Pub Date : 2023-11-16eCollection Date: 2023-01-01DOI: 10.1089/neur.2023.0071
Carla Richetta, Yevgeny Karepov
E-bikes (electrical bicycles and scooters) have been increasingly used as a means of transportation, especially among young adults. E-bikers have more accidents, at higher velocities and more severe kinematics, increasing the rate of neurosurgical injuries. Severe neurosurgical injury patterns result in significant morbidity and mortality. We collected data regarding adult patients (>18 years old), who suffered e-bike-related neurosurgical injuries, in a single tertiary medical center in Israel, between July 2019 and June 2020. Fifty-eight consecutive patients were included in this study. The average age was 34.9, and the average Glasgow Coma Scale (GCS) score upon admission was 13.2 and was significantly lower in operated patients (10.75). Fifty-four patients were riders; 51 (94.5%!) were not wearing a helmet. Fifty percent of patients had multiple types of trauma. Six patients suffered a spinal injury. Sixteen patients required either cranial or spinal surgery. Three patients died, and 1 remained in a vegetative state. Median Glasgow Outcome Scale-Extended (GOS-E) score at follow-up was 7.1. Operated patients stayed significantly longer in the intensive care unit (ICU) and in the hospital, and their GOS-E scores at discharge and follow-up were significantly lower. Most spinal injuries underwent surgery. Patients who wore helmets had significantly higher GCS scores and a shorter stay in the ICU and hospital. The unacceptable reality of the careless use of this transportation and the unique kinematics lead to severe neurosurgical injuries, comorbidities, and even mortality. Our results reflect the risks of e-bikes in the adult population. Most of our patients were in the mid-age group, and almost none had used a helmet. The results of this study highlight the potential need for neurosurgical treatment, and the need for long-term rehabilitation and follow-up, reflecting the emotional and financial toll of these injuries. Once again, this study showed that helmets save lives and emphasized the importance of protecting our heads.
{"title":"E-Bikes (Electrical Bicycles and Scooters) Related Neurosurgical Injuries in the Adult Population: A Single-Center Experience.","authors":"Carla Richetta, Yevgeny Karepov","doi":"10.1089/neur.2023.0071","DOIUrl":"https://doi.org/10.1089/neur.2023.0071","url":null,"abstract":"<p><p>E-bikes (electrical bicycles and scooters) have been increasingly used as a means of transportation, especially among young adults. E-bikers have more accidents, at higher velocities and more severe kinematics, increasing the rate of neurosurgical injuries. Severe neurosurgical injury patterns result in significant morbidity and mortality. We collected data regarding adult patients (>18 years old), who suffered e-bike-related neurosurgical injuries, in a single tertiary medical center in Israel, between July 2019 and June 2020. Fifty-eight consecutive patients were included in this study. The average age was 34.9, and the average Glasgow Coma Scale (GCS) score upon admission was 13.2 and was significantly lower in operated patients (10.75). Fifty-four patients were riders; 51 (94.5%!) were not wearing a helmet. Fifty percent of patients had multiple types of trauma. Six patients suffered a spinal injury. Sixteen patients required either cranial or spinal surgery. Three patients died, and 1 remained in a vegetative state. Median Glasgow Outcome Scale-Extended (GOS-E) score at follow-up was 7.1. Operated patients stayed significantly longer in the intensive care unit (ICU) and in the hospital, and their GOS-E scores at discharge and follow-up were significantly lower. Most spinal injuries underwent surgery. Patients who wore helmets had significantly higher GCS scores and a shorter stay in the ICU and hospital. The unacceptable reality of the careless use of this transportation and the unique kinematics lead to severe neurosurgical injuries, comorbidities, and even mortality. Our results reflect the risks of e-bikes in the adult population. Most of our patients were in the mid-age group, and almost none had used a helmet. The results of this study highlight the potential need for neurosurgical treatment, and the need for long-term rehabilitation and follow-up, reflecting the emotional and financial toll of these injuries. Once again, this study showed that helmets save lives and emphasized the importance of protecting our heads.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"797-804"},"PeriodicalIF":0.0,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464902","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 : 2023-11-06eCollection Date: 2023-01-01DOI: 10.1089/neur.2023.0036
William M Muter, Linda Mansson, Christopher Tuthill, Shreya Aalla, Stella Barth, Emily Evans, Kelly McKenzie, Sara Prokup, Chen Yang, Milap Sandhu, W Zev Rymer, Victor R Edgerton, Parag Gad, Gordon S Mitchell, Samuel S Wu, Guogen Shan, Arun Jayaraman, Randy D Trumbower
Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI.
