Pub Date : 2025-09-11eCollection Date: 2025-01-01DOI: 10.1177/2689288X251377030
Pooja M Datta Roy, Jens Cuba, Kyle S Milligan, Wenqi Shi, Dongmei Wang, Michelle C LaPlaca
Neuroinflammation is a nearly ubiquitous secondary injury process after traumatic brain injury (TBI) involving microglia. The time course of microglial functional transition between pro-inflammatory and anti-inflammatory states after mild TBI (mTBI) and the potential influence of sex in microglial response is not well-understood. To investigate interactions between sex and microglial activation states in the subacute post-mTBI period, we performed a morphological and phenotypic marker analysis on cells from male and female rats following closed head single impact (smTBI), repetitive impacts (rmTBI), or sham conditions at 24 h, 72 h, or 1 week postinjury. There was a significant increase in microglia population 24 h post-smTBI and at all time points for rmTBI in both male and female cells. Single-cell morphological analysis (24 microglia per animal) revealed no clear sex differences in microglial activation state. However, Sholl analysis demonstrated an increase in branching complexity for smTBI female cells at 24 h (area under the curve [AUC] 154 ± 2.1, p = 0.03) and at 72 h for rmTBI (AUC 229 ± 6.6, p = 0.006), but no increase in branching was observed in male cells. Principal component analysis similarly demonstrated that female cells formed distinct clusters at 72 h and 1 week, suggesting a change in morphology. There was an increase in anti-inflammatory marker, CD206, at 72 h for female cells in both smTBI and rmTBI groups. However, for males, most cells were KV1.3-positive (pro-inflammatory) even at 1 week in smTBI and rmTBI groups. Altogether, these data demonstrate microglial cells are pro-inflammatory 24 h after mTBI, but there is a robust difference between sexes, with female cells transitioning earlier from the pro-inflammatory state to the anti-inflammatory state compared with male cells. These results contribute to our understanding of sexual dimorphism associated with microglial recovery following mTBI and warrant further study of associated cellular pathways.
{"title":"Sex Dimorphism Influences Cortical Microglial Morphological and Phenotypic Marker Profile after Closed Head Mild Traumatic Brain Injury in Rats.","authors":"Pooja M Datta Roy, Jens Cuba, Kyle S Milligan, Wenqi Shi, Dongmei Wang, Michelle C LaPlaca","doi":"10.1177/2689288X251377030","DOIUrl":"10.1177/2689288X251377030","url":null,"abstract":"<p><p>Neuroinflammation is a nearly ubiquitous secondary injury process after traumatic brain injury (TBI) involving microglia. The time course of microglial functional transition between pro-inflammatory and anti-inflammatory states after mild TBI (mTBI) and the potential influence of sex in microglial response is not well-understood. To investigate interactions between sex and microglial activation states in the subacute post-mTBI period, we performed a morphological and phenotypic marker analysis on cells from male and female rats following closed head single impact (smTBI), repetitive impacts (rmTBI), or sham conditions at 24 h, 72 h, or 1 week postinjury. There was a significant increase in microglia population 24 h post-smTBI and at all time points for rmTBI in both male and female cells. Single-cell morphological analysis (24 microglia per animal) revealed no clear sex differences in microglial activation state. However, Sholl analysis demonstrated an increase in branching complexity for smTBI female cells at 24 h (area under the curve [AUC] 154 ± 2.1, <i>p</i> = 0.03) and at 72 h for rmTBI (AUC 229 ± 6.6, <i>p</i> = 0.006), but no increase in branching was observed in male cells. Principal component analysis similarly demonstrated that female cells formed distinct clusters at 72 h and 1 week, suggesting a change in morphology. There was an increase in anti-inflammatory marker, CD206, at 72 h for female cells in both smTBI and rmTBI groups. However, for males, most cells were KV1.3-positive (pro-inflammatory) even at 1 week in smTBI and rmTBI groups. Altogether, these data demonstrate microglial cells are pro-inflammatory 24 h after mTBI, but there is a robust difference between sexes, with female cells transitioning earlier from the pro-inflammatory state to the anti-inflammatory state compared with male cells. These results contribute to our understanding of sexual dimorphism associated with microglial recovery following mTBI and warrant further study of associated cellular pathways.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"790-803"},"PeriodicalIF":1.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330938","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 : 2025-09-09eCollection Date: 2025-01-01DOI: 10.1177/2689288X251370703
Noah Xin Ying Yeo, Hui Jun Zhou, Jan Hau Lee, Paula Caporal, Juan D Roa G, Sebastián González-Dambrauskas, Jane Pei Wen Ng, Yoko Wong, Adriana Yock-Corrales, Yasser Kazzaz, Qalab Abbas, Shu-Ling Chong
