Jose Castillo, Jonathan T Mo, Dharminder S Ojla, Nina Yu, Jonathan E Kohler, James P Marcin, Daniel K Nishijima, Kiarash Shahlaie, Marike Zwienenberg
Children with mild traumatic brain injury (TBI) often receive unnecessary imaging studies, hospital admissions, and interhospital transfers leading to avoidable burdens to patients, caregivers, and health systems. The Brain Injury Guidelines (BIG) consider a non-displaced skull fracture as a BIG-2 injury warranting hospitalization. In our clinical experience, patients with simple isolated non-displaced linear skull fractures seldom develop TBI-related complications. In this study, we evaluated the need for hospital admission for simple isolated linear skull fractures by examining the occurrence of clinically important TBI (ci-TBI) and patient outcome. We performed a retrospective study evaluating pediatric TBI admissions from 2018 to 2023 using an institutional registry of TBI patients requiring neurosurgery consultation. Patients included in our study cohort were 17 years and younger at injury, had a head computed tomography with an isolated skull fracture and a Glasgow Coma Scale (GCS) of 14 to 15. We excluded patients who had an intracranial injury (ICI), fractures extending into the skull base, or crossing the sagittal sinus. We reviewed medical records to identify the presence of ci-TBI: ICI resulting in death, neurosurgical intervention, intubation for more than 24 h, or hospital admission for at least 2 nights due to TBI. Repeat imaging studies obtained were reviewed to assess the progression of injury and association with clinical deterioration. Patient outcome was evaluated with the Glasgow Outcome Score Extended (GOS-E) 6 months after injury. Univariable statistics were calculated for continuous variables and 95% confidence intervals were calculated using the Clopper-Pearson exact method for proportions that were very close to 0 or 1 and the Wilson score interval for small-to-moderate proportions. A total of 804 subjects were analyzed, and 402 (50.0%) patients had a BIG-2 injury. A total of 247 of these BIG-2 patients (61.4%) had a simple, non-displaced fracture, and no associated ICI; 198 of these patients (80.2%) were transferred from referring hospitals. In both primary admissions and transfers, no significant injury progression on imaging was noted, no neurosurgical intervention occurred, and no patient had ci-TBI (0/247; 95% CI: 0% to 1.5%). Six-month GOS-E was available in a subset (53.8%) of patients: 98.5% were discharged home and had a favorable outcome (defined as GOS-E 5 to 7). ci-TBI rarely develops in children with simple isolated non-displaced skull fractures indicating that hospital admission and inpatient observation may not be necessary. In the context of the BIG, these patients can be considered for re-classification to a BIG-1 injury, which can reduce interhospital transfer and admission rates following implementation, while maintaining patient safety. A revised BIG classification for pediatric injuries is proposed.
{"title":"Re-Examining the Brain Injury Guidelines in Pediatric Traumatic Brain Injury: Can Simple Isolated Non-Displaced Skull Fractures be Treated as a BIG-1 Injury?","authors":"Jose Castillo, Jonathan T Mo, Dharminder S Ojla, Nina Yu, Jonathan E Kohler, James P Marcin, Daniel K Nishijima, Kiarash Shahlaie, Marike Zwienenberg","doi":"10.1089/neu.2024.0507","DOIUrl":"https://doi.org/10.1089/neu.2024.0507","url":null,"abstract":"<p><p>Children with mild traumatic brain injury (TBI) often receive unnecessary imaging studies, hospital admissions, and interhospital transfers leading to avoidable burdens to patients, caregivers, and health systems. The Brain Injury Guidelines (BIG) consider a non-displaced skull fracture as a BIG-2 injury warranting hospitalization. In our clinical experience, patients with simple isolated non-displaced linear skull fractures seldom develop TBI-related complications. In this study, we evaluated the need for hospital admission for simple isolated linear skull fractures by examining the occurrence of clinically important TBI (ci-TBI) and patient outcome. We performed a retrospective study evaluating pediatric TBI admissions from 2018 to 2023 using an institutional registry of TBI patients requiring neurosurgery consultation. Patients included in our study cohort were 17 years and younger at injury, had a head computed tomography with an isolated skull fracture and a Glasgow Coma Scale (GCS) of 14 to 15. We excluded patients who had an intracranial injury (ICI), fractures extending into the skull base, or crossing the sagittal sinus. We reviewed medical records to identify the presence of ci-TBI: ICI resulting in death, neurosurgical intervention, intubation for more than 24 h, or hospital admission for at least 2 nights due to TBI. Repeat imaging studies obtained were reviewed to assess the progression of injury and association with clinical deterioration. Patient outcome was evaluated with the Glasgow Outcome Score Extended (GOS-E) 6 months after injury. Univariable statistics were calculated for continuous variables and 95% confidence intervals were calculated using the Clopper-Pearson exact method for proportions that were very close to 0 or 1 and the Wilson score interval for small-to-moderate proportions. A total of 804 subjects were analyzed, and 402 (50.0%) patients had a BIG-2 injury. A total of 247 of these BIG-2 patients (61.4%) had a simple, non-displaced fracture, and no associated ICI; 198 of these patients (80.2%) were transferred from referring hospitals. In both primary admissions and transfers, no significant injury progression on imaging was noted, no neurosurgical intervention occurred, and no patient had ci-TBI (0/247; 95% CI: 0% to 1.5%). Six-month GOS-E was available in a subset (53.8%) of patients: 98.5% were discharged home and had a favorable outcome (defined as GOS-E 5 to 7). ci-TBI rarely develops in children with simple isolated non-displaced skull fractures indicating that hospital admission and inpatient observation may not be necessary. In the context of the BIG, these patients can be considered for re-classification to a BIG-1 injury, which can reduce interhospital transfer and admission rates following implementation, while maintaining patient safety. A revised BIG classification for pediatric injuries is proposed.