{"title":"A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO<sub>2</sub>ST Trial.","authors":"William M Muter, Linda Mansson, Christopher Tuthill, Shreya Aalla, Stella Barth, Emily Evans, Kelly McKenzie, Sara Prokup, Chen Yang, Milap Sandhu, W Zev Rymer, Victor R Edgerton, Parag Gad, Gordon S Mitchell, Samuel S Wu, Guogen Shan, Arun Jayaraman, Randy D Trumbower","doi":"10.1089/neur.2023.0036","DOIUrl":"https://doi.org/10.1089/neur.2023.0036","url":null,"abstract":"<p><p>Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALK<sub>tSTIM</sub>) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALK<sub>tSTIM</sub> therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALK<sub>tSTIM</sub> on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALK<sub>tSTIM</sub> will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALK<sub>tSTIM</sub>; Placebo + WALK<sub>tSTIM</sub>; and tAIH + WALK<sub>tSHAM</sub>. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O<sub>2</sub> with 60-sec intervals at 21% O<sub>2</sub>) or daily placebo (fifteen 90-sec episodes at 21% O<sub>2</sub> with 60-sec intervals at 21% O<sub>2</sub>) before a 45-min session of WALK<sub>tSTIM</sub> or WALK<sub>tSHAM</sub>. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT05563103.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"736-750"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464901","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}
Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the “Learning to Learn” index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.
{"title":"Correlation of Insulin-Like Growth Factor 1 With Cognitive Functions in Mild Traumatic Brain Injury Patients","authors":"Ju-Chi Ou, Yin-Hsun Feng, Kai-Yun Chen, Yung-Hsiao Chiang, Tsung-I Hsu, Chung-Che Wu","doi":"10.1089/neur.2023.0085","DOIUrl":"https://doi.org/10.1089/neur.2023.0085","url":null,"abstract":"Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the “Learning to Learn” index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"44 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135564265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin L. Krieg, Anna V. Leonard, Renee J. Tuner, Frances Corrigan
Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets—the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20–1.51 kg; 6–9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.
{"title":"Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)","authors":"Justin L. Krieg, Anna V. Leonard, Renee J. Tuner, Frances Corrigan","doi":"10.1089/neur.2023.0047","DOIUrl":"https://doi.org/10.1089/neur.2023.0047","url":null,"abstract":"Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets—the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20–1.51 kg; 6–9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"261 1-4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Freda M. Warner, Bobo Tong, Jessie McDougall, Kathleen A. Martin Ginis, Alexander G. Rabchevsky, Jacquelyn J. Cragg, John L.K. Kramer
Open data sharing of clinical research aims to improve transparency and support novel scientific discoveries. There are also risks, including participant identification and the potential for stigmatization. The perspectives of persons participating in research are needed to inform open data-sharing policies. The aim of the current study was to determine perspectives on data sharing in persons with spinal cord injury (SCI), including risks and benefits, and types of data people are most willing to share. A secondary aim was to examine predictors of willingness to share data. Persons with SCIs in the United States and Canada completed a survey developed and disseminated through various channels, including our community partner, the North American Spinal Cord Injury Consortium. The study collected data from 232 participants, with 52.2% from Canada and 42.2% from the United States, and the majority completed the survey in English. Most participants had previously participated in research and had been living with an SCI for ≥5 years. Overall, most participants reported that the potential benefits of data sharing outweighed the negatives, with persons with SCI seen as the most trustworthy partners for data sharing. The highest levels of concern were that information could be stolen and companies might use the information for marketing purposes. Persons with SCI were generally supportive of data sharing for research purposes. Clinical trials should consider including a statement on open data sharing in informed consents to better acknowledge the contribution of research participants in future studies.
