Pub Date : 2024-09-01Epub Date: 2024-04-10DOI: 10.1089/neu.2023.0591
Kevin M Koch, Andrew S Nencka, Shekar Kurpad, Matthew D Budde
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.
{"title":"Diffusion Weighted Magnetic Resonance Imaging of Spinal Cord Injuries After Instrumented Fusion Stabilization.","authors":"Kevin M Koch, Andrew S Nencka, Shekar Kurpad, Matthew D Budde","doi":"10.1089/neu.2023.0591","DOIUrl":"10.1089/neu.2023.0591","url":null,"abstract":"<p><p>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, <i>p</i> = 0.001), with ADC at injured levels decreasing over time since injury (z = -9.2, <i>p <</i> 0.001). Below the injury level, ADC was reduced relative to controls (z = -4.4, <i>p <</i> 0.001), with greater reductions after more severe injuries that correlated with lower extremity motor scores (z = 2.56, <i>p</i> = 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2125-2132"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1089/neu.2024.65326.rfs2023
Vanessa Raymont
{"title":"Rosalind Franklin Society Proudly Announces the 2023 Award Recipient for Journal of Neurotrauma.","authors":"Vanessa Raymont","doi":"10.1089/neu.2024.65326.rfs2023","DOIUrl":"https://doi.org/10.1089/neu.2024.65326.rfs2023","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":"9 1","pages":"2055"},"PeriodicalIF":4.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-04-18DOI: 10.1089/neu.2023.0353
Joseph F Welch, Alicia K Vose, Kate Cavka, Gina Brunetti, Louis A DeMark, Hannah Snyder, Clayton N Wauneka, Geneva Tonuzi, Jayakrishnan Nair, Gordon S Mitchell, Emily J Fox
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.
{"title":"Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.","authors":"Joseph F Welch, Alicia K Vose, Kate Cavka, Gina Brunetti, Louis A DeMark, Hannah Snyder, Clayton N Wauneka, Geneva Tonuzi, Jayakrishnan Nair, Gordon S Mitchell, Emily J Fox","doi":"10.1089/neu.2023.0353","DOIUrl":"10.1089/neu.2023.0353","url":null,"abstract":"<p><p>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 O<sub>2</sub> ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O<sub>2</sub> ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (<i>p</i> < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (<i>p</i> = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (<i>p</i> = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, <i>n</i> = 11), whereas others responded minimally (<0.20 L/min/%, <i>n</i> = 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 <i>p</i> > 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2114-2124"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-29DOI: 10.1089/neu.2023.0555
Simon Schading-Sassenhausen, Dario Pfyffer, Lynn Farner, Andreas Grillhösl, Orpheus Mach, Doris Maier, Lukas Grassner, Iris Leister, Armin Curt, Patrick Freund
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.
{"title":"Extent of Traumatic Spinal Cord Injury Is Lesion Level Dependent and Predictive of Recovery: A Multicenter Neuroimaging Study.","authors":"Simon Schading-Sassenhausen, Dario Pfyffer, Lynn Farner, Andreas Grillhösl, Orpheus Mach, Doris Maier, Lukas Grassner, Iris Leister, Armin Curt, Patrick Freund","doi":"10.1089/neu.2023.0555","DOIUrl":"10.1089/neu.2023.0555","url":null,"abstract":"<p><p>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 T<sub>2</sub>-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, <i>p</i> < 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, <i>p</i> = 0.021), a smaller lesion width (F = 13.75, <i>p</i> = 0.0003), and greater tissue bridges (F = 12.87, <i>p</i> = 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.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2146-2157"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-03DOI: 10.1089/neu.2024.0168
Jotaro Tachino, Andreas K Demetriades, Wilco Peul, Shunichiro Nakao, Yusuke Katayama, Kenta Tanaka, Tetsuhisa Kitamura, Tomoya Hirose, Kosuke Kiyohara, Yutaka Umemura, Takeyuki Kiguchi, Masahiro Ojima, Kenichiro Ishida, Jun Oda
Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.
