Pub Date : 2024-12-01Epub Date: 2024-11-12DOI: 10.1089/neu.2016.4834.correx
{"title":"Correction to: Neck Collar with Mild Jugular Vein Compression Ameliorates Brain Activation Changes During a Working Memory Task after a Season of High School Football; DOI: 10.1089/neu.2016.4834.","authors":"","doi":"10.1089/neu.2016.4834.correx","DOIUrl":"10.1089/neu.2016.4834.correx","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2606"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622284","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 : 2024-12-01Epub Date: 2024-11-11DOI: 10.1089/neu.2021.0141.correx
{"title":"Correction to: High School Sports-Related Concussion, and the Effect of a Jugular Vein Compression Collar: A Prospective Longitudinal Investigation of Neuroimaging and Neurofunctional Outcomes; DOI: 10.1089/neu.2021.0141.","authors":"","doi":"10.1089/neu.2021.0141.correx","DOIUrl":"10.1089/neu.2021.0141.correx","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2608"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622339","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 : 2024-12-01Epub Date: 2024-09-04DOI: 10.1089/neu.2024.0248
Alexander Fletcher-Sandersjöö, Anders Lewén, Anders Hånell, David W Nelson, Marc Maegele, Mikael Svensson, Bo-Michael Bellander, Per Enblad, Eric Peter Thelin, Teodor Svedung Wettervik
Accurate measurement of traumatic intracranial hematoma volume is important for assessing disease progression and prognosis, as well as for serving as an important end-point in clinical trials aimed at preventing hematoma expansion. While the ABC/2 formula has traditionally been used for volume estimation in spontaneous intracerebral hemorrhage, its adaptation to traumatic hematomas lacks validation. This study aimed to compare the accuracy of ABC/2 with computer-assisted volumetric analysis (CAVA) in estimating the volumes of traumatic intracranial hematomas. We performed a dual-center observational study that included adult patients with moderate-to-severe traumatic brain injury. Volumes of intracerebral, subdural (SDHs), and epidural hematomas from admission computed tomography scans were measured using ABC/2 and CAVA, and compared using the Wilcoxon signed-rank test, Spearman's rank correlation, Lin's concordance correlation coefficient (CCC), and Bland-Altman plots. Prognostic significance for outcomes was evaluated through logistic and linear regression models. In total, 1,179 patients with 1,543 hematomas were included. Despite a high correlation (Spearman coefficients between 0.95 and 0.98) and excellent concordance (Lin's CCC from 0.89 to 0.96) between ABC/2 and CAVA, ABC/2 overestimated hematoma volumes compared with CAVA, in some instances exceeding 50 ml. Bland-Altman analysis highlighted wide limits of agreement, especially in SDH. While both methods demonstrated comparable accuracy in predicting outcomes, CAVA was slightly better at predicting craniotomies and midline shift. We conclude that while ABC/2 provides a generally reliable volumetric assessment suitable for descriptive purposes and as baseline variables in studies, CAVA should be the gold standard in clinical situations and studies requiring more precise volume estimations, such as those using hematoma expansion as an outcome.