{"title":"Perspectives on Data Sharing in Persons With Spinal Cord Injury","authors":"Freda M. Warner, Bobo Tong, Jessie McDougall, Kathleen A. Martin Ginis, Alexander G. Rabchevsky, Jacquelyn J. Cragg, John L.K. Kramer","doi":"10.1089/neur.2023.0035","DOIUrl":"https://doi.org/10.1089/neur.2023.0035","url":null,"abstract":"Open data sharing of clinical research aims to improve transparency and support novel scientific discoveries. There are also risks, including participant identification and the potential for stigmatization. The perspectives of persons participating in research are needed to inform open data-sharing policies. The aim of the current study was to determine perspectives on data sharing in persons with spinal cord injury (SCI), including risks and benefits, and types of data people are most willing to share. A secondary aim was to examine predictors of willingness to share data. Persons with SCIs in the United States and Canada completed a survey developed and disseminated through various channels, including our community partner, the North American Spinal Cord Injury Consortium. The study collected data from 232 participants, with 52.2% from Canada and 42.2% from the United States, and the majority completed the survey in English. Most participants had previously participated in research and had been living with an SCI for ≥5 years. Overall, most participants reported that the potential benefits of data sharing outweighed the negatives, with persons with SCI seen as the most trustworthy partners for data sharing. The highest levels of concern were that information could be stolen and companies might use the information for marketing purposes. Persons with SCI were generally supportive of data sharing for research purposes. Clinical trials should consider including a statement on open data sharing in informed consents to better acknowledge the contribution of research participants in future studies.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"90 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135564724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.
{"title":"Retrospective Observational Study of Patients With Subdural Hematoma Treated With Idarucizumab","authors":"Eiichi Suehiro, Hideyuki Ishihara, Yohei Kogeichi, Tsunenori Ozawa, Koichi Haraguchi, Masaru Honda, Yumie Honda, Makoto Inaba, Ryusuke Kabeya, Naoaki Kanda, Kenta Koketsu, Nobukuni Murakami, Hidetoshi Nakamoto, Kotaro Oshio, Kuniyasu Saigusa, Takashi Shuto, Shuichi Sugiyama, Kenji Suzuyama, Tsuguaki Terashima, Mitsuharu Tsuura, Mitsutoshi Nakada, Hitoshi Kobata, Toshio Higashi, Nobuyuki Sakai, Michiyasu Suzuki","doi":"10.1089/neur.2023.0065","DOIUrl":"https://doi.org/10.1089/neur.2023.0065","url":null,"abstract":"Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients ≥65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred ≥7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"235 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-31eCollection Date: 2023-01-01DOI: 10.1089/neur.2023.0082
Nicholas S Race, Eleni H Moschonas, Jeffrey P Cheng, Corina O Bondi, Anthony E Kline
Sixty-nine million traumatic brain injuries (TBIs) are reported worldwide each year, and, of those, close to 3 million occur in the United States. In addition to neurobehavioral and cognitive deficits, TBI induces other maladaptive behaviors, such as agitation and aggression, which must be managed for safe, accurate assessment and effective treatment of the patient. The use of antipsychotic drugs (APDs) in TBI is supported by some expert guidelines, which suggests that they are an important part of the pharmacological armamentarium to be used in the management of agitation. Despite the advantages of APDs after TBI, there are significant disadvantages that may not be fully appreciated clinically during decision making because of the lack of a readily available updated compendium. Hence, the aim of this review is to integrate the existing findings and present the current state of APD use in pre-clinical models of TBI. The studies discussed were identified through PubMed and the University of Pittsburgh Library System search strategies and reveal that APDs, particularly those with dopamine2 (D2) receptor antagonism, generally impair the recovery process in rodents of both sexes and, in some instances, attenuate the potential benefits of neurorehabilitation. We believe that the compilation of findings represented by this exhaustive review of pre-clinical TBI + APD models can serve as a convenient source for guiding informed decisions by critical care clinicians and physiatrists contemplating APD use for patients exhibiting agitation.
