Pub Date : 2025-01-24eCollection Date: 2025-01-01DOI: 10.1089/neur.2024.0169
Tyler Shick, Courtney Perkins, Arco Paul, Melissa Martinez, Joseph Joyce, Katy Beach, Jeffrey Swahlan, Justin Weppner
Exercise to treat traumatic brain injury (TBI) is a novel approach that has only become recognized in the past decade. High-intensity gait training (HIGT) has been studied in subjects following stroke; however, little research investigates similar protocols on patients with TBI. The study evaluated HIGT as an intervention for enhancing patient recovery after TBI. Adult subjects (18-65 years) who suffered TBI were randomly allocated to an intervention (HIGT) or control (low-intensity physical therapy) group given three days/week for 1 h over four weeks. Assessments included the 10-m walk test, 6-min walk test, Berg Balance Scale, five-times sit-to-stand (5TSTS), timed up and go (TUG), cognitive TUG, and Montreal Cognitive Assessment (MoCA) at day one, two weeks, four weeks, and a four-week follow-up. In addition to a trend toward improved gait speed (p < 0.1) and significantly improved endurance (p < 0.05) in the HIGT group (n = 5), both the control (n = 4) and HIGT groups demonstrated trends toward improved mobility (5TSTS, p < 0.1; TUG, p < 0.1) and significantly improved cognition (cognitive TUG, p < 0.01; MoCA, p < 0.05) over the four-week time period and at the one-month follow-up. HIGT showed longer-lasting rehabilitative effects on gait distance, endurance, mobility, and cognitive function at the four-week follow-up. This study suggests that HIGT may support functional recovery, and future work will involve increasing sample size.
{"title":"Randomized Controlled Trial: Preliminary Investigation of the Impact of High-Intensity Treadmill Gait Training on Recovery Among Persons with Traumatic Brain Injury.","authors":"Tyler Shick, Courtney Perkins, Arco Paul, Melissa Martinez, Joseph Joyce, Katy Beach, Jeffrey Swahlan, Justin Weppner","doi":"10.1089/neur.2024.0169","DOIUrl":"https://doi.org/10.1089/neur.2024.0169","url":null,"abstract":"<p><p>Exercise to treat traumatic brain injury (TBI) is a novel approach that has only become recognized in the past decade. High-intensity gait training (HIGT) has been studied in subjects following stroke; however, little research investigates similar protocols on patients with TBI. The study evaluated HIGT as an intervention for enhancing patient recovery after TBI. Adult subjects (18-65 years) who suffered TBI were randomly allocated to an intervention (HIGT) or control (low-intensity physical therapy) group given three days/week for 1 h over four weeks. Assessments included the 10-m walk test, 6-min walk test, Berg Balance Scale, five-times sit-to-stand (5TSTS), timed up and go (TUG), cognitive TUG, and Montreal Cognitive Assessment (MoCA) at day one, two weeks, four weeks, and a four-week follow-up. In addition to a trend toward improved gait speed (<i>p</i> < 0.1) and significantly improved endurance (<i>p</i> < 0.05) in the HIGT group (<i>n</i> = 5), both the control (<i>n</i> = 4) and HIGT groups demonstrated trends toward improved mobility (5TSTS, <i>p</i> < 0.1; TUG, <i>p</i> < 0.1) and significantly improved cognition (cognitive TUG, <i>p</i> < 0.01; MoCA, <i>p</i> < 0.05) over the four-week time period and at the one-month follow-up. HIGT showed longer-lasting rehabilitative effects on gait distance, endurance, mobility, and cognitive function at the four-week follow-up. This study suggests that HIGT may support functional recovery, and future work will involve increasing sample size.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"82-92"},"PeriodicalIF":1.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22eCollection Date: 2025-01-01DOI: 10.1089/neur.2024.0122
Nishta R Amin, Mary Beth Nebel, Hsuan-Wei Chen, Tyler A Busch, Elizabeth D Rosenthal, Stewart Mostofsky, Stacy J Suskauer, Adrian Svingos
Adolescents who have sustained a concussion or mild traumatic brain injury (mTBI) are prone to repeat injuries which may be related to subtle motor deficits persisting after clinical recovery. Cross-sectional research has found that these deficits are associated with altered functional connectivity among somatomotor, dorsal attention, and default mode networks. However, our understanding of how these brain-behavior relationships change over time after clinical recovery is limited. In this study, we examined categorical and dimensional trajectories of functional connectivity and subtle motor performance in youth clinically recovered from mTBI and never-injured controls (10-17 years). All participants completed task-based and resting-state functional magnetic resonance imaging scans and the Physical and Neurological Examination of Subtle Signs (PANESS) at initial and 3-month follow-up visits. We examined somatomotor-dorsal attention and somatomotor-default mode network connectivity and their association with PANESS performance. Compared with controls, a larger proportion of youth recovered from mTBI showed increases in somatomotor-dorsal attention functional connectivity over time; in contrast, there were no differences in somatomotor-default mode connectivity trajectories between youth recovered from mTBI and controls. Relative to controls, youth recovered from mTBI who showed greater increases in somatomotor-dorsal attention connectivity over time also completed motor tasks more slowly at the 3-month compared with the initial visit. Collectively, these findings suggest that longitudinal changes in somatomotor-dorsal attention functional connectivity may be associated with lingering motor learning deficits after clinical recovery from pediatric mTBI. Further research is necessary to understand how trajectories of functional connectivity and motor performance can inform individual-level outcomes, for instance, susceptibility to future injuries in both youth who are never injured and those clinically recovered from mTBI.