{"title":"Volumetric Assessment of Traumatic Intracranial Hematomas: Is ABC/2 Reliable?","authors":"Alexander Fletcher-Sandersjöö, Anders Lewén, Anders Hånell, David W Nelson, Marc Maegele, Mikael Svensson, Bo-Michael Bellander, Per Enblad, Eric Peter Thelin, Teodor Svedung Wettervik","doi":"10.1089/neu.2024.0248","DOIUrl":"10.1089/neu.2024.0248","url":null,"abstract":"<p><p>Accurate measurement of traumatic intracranial hematoma volume is important for assessing disease progression and prognosis, as well as for serving as an important end-point in clinical trials aimed at preventing hematoma expansion. While the ABC/2 formula has traditionally been used for volume estimation in spontaneous intracerebral hemorrhage, its adaptation to traumatic hematomas lacks validation. This study aimed to compare the accuracy of ABC/2 with computer-assisted volumetric analysis (CAVA) in estimating the volumes of traumatic intracranial hematomas. We performed a dual-center observational study that included adult patients with moderate-to-severe traumatic brain injury. Volumes of intracerebral, subdural (SDHs), and epidural hematomas from admission computed tomography scans were measured using ABC/2 and CAVA, and compared using the Wilcoxon signed-rank test, Spearman's rank correlation, Lin's concordance correlation coefficient (CCC), and Bland-Altman plots. Prognostic significance for outcomes was evaluated through logistic and linear regression models. In total, 1,179 patients with 1,543 hematomas were included. Despite a high correlation (Spearman coefficients between 0.95 and 0.98) and excellent concordance (Lin's CCC from 0.89 to 0.96) between ABC/2 and CAVA, ABC/2 overestimated hematoma volumes compared with CAVA, in some instances exceeding 50 ml. Bland-Altman analysis highlighted wide limits of agreement, especially in SDH. While both methods demonstrated comparable accuracy in predicting outcomes, CAVA was slightly better at predicting craniotomies and midline shift. We conclude that while ABC/2 provides a generally reliable volumetric assessment suitable for descriptive purposes and as baseline variables in studies, CAVA should be the gold standard in clinical situations and studies requiring more precise volume estimations, such as those using hematoma expansion as an outcome.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2545-2553"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004485","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}
Traumatic brain injury (TBI) affects over 48 million people worldwide each year. Suicide is common in TBI, and there are several known contributing factors, including severe TBI, depression, alcohol use, and male sex. Impulsivity, or the tendency to act quickly with little thought, may be an early predictor of suicidality following TBI. The purpose of this study was to evaluate the risk of suicidality in patients with a prior history of impulsivity following a TBI. Using de-identified electronic health records from the TriNetX U.S. Collaborative Network with Natural Language Processing, three cohorts were generated: the impulsivity TBI cohort (I+TBI+) included subjects with a diagnosis of impulsivity before a diagnosis of TBI; the no impulsivity TBI cohort (I-TBI+) included patients with TBI but no impulsivity; the impulsivity no TBI cohort (I+TBI-) included patients with impulsivity but TBI. Two analyses were conducted, including analysis 1 (impulsivity TBI vs. no impulsivity TBI) and analysis 2 (impulsivity TBI vs. impulsivity no TBI). Patients were 1:1 matched by age, sex, race, ethnicity, psychiatric diagnoses, and antidepressant use. Outcomes included a diagnosis of self-harm, suicidal ideation, or a suicide attempt within 1 year after the index event. The all-time incidence of each outcome was assessed across different age categories. The chi-square test (categorical variables) and t-test (numerical variables) were used to assess for differences between groups. A total of 1,292,776 patients with TBI were identified in the study. After 1:1 matching, there were 20,694 patients (mean [standard deviation, SD] age, 48.1 [21.8]; 8,424 females [40.7%]) with impulsivity and TBI (I+TBI+), 1,272,082 patients (mean [SD] age, 46.0 [23.1]; 562,705 females [44.2%]) with TBI alone (I-TBI+), and 90,669 patients (mean [SD] age, 43.7 [22.6]; 45,188 females [49.8%]) with impulsivity alone (I+TBI-). Within the first year after a TBI, patients with impulsivity were more likely to exhibit self-harm (p < 0.001), suicidal ideation (p < 0.001), or a suicide attempt (p < 0.001). Compared with patients with TBI without impulsivity, those with impulsivity had a 4-fold increase in the incidence of self-harm (2.81% vs. 0.63%), an 8-fold increase in suicidal ideation (52.42% vs. 6.41%), and a 21-fold increase in suicide attempts (32.02% vs. 1.50%). This study suggests that impulsivity diagnosed before a TBI may increase the risk of post-traumatic suicidality, with a 4-fold increased risk of self-harm, an 8-fold increased risk of suicidal ideation and a 21-fold increased risk of suicide attempts. This characterizes a group of at-risk individuals who may benefit from early psychiatric support and targeted interventions following a TBI.