{"title":"Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury.","authors":"Nicholas S Race, Eleni H Moschonas, Jeffrey P Cheng, Corina O Bondi, Anthony E Kline","doi":"10.1089/neur.2023.0082","DOIUrl":"10.1089/neur.2023.0082","url":null,"abstract":"<p><p>Sixty-nine million traumatic brain injuries (TBIs) are reported worldwide each year, and, of those, close to 3 million occur in the United States. In addition to neurobehavioral and cognitive deficits, TBI induces other maladaptive behaviors, such as agitation and aggression, which must be managed for safe, accurate assessment and effective treatment of the patient. The use of antipsychotic drugs (APDs) in TBI is supported by some expert guidelines, which suggests that they are an important part of the pharmacological armamentarium to be used in the management of agitation. Despite the advantages of APDs after TBI, there are significant disadvantages that may not be fully appreciated clinically during decision making because of the lack of a readily available updated compendium. Hence, the aim of this review is to integrate the existing findings and present the current state of APD use in pre-clinical models of TBI. The studies discussed were identified through PubMed and the University of Pittsburgh Library System search strategies and reveal that APDs, particularly those with dopamine<sub>2</sub> (D<sub>2</sub>) receptor antagonism, generally impair the recovery process in rodents of both sexes and, in some instances, attenuate the potential benefits of neurorehabilitation. We believe that the compilation of findings represented by this exhaustive review of pre-clinical TBI + APD models can serve as a convenient source for guiding informed decisions by critical care clinicians and physiatrists contemplating APD use for patients exhibiting agitation.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"724-735"},"PeriodicalIF":1.8,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489695","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 : 2023-10-25eCollection Date: 2023-01-01DOI: 10.1089/neur.2023.0068
Qi Zhang, Hong Min Kuang, Du Juan Qiao, Xiang Lin Zhong, Jia Jia Kang, Rui Na Ma, Min Li
It is unclear who can benefit from tracheal intubation in the moderate (mTBI) traumatic brain injury (TBI) population. Given that mTBI patients are conscious, intubation can cause intense stress, possibly triggering neurological deterioration. Therefore, identifying potential risk factors for intubation in mTBI patients can serve as a valuable clinical warning. We sought to investigate whether elevated D-dimer is a possible risk factor for intubation in mTBI patients. Using the STROBE statement, adult patients with isolated TBI (Glasgow Coma Scale [GCS] score 9-13) treated at a high-volume neurotrauma center between January 2015 and December 2020 were reviewed. The demographics, clinical presentation, neuroimaging, and laboratory information were collected based on the patients' electronic medical record. D-dimer values were assessed from serum when patients were admitted to the hospital. The primary study end-point was that the mTBI patient was intubated within 72 h upon admission. A total of 557 patients with mTBI were finally included in this study. Of these, 85 (15.3%) patients were intubated. Multi-variate logistic regression analysis showed that high-level D-dimer (≥17.9mg/L) was significantly associated with early tracheal intubation in mTBI patients (odds ratio, 3.10 [1.16-8.25]; p = 0.024) after adjusting for age, sex, GCS scores, Marshall scores, and Injury Severity Scores. Sensitivity analysis showed that high-level D-dimer had a robust correlation with intubation in the different subgroups or after propensity score matching. High-level D-dimer on admission is an independent risk factor for early tracheal intubation in isolated mTBI patients.
