Cervical Spinal Cord Injury Research Articles

Comparisons of Evoked Skin Vasomotor and Sudomotor Responses to Single Pulse Median Nerve Stimulation

The sensorimotor dysfunction caused by cervical and thoracic spinal cord injury (SCI) is concomitant with sympathetic nervous system dysfunction, evidenced by the high prevalence of orthostatic hypotension and autonomic dysreflexia. Although the International Standards for Neurological Classification of SCI evaluate sensorimotor function both above and below the injury level, there are limited quantitative measures for gauging sympathetic outflow and the extent of dysautonomia resulting from neurological damage. Despite studies on the effects of SCI on electrodermal activity (EDA) and blood pressure (BP), there is a lack of detailed feature comparisons involving EDA, skin vasomotor activity, and BP. Therefore, we investigated the relationship between EDA, skin vasomotor, and BP responses to sympathetic activation via median nerve stimulation in persons with and without SCI. Adults with and without SCI (cohort demographics presented in poster) participated in this study. Lead II electrocardiogram (ECG), pneumogram (P), photoplethysmogram (PPG), and EDA were recorded from either the trunk (ECG, P) or both limbs (PPG, EDA). Beat-by-beat BP was recorded from the middle finger of the left hand (VitalStream, CareTaker Medical). Evoked responses in the above signals were measured surrounding a cathodal electrical pulse (30 mA, 200 μs) delivered to the distal right median nerve 1-2 cm proximal and medial to the radial styloid process either during systole or diastole of the cardiac cycle. There were notable differences between baseline signals before and after the experimental session, along with a consistent reduction of limb temperature (> 2° Celsius). Increases in EDA (greater than two standard deviations from baseline) were found across non-SCI participants following stimulation both during systole and diastole, along with skin vasoconstriction following the onset of EDA modulation (> 50% of trials). Individual differences were noted in evoked responses to stimulation at systole vs. diastole. Furthermore, attenuated responses were observed in individuals with SCI. Stimulation caused no evoked signal response habituation across trials within participants. Additionally, evoked BP changes were not consistent across all individuals with respect to stimulation. Our results show a fixed relationship between evoked skin vasomotor and sudomotor responses to single pulse stimuli across participants and had consistent waveform features. Potential individual effects of stimulation delivered at systole vs. diastole warrant an in-depth analysis of reflex gating of sudomotor and skin vasomotor responses. This would present insight into the population with SCI, where dysfunction could greatly exaggerate reflex gating. 1R01NS131493-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prognostic Value of Magnetic Resonance Imaging Markers in Predicting Neurological Outcomes in Traumatic Cervical Spinal Cord Injuries: An Observational Study

Abstract Objectives: The objectives of this study were to predict the prognostic value of conventional magnetic resonance imaging (MRI) parameters in predicting neurological outcomes in post-traumatic cervical spinal injuries (cord compression, cord oedema and cord haemorrhage) and to assess the neurological outcomes using the American Spinal Injury Association (ASIA) impairment scale. Materials and Methods: A total of 55 patients with traumatic cervical spinal cord injury (SCI) were recruited; history and neurological examination of the patient was done along with classifications of SCI according to ASIA after the assessment of vital parameters. MRI scan of cervical spine was done and certain parameters like presence or absence of haematoma, maximum spinal cord compression (MSCC), maximum canal compression (MCC) and lesion length were measured. Follow-up of neurological recovery was done on the 15th, 30th and 45th days and recorded in ASIA pro forma. Further to determine the correlation between MRI parameters and neurological recovery, Spearman rank correlation coefficient and multiple regression analysis were used. Results: Lesion length is statistically significant (P-value <0.05) for Asia Impairement Scale improvement at day 15, day 45, also significant for total sensory score and motor score on day 15 and shows significant for total sensory score on day 30, day 45. The presence of haematoma is statistically significant (P < 0.05) for total sensory score at day 30 and day 45, whereas MSCC and haematoma are statistically significant (<0.05) for total pinprick score at day 45. Discussion: Lesion length remains the most important predictor for neurological recovery after cervical spine trauma; however, haematoma and MSCC are potential predictors for neurological recovery and change in ASIA score. The study was registered at the Clinical Trials Registry-India (CTRI/2022/07/044163).