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the Neuropsychiatric Sequelae of Traumatic Brain Injury with Hierarchical Taxonomy of Psychopathology.","authors":"Lucia M Li, David L Brody","doi":"10.1089/neu.2025.0066","DOIUrl":"https://doi.org/10.1089/neu.2025.0066","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thierno Madjou Bah, Sree Neha Yeturu, Nikhil Samudrala, Sarah Feller, Benjamin Bui, Laura Villasana
Traumatic brain injury (TBI) causes transient but robust increases in hippocampal neurogenesis, referred to here as the neurogenic response, which is distinct from baseline or constitutive levels of neurogenesis. The neurogenic response may reflect a restorative process for cognitive recovery from TBI. It is unknown whether the hippocampus remains capable of eliciting another neurogenic response to a subsequent TBI, and whether a potential loss in this endogenous repair mechanism affects cognitive recovery from a repeated TBI. To address this, 2-month-old male and female mice received a sham or mild TBI (mTBI) using the closed-head concussive injury model. Mice received another sham or mTBI procedure 3 weeks later. Mitotic and immature neuronal markers were used to assess the proliferative and neurogenic responses. Neurogenesis-sensitive strategy flexibility was assessed as the functional outcome using the reversal water maze task 1 month after the second procedure. The experimenters collecting the data were blind to the group assignment of each mouse. Proliferation and neurogenesis were higher after a single mTBI but not after a second mTBI. Noteworthy, deficits in the neurogenic response were observed despite normal levels of constitutive neurogenesis. There were no deficits in the radial glia-like stem cell pool, but their proliferative rates to the second mTBI did not increase. The lack of a proliferative response was unlikely due to the injury interval as the dampened responses, which included blunted increases in glial fibrillary acidic protein (GFAP) immunoreactivity, were as pronounced when a longer injury interval (2 month) was used. In contrast to the aberrant neurogenesis observed in more severe TBI models, neurons born after a single or second mTBI had normal dendritic branches, suggesting a beneficial role in hippocampal restoration. In line with this finding, mice with a second mTBI had impairments in neurogenesis-sensitive strategy flexibility, whereas mice with a single mTBI did not. These impairments were specific to strategy flexibility: Mice with two mTBIs had intact reference memory in the water maze. In conclusion, our findings demonstrate that a loss in the neurogenic response to a subsequent mTBI occurs weeks after a single mTBI and that this deficit is not transient. A loss in this endogenous repair mechanism could in part contribute to worse cognitive recovery after a repeated mTBI. Although our data may indicate that the absence of the neurogenic response could include impairments in the proliferative capacity of the radial glia-like stem cells, an alternative explanation could involve adaptative responses that alter the injury severity of the second mTBI. These possible explanations need to be validated in order to move forward with therapeutic strategies to reengage the neurogenic response.
{"title":"Absence of the Neurogenic Response to a Repeated Concussive-Like Injury and Associated Deficits in Strategy Flexibility.","authors":"Thierno Madjou Bah, Sree Neha Yeturu, Nikhil Samudrala, Sarah Feller, Benjamin Bui, Laura Villasana","doi":"10.1089/neu.2024.0405","DOIUrl":"https://doi.org/10.1089/neu.2024.0405","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) causes transient but robust increases in hippocampal neurogenesis, referred to here as the neurogenic response, which is <i>distinct</i> from baseline or constitutive levels of neurogenesis. The neurogenic response may reflect a restorative process for cognitive recovery from TBI. It is unknown whether the hippocampus remains capable of eliciting another neurogenic response to a subsequent TBI, and whether a potential loss in this endogenous repair mechanism affects cognitive recovery from a repeated TBI. To address this, 2-month-old male and female mice received a sham or mild TBI (mTBI) using the closed-head concussive injury model. Mice received another sham or mTBI procedure 3 weeks later. Mitotic and immature neuronal markers were used to assess the proliferative and neurogenic responses. Neurogenesis-sensitive strategy flexibility was assessed as the functional outcome using the reversal water maze task 1 month after the second procedure. The experimenters collecting the data were blind to the group assignment of each mouse. Proliferation and neurogenesis were higher after a single mTBI but not after a second mTBI. Noteworthy, deficits in the neurogenic response were observed despite normal levels of constitutive neurogenesis. There were no deficits in the radial glia-like stem cell pool, but their proliferative rates to the second mTBI did not increase. The lack of a proliferative response was unlikely due to the injury interval as the dampened responses, which included blunted increases in glial fibrillary acidic protein (GFAP) immunoreactivity, were as pronounced