{"title":"Association Between High-Level D-Dimer at Admission and Early Intubation in Patients With Moderate Traumatic Brain Injury.","authors":"Qi Zhang, Hong Min Kuang, Du Juan Qiao, Xiang Lin Zhong, Jia Jia Kang, Rui Na Ma, Min Li","doi":"10.1089/neur.2023.0068","DOIUrl":"https://doi.org/10.1089/neur.2023.0068","url":null,"abstract":"<p><p>It is unclear who can benefit from tracheal intubation in the moderate (mTBI) traumatic brain injury (TBI) population. Given that mTBI patients are conscious, intubation can cause intense stress, possibly triggering neurological deterioration. Therefore, identifying potential risk factors for intubation in mTBI patients can serve as a valuable clinical warning. We sought to investigate whether elevated D-dimer is a possible risk factor for intubation in mTBI patients. Using the STROBE statement, adult patients with isolated TBI (Glasgow Coma Scale [GCS] score 9-13) treated at a high-volume neurotrauma center between January 2015 and December 2020 were reviewed. The demographics, clinical presentation, neuroimaging, and laboratory information were collected based on the patients' electronic medical record. D-dimer values were assessed from serum when patients were admitted to the hospital. The primary study end-point was that the mTBI patient was intubated within 72 h upon admission. A total of 557 patients with mTBI were finally included in this study. Of these, 85 (15.3%) patients were intubated. Multi-variate logistic regression analysis showed that high-level D-dimer (≥17.9mg/L) was significantly associated with early tracheal intubation in mTBI patients (odds ratio, 3.10 [1.16-8.25]; <i>p</i> = 0.024) after adjusting for age, sex, GCS scores, Marshall scores, and Injury Severity Scores. Sensitivity analysis showed that high-level D-dimer had a robust correlation with intubation in the different subgroups or after propensity score matching. High-level D-dimer on admission is an independent risk factor for early tracheal intubation in isolated mTBI patients.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"715-723"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429947","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 : 2023-10-17eCollection Date: 2023-01-01DOI: 10.1089/neur.2023.0007
Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy
Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of which 152 met the criteria for full-text review, and 32 were included in this review. Males predominantly suffered from pTBIs (78%). Motor vehicle accidents, followed by child abuse, were the leading causes of pTBI. Overall, 0.39% of cases were mild, 0.58% moderate, 16.25% severe, and 82.27% unclassified. The mortality rate was 13.11%. Most studies used the computed tomography scan, Glasgow Coma Scale, Abbreviated Injury Scale, and Injury Severity Score as investigation methods. This review reports on the alarming rate of child-abuse-related pTBI and offers further understanding of pTBI-associated risk factors and insight into the development of strategies to reduce their occurrence, as well as policies to promote child well-being.
儿童创伤性脑损伤(pTBI)是中东和北非(MENA)地区儿童损伤的主要原因。本综述旨在评估中东和北非地区的pTBI,并报告其临床严重程度和结果。使用主要的电子数据库进行搜索,包括Medline/Ovid、PubMed、EMBASE、Web of Science和SCOPUS。摘要是独立筛选的,一式两份,以检测原始研究。记录每篇文章的目的和研究结果,以及pTBI的机制、患者年龄和性别、使用的损伤评估工具和结果。共检索到1345篇文章,其中152篇符合全文审查标准,32篇被纳入本次审查。雄性主要患有pTBI(78%)。机动车事故,其次是虐待儿童,是pTBI的主要原因。总体而言,0.39%的病例为轻度,0.58%为中度,16.25%为重度,82.27%为未分类。死亡率为13.11%。大多数研究使用计算机断层扫描、格拉斯哥昏迷量表、缩写损伤量表和损伤严重程度评分作为调查方法。这篇综述报告了与儿童虐待相关的pTBI的惊人比率,并进一步了解了与pTBI相关的风险因素,深入了解了减少其发生的策略以及促进儿童福祉的政策的制定。
{"title":"Pediatric Traumatic Brain Injury in the Middle East and North Africa Region: A Systematic Review and Meta-Analysis to Assess Characteristics, Mechanisms, and Risk Factors.","authors":"Samar Al-Hajj, Sarah H Farran, Batoul Dekmak, Layal Hneiny, Hussein Abou Abbas, Aya Hassoun, Nadine Youness, Sarah Ghalayini, Nour Abou Khalil, Fiona Lecky, Shima Shahjouieh, Layal Ghamlouche, Zainab Nasrallah, Firas Kobeissy","doi":"10.1089/neur.2023.0007","DOIUrl":"10.1089/neur.2023.0007","url":null,"abstract":"<p><p>Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of which 152 met the criteria for full-text review, and 32 were included in this review. Males predominantly suffered from pTBIs (78%). Motor vehicle accidents, followed by child abuse, were the leading causes of pTBI. Overall, 0.39% of cases were mild, 0.58% moderate, 16.25% severe, and 82.27% unclassified. The mortality rate was 13.11%. Most studies used the computed tomography scan, Glasgow Coma Scale, Abbreviated Injury Scale, and Injury Severity Score as investigation methods. This review reports on the alarming rate of child-abuse-related pTBI and offers further understanding of pTBI-associated risk factors and insight into the development of strategies to reduce their occurrence, as well as policies to promote child well-being.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"693-714"},"PeriodicalIF":1.8,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429949","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 : 2023-10-16eCollection Date: 2023-01-01DOI: 10.1089/neur.2023.0060