Impact of Reduced Activity on Endurance of Rat Diaphragm Muscle

The diaphragm muscle (DIAm) as the major inspiratory pump is highly active. During breathing, fatigue resistant DIAm motor units are recruited that comprise type I and IIa fibers. Accordingly, these fibers have substantially higher mitochondrial volume density (MVD) and mitochondrial respiratory capacity (SDHmax) compared to more fatigable type IIx/IIb fibers. Cervical spinal cord injury disrupts descending inspiratory drive and markedly reduces eupneic activity of the DIAm. With C2 spinal cord hemisection (C2SH) DIAm activity on the ipsilateral side is reduced. Following a two-week period of C2SH, we found reduced MVD and SDHmax in type I and IIa DIAm fibers. As a result, we hypothesize that endurance of the DIAm is reduced. Female and male Sprague Dawley rats were used. EMG electrodes were placed in the left and right DIAm 3 days prior to C2SH surgery, and baseline recordings of eupneic DIAm activity were obtained in awake animals. The right C2 spinal cord was hemisected, and the extent of injury was confirmed by the absence of eupneic DIAm activity on the ipsilateral side while animals were anesthetized. Subsequently, DIAm EMG activity was recorded at 3, 7 and 14 days post C2SH. After two weeks, rats were anesthetized and the DIAm was excised. DIAm strips were cut and suspended in a tissue chamber containing Rees-Simpson solution maintained at 26oC, with thecostal margin clamped and the central tendon attached to a Cambridge Dual-Mode force/length transducer. DIAm strips were stimulated using platinum plate electrodes with supramaximal current (~250 mA) pulses (1 ms), and maximum specific force was determined at 75 Hz. The force-velocity relationship was then determined by systematically changing load, and maximum velocity (Vmax) was estimated based on curve fitting with the Hill-equation. Based on the force-velocity measurements peak power of the DIAm was calculated. Subsequently, the DIAm was repetitively stimulated and allowed to shorten at 30% maximum velocity (isovelocity approximating peak power output). Endurance of the DIAm was then determined as the duration that peak power output was sustained. Finally, the DIAm was rapidly frozen, and cross-sections were cut for fiber type and cross-sectional area (CSA) measurements. C2SH resulted in a marked decrease in eupneic DIAm EMG activity across the two-week period, which disproportionately affected type I and IIa DIAm fibers. However, there was no impact of C2SH on DIAm fiber type proportions or CSA. Following two-weeks C2SH, maximum specific force, Vmax, and peak power output of the DIAm were comparable between intact and injured sides. However, endurance of the DIAm was reduced on the injured side compared to the intact side. These results support our hypothesis that reduced activity of DIAm, reduces oxidative capacity of type I and IIa fibers and thereby reduces endurance. In clinical conditions such as mechanical ventilation DIAm activity is reduced and if maintained for longer periods of time this may affect DIAm endurance post weaning. Research supported by NIH grant: HL146114 (GCS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Cardiac Pacemaker Implantation in Patients With Acute Traumatic Cervical Spinal Cord Injury.

Cardiac pacemaker implantation may be indicated in patients with refractory bradycardia following a cervical spinal cord injury (CSCI). However, evidence about the impact of this procedure on outcomes is lacking. We planned a study to assess whether the implantation of a pacemaker would decrease mortality and hospital resource utilization in patients with CSCI. Adult patients with CSCI in the Trauma Quality Improvement Program (TQIP) database between 2016 and 2019 were retrospectively analyzed. Patients were divided into "pacemaker" and "non-pacemaker" groups, and their baseline characteristics and clinical outcomes were analyzed. A total of 6774 cases were analyzed. The pacemaker group showed higher in-hospital rates of cardiac arrest, myocardial infarction, and longer duration of mechanical ventilation and ICU stay than the non-pacemaker group. Nevertheless, pacemaker placement was associated with a significant decrease in mortality (4.2% vs 26.0%, P < .01). Patients with CSCI requiring a pacemaker placement had better survival than those treated without a pacemaker. Pacemaker implantation should be highly considered in patients who develop refractory bradycardia after CSCI.

