Concussion is a common diagnosis in emergency rooms, yet contemporary incidence and prevalence estimates are sparse and rely on self-reported data. A nationwide cohort study was conducted to provide up-to-date information, covering the entire Danish population from 1999 to 2018. Hospital contacts with a concussion diagnosis, including emergency room visits, hospital admissions, and outpatient contacts, were retrieved from the Danish National Patient Registry (DNPR), and incidence rates were age-standardized and stratified. The 20-year prevalence was defined as the percentage of Danes alive in 2018 who had experienced a concussion since 1999. The diagnostic codes used were the ICD-10 code S06.0 and a local Danish code for 'observation for concussion' (DZ033D). Additional data on activities related to concussion injuries were obtained from the Accident Analysis Group at Odense University Hospital through DNPR. Findings from the study showed that during the period 1999-2018, the total age-standardized concussion incidence rate increased by 10% to 308 per 100,000 person-years (95% confidence interval [CI]: 304-313). Notable time trends included (1) a reduced sex difference from 40% to 6% (95% CI: 3%-9%), (2) a doubled incidence rate in children aged 0-1 and in seniors aged over 80, (3) an increased utilization of head imaging across all age groups, except children, (4) a decline in the proportion of traffic-related concussions, and (5) a prevalence of concussion of 4.9% (95% CI: 4.89%-4.93%) in 2018. The increasing incidence of concussions among the elderly is concerning in light of an aging population and warrants further investigation, as evidence-based preventive interventions for falls exist. In addition, the increased utilization of head imaging across all age groups except children calls for attention toward avoidance of unnecessary radiation exposure. Despite a drop in traffic-related cases, concussions remain highly prevalent. In conclusion, these findings indicate that concussions are an important public health concern, necessitating ongoing surveillance, research, and targeted resource allocation to address concussion management and prevention effectively.
Cervical spinal cord injury (SCI) results in significant sensorimotor impairments below the injury level, notably in the upper extremities (UEs), impacting daily activities and quality of life. Regaining UE function remains the top priority for individuals post-cervical SCI. Recent advances in understanding adaptive plasticity within the sensorimotor system have led to the development of novel non-invasive neurostimulation strategies, such as spinal cord transcutaneous stimulation (scTS), to facilitate UE motor recovery after SCI. This comprehensive review investigates the neuromotor control of UE, the typical recovery trajectories following SCI, and the therapeutic potential of scTS to enhance UE motor function in individuals with cervical SCI. Although limited in number with smaller sample sizes, the included research articles consistently suggest that scTS, when combined with task-specific training, improves voluntary control of arm and hand function and sensation. Further, the reported improvements translate to the recovery of various UE functional tasks and positively impact the quality of life in individuals with cervical SCI. Several methodological limitations, including stimulation site selection and parameters, training strategies, and sensitive outcome measures, require further advancements to allow successful translation of scTS from research to clinical settings. This review also summarizes the current literature and proposes future directions to support establishing approaches for scTS as a viable neuro-rehabilitative tool.
Spinal cord contusion injury results in Wallerian degeneration of spinal cord axonal tracts, which are necessary for locomotor function. Axonal swelling and loss of axonal density at the contusion site, characteristic of Wallerian degeneration, commence within hours of injury. Tempol, a superoxide dismutase mimetic, was previously shown to reduce the loss of spinal cord white matter and improve locomotor function in an experimental model of spinal cord contusion, suggesting that tempol treatment might inhibit Wallerian degeneration of spinal cord axons. Here, we report that tempol partially inhibits Wallerian degeneration, resulting in improved locomotor recovery. We previously reported that Wallerian degeneration is reduced by inhibitors of aldose reductase (AR), which converts glucose to sorbitol in the polyol pathway. We observed that tempol inhibited sorbitol production in the injured spinal cord to the same extent as the AR inhibitor, sorbinil. Tempol also prevented post-contusion upregulation of AR (AKR1B10) protein expression within degenerating axons, as previously observed for AR inhibitors. Additionally, we hypothesized that tempol inhibits axonal degeneration by preventing loss of the glutathione pool due to polyol pathway activity. Consistent with our hypothesis, tempol treatment resulted in greater glutathione content in the injured spinal cord, which was correlated with increased expression and activity of gamma glutamyl cysteine ligase (γGCL; EC 6.3.2.2), the rate-limiting enzyme for glutathione synthesis. Administration of the γGCL inhibitor buthionine sulfoximine abolished all observed effects of tempol administration. Together, these results support a pathological role for polyol pathway activation in glutathione depletion, resulting in Wallerian degeneration after spinal cord injury (SCI). Interestingly, methylprednisolone, oxandrolone, and clenbuterol, which are known to spare axonal tracts after SCI, were equally effective in inhibiting polyol pathway activation. These results suggest that prevention of AR activation is a common target of many disparate post-SCI interventions.
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.
Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.
Assessing the extent of the intramedullary lesion after spinal cord injury (SCI) might help to improve prognostication. However, because the neurological level of injury impacts the recovery potential of SCI patients, the question arises whether lesion size parameters and predictive models based on those parameters are affected as well. In this retrospective observational study, the extent of the intramedullary lesion between individuals who sustained cervical and thoracolumbar SCI was compared, and its relation to clinical recovery was assessed. In total, 154 patients with subacute SCI (89 individuals with cervical lesions and 65 individuals with thoracolumbar lesions) underwent conventional clinical magnetic resonance imaging 1 month after injury and clinical examination at 1 and 12 months. The morphology of the focal lesion within the spinal cord was manually assessed on the midsagittal slice of T2-weighted magnetic resonance images and compared between cervical and thoracolumbar SCI patients, as well as between patients who improved at least one American Spinal Injury Association Impairment Scale (AIS) grade (converters) and patients without AIS grade improvement (nonconverters). The predictive value of lesion parameters including lesion length, lesion width, and preserved tissue bridges for predicting AIS grade conversion was assessed using regression models (conditional inference tree analysis). Lesion length was two times longer in thoracolumbar compared with cervical SCI patients (F = 39.48, p < 0.0001), whereas lesion width and tissue bridges width did not differ. When comparing AIS grade converters and nonconverters, converters showed a smaller lesion length (F = 5.46, p = 0.021), a smaller lesion width (F = 13.75, p = 0.0003), and greater tissue bridges (F = 12.87, p = 0.0005). Using regression models, tissue bridges allowed more refined subgrouping of patients in AIS groups B, C, and D according to individual recovery profiles between 1 month and 12 months after SCI, whereas lesion length added no additional information for further subgrouping. This study characterizes differences in the anteroposterior and craniocaudal lesion extents after SCI. The two times greater lesion length in thoracolumbar compared with cervical SCI might be related to differences in the anatomy, biomechanics, and perfusion between the cervical and thoracic spines. Preserved tissue bridges were less influenced by the lesion level while closely related to the clinical impairment. These results highlight the robustness and utility of tissue bridges as a neuroimaging biomarker for predicting the clinical outcome after SCI in heterogeneous patient populations and for patient stratification in clinical trials.
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