when a longer injury interval (2 month) was used. In contrast to the aberrant neurogenesis observed in more severe TBI models, neurons born after a single or second mTBI had normal dendritic branches, suggesting a beneficial role in hippocampal restoration. In line with this finding, mice with a second mTBI had impairments in neurogenesis-sensitive strategy flexibility, whereas mice with a single mTBI did not. These impairments were specific to strategy flexibility: Mice with two mTBIs had intact reference memory in the water maze. In conclusion, our findings demonstrate that a loss in the neurogenic response to a subsequent mTBI occurs weeks after a single mTBI and that this deficit is not transient. A loss in this endogenous repair mechanism could in part contribute to worse cognitive recovery after a repeated mTBI. Although our data may indicate that the absence of the neurogenic response could include impairments in the proliferative capacity of the radial glia-like stem cells, an alternative explanation could involve adaptative responses that alter the injury severity of the second mTBI. These possible explanations need to be validated in order to move forward with therapeutic strategies to reengage the neurogenic response.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Josephina Rau, Rose Joseph, Lara Weise, Jessica Bryan, Jad Wardeh, Alekya Konda, Landon Duplessis, Michelle A Hook
Previous studies have shown that administration of high doses of morphine in the acute phase of spinal cord injury (SCI) significantly undermines locomotor recovery and increases symptoms of chronic pain in a rat spinal contusion model. Similarly, SCI patients treated with high doses of opioid for the first 24 h postinjury have increased symptoms of chronic pain 1 year later. Whether these adverse effects are driven by morphine only or all opioids compromise recovery after SCI, however, is unknown. Based on our previous findings we hypothesized that activation of the kappa opioid receptor (KOR) is key in the morphine-induced attenuation of locomotor recovery after SCI. Thus, we posited that opioids that engage KOR-mediated signaling pathways (morphine, oxycodone) would undermine recovery, and clinically relevant opioids with less KOR activity (fentanyl and buprenorphine) would not. To test this, we compared the effects of the clinically relevant opioids on locomotor recovery and pain in a male rat spinal contusion model. Rats were given a moderate spinal contusion injury followed by 7 days of intravenous morphine, oxycodone, fentanyl, buprenorphine, or saline, and recovery was assessed for 28 days. All opioids produced analgesia on tests of thermal, mechanical, and incremented shock reactivity. However, tolerance developed rapidly with buprenorphine administration, particularly with daily administrations of 5 morphine milligram equivalent (MME) buprenorphine. Opioid-induced hyperalgesia (OIH) also developed across days following administration of higher doses (10 MME, 20 MME) of morphine and oxycodone. Fentanyl and buprenorphine did not produce OIH. Contrary to our hypothesis, however, we found that high doses of all opioids reduced recovery of locomotor function. Unlike the other opioids, the effects of buprenorphine on locomotor recovery appeared transient, but it also produced chronic pain. Morphine, oxycodone, and buprenorphine decreased reactivity thresholds on tests of mechanical and incremented shock stimulation. In sum, all opioids undermined long-term recovery in the rat model. Further interrogation of the molecular mechanisms driving the adverse effects is essential. This study provides critical insight into pain management strategies in the acute phase of SCI and potential long-term consequences of early opioid administration.
{"title":"Acute Opioid Administration Undermines Recovery after SCI: Adverse Effects Are Not Restricted to Morphine.","authors":"Josephina Rau, Rose Joseph, Lara Weise, Jessica Bryan, Jad Wardeh, Alekya Konda, Landon Duplessis, Michelle A Hook","doi":"10.1089/neu.2024.0375","DOIUrl":"https://doi.org/10.1089/neu.2024.0375","url":null,"abstract":"<p><p>Previous studies have shown that administration of high doses of morphine in the acute phase of spinal cord injury (SCI) significantly undermines locomotor recovery and increases symptoms of chronic pain in a rat spinal contusion model. Similarly, SCI patients treated with high doses of opioid for the first 24 h postinjury have increased symptoms of chronic pain 1 year later. Whether these adverse effects are driven by morphine only or all opioids compromise recovery after SCI, however, is unknown. Based on our previous findings we hypothesized that activation of the kappa opioid receptor (KOR) is key in the morphine-induced attenuation of locomotor recovery after SCI. Thus, we posited that opioids that engage KOR-mediated signaling pathways (morphine, oxycodone) would undermine recovery, and clinically relevant opioids with less KOR activity (fentanyl and buprenorphine) would not. To test this, we compared the effects of the clinically relevant opioids on locomotor recovery and pain in a male rat spinal contusion model. Rats were given a moderate spinal contusion injury followed by 7 days of intravenous morphine, oxycodone, fentanyl, buprenorphine, or saline, and recovery was assessed for 28 days. All opioids produced analgesia on tests of thermal, mechanical, and incremented shock reactivity. However, tolerance developed rapidly with buprenorphine administration, particularly with daily administrations of 5 morphine milligram equivalent (MME) buprenorphine. Opioid-induced hyperalgesia (OIH) also developed across days following administration of higher doses (10 MME, 20 MME) of morphine and oxycodone. Fentanyl and buprenorphine did not produce OIH. Contrary to our hypothesis, however, we found that high doses of all opioids reduced recovery of locomotor function. Unlike the other opioids, the effects of buprenorphine on locomotor recovery appeared transient, but it also produced chronic pain. Morphine, oxycodone, and buprenorphine decreased reactivity thresholds on tests of mechanical and incremented shock stimulation. In sum, all opioids undermined long-term recovery in the rat model. Further interrogation of the molecular mechanisms driving the adverse effects is essential. This study provides critical insight into pain management strategies in the acute phase of SCI and potential long-term consequences of early opioid administration.