{"title":"Patterns of Change in Functional Connectivity and Motor Performance Are Different in Youth Recently Recovered from Concussion.","authors":"Nishta R Amin, Mary Beth Nebel, Hsuan-Wei Chen, Tyler A Busch, Elizabeth D Rosenthal, Stewart Mostofsky, Stacy J Suskauer, Adrian Svingos","doi":"10.1089/neur.2024.0122","DOIUrl":"https://doi.org/10.1089/neur.2024.0122","url":null,"abstract":"<p><p>Adolescents who have sustained a concussion or mild traumatic brain injury (mTBI) are prone to repeat injuries which may be related to subtle motor deficits persisting after clinical recovery. Cross-sectional research has found that these deficits are associated with altered functional connectivity among somatomotor, dorsal attention, and default mode networks. However, our understanding of how these brain-behavior relationships change over time after clinical recovery is limited. In this study, we examined categorical and dimensional trajectories of functional connectivity and subtle motor performance in youth clinically recovered from mTBI and never-injured controls (10-17 years). All participants completed task-based and resting-state functional magnetic resonance imaging scans and the Physical and Neurological Examination of Subtle Signs (PANESS) at initial and 3-month follow-up visits. We examined somatomotor-dorsal attention and somatomotor-default mode network connectivity and their association with PANESS performance. Compared with controls, a larger proportion of youth recovered from mTBI showed increases in somatomotor-dorsal attention functional connectivity over time; in contrast, there were no differences in somatomotor-default mode connectivity trajectories between youth recovered from mTBI and controls. Relative to controls, youth recovered from mTBI who showed greater increases in somatomotor-dorsal attention connectivity over time also completed motor tasks more slowly at the 3-month compared with the initial visit. Collectively, these findings suggest that longitudinal changes in somatomotor-dorsal attention functional connectivity may be associated with lingering motor learning deficits after clinical recovery from pediatric mTBI. Further research is necessary to understand how trajectories of functional connectivity and motor performance can inform individual-level outcomes, for instance, susceptibility to future injuries in both youth who are never injured and those clinically recovered from mTBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"53-67"},"PeriodicalIF":1.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-16eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0116
Brian L Edlow, Chieh-En J Tseng, Natalie Gilmore, Isabella R McKinney, Samantha L Tromly, Katryna B Deary, Collin G Hu, Brian C Healy, David S Priemer, Christine L Mac Donald, Kristen Dams-O'Connor, Douglas N Greve, Yelena G Bodien, Daniel P Perl, Jacob M Hooker, Nicole R Zürcher
Emerging evidence from autopsy studies indicates that interface astroglial scarring (IAS) at the gray-white matter junction is a pathological signature of repeated blast brain injury in military personnel. However, there is currently no in vivo neuroimaging test that detects IAS, which is a major barrier to diagnosis, prevention, and treatment. In 27 active-duty U.S. Special Operations Forces personnel with high levels of cumulative blast exposure, we performed translocator protein (TSPO) positron emission tomography (PET) using [11C]PBR28 to detect neuroinflammation at the cortical gray-white matter interface, a neuroanatomic location where IAS has been reported in autopsy studies. TSPO signal in individual Operators was compared with the mean TSPO signal in a control group of nine healthy civilian volunteers. We identified five Operators (18.5%) with TSPO signal at the cortical gray-white matter interface that was more than 2 standard deviations above the control mean. Cumulative blast exposure, as measured by the generalized blast exposure value, did not differ between the five Operators with elevated TSPO signal and the 22 Operators without elevated TSPO signal. While the pathophysiologic link between neuroinflammation and IAS remains uncertain, these preliminary observations provide the basis for further investigation into TSPO PET as a potential biomarker of repeated blast brain injury.