Angela Mitevska, Citlally Santacruz, Eric J Martin, Ian E Jones, Arian Ghiacy, Simon Dixon, Nima Mostafazadeh, Zhangli Peng, Evangelos Kiskinis, John D Finan
Human induced pluripotent stem cell (hiPSC)-derived cells can reproduce human-specific pathophysiology, patient-specific vulnerability, and gene-environment interactions in neurological disease. Human in vitro models of neurotrauma therefore have great potential to advance the field. However, this potential cannot be realized until important biomaterials challenges are addressed. Status quo stretch injury models of neurotrauma culture cells on sheets of polydimethylsiloxane (PDMS) that are incompatible with long-term monoculture of hiPSC-derived neurons. Here, we overcame this challenge in an established human in vitro neurotrauma model by replacing PDMS with a highly biocompatible form of polyurethane (PU). This substitution allowed long-term monoculture of hiPSC-derived neurons. It also changed the biomechanics of stretch injury. We quantified these changes experimentally using high-speed videography and digital image correlation. We used finite element modeling to quantify the influence of the culture substrate's thickness, stiffness, and coefficient of friction on membrane stretch and concluded that the coefficient of friction explained most of the observed biomechanical changes. Despite these changes, we demonstrated that the modified model produced a robust, dose-dependent trauma phenotype in hiPSC-derived neuron monocultures. In summary, the introduction of this PU film makes it possible to maintain hiPSC-derived neurons in monoculture for long periods in a human in vitro neurotrauma model. In doing so, it opens new horizons in the field of neurotrauma by enabling the unique experimental paradigms (e.g., isogenic models) associated with hiPSC-derived neurons.
{"title":"Polyurethane Culture Substrates Enable Long-Term Neuron Monoculture in a Human <i>in vitro</i> Model of Neurotrauma.","authors":"Angela Mitevska, Citlally Santacruz, Eric J Martin, Ian E Jones, Arian Ghiacy, Simon Dixon, Nima Mostafazadeh, Zhangli Peng, Evangelos Kiskinis, John D Finan","doi":"10.1089/neur.2023.0060","DOIUrl":"10.1089/neur.2023.0060","url":null,"abstract":"<p><p>Human induced pluripotent stem cell (hiPSC)-derived cells can reproduce human-specific pathophysiology, patient-specific vulnerability, and gene-environment interactions in neurological disease. Human <i>in vitro</i> models of neurotrauma therefore have great potential to advance the field. However, this potential cannot be realized until important biomaterials challenges are addressed. <i>Status quo</i> stretch injury models of neurotrauma culture cells on sheets of polydimethylsiloxane (PDMS) that are incompatible with long-term monoculture of hiPSC-derived neurons. Here, we overcame this challenge in an established human <i>in vitro</i> neurotrauma model by replacing PDMS with a highly biocompatible form of polyurethane (PU). This substitution allowed long-term monoculture of hiPSC-derived neurons. It also changed the biomechanics of stretch injury. We quantified these changes experimentally using high-speed videography and digital image correlation. We used finite element modeling to quantify the influence of the culture substrate's thickness, stiffness, and coefficient of friction on membrane stretch and concluded that the coefficient of friction explained most of the observed biomechanical changes. Despite these changes, we demonstrated that the modified model produced a robust, dose-dependent trauma phenotype in hiPSC-derived neuron monocultures. In summary, the introduction of this PU film makes it possible to maintain hiPSC-derived neurons in monoculture for long periods in a human <i>in vitro</i> neurotrauma model. In doing so, it opens new horizons in the field of neurotrauma by enabling the unique experimental paradigms (e.g., isogenic models) associated with hiPSC-derived neurons.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"4 1","pages":"682-692"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429951","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}