Therapeutic efficacy of adrenergic agents on systemic and spinal hemodynamics in an acute cervical spinal cord injury rodent model

BACKGROUNDCervical spinal cord injury usually results in cardiorespiratory dysfunctions due to interruptions of the bulbospinal pathways innervating the cervical phrenic motoneurons and thoracic sympathetic preganglionic neurons. PURPOSEThe present study aimed to evaluate the therapeutic effects of adrenergic agents on systemic and spinal hemodynamics during acute cervical spinal cord injury. STUDY DESIGNIn vivo animal study. METHODSThe cardiorespiratory function and spinal cord blood flow and oxygenation level were monitored in response to cervical spinal cord contusion and intravenous infusion of three types of adrenergic agents (phenylephrine, dobutamine, and norepinephrine). RESULTSCervical spinal cord contusion resulted in immediate reduction of respiratory airflow, arterial blood pressure, and spinal cord blood flow. The arterial blood pressure and spinal cord blood flow remained lower than the preinjury value in contused animals infused with saline at 60 min postinjury. Infusion of phenylephrine (500, 1000, and 2000 μg/kg) and norepinephrine (125, 250, and 500 μg/kg) significantly increased the arterial blood pressure, while only norepinephrine augmented the spinal cord blood flow. Conversely, dobutamine (1000 and 2000 μg/kg) reduced both arterial blood pressure and spinal cord blood flow. Notably, administration of adrenergic agents tended to increase spinal cord hemorrhage in contused animals. CONCLUSIONSInfusion of norepinephrine can effectively maintain the blood pressure and improve spinal cord blood flow during acute spinal cord injury. CLINICAL SIGNIFICANCENorepinephrine may be a superior medicine for hemodynamic management; however, the potential hemorrhage should be considered when utilizing the vasopressor to regulate systemic and spinal hemodynamics at the acute injured stage.

Musculoskeletal morbidity in adults with spinal cord injuries: A nationwide cohort study.

An increase in the demand for quality of life following spinal cord injuries (SCIs) is associated with an increase in musculoskeletal (MSK) pain, highlighting the need for preventive measure research. This study aimed to evaluate the incidence and hazards of MSK morbidities among Korean adults with SCIs, as well as the influence of SCI location on MSK morbidities. Patient populations were selected from Korean National Health Insurance Service data (n = 276). The control group included individuals without SCIs (n = 10,000). We compared the incidences and determined the unadjusted and adjusted hazard ratios (HRs) of common MSK morbidities (osteoarthritis, connective tissue disorders, sarcopenia, myalgia, neuralgia, rheumatoid arthritis, myositis, and musculoskeletal infections) based on the location of injury (cervical, thoracic, or lumbar). Adults with SCIs had a higher incidence of MSK morbidity (48.45% vs. 36.6%) and a lower survival probability than those without SCIs. The incidence of MSK morbidity and survival probabilities were not significantly different for cervical cord injuries, whereas both measures were significantly different for thoracic and lumbar injuries. SCI increases the risk of MSK morbidity. Lumbar SCI is associated with a higher incidence and risk of MSK morbidity than are cervical or thoracic SCIs.

Race and socioeconomic disparities persist in treatment and outcomes of patients with cervical spinal cord injuries: An analysis of the national inpatient sample from 2016 - 2020

ObjectivePrevious literature has described race and socioeconomic disparities in both treatment and outcomes following cervical spinal cord injuries (SCI). The goal of this study is to investigate the current state of parity in management and outcomes following SCI. MethodsWe surveyed the National Inpatient Sample database (NIS) for patients admitted with primary diagnosis of cervical SCI. 49,320 patients were identified. Univariate and multivariate analyses were performed to evaluate racial and socioeconomic differences in SCI care and outcomes. ResultsCompared to white patients, minority race was associated with a longer time from presentation to operative intervention (p < 0.001) and longer length of stay following admission for cervical SCI (16 vs 13 days, p < 0.001). Minority patients were more likely to have an unfavorable discharge (skilled nursing facility, against medical advice, death) status than white patients (p < 0.001). Patients in the bottom quartile of median household income were associated with more unfavorable discharges than the top two quartiles (p < 0.001). Patients with the lowest median household income quartile also had higher total costs than those in the top quartiles ($221,654 vs 191,723, p < 0.001). Black, Hispanic, and Asian/Pacific Islander incurred higher treatment costs than White patients. ConclusionMinority and lower socioeconomic status are independently associated with unfavorable discharge and LOS in cervical SCI. Furthermore, racial and economically disadvantaged groups have longer wait times from admission to surgical intervention. These disparities persist despite being highlighted by previous publications and increased societal awareness of healthcare inequities, necessitating further work to reach parity.