{"title":"Neuroinflammation at the Gray-White Matter Interface in Active-Duty U.S. Special Operations Forces.","authors":"Brian L Edlow, Chieh-En J Tseng, Natalie Gilmore, Isabella R McKinney, Samantha L Tromly, Katryna B Deary, Collin G Hu, Brian C Healy, David S Priemer, Christine L Mac Donald, Kristen Dams-O'Connor, Douglas N Greve, Yelena G Bodien, Daniel P Perl, Jacob M Hooker, Nicole R Zürcher","doi":"10.1089/neur.2024.0116","DOIUrl":"10.1089/neur.2024.0116","url":null,"abstract":"<p><p>Emerging evidence from autopsy studies indicates that interface astroglial scarring (IAS) at the gray-white matter junction is a pathological signature of repeated blast brain injury in military personnel. However, there is currently no <i>in vivo</i> neuroimaging test that detects IAS, which is a major barrier to diagnosis, prevention, and treatment. In 27 active-duty U.S. Special Operations Forces personnel with high levels of cumulative blast exposure, we performed translocator protein (TSPO) positron emission tomography (PET) using [<sup>11</sup>C]PBR28 to detect neuroinflammation at the cortical gray-white matter interface, a neuroanatomic location where IAS has been reported in autopsy studies. TSPO signal in individual Operators was compared with the mean TSPO signal in a control group of nine healthy civilian volunteers. We identified five Operators (18.5%) with TSPO signal at the cortical gray-white matter interface that was more than 2 standard deviations above the control mean. Cumulative blast exposure, as measured by the generalized blast exposure value, did not differ between the five Operators with elevated TSPO signal and the 22 Operators without elevated TSPO signal. While the pathophysiologic link between neuroinflammation and IAS remains uncertain, these preliminary observations provide the basis for further investigation into TSPO PET as a potential biomarker of repeated blast brain injury.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"1205-1211"},"PeriodicalIF":1.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0134
Heather R Siedhoff, Shanyan Chen, Ashley Balderrama, Dejun Jackson, Runting Li, Grace Y Sun, Ralph G DePalma, Jiankun Cui, Zezong Gu
Primary blast exposure is a predominant cause of mild traumatic brain injury (mTBI) among veterans and active-duty military personnel, and affected individuals may develop long-lasting behavioral disturbances that interfere with quality of life. Our prior research with the "Missouri Blast" model demonstrated behavioral changes relevant to deficits in cognitive and affective domains after exposure to low-intensity blast (LIB). In this study, behavioral evaluations were extended to 3 months post-LIB injury using multifaceted conventional and advanced behavioral paradigms. C57BL/6J male mice, aged 2 months old, were subjected to a non-inertial primary LIB-induced mTBI by detonating 350 g of C-4 at a 3-m distance on 1-m-tall platforms. Three months after injury, mice were evaluated using the open-field test (OFT), social interaction test, and advanced Erasmus Ladder paradigm. With OFT, no apparent anxiety-like changes were detected with the LIB-exposed mice and sham controls, and both groups displayed similar center-zone activities. Although no social interaction parameters reached significance, a majority of LIB-exposed mice initiated less than 50% of interactions compared with their interaction partners, suggesting decreased sociability. With the Erasmus Ladder test to assess motor functions, associative learning, and stimulus response, LIB-exposed mice appeared to display increased instances of leaving before the cue, reminiscent of "escape behavior," indicative of anxiety-related activity different from that OFT detected. Overall, these results revealed subtle multifaceted long-lasting anxiety-relevant effects following LIB exposure. The "Missouri Blast" platform offers a basis for future research to investigate the underlying biological mechanism(s) leading to domain-specific behavioral changes.