Use of the intracranial pressure (ICP) monitor in pediatric traumatic brain injury (TBI) remains variable. Clinical prediction models of raised ICP have been reported in adult TBI but have not been validated in pediatric TBI. We aimed to investigate clinical predictors and derive a prediction model for raised ICP in pediatric patients with TBI. A real-world observational study was conducted among pediatric intensive care units from the Pediatric Acute & Critical Care Medicine Asian Network and Red Colaborativa Pediátrica de Latinoamerica. Children <18 years with moderate-to-severe TBI and who were hospitalized between 2014 and 2022 were included. We defined raised ICP as >20 mmHg. Multivariable logistic regression models were built to identify significant predictors for raised ICP, and performance was assessed using the area under the receiver operating characteristic curve (AUC). Among 706 pediatric patients, only 151 (21.4%) had ICP monitoring, and 75 (49.7%) were confirmed to have raised ICP. Mortality was 13.2%, 8.0%, and 4.0% for patients who did not receive ICP monitoring, those with raised ICP, and those with normal ICP, respectively (p = 0.037). A model predicting for raised ICP comprising sex, Glasgow Coma Scale motor score, leukocytosis, thrombocytopenia, and skull fracture on computed tomography performed with a sensitivity, specificity, and AUC of 56.0% (95% confidence interval [CI]: 44.8%-67.2%), 75.0% (95% CI: 65.3%-84.7%), and 73.7% (95% CI: 65.7%-81.6%), respectively. We report clinical predictors associated with raised ICP in pediatric TBI. The clinical prediction model was not sensitive, and future large-scale prospective studies should stratify predictors by specific intracranial pathologies.
{"title":"Identifying Clinical Predictors of Raised Intracranial Pressure in Pediatric Traumatic Brain Injury-A Multinational Initiative.","authors":"Noah Xin Ying Yeo, Hui Jun Zhou, Jan Hau Lee, Paula Caporal, Juan D Roa G, Sebastián González-Dambrauskas, Jane Pei Wen Ng, Yoko Wong, Adriana Yock-Corrales, Yasser Kazzaz, Qalab Abbas, Shu-Ling Chong","doi":"10.1177/2689288X251370703","DOIUrl":"10.1177/2689288X251370703","url":null,"abstract":"<p><p>Use of the intracranial pressure (ICP) monitor in pediatric traumatic brain injury (TBI) remains variable. Clinical prediction models of raised ICP have been reported in adult TBI but have not been validated in pediatric TBI. We aimed to investigate clinical predictors and derive a prediction model for raised ICP in pediatric patients with TBI. A real-world observational study was conducted among pediatric intensive care units from the Pediatric Acute & Critical Care Medicine Asian Network and Red Colaborativa Pediátrica de Latinoamerica. Children <18 years with moderate-to-severe TBI and who were hospitalized between 2014 and 2022 were included. We defined raised ICP as >20 mmHg. Multivariable logistic regression models were built to identify significant predictors for raised ICP, and performance was assessed using the area under the receiver operating characteristic curve (AUC). Among 706 pediatric patients, only 151 (21.4%) had ICP monitoring, and 75 (49.7%) were confirmed to have raised ICP. Mortality was 13.2%, 8.0%, and 4.0% for patients who did not receive ICP monitoring, those with raised ICP, and those with normal ICP, respectively (<i>p</i> = 0.037). A model predicting for raised ICP comprising sex, Glasgow Coma Scale motor score, leukocytosis, thrombocytopenia, and skull fracture on computed tomography performed with a sensitivity, specificity, and AUC of 56.0% (95% confidence interval [CI]: 44.8%-67.2%), 75.0% (95% CI: 65.3%-84.7%), and 73.7% (95% CI: 65.7%-81.6%), respectively. We report clinical predictors associated with raised ICP in pediatric TBI. The clinical prediction model was not sensitive, and future large-scale prospective studies should stratify predictors by specific intracranial pathologies.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"778-789"},"PeriodicalIF":1.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330968","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 : 2025-09-08eCollection Date: 2025-01-01DOI: 10.1177/2689288X251376991
Dean M Cordingley, Izabella Marquez, Serena C L Buchwald, Frederick A Zeiler
The objective of this study was to identify whether physical fitness influences outcomes following traumatic brain injury (TBI) in humans and animals, and to highlight any knowledge gaps in the current literature. A search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane Libraries was performed on December 4, 2023 (from database inception), and a systematic scoping review of the resulting literature was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews was used for reporting the results. An online systematic review management system was used to remove all duplicates and for subsequent article screening. Following the removal of duplicates, the search identified 6,818 articles for screening, of which 10 articles met the inclusion/exclusion criteria and were included. One study was conducted in humans, while the remaining nine utilized murine models. The available literature is limited and has investigated a large variety of outcomes that were not consistent across studies. Additionally, the pre-TBI exercise intervention or fitness assessment method varied between the studies. With the current literature, it is not possible to draw conclusions regarding the effects of physical fitness level and outcomes following a TBI.