Participation and autonomy, independence in activities of daily living and upper extremity functioning in individuals with spinal cord injury

Improvements in care and rehabilitation have resulted in a higher proportion of people living with spinal cord injury (SCI), which calls for an increased focus on participation and autonomy. This observational cross-sectional study investigated the impact of SCI on autonomy and how it correlates to activity performance and upper extremity functioning. A total of 25 adults (mean age 58 years) with chronic cervical or thoracic SCI were included. Self-perceived autonomy was measured with Impact on Participation and Autonomy questionnaire, independence in activities of daily living (ADL) with Spinal Cord Independence Measure, upper extremity functioning with Action Research Arm Test (ARAT) and kinematic measures of the drinking task. The results showed that most participants perceived injury-related restrictions in outdoor autonomy (80%), family role (76%), and in indoor autonomy (72%). Independence in self-care (r = 0.72), mobility (r = 0.59) and upper extremity kinematics of movement time (r = 0.63) and smoothness (r = 0.49) were correlated to indoors autonomy. Social life autonomy was correlated to self-care (r = 0.50) and ARAT (r = 0.41). In conclusion, autonomy was perceived restricted after SCI in several major life areas and correlated with independence in ADL and upper extremity functioning. The aspects of autonomy should be considered more in goal setting and clinical decision-making.

Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation.

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.

Advances in cervical spinal cord injury rehabilitation

Objective Provide background in cervical spinal cord injury and updates in rehabilitation for patients with cervical spinal cord injury.Findings Cervical Spinal Cord injury is a catastrophic event that can be life-altering. The introduction of physiatrists, along with the rehabilitation team, early after cervical spinal cord injury has been shown to help decrease acute care length of stay and medical complications and provide education to patients and families facing life with spinal cord injury.Conclusion There are newer technologies and modalities in spinal cord rehabilitation, including but not limited to functional electrical stimulation, epidural stimulation, and robot-assist gait training that are opening up the prospect of prolonged recovery after spinal cord injury and are an area of future potential and innovation.

Advances in Medical and Surgical Care of Acute Spinal Cord injury

Acute cervical spinal cord injury (SCI) represents a significant challenge, with substantial implications for individual well-being and societal costs. In this chapter, we highlighted the importance of early surgical intervention within a critical time frame following injury to mitigate the risk of secondary damage and optimize neurological recovery. The chapter also delineated the dichotomy of primary and secondary injuries in traumatic cervical SCI, elucidating the pathophysiological mechanisms underlying each phase. Insights into the inflammatory cascade and cellular responses offer a nuanced understanding of injury progression, paving the way for targeted therapeutic interventions. Therefore, we delved into the current landscape of traumatic cervical SCI, addressing the advances in the medical and surgical care. Regarding surgical management, attention was directed towards established practices such as immobilization, respiratory support, and optimal timing of surgery, alongside emerging modalities including intraspinal pressure management, stem cell therapy, and nerve/tendon transfer. Similarly, the medical management section highlighted the importance of spinal cord perfusion, neurogenic shock management, and the role of steroids, while also exploring novel avenues such as genetic modification for spinal recovery. Overall, this chapter underscored the dynamic nature of SCI care, advocating for a holistic approach that integrates traditional and innovative treatment modalities.

Trend differences in cervical spinal cord injuries before and after the coronavirus disease 2019 pandemic.

Cross-Sectional Study. To investigate the changes in the characteristics of cervical spinal cord injuries (CSCI) before and after the coronavirus disease 2019 (COVID-19) pandemic among patients transported to our hospital in Japan. Hospital with an emergency center in Chiba, Japan. Patients eligible for the study were those transported within 24 h of injury and diagnosed with cervical spinal cord injury between January 2018 and December 2021 at our hospital. Medical records were retrospectively examined to investigate the number and characteristics of patients with CSCI. The clinical variables of patients with CSCI were compared according to the time of admission as related to the COVID-19 pandemic: 2018-19 (before) or 2020-21 (after). The total number of patients with CSCI from 2018 to 2021 was 108, with 57 before the COVID-19 pandemic and 51 after the COVID-19 pandemic. The number of severe cases with an injury severity score (ISS) of >16 decreased after COVID-19 (p < 0.05). Falls on level surfaces were the most common cause of injury both before and after COVID-19. Although the ranking of traffic accidents decreased after COVID-19, among those, the number of bicycle injuries tended to increase. The number of serious cases with an ISS > 16 decreased, presumably because of the decline in high-energy trauma due to the background decrease in the number of traffic accidents.