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Mansour, Elena Badillo, Ronald Alvarado-Dyer, Olga Pasternak, Huy Tram N Nguyen, Farima Fakhri, Elaine Lo, Joseph Wilson, Mark DeGuzman, Molly Lawrence, John Nugent, Harsh Desai, William Roth, Jordan Fuhrman, Peleg Horowitz, Paramita Das, Andrii Sirko, Tracey Fan, Elizabeth Carroll, Susan Rowell, Christos Lazaridis, Maryellen Giger, Fernando D Goldenberg
<p><p>To introduce the UChicago PBI Imaging score, a novel characterization of imaging features using head computed tomography (HCT) in patients with gunshot wounds to the head (GSWH) resulting in penetrating brain injury (PBI) and to quantify the association with mortality. We retrospectively collected and analyzed data from 230 patients with GSWH admitted to our Level 1 trauma center between May 1, 2018, and October 31, 2023. HCT images obtained on hospital arrival were evaluated for predefined imaging features by two blinded readers and arbitrated, when needed, by a third. The average contribution of each radiological feature to mortality at hospital discharge was assessed using a SuperLearner ensemble model trained on ∼77% of the cohort. Each feature's contribution was scaled to ensure the additive final score per patient ranged between 0 and 100. The HCT features predicting in-hospital mortality, ranked from highest to lowest importance, were transhemispheric projectile below the level of the third ventricle (18 [16.8, 19.9]), presence of blood in the lateral ventricles (ventricles casted) (18[16.8, 19.6]), brainstem involvement (14 [12.7, 15.1]), transhemispheric projectile above the level of the third ventricle (11 [9.7, 11.6]), presence of any amount of blood in the ambient cistern (9[8.2, 10]), presence of any amount of blood in the lateral ventricles (9 [7.9, 9.8]), cerebellar involvement (9 [7.9, 9.5]), any evidence of ventricular effacement (4 [3.4, 4.6]), midline shift (MLS) >0 mm (4 [3.4, 4.4]), perforating injury (3 [2.4, 3.2]), and presence of an intracerebral hematoma (ICH) >20 mm in the largest diameter (2 [1.4, 1.9]). The UChicago PBI Imaging score showed a strong performance, achieving an area under the curve (AUC) of 0.86 (95% CI: [0.77, 0.96]) on a test set of 56 patients who were not included in model training. This indicates better prediction accuracy compared to both the Rotterdam score (AUC 0.8, 95% CI: [0.68, 0.96]) and the Marshall score (AUC 0.66, 95% CI: [0.52, 0.81]). Our model performed particularly well for patients with a Glasgow Coma Scale (GCS) score between 5 and 9. In this range, our model's performance (AUC 0.86) remained stable, while the Rotterdam and Marshall Scores showed notably lower predictive accuracy, with AUCs of 0.61 and 0.52, respectively. A dedicated evaluation of GSWH HCT reveals an association between disease burden, as quantified by unique features not native to blunt TBI imaging models, and mortality. Specifically, transhemispheric injury below the level of the third ventricle along with blood-casting bilateral ventricles and brainstem involvement was highly associated with mortality. The model is optimized for intermediate GCS scores where greater prognostic uncertainty exists. This study parallels efforts to refine TBI classification, underscoring the necessity for precise imaging-based classification in PBI to identify imaging biomarkers and ultimately enhance prognostication and targeted
{"title":"Brain Imaging Features in Patients with Gunshot Wounds to the Head.","authors":"Ali Mansour, Elena Badillo, Ronald Alvarado-Dyer, Olga Pasternak, Huy Tram N Nguyen, Farima Fakhri, Elaine Lo, Joseph Wilson, Mark DeGuzman, Molly Lawrence, John Nugent, Harsh Desai, William Roth, Jordan Fuhrman, Peleg Horowitz, Paramita Das, Andrii Sirko, Tracey Fan, Elizabeth Carroll, Susan Rowell, Christos Lazaridis, Maryellen Giger, Fernando D Goldenberg","doi":"10.1089/neu.2024.0464","DOIUrl":"https://doi.org/10.1089/neu.2024.0464","url":null,"abstract":"<p><p>To introduce the UChicago PBI Imaging score, a novel characterization of imaging features using head computed tomography (HCT) in patients with gunshot wounds to the head (GSWH) resulting in penetrating brain injury (PBI) and to quantify the association with mortality. We retrospectively collected and analyzed data from 230 patients with GSWH admitted to our Level 1 trauma center between May 1, 2018, and October 31, 2023. HCT images obtained on hospital arrival were evaluated for predefined imaging features by two blinded readers and arbitrated, when needed, by a third. The average contribution of each radiological feature to mortality at hospital discharge was assessed using a SuperLearner ensemble model trained on ∼77% of the cohort. Each feature's contribution was scaled to ensure the additive final score per patient ranged between 0 and 100. The HCT features predicting in-hospital mortality, ranked from highest to lowest importance, were transhemispheric projectile below the level of the third ventricle (18 [16.8, 19.9]), presence of blood in the lateral ventricles (ventricles casted) (18[16.8, 19.6]), brainstem involvement (14 [12.7, 