{"title":"Does Physical Fitness Prior to Traumatic Brain Injury Affect Recovery Outcomes? A Scoping Review of Human and Animal Research.","authors":"Dean M Cordingley, Izabella Marquez, Serena C L Buchwald, Frederick A Zeiler","doi":"10.1177/2689288X251376991","DOIUrl":"10.1177/2689288X251376991","url":null,"abstract":"<p><p>The objective of this study was to identify whether physical fitness influences outcomes following traumatic brain injury (TBI) in humans and animals, and to highlight any knowledge gaps in the current literature. A search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane Libraries was performed on December 4, 2023 (from database inception), and a systematic scoping review of the resulting literature was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews was used for reporting the results. An online systematic review management system was used to remove all duplicates and for subsequent article screening. Following the removal of duplicates, the search identified 6,818 articles for screening, of which 10 articles met the inclusion/exclusion criteria and were included. One study was conducted in humans, while the remaining nine utilized murine models. The available literature is limited and has investigated a large variety of outcomes that were not consistent across studies. Additionally, the pre-TBI exercise intervention or fitness assessment method varied between the studies. With the current literature, it is not possible to draw conclusions regarding the effects of physical fitness level and outcomes following a TBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"768-777"},"PeriodicalIF":1.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330953","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 : 2025-09-05eCollection Date: 2025-01-01DOI: 10.1177/2689288X251371125
Natalie M Bell, Cameron Johnson, Fang F Yu, Jillian E Urban, Amy L Proskovec, Ananth Madhuranthakam, Joseph A Maldjian, Elizabeth M Davenport
Mild traumatic brain injury (mTBI) or concussion results from a bump or blow to the head followed by clinical symptoms. In contrast, repetitive head impacts (RHI) in sports result from a bump or blow to the head but are not accompanied by acute clinical symptoms. Neither RHI nor mTBI is detectable with traditional neuroimaging. Additionally, pediatric populations remain understudied in this field. Further research in pediatric populations exposed to mTBI/RHI is essential due to ongoing neurological development. This review aims to: (1) evaluate differences in neuroimaging findings in pediatrics and adults, (2) compare differences between RHI findings and mTBI findings within pediatrics, and (3) compare adult and pediatric studies across multiple modalities using the most current neuroimaging literature in the field of pediatric head injury. This narrative review will provide insight into future research directions of the field and potentially inform clinical considerations to be made in the future.
{"title":"A Comparative Neuroimaging Review of Repetitive Head Impacts and Mild Traumatic Brain Injury from Pediatrics to Professionals.","authors":"Natalie M Bell, Cameron Johnson, Fang F Yu, Jillian E Urban, Amy L Proskovec, Ananth Madhuranthakam, Joseph A Maldjian, Elizabeth M Davenport","doi":"10.1177/2689288X251371125","DOIUrl":"10.1177/2689288X251371125","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) or concussion results from a bump or blow to the head followed by clinical symptoms. In contrast, repetitive head impacts (RHI) in sports result from a bump or blow to the head but are not accompanied by acute clinical symptoms. Neither RHI nor mTBI is detectable with traditional neuroimaging. Additionally, pediatric populations remain understudied in this field. Further research in pediatric populations exposed to mTBI/RHI is essential due to ongoing neurological development. This review aims to: (1) evaluate differences in neuroimaging findings in pediatrics and adults, (2) compare differences between RHI findings and mTBI findings within pediatrics, and (3) compare adult and pediatric studies across multiple modalities using the most current neuroimaging literature in the field of pediatric head injury. This narrative review will provide insight into future research directions of the field and potentially inform clinical considerations to be made in the future.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"740-755"},"PeriodicalIF":1.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330936","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 : 2025-09-04eCollection Date: 2025-01-01DOI: 10.1177/08977151251366985
Cheewin Khawprapa, Sasithorn Khawprapa
This study compares the functional outcomes of post-traumatic neurosurgical patients who underwent surgery within 4 h of diagnosis with those who underwent surgery >4 h after diagnosis. A retrospective analysis was conducted on patients who underwent traumatic neurosurgery at Sakon Nakhon Hospital between 2018 and 2024. The study included 164 patients, divided into two groups of 82 patients each. Group 1 underwent surgery within 4 h of diagnosis, while Group 2 underwent surgery after 4 h. The Glasgow Outcome Scale-Extended scores at 3 months post-operatively were significantly more favorable in Group 1 compared with Group 2 (p = 0.011). Additionally, the Barthel Index at 1 month and 3 months post-operatively was significantly higher in Group 1 (p = 0.044, 0.007, respectively). The findings suggest that early surgical intervention within 4 h of diagnosis leads to better functional outcomes in patients with traumatic brain injury.