在退伍军人和现役军人中,初级爆炸暴露是轻度创伤性脑损伤(mTBI)的主要原因,受影响的个体可能会出现长期的行为障碍,影响生活质量。我们先前对“密苏里爆炸”模型的研究表明,暴露于低强度爆炸(LIB)后,行为变化与认知和情感领域的缺陷有关。在这项研究中,行为评估被扩展到lib损伤后3个月,使用多方面的传统和先进的行为范式。2月龄的C57BL/6J雄性小鼠,在1米高的平台上,在3米距离处引爆350 g C-4,进行非惯性原发性lib诱导的mTBI。损伤后3个月,采用开放场测试(OFT)、社会互动测试和高级伊拉斯谟阶梯范式对小鼠进行评估。对于OFT,暴露于lib的小鼠和假对照组没有发现明显的焦虑样变化,两组都显示出相似的中枢活动。尽管社会互动参数没有达到显著性,但与互动伙伴相比,大多数暴露于lib的小鼠发起的互动少于50%,这表明社交能力下降。通过伊拉斯谟阶梯测试来评估运动功能、联想学习和刺激反应,暴露于lib的小鼠在提示之前离开的情况有所增加,这让人想起了“逃避行为”,这表明与OFT检测到的焦虑相关活动不同。总的来说,这些结果揭示了LIB暴露后微妙的多方面长期焦虑相关影响。“密苏里爆炸”平台为未来的研究提供了基础,以调查导致特定领域行为变化的潜在生物学机制。
{"title":"Low-Intensity Blast Exposure Induces Multifaceted Long-Lasting Anxiety-Related Behaviors in Mice.","authors":"Heather R Siedhoff, Shanyan Chen, Ashley Balderrama, Dejun Jackson, Runting Li, Grace Y Sun, Ralph G DePalma, Jiankun Cui, Zezong Gu","doi":"10.1089/neur.2024.0134","DOIUrl":"10.1089/neur.2024.0134","url":null,"abstract":"<p><p>Primary blast exposure is a predominant cause of mild traumatic brain injury (mTBI) among veterans and active-duty military personnel, and affected individuals may develop long-lasting behavioral disturbances that interfere with quality of life. Our prior research with the \"Missouri Blast\" model demonstrated behavioral changes relevant to deficits in cognitive and affective domains after exposure to low-intensity blast (LIB). In this study, behavioral evaluations were extended to 3 months post-LIB injury using multifaceted conventional and advanced behavioral paradigms. C57BL/6J male mice, aged 2 months old, were subjected to a non-inertial primary LIB-induced mTBI by detonating 350 g of C-4 at a 3-m distance on 1-m-tall platforms. Three months after injury, mice were evaluated using the open-field test (OFT), social interaction test, and advanced Erasmus Ladder paradigm. With OFT, no apparent anxiety-like changes were detected with the LIB-exposed mice and sham controls, and both groups displayed similar center-zone activities. Although no social interaction parameters reached significance, a majority of LIB-exposed mice <i>initiated</i> less than 50% of interactions compared with their interaction partners, suggesting decreased sociability. With the Erasmus Ladder test to assess motor functions, associative learning, and stimulus response, LIB-exposed mice appeared to display increased instances of leaving before the cue, reminiscent of \"escape behavior,\" indicative of anxiety-related activity different from that OFT detected. Overall, these results revealed subtle multifaceted long-lasting anxiety-relevant effects following LIB exposure. The \"Missouri Blast\" platform offers a basis for future research to investigate the underlying biological mechanism(s) leading to domain-specific behavioral changes.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"1195-1204"},"PeriodicalIF":1.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0098
Farzad V Farahani, Lukman E Ismaila, Cristina L Sadowsky, Haris I Sair, Li Min Chen, Visar Belegu, James J Pekar, Martin A Lindquist, Ann S Choe
Neurological recovery in individuals with spinal cord injury (SCI) is multifaceted, involving mechanisms such as remyelination and perilesional spinal neuroplasticity, with cortical reorganization being one contributing factor. Cortical reorganization, in particular, can be evaluated through network (graph) analysis of interregional functional connectivity. This study aimed to investigate cortical reorganization patterns in persons with chronic SCI using a multilayer community detection approach on resting-state functional MRI data. Thirty-eight participants with chronic cervical or thoracic SCI and 32 matched healthy controls were examined. Significant alterations in brain community structures were observed in the SCI cohort, particularly within the sensorimotor network (SMN). Importantly, this revealed a pattern of segregation within the SMN, aligning with borders of representations of the upper and lower body and orofacial regions. The SCI cohort showed reduced recruitment and integration coefficients across multiple brain networks, indicating impaired internetwork communication that may underlie sensory and motor deficits in persons with SCI. These findings highlight the impact of SCI on brain connectivity and suggest potential compensatory mechanisms.