{"title":"Association Between Impulsivity, Self-Harm, Suicidal Ideation, and Suicide Attempts in Patients with Traumatic Brain Injury.","authors":"Liliana Ladner, Tyler Shick, Srijan Adhikari, Eric Marvin, Justin Weppner, Anita Kablinger","doi":"10.1089/neu.2024.0167","DOIUrl":"10.1089/neu.2024.0167","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) affects over 48 million people worldwide each year. Suicide is common in TBI, and there are several known contributing factors, including severe TBI, depression, alcohol use, and male sex. Impulsivity, or the tendency to act quickly with little thought, may be an early predictor of suicidality following TBI. The purpose of this study was to evaluate the risk of suicidality in patients with a prior history of impulsivity following a TBI. Using de-identified electronic health records from the TriNetX U.S. Collaborative Network with Natural Language Processing, three cohorts were generated: the impulsivity TBI cohort (I+TBI+) included subjects with a diagnosis of impulsivity before a diagnosis of TBI; the no impulsivity TBI cohort (I-TBI+) included patients with TBI but no impulsivity; the impulsivity no TBI cohort (I+TBI-) included patients with impulsivity but TBI. Two analyses were conducted, including analysis 1 (impulsivity TBI vs. no impulsivity TBI) and analysis 2 (impulsivity TBI vs. impulsivity no TBI). Patients were 1:1 matched by age, sex, race, ethnicity, psychiatric diagnoses, and antidepressant use. Outcomes included a diagnosis of self-harm, suicidal ideation, or a suicide attempt within 1 year after the index event. The all-time incidence of each outcome was assessed across different age categories. The chi-square test (categorical variables) and <i>t</i>-test (numerical variables) were used to assess for differences between groups. A total of 1,292,776 patients with TBI were identified in the study. After 1:1 matching, there were 20,694 patients (mean [standard deviation, SD] age, 48.1 [21.8]; 8,424 females [40.7%]) with impulsivity and TBI (I+TBI+), 1,272,082 patients (mean [SD] age, 46.0 [23.1]; 562,705 females [44.2%]) with TBI alone (I-TBI+), and 90,669 patients (mean [SD] age, 43.7 [22.6]; 45,188 females [49.8%]) with impulsivity alone (I+TBI-). Within the first year after a TBI, patients with impulsivity were more likely to exhibit self-harm (<i>p</i> < 0.001), suicidal ideation (<i>p</i> < 0.001), or a suicide attempt (<i>p</i> < 0.001). Compared with patients with TBI without impulsivity, those with impulsivity had a 4-fold increase in the incidence of self-harm (2.81% vs. 0.63%), an 8-fold increase in suicidal ideation (52.42% vs. 6.41%), and a 21-fold increase in suicide attempts (32.02% vs. 1.50%). This study suggests that impulsivity diagnosed before a TBI may increase the risk of post-traumatic suicidality, with a 4-fold increased risk of self-harm, an 8-fold increased risk of suicidal ideation and a 21-fold increased risk of suicide attempts. This characterizes a group of at-risk individuals who may benefit from early psychiatric support and targeted interventions following a TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2580-2589"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988161","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 : 2024-12-01Epub Date: 2024-09-20DOI: 10.1089/neu.2024.0095
Marija Markicevic, Francesca Mandino, Takuya Toyonaga, Zhengxin Cai, Arman Fesharaki-Zadeh, Xilin Shen, Stephen M Strittmatter, Evelyn M R Lake
Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild traumatic brain injury (rmTBI) and chronic variable stress mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread decreases in synaptic density coupled with an increase in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with higher synapse density showed a greater increase in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.