{"title":"Effects of Concomitant Traumatic Spinal Cord and Brain Injury on In-Hospital Mortality: A Retrospective Analysis of a Nationwide Trauma Registry in Japan.","authors":"Jotaro Tachino, Andreas K Demetriades, Wilco Peul, Shunichiro Nakao, Yusuke Katayama, Kenta Tanaka, Tetsuhisa Kitamura, Tomoya Hirose, Kosuke Kiyohara, Yutaka Umemura, Takeyuki Kiguchi, Masahiro Ojima, Kenichiro Ishida, Jun Oda","doi":"10.1089/neu.2024.0168","DOIUrl":"10.1089/neu.2024.0168","url":null,"abstract":"<p><p>Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2101-2113"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-02DOI: 10.1089/neu.2024.0194
Brittany Grace Futch, Andreas Seas, Favour Ononogbu-Uche, Shahenda Khedr, Judah Kreinbrook, Christopher I Shaffrey, Theresa Williamson, James David Guest, Michael G Fehlings, Muhammad M Abd-El-Barr, Norah A Foster
Cervical spine injuries (CSIs) are heterogeneous in nature and often lead to long-term disability and morbidity. However, there are few recent and comprehensive epidemiological studies on CSI. The objective of this study was to characterize recent trends in CSI patient demographics, incidence, etiology, and injury level. The National Electronic Injury Surveillance System was used to extract data on CSIs from 2002 to 2022. Weighted national estimates of CSI incidence were computed using yearly population estimates interpolated from U.S. census data. Data analysis involved extracting additional information from patient narratives to categorize injury etiology (i.e., fall) and identify CSI level. K-means clustering was performed on cervical levels to define upper versus lower cervical injuries. Appropriate summary statistics including mean with 95% confidence intervals and frequency were reported for age, sex, race, ethnicity, etiology, and disposition. Age between groups was compared using an independent weighted Z-test. All categorical variables were compared using Pearson chi-squared tests with Bonferroni correction for multiple comparisons. Ordinary least squares linear regression was used to quantify the rate of change of various metrics with time. A total of 11,822 patient records met the study criteria. The mean age of patients was 62.4 ± 22.7 years, 52.4% of whom were male and 61.4% of whom were White, 7.4% were Black, 27.8% were not specified, and the remaining comprised a variety of ethnicities. The most common mechanism of CSI was a fall (67.3%). There was a significant increase in the incidence of cervical injuries between 2003 and 2022 (p < 0.001). Unbiased K-means clustering defined upper cervical injuries as C1-C3 and lower cervical injuries as C4-C7. The mean age of patients with upper CSIs was 72.3 ± 19.6, significantly greater than the age of those with lower CSIs (57.1 ± 23.1, p < 0.001). Compared with lower CSI, White patients were more likely to have an upper CSI (67.4% vs. 73.7%; p < 0.001). While Black/African American (7.5% vs. 3.8%) and Hispanic (2.5% vs. 1.0%) patients were more likely to have a lower CSI (p < 0.001). Our study identified a significant increase in the incidence of CSIs over time, which was associated with increasing patient age. Our study detected a pragmatic demarcation of classifying upper injuries as C1-C3 and lower cervical injuries as C4-C7. Upper injuries were seen more often in older, White females who were treated and admitted, and lower injuries were seen more often in young, Black male patients who were released without admission.