{"title":"The Impact of Time from Diagnosis to Operating Room on Functional Outcomes in Patients with Traumatic Brain Injury: A Retrospective Study.","authors":"Cheewin Khawprapa, Sasithorn Khawprapa","doi":"10.1177/08977151251366985","DOIUrl":"10.1177/08977151251366985","url":null,"abstract":"<p><p>This study compares the functional outcomes of post-traumatic neurosurgical patients who underwent surgery within 4 h of diagnosis with those who underwent surgery >4 h after diagnosis. A retrospective analysis was conducted on patients who underwent traumatic neurosurgery at Sakon Nakhon Hospital between 2018 and 2024. The study included 164 patients, divided into two groups of 82 patients each. Group 1 underwent surgery within 4 h of diagnosis, while Group 2 underwent surgery after 4 h. The Glasgow Outcome Scale-Extended scores at 3 months post-operatively were significantly more favorable in Group 1 compared with Group 2 (<i>p</i> = 0.011). Additionally, the Barthel Index at 1 month and 3 months post-operatively was significantly higher in Group 1 (<i>p</i> = 0.044, 0.007, respectively). The findings suggest that early surgical intervention within 4 h of diagnosis leads to better functional outcomes in patients with traumatic brain injury.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"681-685"},"PeriodicalIF":1.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042374","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}
A substantial number of people experience persistent post-concussion symptoms (PPCS) following a concussion. Traditional retrospective assessments, such as the Rivermead Post Concussion Symptoms Questionnaire (RPQ), are prone to memory biases and do not capture the day-to-day variability of PPCS. In this study, we explored the association between daily registrations of PPCS and the RPQ. We also examined the variability of PPCS trajectories over time. Nineteen participants registered PPCS symptoms for 28 days using an mHealth app and then completed the RPQ. From the final 7 days, average, highest, and last-day symptom scores were calculated and correlated with corresponding RPQ items. Scores from the full 28-day period were used to compute the within-person standard deviation and mean squared successive difference (MSSD) for each symptom that participants rated as the most bothersome. Correlations between the RPQ and daily registrations were weak-to-medium (range: 0.343, 0.590). The retrospective RPQ explained up to 35% of the variance in average daily registrations of PPCS. The MSSD ranged from 0 to 16.29, and the within-person SD from 0 to 3.25. Visual analyses showed that participants with identical RPQ item scores often exhibited different PPCS variability. This was also true for different symptoms within the same participant. This study highlights the potential additional value of daily registrations for capturing the dynamic and fluctuating nature of PPCS, which may be missed by retrospective questionnaires administered at one time point. PPCS vary both within and between individuals over time and reducing this complexity to a single total score oversimplifies a nuanced reality. Larger studies are needed to confirm these findings, and future work should investigate the clinical relevance of capturing daily variations in PPCS.
