensatory mechanism, independent of stimulation. While stimulation did not alter gray matter FOS expression at T4, stimulation decreased white matter FOS positivity in hemisected rats while in intact rats white matter positivity relative to gray was increased with stimulation (proportion of total FOS positivity in white matter: stim intact 56.6 +/- 9.5%, sham intact 38.7 +/- 15.0%, stim C2HS 30.3 +/- 5.4%, sham C2HS 45.6 +/- 8.6%; interaction of stimulation and injury, p = 0.01). Thus, closed-loop epidural stimulation influences neuronal activity in respiratory motor networks after cervical SCI, with distinct effects at local (C4) and distal (T4) spinal segments. These findings contribute to the understanding of ES mechanisms and its potential application for restoring respiratory function after SCI. University Scholars Program (CB), R01HL153102 (ED), T32HL134621 (AM), Bryan Robinson Endowment Grant for the Neurosciences (AM), Grand Aerie Fraternal Order of Eagles (ED) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The Effect of Elevated Mean Arterial Blood Pressure in Cervical Traumatic Spinal Cord Injury with Hemorrhagic Contusion

Causes of, and countermeasures to, increased ventilatory drive in tetraplegia.

Purpose To investigate perceptions of surgical participants and their caregivers regarding novel nerve transfer surgery to restore upper extremity function in cervical level spinal cord injury. Materials and Methods A qualitative study design was used. A multidisciplinary team developed semi-structured interview guides. Interviews were recorded, transcribed and analyzed using basic text analysis. Results Participants had limited information about procedures to improve function after spinal cord injury. When discussing their choice to undergo nerve (as compared to traditional tendon) transfer surgery, they describe a desire to avoid post-operative immobilization. Barriers included the pre-operative testing, cost and inconvenience of travel for surgery, and understanding complex health information related to the procedure. While expectations matched descriptions of outcomes among participants and were generally positive, caregivers expressed disappointment. The long time interval for gains in function to be realized and relatively incremental gains achieved were frustrating to all. Conclusions People with cervical spinal cord injury and their caregivers need more information about options to restore function and about realistic range of improvements with treatment. Further work to mitigate barriers and develop health information materials around nerve transfer surgery may improve medical decision making around and appropriate use of this newer treatment option. IMPLICATIONS FOR REHABILITATION Nerve transfer surgery is a novel and acceptable means of improving upper extremity function in the setting of cervical spinal cord injury. People with cervical spinal cord injury and their caregivers need information about options to restore hand and arm function and mitigation of barriers around these treatment options.

PTEN inhibition promotes robust growth of bulbospinal respiratory axons and partial recovery of diaphragm function in a chronic model of cervical contusion spinal cord injury

A multicenter, retrospective study using computed tomographic and magnetic resonance imaging data to establish quantitative, reliable criteria of canal compromise and cord compression in patients with cervical spinal cord injury. To develop and validate a radiologic assessment tool of spinal canal compromise and cord compression in cervical spinal cord injury for use in clinical trials. There are few quantitative, reliable criteria for radiologic measurement of cervical spinal canal compromise or cord compression after acute spinal cord injury. The study included 71 patients (55 men, 16 women; mean age, 39.7 +/- 18.7 years) with acute cervical spinal cord injury. Causes of spinal cord injury included motor vehicle accidents (n = 36), falls (n = 20), water-related injuries (n = 8), sports (n = 5), assault (n = 1), and farm accidents (n = 1). Canal compromise was measured on computed tomographic scan and T1- and T2-weighted magnetic resonance imaging, and cord compression at the level of maximum injury was measured on T1- and T2-weighted magnetic resonance imaging. All films were assessed by two independent observers. There was a strong correlation of canal compromise and/or cord compression measurements between axial and midsagittal computed tomography, and between axial and midsagittal T2-weighted magnetic resonance imaging. Spinal canal compromise assessed by computed tomography showed a significant although moderate correlation with spinal cord compression assessed by T1- and T2-weighted magnetic resonance imaging. Virtually all patients with canal compromise of 25% or more on computed tomographic scan had evidence of some degree of cord compression on magnetic resonance imaging, but a large number of patients with less than 25% canal compromise on computed tomographic scan also had evidence on magnetic resonance imaging of cord compression. In patients with cervical spinal cord injury, the midsagittal T1- and T2-weighted magnetic resonance imaging provides an objective, quantifiable, and reliable assessment of spinal cord compression that cannot be adequately assessed by computed tomography alone.