{"title":"Shifting Trends in the Epidemiology of Cervical Spine Injuries: An Analysis of 11,822 Patients from the National Electronic Injury Surveillance System over Two Decades.","authors":"Brittany Grace Futch, Andreas Seas, Favour Ononogbu-Uche, Shahenda Khedr, Judah Kreinbrook, Christopher I Shaffrey, Theresa Williamson, James David Guest, Michael G Fehlings, Muhammad M Abd-El-Barr, Norah A Foster","doi":"10.1089/neu.2024.0194","DOIUrl":"10.1089/neu.2024.0194","url":null,"abstract":"<p><p>Cervical spine injuries (CSIs) are heterogeneous in nature and often lead to long-term disability and morbidity. However, there are few recent and comprehensive epidemiological studies on CSI. The objective of this study was to characterize recent trends in CSI patient demographics, incidence, etiology, and injury level. The National Electronic Injury Surveillance System was used to extract data on CSIs from 2002 to 2022. Weighted national estimates of CSI incidence were computed using yearly population estimates interpolated from U.S. census data. Data analysis involved extracting additional information from patient narratives to categorize injury etiology (i.e., fall) and identify CSI level. K-means clustering was performed on cervical levels to define upper versus lower cervical injuries. Appropriate summary statistics including mean with 95% confidence intervals and frequency were reported for age, sex, race, ethnicity, etiology, and disposition. Age between groups was compared using an independent weighted <i>Z</i>-test. All categorical variables were compared using Pearson chi-squared tests with Bonferroni correction for multiple comparisons. Ordinary least squares linear regression was used to quantify the rate of change of various metrics with time. A total of 11,822 patient records met the study criteria. The mean age of patients was 62.4 ± 22.7 years, 52.4% of whom were male and 61.4% of whom were White, 7.4% were Black, 27.8% were not specified, and the remaining comprised a variety of ethnicities. The most common mechanism of CSI was a fall (67.3%). There was a significant increase in the incidence of cervical injuries between 2003 and 2022 (<i>p</i> < 0.001). Unbiased K-means clustering defined upper cervical injuries as C1-C3 and lower cervical injuries as C4-C7. The mean age of patients with upper CSIs was 72.3 ± 19.6, significantly greater than the age of those with lower CSIs (57.1 ± 23.1, <i>p</i> < 0.001). Compared with lower CSI, White patients were more likely to have an upper CSI (67.4% vs. 73.7%; <i>p</i> < 0.001). While Black/African American (7.5% vs. 3.8%) and Hispanic (2.5% vs. 1.0%) patients were more likely to have a lower CSI (<i>p</i> < 0.001). Our study identified a significant increase in the incidence of CSIs over time, which was associated with increasing patient age. Our study detected a pragmatic demarcation of classifying upper injuries as C1-C3 and lower cervical injuries as C4-C7. Upper injuries were seen more often in older, White females who were treated and admitted, and lower injuries were seen more often in young, Black male patients who were released without admission.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2158-2167"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhou Zhou, Christoffer Olsson, T Christian Gasser, Xiaogai Li, Svein Kleiven
White matter (WM) tract-related strains are increasingly used to quantify brain mechanical responses, but their dynamics in live human brains during in vivo impact conditions remain largely unknown. Existing research primarily looked into the normal strain along the WM fiber tracts (i.e., tract-oriented normal strain), but it is rarely the case that the fiber tract only endures tract-oriented normal strain during impacts. In this study, we aim to extend the in vivo measurement of WM fiber deformation by quantifying the normal strain perpendicular to the fiber tract (i.e., tract-perpendicular normal strain) and the shear strain along and perpendicular to the fiber tract (i.e., tract-oriented shear strain and tract-perpendicular shear strain, respectively). To achieve this, we combine the three-dimensional strain tensor from the tagged magnetic resonance imaging with the diffusion tensor imaging (DTI) from an open-access dataset, including 44 volunteer impacts under two head loading modes, i.e., neck rotations (N = 30) and neck extensions (N = 14). The strain tensor is rotated to the coordinate system with one axis aligned with DTI-revealed fiber orientation, and then four tract-related strain measures are calculated. The results show that tract-perpendicular normal strain peaks are the largest among the four strain types (p < 0.05, Friedman's test). The distribution of tract-related strains is affected by the head loading mode, of which laterally symmetric patterns with respect to the midsagittal plane are noted under neck extensions, but not under neck rotations. Our study presents a comprehensive in vivo strain quantification toward a multifaceted understanding of WM dynamics. We find that the WM fiber tract deforms most in the perpendicular direction, illuminating new fundamentals of brain mechanics. The reported strain images can be used to evaluate the fidelity of computational head models, especially those intended to predict fiber deformation under noninjurious conditions.