{"title":"Repetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity.","authors":"Marija Markicevic, Francesca Mandino, Takuya Toyonaga, Zhengxin Cai, Arman Fesharaki-Zadeh, Xilin Shen, Stephen M Strittmatter, Evelyn M R Lake","doi":"10.1089/neu.2024.0095","DOIUrl":"10.1089/neu.2024.0095","url":null,"abstract":"<p><p>Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild traumatic brain injury (rmTBI) and chronic variable stress mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [<sup>18</sup>F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread <i>decreases</i> in synaptic density coupled with an i<i>ncrease</i> in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with <i>higher</i> synapse density showed a <i>greater increase</i> in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2528-2544"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-30DOI: 10.1089/neu.2024.0183
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":"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":"2554-2570"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","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}
Antoine Dionne, David Magnuson, Andréane Richard-Denis, Yvan Petit, Dorothy Barthélémy, Francis Bernard, Jean-Marc Mac-Thiong
Early activity-based therapy (E-ABT) has the potential to decrease complications and radically improve neurofunctional recovery following traumatic spinal cord injury (TSCI). Unfortunately, E-ABT after TSCI has never been attempted in humans due to practical obstacles and potential safety concerns. This study aims to report on the safety and feasibility outcomes of the Protocol for Rapid Onset of Mobilization in Patients with Traumatic SCI (PROMPT-SCI) trial: the first-ever trial of E-ABT in critically ill patients who suffered a severe TSCI. To do so, 45 patients with severe TSCI were recruited to participate in the PROMPT-SCI trial between April 2021 and August 2023. The intervention consisted of daily 30-min sessions of motor-assisted in-bed leg cycling for 14 days, starting within 48 h of early surgery (≈72 h from the initial trauma). Adverse events were closely monitored, and completion rates were evaluated. Out of the 45 participants, 36 (80%) completed a full and safe session within 48 h of surgery and all participants managed to achieve this outcome within 72 h of surgery. Over the full 14-day protocol, the average completion rate of sessions was 87.2 ± 22.7% (range: 7.1-100.0%). A total of three patients were mechanically ventilated during the protocol and all three had 100% completion of sessions. Frequent reasons for unattempted/incomplete sessions were scheduling conflicts with activities related to care (e.g., bronchoscopy) and fatigue/uncontrolled pain before initiating cycling. We also report no neurological deterioration caused by cycling and no major adverse event recorded during or between sessions. In conclusion, this study suggests that E-ABT can be safely initiated within 48-72 h after a severe TSCI with no major adverse event. In the form of daily passive in-bed leg cycling, E-ABT is also acceptable for target users, and feasible over the course of the first weeks after the initial trauma, as shown by our excellent rate of completed sessions (87%). The present results also suggest that improved collaboration with intensive care unit staff, including intensivists and nurses, could improve these rates even further.
{"title":"Safety and Feasibility of Early Activity-Based Therapy Following Severe Traumatic Spinal Cord Injury: Results from a Single-Arm Pilot Trial.","authors":"Antoine Dionne, David Magnuson, Andréane Richard-Denis, Yvan Petit, Dorothy Barthélémy, Francis Bernard, Jean-Marc Mac-Thiong","doi":"10.1089/neu.2024.0297","DOIUrl":"https://doi.org/10.1089/neu.2024.0297","url":null,"abstract":"<p><p>Early activity-based therapy (E-ABT) has the potential to decrease complications and radically improve neurofunctional recovery following traumatic spinal cord injury (TSCI). Unfortunately, E-ABT after TSCI has never been attempted in humans due to practical obstacles and potential safety concerns. This study aims to report on the safety and feasibility outcomes of the Protocol for Rapid Onset of Mobilization in Patients with Traumatic SCI (PROMPT-SCI) trial: the first-ever trial of E-ABT in critically ill patients who suffered a severe TSCI. To do so, 45 patients with severe TSCI were recruited to participate in the PROMPT-SCI trial between April 2021 and August 2023. The intervention consisted of daily 30-min sessions of motor-assisted in-bed leg cycling for 14 days, starting