{"title":"Brain Network Alterations in Chronic Spinal Cord Injury: Multilayer Community Detection Approach.","authors":"Farzad V Farahani, Lukman E Ismaila, Cristina L Sadowsky, Haris I Sair, Li Min Chen, Visar Belegu, James J Pekar, Martin A Lindquist, Ann S Choe","doi":"10.1089/neur.2024.0098","DOIUrl":"10.1089/neur.2024.0098","url":null,"abstract":"<p><p>Neurological recovery in individuals with spinal cord injury (SCI) is multifaceted, involving mechanisms such as remyelination and perilesional spinal neuroplasticity, with cortical reorganization being one contributing factor. Cortical reorganization, in particular, can be evaluated through network (graph) analysis of interregional functional connectivity. This study aimed to investigate cortical reorganization patterns in persons with chronic SCI using a multilayer community detection approach on resting-state functional MRI data. Thirty-eight participants with chronic cervical or thoracic SCI and 32 matched healthy controls were examined. Significant alterations in brain community structures were observed in the SCI cohort, particularly within the sensorimotor network (SMN). Importantly, this revealed a pattern of segregation within the SMN, aligning with borders of representations of the upper and lower body and orofacial regions. The SCI cohort showed reduced recruitment and integration coefficients across multiple brain networks, indicating impaired internetwork communication that may underlie sensory and motor deficits in persons with SCI. These findings highlight the impact of SCI on brain connectivity and suggest potential compensatory mechanisms.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"1048-1059"},"PeriodicalIF":1.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0060
Lulin Li, Andy Nguyen, Brian Zhao, Ryan Vest, Lakshmi Yerra, Bryan Sun, Jian Luo
Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.
{"title":"Small Molecule Drug C381 Attenuates Brain Vascular Damage Following Repetitive Mild Traumatic Injury.","authors":"Lulin Li, Andy Nguyen, Brian Zhao, Ryan Vest, Lakshmi Yerra, Bryan Sun, Jian Luo","doi":"10.1089/neur.2024.0060","DOIUrl":"10.1089/neur.2024.0060","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"1016-1026"},"PeriodicalIF":1.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0017
David Bark, Julia Basu, Dimitrios Toumpanakis, Johan Burwick Nyberg, Tomas Bjerner, Elham Rostami, David Fällmar
This study aimed to evaluate the predictive value and clinical impact of a clinically implemented artificial neural network software model. The software detects intracranial hemorrhage (ICH) from head computed tomography (CT) scans and artificial intelligence (AI)-identified positive cases are then annotated in the work list for early radiologist evaluation. The index test was AI detection by the program Zebra Medical Vision-HealthICH+. Radiologist-confirmed ICH was the reference standard. The study compared whether time benefits from using the AI model led to faster escalation of patient care or surgery within the first 24 h. A total of 2,306 patients were evaluated by the software, and 288 AI-positive cases were included. The AI tool had a positive predictive value of 0.823. There was, however, no significant time reduction when comparing the patients who required escalation of care and those who did not. There was also no significant time reduction in those who required acute surgery compared with those who did not. Among the individual patients with reduced time delay, no cases with evident clinical benefit were identified. Although the clinically implemented AI-based decision support system showed adequate predictive value in identifying ICH, there was no significant clinical benefit for the patients in our setting. While AI-assisted detection of ICH shows great promise from a technical perspective, there remains a need to evaluate the clinical impact and perform external validation across different settings.
本研究旨在评估临床实施的人工神经网络软件模型的预测价值和临床影响。该软件从头部计算机断层扫描(CT)中检测颅内出血(ICH),然后将人工智能(AI)识别的阳性病例注释在工作列表中,供放射科医生进行早期评估。指标测试是由 Zebra Medical Vision-HealthICH+ 程序进行人工智能检测。放射科医生确认的 ICH 为参考标准。研究比较了使用人工智能模型是否能在24小时内更快地升级患者护理或手术。软件共评估了2306名患者,其中人工智能阳性病例288例。人工智能工具的阳性预测值为 0.823。不过,需要升级护理的患者与不需要升级护理的患者相比,时间并没有明显缩短。需要急性手术的患者与不需要急性手术的患者相比,时间也没有明显缩短。在时间延迟缩短的个别患者中,没有发现有明显临床获益的病例。虽然临床实施的人工智能决策支持系统在识别 ICH 方面显示出足够的预测价值,但在我们的环境中,患者并没有明显的临床获益。虽然从技术角度来看,人工智能辅助检测 ICH 显示出了巨大的前景,但仍有必要评估其临床影响,并在不同环境下进行外部验证。