{"title":"The Association Between Daily Registrations of Persistent Post-Concussion Symptoms Using an mHealth App and the Retrospective Rivermead Post-Concussion Symptoms Questionnaire.","authors":"Johanne Rauwenhoff, Gøril Storvig, Bert Lenaert, Anker Stubberud, Toril Skandsen, Erling Tronvik, Alexander Olsen","doi":"10.1177/2689288X251372548","DOIUrl":"10.1177/2689288X251372548","url":null,"abstract":"<p><p>A substantial number of people experience persistent post-concussion symptoms (PPCS) following a concussion. Traditional retrospective assessments, such as the Rivermead Post Concussion Symptoms Questionnaire (RPQ), are prone to memory biases and do not capture the day-to-day variability of PPCS. In this study, we explored the association between daily registrations of PPCS and the RPQ. We also examined the variability of PPCS trajectories over time. Nineteen participants registered PPCS symptoms for 28 days using an mHealth app and then completed the RPQ. From the final 7 days, average, highest, and last-day symptom scores were calculated and correlated with corresponding RPQ items. Scores from the full 28-day period were used to compute the within-person standard deviation and mean squared successive difference (MSSD) for each symptom that participants rated as the most bothersome. Correlations between the RPQ and daily registrations were weak-to-medium (range: 0.343, 0.590). The retrospective RPQ explained up to 35% of the variance in average daily registrations of PPCS. The MSSD ranged from 0 to 16.29, and the within-person SD from 0 to 3.25. Visual analyses showed that participants with identical RPQ item scores often exhibited different PPCS variability. This was also true for different symptoms within the same participant. This study highlights the potential additional value of daily registrations for capturing the dynamic and fluctuating nature of PPCS, which may be missed by retrospective questionnaires administered at one time point. PPCS vary both within and between individuals over time and reducing this complexity to a single total score oversimplifies a nuanced reality. Larger studies are needed to confirm these findings, and future work should investigate the clinical relevance of capturing daily variations in PPCS.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"756-767"},"PeriodicalIF":1.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310255","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 : 2025-09-03eCollection Date: 2025-01-01DOI: 10.1177/2689288X251372910
Hidetaka Onda, Takuya Nishino, Shoji Yokobori
Early post-traumatic seizures (EPTS) after severe traumatic brain injury (TBI) are linked to poor neurological outcomes. While levetiracetam (LEV) is commonly used for seizure prophylaxis, perampanel (PER), an AMPA receptor antagonist, is gaining interest due to its potential neuroprotective effects. This retrospective cohort study included adults (≥18 years) admitted to a tertiary trauma center between 2018 and 2025 who received LEV or PER within 12 h post-injury (N = 200; LEV, n = 145; PER, n = 55). Monotherapy was initiated with either drug. The primary outcome was EPTS incidence within 7 days. Secondary outcomes included mechanical ventilation duration, hospital stay, and Glasgow Outcome Scale (GOS) score. Analyses included Firth's logistic regression and inverse probability of treatment weighting (IPTW) adjusted for key clinical confounders. EPTS occurred at 15.9% (LEV) versus 1.8% (PER). PER significantly reduced seizure risk (Firth-adjusted OR = 0.158; 95% CI, 0.017-0.644; p = 0.007), which was confirmed by IPTW (OR = 0.112; 95% CI, 0.014-0.873; p = 0.037). PER also shortened ventilation duration (IRR = 0.515; 95% CI, 0.303-0.907; p = 0.015). GOS and hospital stay did not differ significantly. No adverse events occurred in either group. PER significantly reduced EPTS and mechanical ventilation duration compared with LEV. The safety and utility of PER in acute care suggest it might be a valuable alternative for seizure prophylaxis in patients with severe TBI.
严重创伤性脑损伤(TBI)后的早期创伤后癫痫发作(EPTS)与神经系统预后不良有关。虽然左乙拉西坦(LEV)通常用于预防癫痫发作,但AMPA受体拮抗剂perampanel (PER)由于其潜在的神经保护作用而受到关注。该回顾性队列研究纳入了2018年至2025年间在三级创伤中心接受LEV或PER治疗的成人(≥18岁),这些患者在损伤后12小时内接受LEV或PER治疗(N = 200; LEV, N = 145; PER, N = 55)。单药治疗开始使用任何一种药物。主要终点为7天内EPTS的发生率。次要结局包括机械通气时间、住院时间和格拉斯哥结局量表(GOS)评分。分析包括Firth逻辑回归和针对关键临床混杂因素调整的治疗加权逆概率(IPTW)。EPTS的发生率分别为15.9% (LEV)和1.8% (PER)。PER显著降低癫痫发作风险(firth校正OR = 0.158; 95% CI, 0.017-0.644; p = 0.007), IPTW证实了这一点(OR = 0.112; 95% CI, 0.014-0.873; p = 0.037)。PER也缩短了通气时间(IRR = 0.515; 95% CI, 0.303-0.907; p = 0.015)。GOS与住院时间无显著差异。两组均未发生不良事件。与LEV相比,PER显著降低了EPTS和机械通气时间。PER在急性护理中的安全性和实用性表明它可能是严重TBI患者癫痫预防的一种有价值的替代方案。