within 48 h of early surgery (≈72 h from the initial trauma). Adverse events were closely monitored, and completion rates were evaluated. Out of the 45 participants, 36 (80%) completed a full and safe session within 48 h of surgery and all participants managed to achieve this outcome within 72 h of surgery. Over the full 14-day protocol, the average completion rate of sessions was 87.2 ± 22.7% (range: 7.1-100.0%). A total of three patients were mechanically ventilated during the protocol and all three had 100% completion of sessions. Frequent reasons for unattempted/incomplete sessions were scheduling conflicts with activities related to care (e.g., bronchoscopy) and fatigue/uncontrolled pain before initiating cycling. We also report no neurological deterioration caused by cycling and no major adverse event recorded during or between sessions. In conclusion, this study suggests that E-ABT can be safely initiated within 48-72 h after a severe TSCI with no major adverse event. In the form of daily passive in-bed leg cycling, E-ABT is also acceptable for target users, and feasible over the course of the first weeks after the initial trauma, as shown by our excellent rate of completed sessions (87%). The present results also suggest that improved collaboration with intensive care unit staff, including intensivists and nurses, could improve these rates even further.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750951","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}
Charles H Tator, Olivia F T Scott, Benjamin S Elkin, Emma Prentice, Umar Muhammad, Mozhgan Khodadadi, Qixuan Li, Ella Huszti, Maria Carmela Tartaglia
At the Canadian Concussion Centre, we treated 136 patients from 2000 to 2020 who sustained concussion plus persisting concussion symptoms (C+PCS) as motor vehicle occupants involved in motor vehicle crashes (MVCs). This center specializes in the treatment of patients with C+PCS. The objective of the present study was to identify strategies for preventing concussion among vehicle occupants involved in MVC. Indeed, this is the first study focused on C+PCS in MVC occupants, and our main purpose was to evaluate the effectiveness of onboard concussion prevention strategies. In this retrospective, consecutive cohort of 136 patients with C+PCS, we examined the patients' demographic and injury features in relation to the nature of the MVC including speed, direction of impact, and availability, deployment, and effectiveness of onboard occupant safety measures including seatbelts, head restraints, and airbags. The most frequent combination of factors was a belted female driver of an automobile struck from behind by another automobile. Surprisingly, the entire patient cohort comprised more females (69.1%) than males (30.9%), and rear-end collision was the most common type in females. Most injured occupants of both sexes were wearing seatbelts, but only a minority of the crashes caused airbag deployment. The seven most common symptoms were headache (84.6%), anxiety (72.8%), sensitivity to light (70.6%), memory problems (69.9%), sensitivity to noise (66.2%), irritability (56.6%), and depression (55.9%). Whiplash was a frequent associated injury in both sexes. Complete recovery from C+PCS was rare, and most patients with known follow-up continued to suffer from persisting symptoms for months to years. The median symptom duration for all 136 patients was 30.0 months (interquartile range: 16.8-56.0 months). Based on these findings, we conclude that females are indeed vulnerable road users with respect to C+PCS, and our literature search showed that there had been some previous evidence of increased injury risk of other injuries in female occupants. We recommend that additional prevention strategies are required to reduce the post-crash acceleration-deceleration "bobble-head" movement of the head on trunk causing both concussion and whiplash as has been accomplished in auto racing. Also, these prevention measures must be investigated in crash studies that include low-to-high speed rear-end collisions using anthropometrically appropriate models of male and female occupants reflecting the range of sizes of both sexes. There is a need for more concussion brain injury prevention research focusing on the vulnerability of female occupants, which has not been sufficiently addressed even though the deficiency was identified many years ago. The sex inequity of current onboard motor vehicle concussion brain injury prevention measures especially with respect to females should be addressed by governments and the automobile and insurance industries.