Implicit and explicit motor imagery ability after SCI: Moving the elbow makes the difference

Cervical spinal cord injury (SCI) causes dramatic sensorimotor deficits that restrict both activity and participation. Restoring activity and participation requires extensive upper limb rehabilitation focusing elbow and wrist movements, which can include motor imagery. Yet, it remains unclear whether MI ability is impaired or spared after SCI. We investigated implicit and explicit MI ability in individuals with C6 or C7 SCI (SCIC6 and SCIC7 groups), as well as in age- and gender-matched controls without SCI. Inspired by previous studies, implicit MI evaluations involved hand laterality judgments, hand orientation judgments (HOJT) and hand-object interaction judgments. Explicit MI evaluations involved mental chronometry assessments of physically possible or impossible movements due to the paralysis of upper limb muscles in both groups of participants with SCI. HOJT was the paradigm in which implicit MI ability profiles differed the most between groups, particularly in the SCIC6 group who had impaired elbow movements in the horizontal plane. MI ability profiles were similar between groups for explicit MI evaluations, but reflected task familiarity with higher durations in the case of unfamiliar movements in controls or attempt to perform movements which were no longer possible in persons with SCI. Present results, obtained from a homogeneous population of individuals with SCI, suggest that people with long-term SCI rely on embodied cognitive motor strategies, similar to controls. Differences found in behavioral response pattern during implicit MI mirrored the actual motor deficit, particularly during tasks that involved internal representations of affected body parts.

Diffusion Weighted Magnetic Resonance Imaging of Spinal Cord Injuries After Instrumented Fusion Stabilization.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for assessing spinal cord injury (SCI) that has historically been challenged by the presence of metallic stabilization hardware. This study leverages recent advances in metal-artifact resistant multi-spectral DW-MRI to enable diffusion quantification throughout the spinal cord even after fusion stabilization. Twelve participants with cervical spinal cord injuries treated with fusion stabilization and 49 asymptomatic able-bodied control participants underwent multi-spectral DW-MRI evaluation. Apparent diffusion coefficient (ADC) values were calculated in axial cord sections. Statistical modeling assessed ADC differences across cohorts and within distinct cord regions of the SCI participants (at, above, or below injured level). Computed models accounted for subject demographics and injury characteristics. ADC was found to be elevated at injured levels compared with non-injured levels (z = 3.2, p = 0.001), with ADC at injured levels decreasing over time since injury (z = -9.2, p < 0.001). Below the injury level, ADC was reduced relative to controls (z = -4.4, p < 0.001), with greater reductions after more severe injuries that correlated with lower extremity motor scores (z = 2.56, p = 0.012). No statistically significant differences in ADC above the level of injury were identified. By enabling diffusion analysis near fusion hardware, the multi-spectral DW-MRI technique allowed intuitive quantification of cord diffusion changes after SCI both at and away from injured levels. This demonstrates the approach's potential for assessing post-surgical spinal cord integrity throughout stabilized regions.

A Study on Interobserver and Intraobserver Reliability of the Huashan Radiologic Classification System for Cervical Spinal Cord Injury Without Fracture and Dislocation.

Observational study. To assess the reproducibility and reliability of the system. The Huashan radiologic classification system for cervical spinal cord injury without fracture and dislocation (CSCIWFD) was recently proposed and found useful for clinical practice. Patients diagnosed with CSCIWFD between 2015 and 2021 were recruited. Six spine surgeons from different institutions, three experienced and other inexperienced respectively, were trained as observers of the system, and these surgeons classified the recruited patients using the system. Then, 8 weeks later, they repeated the classification on the same patients in a different order. The interobserver and intraobserver agreement between the results was analyzed using percentage agreement, weighted kappa, and Cohen kappa (κ) statistics. A total of 60 patients were included in the analysis. Type I was the most frequent type (29 cases, 48.3%), followed by type II (13 cases, 21.7%), type III (12 cases, 20%), and type IV (6 cases, 10%). For all the observers, experienced observers, and inexperienced observers, the overall agreement percentages were 77.6% (κ = 0.78), 84.4% (κ = 0.84), and 72.8% (κ = 0.74), respectively, indicating substantial to nearly perfect interobserver reproducibility. A higher level of agreement was found for differentiating type I from other types, with the percentage agreement ranging from 87.8% to 94.4% (κ= 0.74-0.88). For distinguishing compression on the spinal cord (types I and II vs types III and IV) among the different groups of observers, the percentage agreement was 97.8% (κ = 0.94), indicating nearly perfect reproducibility. As for intraobserver agreement, the percentage agreement ranged from 86.7% to 96.7% (κ = 0.78-0.95), indicating at least substantial reliability. The Huashan radiologic classification system for CSCIWFD was easy to learn and apply in a clinical environment, showing excellent reproducibility and reliability. Therefore, it would be promising to apply and promote this system for the precise evaluation and personalized treatment strategy.

