Journal of neurotrauma最新文献

{"title":"Human Neural Stem Cell Therapy for Traumatic Brain Injury-A Systematic Review of Pre-Clinical Studies.","authors":"Sarah L Schantz, Kylee J Duberstein, Erin E Kaiser, Franklin D West","doi":"10.1089/neu.2024.0544","DOIUrl":"10.1089/neu.2024.0544","url":null,"abstract":"<p><p>Human neural stem cells (hNSCs) possess significant therapeutic potential for the treatment of traumatic brain injury (TBI), a leading cause of global death and disability. Recent pre-clinical studies have shown that hNSCs reduce tissue damage and promote functional recovery through neuroprotective and regenerative signaling and cell replacement. Yet the overall efficacy of hNSCs for TBI indications remains unclear. Therefore, this systematic review aims to evaluate hNSC interventions compared with controls in pre-clinical TBI models. Through this process, variations in hNSC administration protocols were consolidated, and key knowledge gaps were identified. Meta-analysis was applied to primary outcomes of lesion volume, Morris Water Maze (MWM) performance, modified Neurological Severity Scores (mNSS), and the rotarod task. Narrative review of secondary outcomes included hNSC survival and differentiation, endogenous neuron survival, axonal injury, and inflammation. Overall, hNSC intervention reduced lesion volume, enhanced MWM performance, and led to trending decreases in acute and chronic neurological deficits at acute and chronic time points. These results suggest hNSCs demonstrate clear efficacy in pre-clinical TBI models. However, further studies are needed to address key questions regarding optimal hNSC administration (e.g., dosing, treatment window) and underlying mechanisms of action prior to progressing to human clinical trials.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"668-688"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032930","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":"Objective Turning Measures Improve Diagnostic Accuracy and Relate to Simulated Real-World Mobility/Combat Readiness in Chronic Mild Traumatic Brain Injury.","authors":"Peter C Fino, Prokopios Antonellis, Lucy Parrington, Margaret M Weightman, Leland E Dibble, Mark E Lester, Carrie W Hoppes, Laurie A King","doi":"10.1089/neu.2024.0127","DOIUrl":"https://doi.org/10.1089/neu.2024.0127","url":null,"abstract":"<p><p>Balance and mobility problems are common consequences after mild traumatic brain injury (mTBI). However, turning and nonstraight gait, which are required for daily living, are rarely assessed in clinical tests of function after mTBI. Therefore, the primary goals of this study were to assess (1) the added value of clinic-based turning task variables, obtained using wearable sensors, over standard general assessments of mobility, and (2) assess the associations between general assessments of mobility, objective variables from clinic-based turning tasks, and ecologically relevant functional tasks. Fifty-three civilians with mTBI, 57 healthy civilian controls, and 36 healthy active-duty military controls participated across three sites. Participants were tested in a single session that encompassed self-reported questionnaires including demographic information and balance and mobility testing including the use of wearable sensors. Lasso regression models and the area under the receiver-operator characteristic curve (AUC) assessed diagnostic accuracy. Partial correlation coefficients assessed the relationship between each variable with ecologically relevant functional tasks. Multivariate models revealed high diagnostic accuracy, with an AUC of 0.92, using multiple variables from instrumented clinic-based turning tasks. The complex turning course (CTC) yielded the highest multivariate AUC (95% confidence interval [CI]) of 0.90 (0.84, 0.95) for a single task, and the average lap time from the CTC had the highest univariate AUC (95% CI) of 0.70 (0.58, 0.78). Turning variables provided added value, indicated by higher AUCs, over standard general assessments of mobility. Turning variables had strong associations with ecologically relevant functional tasks and outperformed general assessments of mobility, though there were slight differences in the relationship based on civilian versus military population. Clinic-based turning tasks, especially the CTC and modified Illinois Agility Test (mIAT), have high diagnostic accuracy, strong associations with ecologically relevant functional tasks, and require relatively short time(s) to complete. Compared to general assessments of mobility, clinic-based turning tasks may be more ecologically relevant to daily function. Future work should continue to examine the CTC and mIAT alongside other promising tools for return-to-activity assessments.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710032","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":"Three-Dimensional Design and Implementation of a Dual Compartment Imaging Chamber to Assess Effects of Hypertonic Saline on Periaxonal Swelling and Axonal Spheroid Formation Following Cervical Contusive Spinal Cord Injury in Real Time.","authors":"Francisco Cortez-Thomas, Spencer O Ames, Sarayu Alli, Emma Jones, David P Stirling","doi":"10.1089/neu.2024.0454","DOIUrl":"https://doi.org/10.1089/neu.2024.0454","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Contusive and compressive spinal cord injury (SCI) induces pathological changes to spinal cord white matter (WM) including periaxonal swelling and resultant disruption of the axomyelinic interface, axonal swelling/spheroid formation, and secondary axonal transection. To further our knowledge of the role of vascular edema in these pathological changes to WM, we designed, and three-dimensional (3D) printed a dual-compartment imaging chamber separated by a semipermeable membrane to mimic and manipulate interstitial and vascular fluid compartments in real time. We