{"title":"Analysis of Concussions with Persisting Symptoms Caused by Motor Vehicle Crashes in 136 Vehicle Occupants Shows that Females Are Vulnerable Road Users.","authors":"Charles H Tator, Olivia F T Scott, Benjamin S Elkin, Emma Prentice, Umar Muhammad, Mozhgan Khodadadi, Qixuan Li, Ella Huszti, Maria Carmela Tartaglia","doi":"10.1089/neu.2024.0207","DOIUrl":"https://doi.org/10.1089/neu.2024.0207","url":null,"abstract":"<p><p>At the Canadian Concussion Centre, we treated 136 patients from 2000 to 2020 who sustained concussion plus persisting concussion symptoms (C+PCS) as motor vehicle occupants involved in motor vehicle crashes (MVCs). This center specializes in the treatment of patients with C+PCS. The objective of the present study was to identify strategies for preventing concussion among vehicle occupants involved in MVC. Indeed, this is the first study focused on C+PCS in MVC occupants, and our main purpose was to evaluate the effectiveness of onboard concussion prevention strategies. In this retrospective, consecutive cohort of 136 patients with C+PCS, we examined the patients' demographic and injury features in relation to the nature of the MVC including speed, direction of impact, and availability, deployment, and effectiveness of onboard occupant safety measures including seatbelts, head restraints, and airbags. The most frequent combination of factors was a belted female driver of an automobile struck from behind by another automobile. Surprisingly, the entire patient cohort comprised more females (69.1%) than males (30.9%), and rear-end collision was the most common type in females. Most injured occupants of both sexes were wearing seatbelts, but only a minority of the crashes caused airbag deployment. The seven most common symptoms were headache (84.6%), anxiety (72.8%), sensitivity to light (70.6%), memory problems (69.9%), sensitivity to noise (66.2%), irritability (56.6%), and depression (55.9%). Whiplash was a frequent associated injury in both sexes. Complete recovery from C+PCS was rare, and most patients with known follow-up continued to suffer from persisting symptoms for months to years. The median symptom duration for all 136 patients was 30.0 months (interquartile range: 16.8-56.0 months). Based on these findings, we conclude that females are indeed vulnerable road users with respect to C+PCS, and our literature search showed that there had been some previous evidence of increased injury risk of other injuries in female occupants. We recommend that additional prevention strategies are required to reduce the post-crash acceleration-deceleration \"bobble-head\" movement of the head on trunk causing both concussion and whiplash as has been accomplished in auto racing. Also, these prevention measures must be investigated in crash studies that include low-to-high speed rear-end collisions using anthropometrically appropriate models of male and female occupants reflecting the range of sizes of both sexes. There is a need for more concussion brain injury prevention research focusing on the vulnerability of female occupants, which has not been sufficiently addressed even though the deficiency was identified many years ago. The sex inequity of current onboard motor vehicle concussion brain injury prevention measures especially with respect to females should be addressed by governments and the automobile and insurance industries.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739794","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}
Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Hauser, Raluca Niesner, Frank L Heppner, Michael G Fehlings, Peter Vajkoczy
<p><p>Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal <i>in vivo</i> two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54% of existing vessels regaining functional perfusion. Longitudinal <i>in vivo</i> 2PM visualized the progressive degeneration of initially preserved spinal cord axons in the peri-traumatic zone after SCI while displaying a rarefication of functionally perfused vessels up to two weeks after injury. Neurobehavioral recovery started after one week but remained impaired over the whole observation period of four weeks after SCI. With this study, a therapeutic window to address the impaired NVU starting from the first days to two weeks after SCI is identified. A number of lines of evidence including <i>in vivo</i> 2PM, assessment of NVU integrity, and neurobehavioral assessments point to the critical nature of targeting the NVU to enhance axonal preservation and regeneration after SCI. Continuous multifactorial therapy applications targeting the integrity of the NVU over the identified therapeutic window of opportunity appears promising to ameliorate functional vessel perseverance and the spinal cord's rege