{"title":"The White Matter Fiber Tract Deforms Most in the Perpendicular Direction During <i>In Vivo</i> Volunteer Impacts.","authors":"Zhou Zhou, Christoffer Olsson, T Christian Gasser, Xiaogai Li, Svein Kleiven","doi":"10.1089/neu.2024.0183","DOIUrl":"https://doi.org/10.1089/neu.2024.0183","url":null,"abstract":"<p><p>White matter (WM) tract-related strains are increasingly used to quantify brain mechanical responses, but their dynamics in live human brains during <i>in vivo</i> impact conditions remain largely unknown. Existing research primarily looked into the normal strain along the WM fiber tracts (i.e., tract-oriented normal strain), but it is rarely the case that the fiber tract only endures tract-oriented normal strain during impacts. In this study, we aim to extend the <i>in vivo</i> measurement of WM fiber deformation by quantifying the normal strain perpendicular to the fiber tract (i.e., tract-perpendicular normal strain) and the shear strain along and perpendicular to the fiber tract (i.e., tract-oriented shear strain and tract-perpendicular shear strain, respectively). To achieve this, we combine the three-dimensional strain tensor from the tagged magnetic resonance imaging with the diffusion tensor imaging (DTI) from an open-access dataset, including 44 volunteer impacts under two head loading modes, i.e., neck rotations (<i>N</i> = 30) and neck extensions (<i>N</i> = 14). The strain tensor is rotated to the coordinate system with one axis aligned with DTI-revealed fiber orientation, and then four tract-related strain measures are calculated. The results show that tract-perpendicular normal strain peaks are the largest among the four strain types (<i>p</i> < 0.05, Friedman's test). The distribution of tract-related strains is affected by the head loading mode, of which laterally symmetric patterns with respect to the midsagittal plane are noted under neck extensions, but not under neck rotations. Our study presents a comprehensive <i>in vivo</i> strain quantification toward a multifaceted understanding of WM dynamics. We find that the WM fiber tract deforms most in the perpendicular direction, illuminating new fundamentals of brain mechanics. The reported strain images can be used to evaluate the fidelity of computational head models, especially those intended to predict fiber deformation under noninjurious conditions.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara M Wittine, Jessica M Ketchum, Marc A Silva, Flora M Hammond, Joyce S Chung, Karina Loyo, Jose Lezama, Risa Nakase-Richardson
Few studies have examined long-term mortality following traumatic brain injury (TBI) in a military population. This is a secondary analysis of a prospective, longitudinal study that examines long-term mortality (up to 10 years) post-TBI, including analyses of life expectancy, causes of death, and risk factors for death in service members and veterans (SM/V) who survived the acute TBI and inpatient rehabilitation. Among 922 participants in the study, the mortality rate was 8.3% following discharge from inpatient rehabilitation. The mean age of death was 54.5 years, with death occurring on average 3.2 years after injury, and with an average 7-year life expectancy reduction. SM/V with TBI were nearly four times more likely to die compared with the U.S. general population. Leading causes of death were external causes of injury, circulatory disease, and respiratory disorders. Also notable were deaths due to late effects of TBI itself and suicide. Falls were a significant mechanism of injury for those who died. Those who died were also more likely to be older at injury, unemployed, non-active duty status, not currently married, and had longer post-traumatic amnesia, longer rehabilitation stays, worse independence and disability scores at rehabilitation discharge, and a history of mental health issues before injury. These findings indicate that higher disability and less social supportive infrastructure are associated with higher mortality. Our investigation into the vulnerabilities underlying premature mortality and into the major causes of death may help target future prevention, surveillance, and monitoring interventions.