{"title":"Perampanel for Early Seizure Prophylaxis After Severe Traumatic Brain Injury: A Retrospective Comparative Study with Levetiracetam.","authors":"Hidetaka Onda, Takuya Nishino, Shoji Yokobori","doi":"10.1177/2689288X251372910","DOIUrl":"10.1177/2689288X251372910","url":null,"abstract":"<p><p>Early post-traumatic seizures (EPTS) after severe traumatic brain injury (TBI) are linked to poor neurological outcomes. While levetiracetam (LEV) is commonly used for seizure prophylaxis, perampanel (PER), an AMPA receptor antagonist, is gaining interest due to its potential neuroprotective effects. This retrospective cohort study included adults (≥18 years) admitted to a tertiary trauma center between 2018 and 2025 who received LEV or PER within 12 h post-injury (<i>N</i> = 200; LEV, <i>n</i> = 145; PER, <i>n</i> = 55). Monotherapy was initiated with either drug. The primary outcome was EPTS incidence within 7 days. Secondary outcomes included mechanical ventilation duration, hospital stay, and Glasgow Outcome Scale (GOS) score. Analyses included Firth's logistic regression and inverse probability of treatment weighting (IPTW) adjusted for key clinical confounders. EPTS occurred at 15.9% (LEV) versus 1.8% (PER). PER significantly reduced seizure risk (Firth-adjusted OR = 0.158; 95% CI, 0.017-0.644; <i>p</i> = 0.007), which was confirmed by IPTW (OR = 0.112; 95% CI, 0.014-0.873; <i>p</i> = 0.037). PER also shortened ventilation duration (IRR = 0.515; 95% CI, 0.303-0.907; <i>p</i> = 0.015). GOS and hospital stay did not differ significantly. No adverse events occurred in either group. PER significantly reduced EPTS and mechanical ventilation duration compared with LEV. The safety and utility of PER in acute care suggest it might be a valuable alternative for seizure prophylaxis in patients with severe TBI.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"732-739"},"PeriodicalIF":1.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294575","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 : 2025-08-27eCollection Date: 2025-01-01DOI: 10.1177/2689288X251369274
Keyun Lai, Xiao Chen, Liyun He, Qi Liu, Changsheng Lai, Yang Bai, Ye Zhang, Kaiyue Wang, Fangzhao Wang, Shuai He, Guangjun Wang
Accurate differentiation between persistent vegetative state (PVS) and minimally conscious state and estimation of recovery likelihood in patients in PVS are crucial. This study analyzed electroencephalography (EEG) metrics to investigate their relationship with consciousness improvements in patients in PVS and developed a machine learning prediction model. We retrospectively evaluated 19 patients in PVS, categorizing them into two groups: those with improved consciousness (n = 7) and those without improvement (n = 12). Spectral and complexity analyses were performed on patients' EEG data to obtain spectral power and multiscale entropy (MSE) values. These metrics served as features in developing an EEG-based prediction model for consciousness improvement. Spectral power and MSE values were used as features in six machine learning models-support vector machine (SVM), Classification and Regression Tree, chi-squared automatic interaction detector, neural network, C5.0, and logistic regression-to perform classification via data mining methods. The dataset, containing data of 19 cases, was divided into training and test sets at a 50% ratio. The SVM model using MSE features yielded the best classification results, with prediction accuracies of 95.18% (training set) and 92.93% (test set). The logistic regression model achieved 93.25% and 84.51% accuracy, respectively. In the test set, the MSE-based SVM model demonstrated a 27.67% improvement in classification accuracy compared with models using spectral analysis features, indicating that MSE achieves better classification performance. This study demonstrates that MSE is a promising predictor of prognosis in patients in EEG-confirmed vegetative states.
{"title":"Identifying Features of Electroencephalography Associated with Improved Awareness in Persistent Vegetative State via Multiscale Entropy: A Machine Learning Modeling Study.","authors":"Keyun Lai, Xiao Chen, Liyun He, Qi Liu, Changsheng Lai, Yang Bai, Ye Zhang, Kaiyue Wang, Fangzhao Wang, Shuai He, Guangjun Wang","doi":"10.1177/2689288X251369274","DOIUrl":"10.1177/2689288X251369274","url":null,"abstract":"<p><p>Accurate differentiation between persistent vegetative state (PVS) and minimally conscious state and estimation of recovery likelihood in patients in PVS are crucial. This study analyzed electroencephalography (EEG) metrics to investigate their relationship with consciousness improvements in patients in PVS and developed a machine learning prediction model. We retrospectively evaluated 19 patients in PVS, categorizing them into two groups: those with improved consciousness (<i>n</i> = 7) and those without improvement (<i>n</i> = 12). Spectral and complexity analyses were performed on patients' EEG data to obtain spectral power and multiscale entropy (MSE) values. These metrics served as features in developing an EEG-based prediction model for consciousness improvement. Spectral power and MSE values were used as features in six machine learning models-support vector machine (SVM), Classification and Regression Tree, chi-squared automatic interaction detector, neural network, C5.0, and logistic regression-to perform classification via data mining methods. The dataset, containing data of 19 cases, was divided into training and test sets at a 50% ratio. The SVM model using MSE features yielded the best classification results, with prediction accuracies of 95.18% (training set) and 92.93% (test set). The logistic regression model achieved 93.25% and 84.51% accuracy, respectively. In the test set, the MSE-based SVM model demonstrated a 27.67% improvement in classification accuracy compared with models using spectral analysis features, indicating that MSE achieves better classification performance. This study demonstrates that MSE is a promising predictor of prognosis in patients in EEG-confirmed vegetative states.