{"title":"Clinical Impact of an AI Decision Support System for Detection of Intracranial Hemorrhage in CT Scans.","authors":"David Bark, Julia Basu, Dimitrios Toumpanakis, Johan Burwick Nyberg, Tomas Bjerner, Elham Rostami, David Fällmar","doi":"10.1089/neur.2024.0017","DOIUrl":"https://doi.org/10.1089/neur.2024.0017","url":null,"abstract":"<p><p>This study aimed to evaluate the predictive value and clinical impact of a clinically implemented artificial neural network software model. The software detects intracranial hemorrhage (ICH) from head computed tomography (CT) scans and artificial intelligence (AI)-identified positive cases are then annotated in the work list for early radiologist evaluation. The index test was AI detection by the program Zebra Medical Vision-HealthICH+. Radiologist-confirmed ICH was the reference standard. The study compared whether time benefits from using the AI model led to faster escalation of patient care or surgery within the first 24 h. A total of 2,306 patients were evaluated by the software, and 288 AI-positive cases were included. The AI tool had a positive predictive value of 0.823. There was, however, no significant time reduction when comparing the patients who required escalation of care and those who did not. There was also no significant time reduction in those who required acute surgery compared with those who did not. Among the individual patients with reduced time delay, no cases with evident clinical benefit were identified. Although the clinically implemented AI-based decision support system showed adequate predictive value in identifying ICH, there was no significant clinical benefit for the patients in our setting. While AI-assisted detection of ICH shows great promise from a technical perspective, there remains a need to evaluate the clinical impact and perform external validation across different settings.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"1009-1015"},"PeriodicalIF":1.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0076
Johanne C C Rauwenhoff, Roger Hagen, Migle Karaliute, Odin Hjemdal, Leif Edward Ottesen Kennair, Stian Solem, Robert F Asarnow, Cathrine Einarsen, Joar Øveraas Halvorsen, Stephanie Paoli, Simen Berg Saksvik, Hanne Smevik, Gøril Storvig, Adrian Wells, Toril Skandsen, Alexander Olsen
After mild traumatic brain injury (mTBI), a subgroup of individuals experience persistent post-concussion symptoms (PPCS) that include headaches, cognitive difficulties, and fatigue. The aim of this preliminary study was to investigate possible effects associated with metacognitive therapy (MCT) on PPCS, maladaptive coping strategies, and positive and negative metacognitive beliefs following mTBI. A pre-post design supplemented with single-case A-B replication series to assess potential MCT mechanisms was used. Of the nine participants who received MCT, all experienced a decrease in PPCS, which constituted a reliable improvement for eight participants. For eight participants (we could calculate effect sizes for eight out of nine participants), moderate to very large decreases in maladaptive coping styles and positive and negative metacognitive beliefs were observed. However, based on visual analyses, participants 6, 8, and 9 show a downward baseline trend regarding MCT mechanisms that may have persisted into the intervention phase. No adverse events were reported. In conclusion, MCT was associated with improvements in PPCS and unhelpful psychological mechanisms, but caution is required in interpreting this association. Future research using formal single-case replication on symptom measures and randomized controlled trials appears to be justified.
{"title":"Metacognitive Therapy for People Experiencing Persistent Post-Concussion Symptoms Following Mild Traumatic Brain Injury: A Preliminary Multiple Case-Series Study.","authors":"Johanne C C Rauwenhoff, Roger Hagen, Migle Karaliute, Odin Hjemdal, Leif Edward Ottesen Kennair, Stian Solem, Robert F Asarnow, Cathrine Einarsen, Joar Øveraas Halvorsen, Stephanie Paoli, Simen Berg Saksvik, Hanne Smevik, Gøril Storvig, Adrian Wells, Toril Skandsen, Alexander Olsen","doi":"10.1089/neur.2024.0076","DOIUrl":"https://doi.org/10.1089/neur.2024.0076","url":null,"abstract":"<p><p>After mild traumatic brain injury (mTBI), a subgroup of individuals experience persistent post-concussion symptoms (PPCS) that include headaches, cognitive difficulties, and fatigue. The aim of this preliminary study was to investigate possible effects associated with metacognitive therapy (MCT) on PPCS, maladaptive coping strategies, and positive and negative metacognitive beliefs following mTBI. A pre-post design supplemented with single-case A-B replication series to assess potential MCT mechanisms was used. Of the nine participants who received MCT, all experienced a decrease in PPCS, which constituted a reliable improvement for eight participants. For eight participants (we could calculate effect sizes for eight out of nine participants), moderate to very large decreases in maladaptive coping styles and positive and negative metacognitive beliefs were observed. However, based on visual analyses, participants 6, 8, and 9 show a downward baseline trend regarding MCT mechanisms that may have persisted into the intervention phase. No adverse events were reported. In conclusion, MCT was associated with improvements in PPCS and unhelpful psychological mechanisms, but caution is required in interpreting this association. Future research using formal single-case replication on symptom measures and randomized controlled trials appears to be justified.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"890-902"},"PeriodicalIF":1.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0097