15.1]), transhemispheric projectile above the level of the third ventricle (11 [9.7, 11.6]), presence of any amount of blood in the ambient cistern (9[8.2, 10]), presence of any amount of blood in the lateral ventricles (9 [7.9, 9.8]), cerebellar involvement (9 [7.9, 9.5]), any evidence of ventricular effacement (4 [3.4, 4.6]), midline shift (MLS) >0 mm (4 [3.4, 4.4]), perforating injury (3 [2.4, 3.2]), and presence of an intracerebral hematoma (ICH) >20 mm in the largest diameter (2 [1.4, 1.9]). The UChicago PBI Imaging score showed a strong performance, achieving an area under the curve (AUC) of 0.86 (95% CI: [0.77, 0.96]) on a test set of 56 patients who were not included in model training. This indicates better prediction accuracy compared to both the Rotterdam score (AUC 0.8, 95% CI: [0.68, 0.96]) and the Marshall score (AUC 0.66, 95% CI: [0.52, 0.81]). Our model performed particularly well for patients with a Glasgow Coma Scale (GCS) score between 5 and 9. In this range, our model's performance (AUC 0.86) remained stable, while the Rotterdam and Marshall Scores showed notably lower predictive accuracy, with AUCs of 0.61 and 0.52, respectively. A dedicated evaluation of GSWH HCT reveals an association between disease burden, as quantified by unique features not native to blunt TBI imaging models, and mortality. Specifically, transhemispheric injury below the level of the third ventricle along with blood-casting bilateral ventricles and brainstem involvement was highly associated with mortality. The model is optimized for intermediate GCS scores where greater prognostic uncertainty exists. This study parallels efforts to refine TBI classification, underscoring the necessity for precise imaging-based classification in PBI to identify imaging biomarkers and ultimately enhance prognostication and targeted","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-10-25DOI: 10.1089/neu.2023.0592
Lukas Grassner, Iris Leister, Florian Högel, Ludwig Sanktjohanser, Matthias Vogel, Orpheus Mach, Doris Maier, Andreas Grillhösl
Magnetic resonance imaging (MRI) remains the gold standard for evaluating spinal cord tissue damage after spinal cord injury (SCI). Several MRI findings may have some prognostic potential, but their evolution over time, especially from the subacute to the chronic phase has not been studied extensively. We performed a prospective observational longitudinal study exploring the evolution of MRI parameters from the subacute to chronic phase after human traumatic cervical SCI. The study, conducted between 2016 and 2021, involved standardized neurological examinations and MRI scans 1 month, 3 months, and 1 year after SCI. The study cohort comprises 52 patients with cervical SCI. Patients were classified into AIS grades (American Spinal Injury Association Impairment Scale), and neurological recovery was assessed using the Integrated Neurological Change Score. The MRI protocol included various routine sequences, allowing the evaluation of established parameters such as intramedullary hemorrhage, lesion dimensions, maximum spinal cord compression, and various grading scales. The persistence of intramedullary hemorrhage one month after injury was associated with worse lower extremity motor scores and pinprick values after 3 months, and also in the chronic phase. In addition, dorsal column T2-weighted hyperintensities detected 3 months post-injury and in the chronic phase were related to lower pinprick sensory scores. The basic score and Sagittal Grade at 1 month were predictive for motor function 3 months after SCI and for neurological recovery between 1 and 3 months after injury. The study contributes valuable insights into the utility of routine MRI sequences for evaluating traumatic cervical SCI during the subacute to chronic phase. The identified MRI parameters and scores offer prognostic information and could support clinical decision-making.
{"title":"Magnetic Resonance Imaging Parameters in the Subacute Phase after Traumatic Cervical Spinal Cord Injury: A Prospective, Observational Longitudinal Study. Part 1: Conventional Imaging Characteristics.","authors":"Lukas Grassner, Iris Leister, Florian Högel, Ludwig Sanktjohanser, Matthias Vogel, Orpheus Mach, Doris Maier, Andreas Grillhösl","doi":"10.1089/neu.2023.0592","DOIUrl":"10.1089/neu.2023.0592","url":null,"abstract":"<p><p>Magnetic resonance imaging (MRI) remains the gold standard for evaluating spinal cord tissue damage after spinal cord injury (SCI). Several MRI findings may have some prognostic potential, but their evolution over time, especially from the subacute to the chronic phase has not been studied extensively. We performed a prospective observational longitudinal study exploring the evolution of MRI parameters from the subacute to chronic phase after human traumatic cervical SCI. The study, conducted between 2016 and 2021, involved standardized neurological examinations and MRI scans 1 month, 3 months, and 1 year after SCI. The study cohort comprises 52 patients with cervical SCI. Patients were classified into AIS grades (American Spinal Injury Association Impairment Scale), and neurological recovery was assessed using the Integrated Neurological Change Score. The MRI protocol included various routine sequences, allowing the evaluation of established parameters such as intramedullary hemorrhage, lesion dimensions, maximum spinal cord compression, and various grading scales. The persistence of intramedullary hemorrhage one month after injury was associated with worse lower extremity motor scores and pinprick values after 3 months, and also in the chronic phase. In addition, dorsal column T2-weighted hyperintensities detected 3 months post-injury and in the chronic phase were related to lower pinprick sensory scores. The basic score and Sagittal Grade at 1 month were predictive for motor function 3 months after SCI and for neurological recovery between 1 and 3 months after injury. The study contributes valuable insights into the utility of routine MRI sequences for evaluating traumatic cervical SCI during the subacute to chronic phase. The identified MRI parameters and scores offer prognostic information and could support clinical decision-making.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"307-315"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-11-26DOI: 10.1089/neu.2024.0233
Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Hauser, Raluca Niesner, Frank L Heppner, Michael G Fehlings, Peter Vajkoczy
<p><p>Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal <i>in vivo</i> two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54% of existing vessels regaining functional perfusion. Longitudinal <i>in vivo</i> 2PM visualized the progressive degeneration of initially preserved spinal cord axons in the peri-traumatic zone after SCI while displaying a rarefication of functionally perfused vessels up to two weeks after injury. Neurobehavioral recovery started after one week but remained impaired over the whole observation period of four weeks after SCI. With this study, a therapeutic window to address the impaired NVU starting from the first days to two weeks after SCI is identified. A number of lines of evidence including <i>in vivo</i> 2PM, assessment of NVU integrity, and neurobehavioral assessments point to the critical nature of targeting the NVU to enhance axonal preservation and regeneration after SCI. Continuous multifactorial therapy applications targeting the integrity of the NVU over the identified therapeutic window of opportunity appears promising to ameliorate functional vessel perseverance and the spinal cord's rege
{"title":"Identification of a Therapeutic Window for Neurovascular Unit Repair after Experimental Spinal Cord Injury.","authors":"Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Hauser, Raluca Niesner, Frank L Heppner, Michael G Fehlings, Peter Vajkoczy","doi":"10.1089/neu.2024.0233","DOIUrl":"10.1089/neu.2024.0233","url":null,"abstract":"<p><p>Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal <i>in vivo</i> two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54% of existing vessels regaining functional perfusion. Longitudinal <i>in vivo</i> 2PM visualized the progressive degeneration of initially preserved spinal cord axons in the peri-traumatic zone after SCI while displaying a rarefication of functionally perfused vessels up to two weeks after injury. Neurobehavioral recovery started after one week but remained impaired over the whole observation period of four weeks after SCI. With this study, a therapeutic window to address the impaired NVU starting from the first days to two weeks after SCI is identified. A number of lines of evidence including <i>in vivo</i> 2PM, assessment of NVU integrity, and neurobehavioral assessments point to the critical nature of targeting the NVU to enhance axonal preservation and regeneration after SCI. Continuous multifactorial therapy applications targeting the integrity of the NVU over the identified therapeutic window of opportunity appears promising to ameliorate functional vessel perseverance and the spinal cord's rege","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"212-228"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2025-01-06DOI: 10.1089/neu.2024.0308
Femke Streijger, Aysha Allard Brown, Lukas Grassner, Kyoung-Tae Kim, Michael Rizzuto, Kitty So, Neda Manouchehri, Megan Webster, Shera Fisk, Mypinder Sekhon, Donald Griesdale, Brian Kwon
Recent studies have reported that monitoring spinal cord perfusion pressure (SCPP) using a pressure probe to measure "intraspinal pressure" (ISP) within the subdural space at the injury site may improve the hemodynamic management of acute spinal cord injury (SCI) patients. This study aimed to investigate, within a pig model of SCI, the relationship between the ISP measured within the subdural space and the "spinal cord pressure" (SCP) measured within the spinal cord itself. Specifically, we sought to characterize the changes to ISP and SCP over time, both rostral and caudal to the injury epicenter, and in relation to native spinal cord morphometry. Female Yucatan mini-pigs were subjected to a T10 contusion-compression injury. Pressure probes were inserted inside the spinal cord parenchyma for SCP and within the subdural space for ISP, 5-mm rostral, and caudal from the injury site. SCP and ISP were then measured over an 8-hour period post-SCI. Ultrasound images were taken before and after SCI to monitor changes in spinal cord morphometry in the early hours post-injury. Spinal cord swelling was observed in all cases; however, only half of the animals exhibited increased SCP and ISP rostrally. In these, a gradient across the injury site was observed in the ISP measured rostrally and caudally when swelling of the spinal cord filled the subdural space, and the cord was seen to be abutting against the dura. The remaining animals showed a negligible increase in ISP and SCP (<+1 mmHg). The variation in pressure response was influenced heavily by the size of the subdural space surrounding the cord. In cases where we could establish an "optimal SCPP" based on the autoregulatory function of the spinal cord, a discernible variance of approximately 10 mmHg was detected between the values derived from ISP versus SCP. These results suggest that changes in ISP and SCP after SCI are influenced by native spinal cord morphometry and that the location of measurement is important to consider, particularly in situations where the swelling of the injured cord results in an occlusion of the cerebrospinal fluid (CSF) flow through the subdural space.