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"720-731"},"PeriodicalIF":1.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031396","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 : 2025-08-26eCollection Date: 2025-01-01DOI: 10.1177/2689288X251370997
Giacomo Scanavini, Isabelle Martin, Ludvik Alkhoury, Ana Radanovic, Yakira Tepler, Abhishek Jaywant, N Jeremy Hill, Tracy Butler, Keith W Jamison, Amy Kuceyeski, Nicholas D Schiff, Sudhin A Shah
Traumatic brain injury (TBI) impairs attention and executive function, often through disrupted coordination between cognitive and autonomic systems. While electroencephalography (EEG) and pupillometry are widely used to assess neural and autonomic responses independently, little is known about how these systems interact in TBI. Understanding their coordination is essential to identify compensatory mechanisms that may support attention under conditions of neural inefficiency. In this study, we examined pupil dilation during the Attention Network Test in individuals with TBI (n = 25) and controls without brain injury (n = 45). TBI participants exhibited preserved accuracy but slower reaction times (RTs), suggesting increased cognitive effort. Paradoxically, this effort was not reflected in heightened pupil dilation. Instead, pupil responses were attenuated, suggesting impaired recruitment of the locus coeruleus-norepinephrine system and possible autonomic dysregulation. We further assessed the relationship between simultaneously recorded pupillary responses and visual evoked responses in a subset of those in whom both measures were available (n = 23, TBI; n = 35, controls). Crucially, while both pupil dilation and amplitude of the visual P3 event-related potential were reduced in TBI, these measures showed a positive correlation across participants with TBI; this was absent in controls. Our results suggest that TBI may induce a compensatory coupling between cortical and autonomic systems to sustain cognitive performance despite underlying dysfunction. Positive correlation between pupil dilation and event-related potential suggest a role for arousal dysregulation in subjects with TBI. Our findings provide new evidence for altered EEG-pupil dynamics in TBI and highlight the potential of combining cortical and autonomic measures as a multimodal biomarker for tracking recovery, stratifying injury severity, and guiding individualized rehabilitation strategies.
{"title":"Coupling of Event-Related Potential and Pupil Dilation as a Compensatory Marker of Executive Attention in Traumatic Brain Injury.","authors":"Giacomo Scanavini, Isabelle Martin, Ludvik Alkhoury, Ana Radanovic, Yakira Tepler, Abhishek Jaywant, N Jeremy Hill, Tracy Butler, Keith W Jamison, Amy Kuceyeski, Nicholas D Schiff, Sudhin A Shah","doi":"10.1177/2689288X251370997","DOIUrl":"10.1177/2689288X251370997","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) impairs attention and executive function, often through disrupted coordination between cognitive and autonomic systems. While electroencephalography (EEG) and pupillometry are widely used to assess neural and autonomic responses independently, little is known about how these systems interact in TBI. Understanding their coordination is essential to identify compensatory mechanisms that may support attention under conditions of neural inefficiency. In this study, we examined pupil dilation during the Attention Network Test in individuals with TBI (<i>n</i> = 25) and controls without brain injury (<i>n</i> = 45). TBI participants exhibited preserved accuracy but slower reaction times (RTs), suggesting increased cognitive effort. Paradoxically, this effort was not reflected in heightened pupil dilation. Instead, pupil responses were attenuated, suggesting impaired recruitment of the locus coeruleus-norepinephrine system and possible autonomic dysregulation. We further assessed the relationship between simultaneously recorded pupillary responses and visual evoked responses in a subset of those in whom both measures were available (<i>n</i> = 23, TBI; <i>n</i> = 35, controls). Crucially, while both pupil dilation and amplitude of the visual P3 event-related potential were reduced in TBI, these measures showed a positive correlation across participants with TBI; this was absent in controls. Our results suggest that TBI may induce a compensatory coupling between cortical and autonomic systems to sustain cognitive performance despite underlying dysfunction. Positive correlation between pupil dilation and event-related potential suggest a role for arousal dysregulation in subjects with TBI. Our findings provide new evidence for altered EEG-pupil dynamics in TBI and highlight the potential of combining cortical and autonomic measures as a multimodal biomarker for tracking recovery, stratifying injury severity, and guiding individualized rehabilitation strategies.