Timbre Backen, Kristin Salottolo, David Acuna, Carlos H Palacio, Gina Berg, Andrea Tsoris, Robert Madayag, Kaysie Banton, David Bar-Or
The aging US population has altered the epidemiology of traumatic injury, but there are few studies examining changing patterns of traumatic intracranial hemorrhage (tICH). We examined temporal changes in incidence, demographics, severity, management, and outcomes of tICH among trauma admissions at six US Level I trauma centers over 6 years (July 1, 2016-June 30, 2022). Patients with tICH (subdural, epidural, subarachnoid, and intracerebral hemorrhage) were identified by 10th revision of the International Statistical Classification of Diseases diagnosis codes. Temporal trends were examined over 12 six-month intervals using joinpoint regression and reported as biannual percent change (BPC); models without joinpoints are described as linear trends over time. There were 67,514 trauma admissions over 6 years and 11,935 (17.7%) patients had a tICH. The proportion of tICH injuries significantly increased 2.6% biannually from July 2016 to July 2019 (BPC = 2.6, p = 0.04), then leveled off through June 2022 (BPC = -0.9, p = 0.19). Similarly, the proportion of geriatric patients (≥65 years old) increased 2.4% biannually from July 2016 to July 2019 (BPC = 2.4, p = 0.001) as did injuries due to falls (BPC = 2.2, p = 0.01). Three of the four most prevalent comorbidities significantly increased: hypertension linearly increased 2.1% biannually, functional dependence increased 25.5% biannually through June 2019, and chronic anticoagulant use increased 19.0% biannually through June 2019 and then 3.1% thereafter. There were no trends in the rates of neurosurgical intervention (BPC = -0.89, p = 0.40), ED Glasgow coma score 3-8 (BPC = -0.4, p = 0.77), or presence of severe extracranial injuries (BPC = -0.7, p = 0.45). In-hospital mortality linearly declined 2.6% biannually (BPC = 2.6, p = 0.05); however, there was a 10.3% biannual linear increase in discharge to hospice care (BPC = 10.3, p < 0.001). These results demonstrate the incidence of tICH admissions is temporally increasing, and the population is growing older with more comorbidities and injuries from falls. Yet, traumatic brain injury severity and neurosurgical management are unchanged. The shift from in-patient death to hospice care suggests an increased need for palliative care services.
{"title":"Multicenter Study Examining Temporal Trends in Traumatic Intracranial Hemorrhage Over Six Years Using Joinpoint Regression.","authors":"Timbre Backen, Kristin Salottolo, David Acuna, Carlos H Palacio, Gina Berg, Andrea Tsoris, Robert Madayag, Kaysie Banton, David Bar-Or","doi":"10.1089/neur.2024.0097","DOIUrl":"https://doi.org/10.1089/neur.2024.0097","url":null,"abstract":"<p><p>The aging US population has altered the epidemiology of traumatic injury, but there are few studies examining changing patterns of traumatic intracranial hemorrhage (tICH). We examined temporal changes in incidence, demographics, severity, management, and outcomes of tICH among trauma admissions at six US Level I trauma centers over 6 years (July 1, 2016-June 30, 2022). Patients with tICH (subdural, epidural, subarachnoid, and intracerebral hemorrhage) were identified by 10th revision of the International Statistical Classification of Diseases diagnosis codes. Temporal trends were examined over 12 six-month intervals using joinpoint regression and reported as biannual percent change (BPC); models without joinpoints are described as linear trends over time. There were 67,514 trauma admissions over 6 years and 11,935 (17.7%) patients had a tICH. The proportion of tICH injuries significantly increased 2.6% biannually from July 2016 to July 2019 (BPC = 2.6, <i>p</i> = 0.04), then leveled off through June 2022 (BPC = -0.9, <i>p</i> = 0.19). Similarly, the proportion of geriatric patients (≥65 years old) increased 2.4% biannually from July 2016 to July 2019 (BPC = 2.4, <i>p</i> = 0.001) as did injuries due to falls (BPC = 2.2, <i>p</i> = 0.01). Three of the four most prevalent comorbidities significantly increased: hypertension linearly increased 2.1% biannually, functional dependence increased 25.5% biannually through June 2019, and chronic anticoagulant use increased 19.0% biannually through June 2019 and then 3.1% thereafter. There were no trends in the rates of neurosurgical intervention (BPC = -0.89, <i>p</i> = 0.40), ED Glasgow coma score 3-8 (BPC = -0.4, <i>p</i> = 0.77), or presence of severe extracranial injuries (BPC = -0.7, <i>p</i> = 0.45). In-hospital mortality linearly declined 2.6% biannually (BPC = 2.6, <i>p</i> = 0.05); however, there was a 10.3% biannual linear increase in discharge to hospice care (BPC = 10.3, <i>p</i> < 0.001). These results demonstrate the incidence of tICH admissions is temporally increasing, and the population is growing older with more comorbidities and injuries from falls. Yet, traumatic brain injury severity and neurosurgical management are unchanged. The shift from in-patient death to hospice care suggests an increased need for palliative care services.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"999-1008"},"PeriodicalIF":1.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09eCollection Date: 2024-01-01DOI: 10.1089/neur.2024.0075