Impact of Upper Limb Motor Recovery on Functional Independence After Traumatic Low Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) causes devastating loss of upper limb function and independence. Restoration of upper limb function can have a profound impact on independence and quality of life. In low-cervical SCI (level C5-C8), upper limb function can be restored via reinnervation strategies such as nerve transfer surgery. The translation of recovered upper limb motor function into functional independence in activities of daily living (ADLs), however, remains unknown in low cervical SCI (i.e., tetraplegia). The objective of this study was to evaluate the association of patterns in upper limb motor recovery with functional independence in ADLs. This will then inform prioritization of reinnervation strategies focused to maximize function in patients with tetraplegia. This retrospective study performed a secondary analysis of patients with low cervical (C5-C8) enrolled in the SCI Model Systems (SCIMS) database. Baseline neurological examinations and their association with functional independence in major ADLs-i.e., eating, bladder management, and transfers (bed/wheelchair/chair)-were evaluated. Motor functional recovery was defined as achieving motor strength, in modified research council (MRC) grade, of ≥ 3 /5 at one year from ≤ 2/5 at baseline. The association of motor function recovery with functional independence at one-year follow-up was compared in patients with recovered elbow flexion (C5), wrist extension (C6), elbow extension (C7), and finger flexion (C8). A multi-variable logistic regression analysis, adjusting for known factors influencing recovery after SCI, was performed to evaluate the impact of motor function at one year on a composite outcome of functional independence in major ADLs. Composite outcome was defined as functional independence measure score of 6 or higher (complete independence) in at least two domains among eating, bladder management, and transfers. Between 1992 and 2016, 1090 patients with low cervical SCI and complete neurological/functional measures were included. At baseline, 67% of patients had complete SCI and 33% had incomplete SCI. The majority of patients were dependent in eating, bladder management, and transfers. At one-year follow-up, the largest proportion of patients who recovered motor function in finger flexion (C8) and elbow extension (C7) gained independence in eating, bladder management, and transfers. In multi-variable analysis, patients who had recovered finger flexion (C8) or elbow extension (C7) had higher odds of gaining independence in a composite of major ADLs (odds ratio [OR] = 3.13 and OR = 2.87, respectively, p < 0.001). Age 60 years (OR = 0.44, p = 0.01), and complete SCI (OR = 0.43, p = 0.002) were associated with reduced odds of gaining independence in ADLs. After cervical SCI, finger flexion (C8) and elbow extension (C7) recovery translate into greater independence in eating, bladder management, and transfers. These results can be used to design individualized reinnervation plans to reanimate upper limb function and maximize independence in patients with low cervical SCI.

Determinants of prolonged baseline blood pressure restoration following autonomic dysreflexia for individuals with spinal cord injuries

Objective This study aimed to identify the determinants affecting the time required for blood pressure (BP) restoration after autonomic dysreflexia (AD) and to propose a new method for BP measurement in individuals with cervical spinal cord injury (SCI) who experience AD. Methods In a prospective, single-center observational study, participants’ bladders were filled with body-temperature saline until reaching cystometric capacity, as confirmed by previous urodynamic studies. Restoration time (RT), defined as the time from the onset of voiding until BP returned to baseline, was measured during the morning voiding session. This session involved the use of a 10F hydrophilic transurethral catheter. Data were then compared with various clinical determinants including demographic, urodynamic, and cystographic variables. Results The study included 29 individuals with cervical SCI. Notable variations in RT were observed among individuals with differing levels of detrusor overactivity (DO) and bladder compliance. An inverse correlation was noted between RT and bladder compliance, whereas positive correlations were identified with maximal detrusor pressure, peak systolic BP (SBP), and the magnitude of BP changes. Factors associated with prolonged RT included injury completeness, bladder trabeculation, vesicoureteral reflux (VUR), DO, and changes in SBP. Conclusions A significant association was found between BP elevation and prolonged RT. Determinants such as the severity of the SCI, bladder trabeculation, VUR, and DO were correlated with prolonged RT, considering their importance in the assessment of baseline BP following AD.