{"title":"Mortality Among Veterans Following Traumatic Brain Injury: A Veterans Administration Traumatic Brain Injury Model System Study.","authors":"Lara M Wittine, Jessica M Ketchum, Marc A Silva, Flora M Hammond, Joyce S Chung, Karina Loyo, Jose Lezama, Risa Nakase-Richardson","doi":"10.1089/neu.2024.0043","DOIUrl":"10.1089/neu.2024.0043","url":null,"abstract":"<p><p>Few studies have examined long-term mortality following traumatic brain injury (TBI) in a military population. This is a secondary analysis of a prospective, longitudinal study that examines long-term mortality (up to 10 years) post-TBI, including analyses of life expectancy, causes of death, and risk factors for death in service members and veterans (SM/V) who survived the acute TBI and inpatient rehabilitation. Among 922 participants in the study, the mortality rate was 8.3% following discharge from inpatient rehabilitation. The mean age of death was 54.5 years, with death occurring on average 3.2 years after injury, and with an average 7-year life expectancy reduction. SM/V with TBI were nearly four times more likely to die compared with the U.S. general population. Leading causes of death were external causes of injury, circulatory disease, and respiratory disorders. Also notable were deaths due to late effects of TBI itself and suicide. Falls were a significant mechanism of injury for those who died. Those who died were also more likely to be older at injury, unemployed, non-active duty status, not currently married, and had longer post-traumatic amnesia, longer rehabilitation stays, worse independence and disability scores at rehabilitation discharge, and a history of mental health issues before injury. These findings indicate that higher disability and less social supportive infrastructure are associated with higher mortality. Our investigation into the vulnerabilities underlying premature mortality and into the major causes of death may help target future prevention, surveillance, and monitoring interventions.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James P Barrett, Taryn G Aubrecht, Aidan Smith, Maria Vaida, Rebecca J Henry, Sarah J Doran, Alan I Faden, Bogdan A Stoica
<p><p>Traumatic brain injury (TBI) causes complex, time-dependent molecular and cellular responses, which include adaptive changes that promote repair and recovery, as well as maladaptive processes such as chronic inflammation that contribute to chronic neurodegeneration and neurological dysfunction. Hormesis is a well-established biological phenomenon in which exposure to low-dose toxins or stressors results in protective responses to subsequent higher-level stressors or insults. Hormetic stimuli show a characteristic U-shaped or inverted J-shaped dose-response curve, as well as being time and exposure-frequency dependent, similar to pre-conditioning and post-conditioning actions. Voluntary exercise interventions, before or after injury, appear to follow these general hormetic principles. But the molecular alterations associated with exercise interventions or more general hormetic responses have received only limited attention. In this study, we used a well-characterized mouse TBI model to assess the effects of different post-conditioning exercise-intervention paradigms on diverse molecular pathways, including neuroinflammation regulators, and post-traumatic neurological deficits. We generated high-throughput gene expression data and associated molecular pathway analyses to assess the potential molecular mechanisms associated with time- and duration-dependent voluntary exercise intervention, as well as time after treatment. Importantly, we also used newer analytical methods to more broadly assess the impact of exercise on diverse molecular pathways. TBI caused long-term changes in multiple neuroinflammation markers and chronic cognitive dysfunction. Notably, all delayed, post-conditioning exercise interventions reduced post-traumatic neuroinflammation and/or attenuated the related cognitive changes, albeit with different pathway specificity and effects magnitude. Exercise comprehensively reversed injury-associated effects in the hippocampus across both activated inflammatory and inhibited neuronal pathways, consistent with a return toward the noninjured, homeostatic state. In contrast, the cortex showed a less consistent pattern with more limited attenuation of inflammatory pathway activation and an amplification in the injury-dependent inhibition of select noninflammatory pathways, indicating less effective and potentially detrimental responses to exercise. Exercise intervention beginning 2 weeks after injury and lasting 2 weeks was less effective than exercise continuing for 4 weeks. Exercise initiated at a more delayed timepoint of 6 weeks after injury and continuing for 4 weeks was more effective than that during the acute phase. The delayed paradigm was also more effective than exercise initiated at 10 weeks after injury and continuing for 8 weeks, consistent with hormetic responses in other models and species. Overall, our study delineates regional and interventional parameters, as well as related molecular pathway changes, associated with