{"title":"Understanding the Measurement of Pressure Within the Spinal Cord to Optimize Spinal Cord Perfusion Pressure Using a Porcine Model of Spinal Cord Injury.","authors":"Femke Streijger, Aysha Allard Brown, Lukas Grassner, Kyoung-Tae Kim, Michael Rizzuto, Kitty So, Neda Manouchehri, Megan Webster, Shera Fisk, Mypinder Sekhon, Donald Griesdale, Brian Kwon","doi":"10.1089/neu.2024.0308","DOIUrl":"https://doi.org/10.1089/neu.2024.0308","url":null,"abstract":"<p><p>Recent studies have reported that monitoring spinal cord perfusion pressure (SCPP) using a pressure probe to measure \"intraspinal pressure\" (ISP) within the subdural space at the injury site may improve the hemodynamic management of acute spinal cord injury (SCI) patients. This study aimed to investigate, within a pig model of SCI, the relationship between the ISP measured within the subdural space and the \"spinal cord pressure\" (SCP) measured within the spinal cord itself. Specifically, we sought to characterize the changes to ISP and SCP over time, both rostral and caudal to the injury epicenter, and in relation to native spinal cord morphometry. Female Yucatan mini-pigs were subjected to a T10 contusion-compression injury. Pressure probes were inserted inside the spinal cord parenchyma for SCP and within the subdural space for ISP, 5-mm rostral, and caudal from the injury site. SCP and ISP were then measured over an 8-hour period post-SCI. Ultrasound images were taken before and after SCI to monitor changes in spinal cord morphometry in the early hours post-injury. Spinal cord swelling was observed in all cases; however, only half of the animals exhibited increased SCP and ISP rostrally. In these, a gradient across the injury site was observed in the ISP measured rostrally and caudally when swelling of the spinal cord filled the subdural space, and the cord was seen to be abutting against the dura. The remaining animals showed a negligible increase in ISP and SCP (<+1 mmHg). The variation in pressure response was influenced heavily by the size of the subdural space surrounding the cord. In cases where we could establish an \"optimal SCPP\" based on the autoregulatory function of the spinal cord, a discernible variance of approximately 10 mmHg was detected between the values derived from ISP versus SCP. These results suggest that changes in ISP and SCP after SCI are influenced by native spinal cord morphometry and that the location of measurement is important to consider, particularly in situations where the swelling of the injured cord results in an occlusion of the cerebrospinal fluid (CSF) flow through the subdural space.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":"42 3-4","pages":"165-181"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-11-07DOI: 10.1089/neu.2024.0125
Ahmad Essa, Armaan K Malhotra, Husain Shakil, Jetan Badhiwala, Avery B Nathens, Eva Y Yuan, Yingshi He, Andrew S Jack, Francois Mathieu, Jefferson R Wilson, Christopher D Witiw
This study aims to estimate real-world clinical practice trends in time to surgery following thoracolumbar spinal cord injury (SCI) in trauma centers across North America over the last decade (2010-2020). A multi-center retrospective observational study was conducted using Trauma Quality Improvement Program data from 2010 to 2020. All surgically treated patients with thoracic and lumbar SCI were included. Descriptive plots and a multivariable Poisson regression model with time to spine surgery as the primary outcome were constructed. This study included 4350 adult patients with complete SCI surgically treated across 449 trauma centers. Within this group, 3978 (91.4%) patients were diagnosed with thoracic SCI and 372 (8.6%) patients were diagnosed with lumbar SCI. The overall mean time to surgery was 31.6 h (±34.1). Early surgery (≤24 h) was performed in 2599 patients (59.7%). An estimated annual reduction of 1.6 h in time to surgery was demonstrated over the study period, starting initially at a mean of 47.6 h (±40.6) in 2010, and reaching a mean of 25.3 h (±30) in 2020. Multivariable Poisson regression adjusting for patient, injury, and institution confounders, demonstrated a significant decrease in time to surgery by 5% per year over the study period (incidence rate ratios [IRR] = 0.95, 95% confidence interval [CI]: 0.93-0.96). Moreover, in a secondary analysis including 3270 patients with incomplete thoracolumbar SCI, a comparable significant annual reduction in time to surgery was demonstrated (IRR = 0.93, 95% CI: 0.91-0.94). This study provides real-world data on practice pattern trends with respect to time to spine surgery following traumatic thoracolumbar SCI. Over the years from 2010 to 2020, we found a significant reduction in time to surgery across trauma centers in North America.