Decoding of unimanual and bimanual reach-and-grasp actions from EMG and IMU signals in persons with cervical spinal cord injury.

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.

Individuals With Prior Chronic Pain and Long-Term Opioid Treatment May Experience Persistence of That Pain Even After Subsequent Complete Cervical Spinal Cord Injury: Suggestions From a Prospective Case-Controlled Study

ObjectiveTo determine whether chronic pain persists after complete spinal cord injury (SCI). DesignProspective observational study regarding the outcome of pre-existent chronic pain of inpatients admitted with new clinically diagnosed complete cervical SCI. For patients who acknowledged chronic pain of ≥3 years duration before the SCI, further questions explored whether they still experienced that pain, whether they were experiencing current posttraumatic pain, and whether they had any past exposure to opioids. The included patients were identified during the initial consultation in the trauma center for treatment of the SCI. SettingLevel I trauma center. ParticipantsFrom a total of 49 participants with acute cervical SCI with clinically diagnosed complete motor and sensory tetraplegia admitted between 2018 and 2020, 7 were selected on the basis of a history of chronic pain. InterventionCollected complete history and performed physical examination with serial follow-ups during the acute hospital stay until death or discharge. Main Outcome MeasuresThe primary outcome was a finding of chronic pain experienced before new clinical diagnosis of complete SCI, compared with whether or not that pain continued after the SCI injury. The secondary outcome was the relation of persistent pain with opioid use; it was formulated after data collection. ResultsAmong 49 patients with clinically diagnosed complete cervical SCIs, 7 had experienced prior chronic pain. Four participants experienced a continuation of the prior pain after their complete tetraplegia (4/7), whereas 3 participants did not (3/7). All the participants with continued pain had been previously treated with opioids, whereas those whose pain ceased had not received chronic opioid therapy. ConclusionsThere may be a unique form of chronic pain that is based in the brain, irrespective of peripheral pain or spinal mechanisms. Otherwise healthy people with longstanding antecedent chronic pain whose pain persists after acute clinically complete SCI with tetraplegia may provide a new model for evaluation of brain-based pain. Opioids may be requisite for this type of pain.

250 Harnessing the Endogenous Stem Cell Response After Spinal Cord Injury: A Novel and Translationally Relevant Therapeutic Strategy

INTRODUCTION: The adult spinal cord contains a population of endogenous ependymal-derived neural stem/progenitor cells (epNSPCs) that hold the potential to promote regeneration and repair after injury. epNSPCs are normally quiescent but are acutely activated after spinal cord injury (SCI). Despite this, the activation of these cells remains insufficient to promote robust neural regeneration and recovery. Understanding the mechanisms that govern the biology of epNSPCs is critical in developing a therapeutic strategy to harness their regenerative potential after SCI. METHODS: epNSPCs isolated from the adult spinal cord were used for in vitro mechanistic analysis. In vivo, cervical SCI was induced in adult rodents using a clinically relevant compression-contusion model of cervical SCI. FoxJ1-Cre-tdT reporter mice were used for lineage tracing studies. One-week post-SCI, animals (n = 15/group) were randomized to receive CX546 (a positive AMPA receptor modulator), or vehicle-control. Animals underwent weekly behavioural testing and spinal cords were extracted for histological/molecular analysis. RESULTS: Glutamate excitotoxicity, a hallmark in the pathogenesis of acute SCI, leads to calcium influx in spinal cord epNSPCs via AMPA receptors (AMPARs) and this change in calcium in concert with Notch signaling drives their proliferation and astrocytic differentiation. Blockade of AMPARs in vivo inhibits the activation of epNSPCs post-SCI. Positive modulation of AMPARs after SCI using the clinically relevant class of drugs known as ampakines, enhances epNSPC proliferation, increases pro-regenerative astrocytes and neurotrophic factor production, and promotes neuronal survival and motor recovery. CONCLUSIONS: We report on a novel mechanism by which AMPARs regulate the growth and phenotype of endogenous epNSPCs. Pharmacological targeting of this mechanism could be used to harness the regenerative potential of endogenous neural stem cells and improve motor recovery after SCI.