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"706-719"},"PeriodicalIF":1.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031383","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 : 2025-08-25eCollection Date: 2025-01-01DOI: 10.1177/08977151251367345
Sarah E Svirsky, Christopher C Wood, Olivia Raymond, Peyton McIntyre, Hannah Appleton, Chelsea Wagner, Jessica Gill, Ava M Puccio
The sports medicine community and society at large have recognized traumatic brain injury (TBI) as a major public health concern. It is estimated that more than 150 million youths have played football in the United States. As an alternative to blood, sweat is a potential source for protein biomarkers, providing a non-invasive method for objective measurements for head safety guidelines. This pilot study explores sweat as a means of detecting protein biomarkers of brain injury before and after a football season. Participants were football players from an NCAA Division III college (N = 34 pre-season, N = 18 post-season). At pre- and post-season time points, demographic, injury history, and physical activity assessments were conducted, including application of a non-invasive sweat patch for approximately 24 h. Sweat protein biomarkers total-tau, neurofilament light, glial fibrillary acidic protein, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) were measured via immunoarray. Paired and un-paired non-parametric statistical analyses were conducted. Athletes reported little to no concussion injuries from the season and experienced minimal symptoms. There was a significant increase in pre-season GFAP and UCH-L1 protein levels in athletes with a history of TBI compared to those without. Comparing between pre- and post-season, there was an increase in total-tau and UCH-L1 levels. These data suggest that sweat may be a viable biofluid to assess head injury using hallmark TBI biomarkers.
运动医学界和整个社会已经认识到创伤性脑损伤(TBI)是一个主要的公共卫生问题。据估计,在美国有超过1.5亿的年轻人踢过足球。作为血液的替代品,汗液是蛋白质生物标志物的潜在来源,为头部安全指南提供了一种非侵入性的客观测量方法。这项初步研究探讨了汗液作为一种检测足球赛季前后脑损伤蛋白质生物标志物的方法。参与者是来自NCAA三级学院的橄榄球运动员(N = 34, N = 18)。在赛季前和赛季后的时间点,进行了人口统计学、损伤史和身体活动评估,包括使用无创汗液贴片约24小时。通过免疫阵列测量汗液蛋白生物标志物total-tau、神经丝光、胶质纤维酸性蛋白和泛素羧基末端水解酶L1 (UCH-L1)。进行配对和非配对非参数统计分析。运动员在本赛季几乎没有脑震荡,症状也很轻微。与没有TBI病史的运动员相比,有TBI病史的运动员季前GFAP和UCH-L1蛋白水平显著增加。与赛季前和赛季后相比,总tau和UCH-L1水平有所增加。这些数据表明,汗液可能是一种可行的生物体液,可以使用标志性的脑外伤生物标志物来评估头部损伤。
{"title":"Detection of Injury Biomarkers in Sweat of Collegiate Athletes Pre- and Post-Football Season: A Pilot Study.","authors":"Sarah E Svirsky, Christopher C Wood, Olivia Raymond, Peyton McIntyre, Hannah Appleton, Chelsea Wagner, Jessica Gill, Ava M Puccio","doi":"10.1177/08977151251367345","DOIUrl":"10.1177/08977151251367345","url":null,"abstract":"<p><p>The sports medicine community and society at large have recognized traumatic brain injury (TBI) as a major public health concern. It is estimated that more than 150 million youths have played football in the United States. As an alternative to blood, sweat is a potential source for protein biomarkers, providing a non-invasive method for objective measurements for head safety guidelines. This pilot study explores sweat as a means of detecting protein biomarkers of brain injury before and after a football season. Participants were football players from an NCAA Division III college (<i>N</i> = 34 pre-season, <i>N</i> = 18 post-season). At pre- and post-season time points, demographic, injury history, and physical activity assessments were conducted, including application of a non-invasive sweat patch for approximately 24 h. Sweat protein biomarkers total-tau, neurofilament light, glial fibrillary acidic protein, and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) were measured via immunoarray. Paired and un-paired non-parametric statistical analyses were conducted. Athletes reported little to no concussion injuries from the season and experienced minimal symptoms. There was a significant increase in pre-season GFAP and UCH-L1 protein levels in athletes with a history of TBI compared to those without. Comparing between pre- and post-season, there was an increase in total-tau and UCH-L1 levels. These data suggest that sweat may be a viable biofluid to assess head injury using hallmark TBI biomarkers.</p>","PeriodicalId":74300,"journal":{"name":"Neurotrauma reports","volume":"6 1","pages":"700-705"},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016857","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}