Leon Ruiter-Lopez, Jack K Donohue, Hemika Vempalli, Rebecca C Thurston, Michele D Levine, Katherine Snedaker, Kyla Z Donnelly, David O Okonkwo, Martina Anto-Ocrah
Resilience is associated with the degree to which post-concussion symptoms (PCS) are experienced. However, the role of resilience in the recovery trajectory of minority women, who tend to have prolonged concussion recovery, is poorly characterized. We evaluated the association between resilience and PCS, to determine if the association differed by race. A secondary data analysis was performed. Resilience was assessed using the Resilience Scale and PCS with the Rivermead questionnaire. Both variables were evaluated 6-10 weeks post-injury. Baseline demographics, spearman correlation, and multivariable linear regression models were used to determine the association between resilience and PCS. Seventy-seven women (mean age 28 ± 7.6) were included, 57% were White, and 43% were Black or Hispanic. The overall cohort had a moderate association between resilience and PCS (R = -0.304, p = 0.007). The association was present in minorities (R = -0.486, p = 0.004), and was stronger for Blacks (R = -0.745, p < 0.001). After adjusting for religion as a covariate separately, resilience (β = -0.156, 95% confidence interval [CI]: -0.285, -0.026; p = 0.019) and mood (β = 1.082, 95% CI: 0.847, 1.317; p < 0.001), were both independent predictors of PCS. The adjusted associations were stronger for the minority subgroup for both resilience (β = -0.231, 95% CI: -0.413, -0.050; p = 0.014) and mood (β = 1.122, 95% CI: 0.753, 1.491; p < 0.001). Our findings show that compared with Whites, minority individuals with higher resilience have greater resolution of PCS. However, mood is also of importance in this association. Thus resilience-based interventions must also target mood. Interventions that strengthen resilience may have promise in promoting equitable recovery in the setting of female concussions.
{"title":"Resilience and Concussion Recovery in Minority Women: Promoting Health Equity.","authors":"Leon Ruiter-Lopez, Jack K Donohue, Hemika Vempalli, Rebecca C Thurston, Michele D Levine, Katherine Snedaker, Kyla Z Donnelly, David O Okonkwo, Martina Anto-Ocrah","doi":"10.1089/neur.2024.0075","DOIUrl":"https://doi.org/10.1089/neur.2024.0075","url":null,"abstract":"<p><p>Resilience is associated with the degree to which post-concussion symptoms (PCS) are experienced. However, the role of resilience in the recovery trajectory of minority women, who tend to have prolonged concussion recovery, is poorly characterized. We evaluated the association between resilience and PCS, to determine if the association differed by race. A secondary data analysis was performed. Resilience was assessed using the Resilience Scale and PCS with the Rivermead questionnaire. Both variables were evaluated 6-10 weeks post-injury. Baseline demographics, spearman correlation, and multivariable linear regression models were used to determine the association between resilience and PCS. Seventy-seven women (mean age 28 ± 7.6) were included, 57% were White, and 43% were Black or Hispanic. The overall cohort had a moderate association between resilience and PCS (<i>R</i> = -0.304, <i>p</i> = 0.007). The association was present in minorities (<i>R</i> = -0.486, <i>p</i> = 0.004), and was stronger for Blacks (<i>R</i> = -0.745, <i>p</i> < 0.001). After adjusting for religion as a covariate separately, resilience (<i>β</i> = -0.156, 95% confidence interval [CI]: -0.285, -0.026; <i>p</i> = 0.019) and mood (<i>β</i> = 1.082, 95% CI: 0.847, 1.317; <i>p</i> < 0.001), were both independent predictors of PCS. The adjusted associations were stronger for the minority subgroup for both resilience (<i>β</i> = -0.231, 95% CI: -0.413, -0.050; <i>p</i> = 0.014) and mood (<i>β</i> = 1.122, 95% CI: 0.753, 1.491; <i>p</i> < 0.001). Our findings show that compared with Whites, minority individuals with higher resilience have greater resolution of PCS. However, mood is also of importance in this association. Thus resilience-based interventions must also target mood. Interventions that strengthen resilience may have promise in promoting equitable recovery in the setting of female concussions.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"5 1","pages":"989-997"},"PeriodicalIF":1.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}