{"title":"Identification of a Therapeutic Window for Neurovascular Unit Repair after Experimental Spinal Cord Injury.","authors":"Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Hauser, Raluca Niesner, Frank L Heppner, Michael G Fehlings, Peter Vajkoczy","doi":"10.1089/neu.2024.0233","DOIUrl":"https://doi.org/10.1089/neu.2024.0233","url":null,"abstract":"<p><p>Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal <i>in vivo</i> two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54% of existing vessels regaining functional perfusion. Longitudinal <i>in vivo</i> 2PM visualized the progressive degeneration of initially preserved spinal cord axons in the peri-traumatic zone after SCI while displaying a rarefication of functionally perfused vessels up to two weeks after injury. Neurobehavioral recovery started after one week but remained impaired over the whole observation period of four weeks after SCI. With this study, a therapeutic window to address the impaired NVU starting from the first days to two weeks after SCI is identified. A number of lines of evidence including <i>in vivo</i> 2PM, assessment of NVU integrity, and neurobehavioral assessments point to the critical nature of targeting the NVU to enhance axonal preservation and regeneration after SCI. Continuous multifactorial therapy applications targeting the integrity of the NVU over the identified therapeutic window of opportunity appears promising to ameliorate functional vessel perseverance and the spinal cord's rege","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716347","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}
Dena Johnson-Schlitz, Amanda R Seidl, Zachariah P G Olufs, Wen Huang, David A Wassarman, Misha Perouansky
Pre-clinical vertebrate models of traumatic brain injury (TBI) routinely use anesthetics for animal welfare; however, humans experience TBI without anesthetics. Therefore, translation of findings from vertebrate models to humans hinges on understanding how anesthetics influence cellular and molecular events that lead to secondary injuries following TBI. To investigate the effects of anesthetics on TBI outcomes, we used an invertebrate Drosophila melanogaster model to compare outcomes between animals exposed or not exposed to anesthetics prior to the same primary injury. Using a common laboratory fly line, w1118, we found that exposure to the volatile anesthetics isoflurane or sevoflurane, but not ether, prior to TBI produced a dose-dependent reduction in mortality within 24 h following TBI. Thus, isoflurane and sevoflurane precondition w1118 flies to deleterious effects of TBI. To examine the effects of genetic differences on anesthetic preconditioning of TBI, we repeated the experiment with the Drosophila Genetic Reference Panel (DGRP) collection of genetically diverse, inbred fly lines. Pre-exposure to either isoflurane or sevoflurane revealed a wide range of preconditioning levels among 171 and 144 DGRP lines, respectively, suggesting a genetic component for variation in anesthetic preconditioning of mortality following TBI. Finally, genome-wide association study analyses identified single-nucleotide polymorphisms in genes associated with isoflurane or sevoflurane preconditioning of TBI. Several of the genes, including the fly ortholog of mammalian Calcium Voltage-Gated Subunit Alpha1 D (CACNA1D), are highly expressed in neurons and are functionally linked to both anesthetics and TBI. These data indicate that anesthetic dose and genetic background should be considered when investigating effects of anesthetics in vertebrate TBI models, and they support use of the fly model for elucidating the mechanisms underlying anesthetic preconditioning of TBI.
{"title":"Genetic Differences Modify Anesthetic Preconditioning of Traumatic Brain Injury in Drosophila.","authors":"Dena Johnson-Schlitz, Amanda R Seidl, Zachariah P G Olufs, Wen Huang, David A Wassarman, Misha Perouansky","doi":"10.1089/neu.2024.0314","DOIUrl":"10.1089/neu.2024.0314","url":null,"abstract":"<p><p>Pre-clinical vertebrate models of traumatic brain injury (TBI) routinely use anesthetics for animal welfare; however, humans experience TBI without anesthetics. Therefore, translation of findings from vertebrate models to humans hinges on understanding how anesthetics influence cellular and molecular events that lead to secondary injuries following TBI. To investigate the effects of anesthetics on TBI outcomes, we used an invertebrate <i>Drosophila melanogaster</i> model to compare outcomes between animals exposed or not exposed to anesthetics prior to the same primary injury. Using a common laboratory fly line, <i>w<sup>1118</sup></i>, we found that exposure to the volatile anesthetics isoflurane or sevoflurane, but not ether, prior to TBI produced a dose-dependent reduction in mortality within 24 h following TBI. Thus, isoflurane and sevoflurane precondition <i>w<sup>1118</sup></i> flies to deleterious effects of TBI. To examine the effects of genetic differences on anesthetic preconditioning of TBI, we repeated the experiment with the Drosophila Genetic Reference Panel (DGRP) collection of genetically diverse, inbred fly lines. Pre-exposure to either isoflurane or sevoflurane revealed a wide range of preconditioning levels among 171 and 144 DGRP lines, respectively, suggesting a genetic component for variation in anesthetic preconditioning of mortality following TBI. Finally, genome-wide association study analyses identified single-nucleotide polymorphisms in genes associated with isoflurane or sevoflurane preconditioning of TBI. Several of the genes, including the fly ortholog of mammalian <i>Calcium Voltage-Gated Subunit Alpha1 D</i> (<i>CACNA1D</i>), are highly expressed in neurons and are functionally linked to both anesthetics and TBI. These data indicate that anesthetic dose and genetic background should be considered when investigating effects of anesthetics in vertebrate TBI models, and they support use of the fly model for elucidating the mechanisms underlying anesthetic preconditioning of TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668289","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}