{"title":"Evolution of Real-World Clinical Practice in Time to Surgery Following Thoracolumbar Spinal Cord Injury: An Observational Study of North American Trauma Centers from 2010 to 2020.","authors":"Ahmad Essa, Armaan K Malhotra, Husain Shakil, Jetan Badhiwala, Avery B Nathens, Eva Y Yuan, Yingshi He, Andrew S Jack, Francois Mathieu, Jefferson R Wilson, Christopher D Witiw","doi":"10.1089/neu.2024.0125","DOIUrl":"10.1089/neu.2024.0125","url":null,"abstract":"<p><p>This study aims to estimate real-world clinical practice trends in time to surgery following thoracolumbar spinal cord injury (SCI) in trauma centers across North America over the last decade (2010-2020). A multi-center retrospective observational study was conducted using Trauma Quality Improvement Program data from 2010 to 2020. All surgically treated patients with thoracic and lumbar SCI were included. Descriptive plots and a multivariable Poisson regression model with time to spine surgery as the primary outcome were constructed. This study included 4350 adult patients with complete SCI surgically treated across 449 trauma centers. Within this group, 3978 (91.4%) patients were diagnosed with thoracic SCI and 372 (8.6%) patients were diagnosed with lumbar SCI. The overall mean time to surgery was 31.6 h (±34.1). Early surgery (≤24 h) was performed in 2599 patients (59.7%). An estimated annual reduction of 1.6 h in time to surgery was demonstrated over the study period, starting initially at a mean of 47.6 h (±40.6) in 2010, and reaching a mean of 25.3 h (±30) in 2020. Multivariable Poisson regression adjusting for patient, injury, and institution confounders, demonstrated a significant decrease in time to surgery by 5% per year over the study period (incidence rate ratios [IRR] = 0.95, 95% confidence interval [CI]: 0.93-0.96). Moreover, in a secondary analysis including 3270 patients with incomplete thoracolumbar SCI, a comparable significant annual reduction in time to surgery was demonstrated (IRR = 0.93, 95% CI: 0.91-0.94). This study provides real-world data on practice pattern trends with respect to time to spine surgery following traumatic thoracolumbar SCI. Over the years from 2010 to 2020, we found a significant reduction in time to surgery across trauma centers in North America.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"262-271"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-10-22DOI: 10.1089/neu.2024.0267
Anna Lebret, Sabina Frese, Simon Lévy, Armin Curt, Virginie Callot, Patrick Freund, Maryam Seif
Spinal cord injury (SCI) results in intramedullary microvasculature disruption and blood perfusion deficit at and remote from the injury site. However, the relationship between remote vascular impairment and functional recovery remains understudied. We characterized perfusion impairment in vivo, rostral to the injury, using magnetic resonance imaging (MRI), and investigated its association with lesion extent and impairment following SCI. Twenty-one patients with chronic cervical SCI and 39 healthy controls (HC) underwent a high-resolution MRI protocol, including intravoxel incoherent motion (IVIM) and T2*-weighted MRI covering C1-C3 cervical levels, as well as T2-weighted MRI to determine lesion volumes. IVIM matrices (i.e., blood volume fraction, velocity, flow indices, and diffusion) and cord structural characteristics were calculated to assess perfusion changes and cervical cord atrophy, respectively. Patients with SCI additionally underwent a standard clinical examination protocol to assess functional impairment. Correlation analysis was used to investigate associations between IVIM parameters with lesion volume and sensorimotor dysfunction. Cervical cord white and gray matter were atrophied (27.60% and 21.10%, p < 0.0001, respectively) above the cervical cord injury, accompanied by a lower blood volume fraction (-22.05%, p < 0.001) and a higher blood velocity-related index (+38.72%, p < 0.0001) in patients with SCI compared with HC. Crucially, gray matter remote perfusion deficit correlated with larger lesion volumes and clinical impairment. This study shows clinically eloquent perfusion deficit rostral to a SCI, its magnitude driven by injury severity. These findings indicate trauma-induced widespread microvascular alterations beyond the injury site. Perfusion MRI matrices in the spinal cord hold promise as biomarkers for monitoring treatment effects and dynamic changes in microvasculature integrity following SCI.
{"title":"Spinal Cord Blood Perfusion Deficit is Associated with Clinical Impairment after Spinal Cord Injury.","authors":"Anna Lebret, Sabina Frese, Simon Lévy, Armin Curt, Virginie Callot, Patrick Freund, Maryam Seif","doi":"10.1089/neu.2024.0267","DOIUrl":"10.1089/neu.2024.0267","url":null,"abstract":"<p><p>Spinal cord injury (SCI) results in intramedullary microvasculature disruption and blood perfusion deficit at and remote from the injury site. However, the relationship between remote vascular impairment and functional recovery remains understudied. We characterized perfusion impairment <i>in vivo</i>, rostral to the injury, using magnetic resonance imaging (MRI), and investigated its association with lesion extent and impairment following SCI. Twenty-one patients with chronic cervical SCI and 39 healthy controls (HC) underwent a high-resolution MRI protocol, including intravoxel incoherent motion (IVIM) and T2*-weighted MRI covering C1-C3 cervical levels, as well as T2-weighted MRI to determine lesion volumes. IVIM matrices (i.e., blood volume fraction, velocity, flow indices, and diffusion) and cord structural characteristics were calculated to assess perfusion changes and cervical cord atrophy, respectively. Patients with SCI additionally underwent a standard clinical examination protocol to assess functional impairment. Correlation analysis was used to investigate associations between IVIM parameters with lesion volume and sensorimotor dysfunction. Cervical cord white and gray matter were atrophied (27.60% and 21.10%, <i>p</i> < 0.0001, respectively) above the cervical cord injury, accompanied by a lower blood volume fraction (-22.05%, <i>p</i> < 0.001) and a higher blood velocity-related index (+38.72%, <i>p</i> < 0.0001) in patients with SCI compared with HC. Crucially, gray matter remote perfusion deficit correlated with larger lesion volumes and clinical impairment. This study shows clinically eloquent perfusion deficit rostral to a SCI, its magnitude driven by injury severity. These findings indicate trauma-induced widespread microvascular alterations beyond the injury site. Perfusion MRI matrices in the spinal cord hold promise as biomarkers for monitoring treatment effects and dynamic changes in microvasculature integrity following SCI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"280-291"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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