{"title":"Molecular Pathway Changes Associated with Different Post-Conditioning Exercise Interventions After Experimental TBI.","authors":"James P Barrett, Taryn G Aubrecht, Aidan Smith, Maria Vaida, Rebecca J Henry, Sarah J Doran, Alan I Faden, Bogdan A Stoica","doi":"10.1089/neu.2024.0120","DOIUrl":"10.1089/neu.2024.0120","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) causes complex, time-dependent molecular and cellular responses, which include adaptive changes that promote repair and recovery, as well as maladaptive processes such as chronic inflammation that contribute to chronic neurodegeneration and neurological dysfunction. Hormesis is a well-established biological phenomenon in which exposure to low-dose toxins or stressors results in protective responses to subsequent higher-level stressors or insults. Hormetic stimuli show a characteristic U-shaped or inverted J-shaped dose-response curve, as well as being time and exposure-frequency dependent, similar to pre-conditioning and post-conditioning actions. Voluntary exercise interventions, before or after injury, appear to follow these general hormetic principles. But the molecular alterations associated with exercise interventions or more general hormetic responses have received only limited attention. In this study, we used a well-characterized mouse TBI model to assess the effects of different post-conditioning exercise-intervention paradigms on diverse molecular pathways, including neuroinflammation regulators, and post-traumatic neurological deficits. We generated high-throughput gene expression data and associated molecular pathway analyses to assess the potential molecular mechanisms associated with time- and duration-dependent voluntary exercise intervention, as well as time after treatment. Importantly, we also used newer analytical methods to more broadly assess the impact of exercise on diverse molecular pathways. TBI caused long-term changes in multiple neuroinflammation markers and chronic cognitive dysfunction. Notably, all delayed, post-conditioning exercise interventions reduced post-traumatic neuroinflammation and/or attenuated the related cognitive changes, albeit with different pathway specificity and effects magnitude. Exercise comprehensively reversed injury-associated effects in the hippocampus across both activated inflammatory and inhibited neuronal pathways, consistent with a return toward the noninjured, homeostatic state. In contrast, the cortex showed a less consistent pattern with more limited attenuation of inflammatory pathway activation and an amplification in the injury-dependent inhibition of select noninflammatory pathways, indicating less effective and potentially detrimental responses to exercise. Exercise intervention beginning 2 weeks after injury and lasting 2 weeks was less effective than exercise continuing for 4 weeks. Exercise initiated at a more delayed timepoint of 6 weeks after injury and continuing for 4 weeks was more effective than that during the acute phase. The delayed paradigm was also more effective than exercise initiated at 10 weeks after injury and continuing for 8 weeks, consistent with hormetic responses in other models and species. Overall, our study delineates regional and interventional parameters, as well as related molecular pathway changes, associated with","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa G Papini, André N Avila, Melinda Fitzgerald, Sarah C Hellewell
Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. Evidence suggests that diffusion magnetic resonance imaging (dMRI) and blood-based biomarkers could be used as surrogate markers of WM organization. We conducted a scoping review according to PRISMA-ScR guidelines, aiming to collate evidence for the use of dMRI and/or blood-based biomarkers of WM organization, in mTBI and PPCS, and document relationships between WM biomarkers and symptoms. We focused specifically on biomarkers of axonal or myelin integrity post-mTBI. Biomarkers excluded from this review therefore included the following: astroglial, perivascular, endothelial, and inflammatory markers. A literature search performed across four databases, EMBASE, Scopus, Google Scholar, and ProQuest, identified 100 records: 68 analyzed dMRI, 28 assessed blood-based biomarkers, and 4 used both. Blood biomarker studies commonly assessed axonal cytoskeleton proteins (i.e., tau); dMRI studies assessed measures of WM organization (i.e., fractional anisotropy). Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.
{"title":"Evidence for Altered White Matter Organization After Mild Traumatic Brain Injury: A Scoping Review on the Use of Diffusion Magnetic Resonance Imaging and Blood-Based Biomarkers to Investigate Acute Pathology and Relationship to Persistent Post-Concussion Symptoms.","authors":"Melissa G Papini, André N Avila, Melinda Fitzgerald, Sarah C Hellewell","doi":"10.1089/neu.2024.0039","DOIUrl":"10.1089/neu.2024.0039","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. Evidence suggests that diffusion magnetic resonance imaging (dMRI) and blood-based biomarkers could be used as surrogate markers of WM organization. We conducted a scoping review according to PRISMA-ScR guidelines, aiming to collate evidence for the use of dMRI and/or blood-based biomarkers of WM organization, in mTBI and PPCS, and document relationships between WM biomarkers and symptoms. We focused specifically on biomarkers of axonal or myelin integrity post-mTBI. Biomarkers excluded from this review therefore included the following: astroglial, perivascular, endothelial, and inflammatory markers. A literature search performed across four databases, EMBASE, Scopus, Google Scholar, and ProQuest, identified 100 records: 68 analyzed dMRI, 28 assessed blood-based biomarkers, and 4 used both. Blood biomarker studies commonly assessed axonal cytoskeleton proteins (i.e., tau); dMRI studies assessed measures of WM organization (i.e., fractional anisotropy). Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}