hypothesized that hypertonic saline (HTS) applied to the \"vascular\" chamber would osmotically shift fluid out of the periaxonal space and preserve myelinated fibers after SCI. Adult male and female 6- to 8-week-old &lt;i&gt;Thy1&lt;/i&gt;&lt;sup&gt;YFP+&lt;/sup&gt; transgenic mice underwent a C5, mild contusive SCI (30 kilodyne, IH Impactor) &lt;i&gt;in vivo,&lt;/i&gt; and their spinal cords were harvested for &lt;i&gt;ex vivo&lt;/i&gt; imaging. Utilizing longitudinal two-photon excitation microscopy (2PE), we imaged both myelin (Nile red) and axons (YFP+) simultaneously up to 4 h after SCI. C5 contusive SCI conditions induced significant increases in periaxonal swelling and axonal spheroid formation within the dorsal column fibers over time. In contrast, perfusion of 3% and 5% HTS in the \"vascular\" compartment beginning 30 min after SCI was highly protective and significantly reduced periaxonal swelling and axonal spheroid formation from 1 h 30 min to the last hour recorded (4 h post-SCI) compared to normal saline (NS) controls. At 2 post-SCI, treatment with 3% and 5% HTS significantly (Kruskal-Wallis ANOVA on Ranks, &lt;i&gt;H&lt;/i&gt;(3) = 3, &lt;i&gt;p&lt;/i&gt; = 0.05, &lt;i&gt;n&lt;/i&gt; = 5-6/group) reduced periaxonal swelling compared to NS (median, 25th percentile; 11.00, 4.00 &lt;i&gt;versus&lt;/i&gt; 9.00, 7.00 &lt;i&gt;versus&lt;/i&gt; 48.00, 29.50, respectively; Dunn's method, both &lt;i&gt;p&lt;/i&gt; &lt; 0.05). By 4 h post-SCI, treatment with 3% and 5% HTS significantly (&lt;i&gt;H&lt;/i&gt;(3) = 15.74, &lt;i&gt;p&lt;/i&gt; = 0.001, &lt;i&gt;n&lt;/i&gt; = 5-6/group) decreased axonal spheroids compared to NS (5.00, 3.00 &lt;i&gt;versus&lt;/i&gt; 4.00, 3.00 &lt;i&gt;versus&lt;/i&gt; 95.00, 38.75, &lt;i&gt;p&lt;/i&gt; = 0.001, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, respectively). In contrast, 7.5% HTS had no beneficial effect. Collectively, these data provide insight into the dynamic interplay between interstitial fluid exchange within the periaxonal space and pathological changes in myelinated fibers following SCI. Delayed &lt;i&gt;in vivo&lt;/i&gt; administration of 3% HTS significantly increased axonal survival and reduced periaxonal swellings 24 h post SCI compared to NS control, validating the translatability of our dual compartment imaging chamber (mean, standard deviation; 58.09, 3.34 &lt;i&gt;versus&lt;/i&gt; 32.08, 5.98, &lt;i&gt;p =&lt;/i&gt; 0.003; 595.19, 326.10 &lt;i&gt;versus&lt;/i&gt; 1525.25, 259.82, &lt;i&gt;p&lt;/i&gt; = 0.018, respectively). Our findings suggest that low-dose hypertonic solutions may have a protective effect in part by mitigating periaxonal swelling and thereby potentially reducing the occurrence of axona","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567455","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":"Diffuse Axonal and Vascular Pathology in the Gyrencephalic Brain after High-Energy Blunt Injury: Clinicopathological Correlations Involving the Brainstem.","authors":"Athanasios S Alexandris, Karin Rafaels, Michael Horsmon, Samantha Wozniak, Joseph Belamarich, Payton Flores, Constantine E Frangakis, Jiwon Ryu, Diego Iacono, Daniel Perl, Vassilis E Koliatsos","doi":"10.1089/neu.2024.0306","DOIUrl":"10.1089/neu.2024.0306","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem. The majority of cases were characterized by fractures of the cranium at or about the impact site, extensive subarachnoid hemorrhages, coup and contrecoup contusions, and primarily diffuse axonal and vascular lesions throughout the cerebrum, particularly in the brainstem. Absence of spontaneous respiration that was encountered frequently was associated with both severity of impact and the severity of brainstem axonal and vascular lesions. A focused regional examination of brainstem pathology indicated a link between adverse outcomes and diffuse axonal lesions within the medial medulla or vascular lesions within the anteroventral brainstem, a pattern suggesting that injury to brainstem respiratory centers may play a role in apnea following BHBT. In addition, while the overall burden of diffuse axonal and vascular pathologies correlated with each other, we found minimal overlap in their regional distribution. Our findings indicate that high-energy, blunt-force impact TBI causes diffuse lesions in axons and blood vessels associated with poor outcomes. They also suggest that axons and vessels may have distinct responses to tissue deformation and that commonly used markers of vascular pathology, for example, in diagnostic radiology, cannot be used as direct surrogates of diffuse axonal injury. In concert, our study underscores the role of regional axonal and vascular injuries in the brainstem in acute respiratory decompensation after high-rate blunt TBI, even in the presence of head protection; it also emphasizes the importance of detailed clinicopathological work in complex brains in the field of TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"417-436"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894923","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":"Impact of Post-Traumatic Epilepsy on Mental Health and Multidimensional Outcome and Quality of Life: An NIDILRR TBIMS Study.","authors":"Nabil Awan, Justin Weppner, Raj G Kumar, Shannon B Juengst, Kristen Dams-O'Connor, Mitch Sevigny, Ross D Zafonte, William C Walker, Jerzy P Szaflarski, Amy K Wagner","doi":"10.1089/neu.2024.0117","DOIUrl":"10.1089/neu.2024.0117","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Traumatic brain injury (TBI) and subsequent post-traumatic epilepsy (PTE) often impair daily activities and mental health (MH), which contribute to long-term TBI-related disability. PTE also affects driving capacity, which impacts functional independence, community participation, and satisfaction with life (SWL). However, studies evaluating the collective impact of PTE on multidimensional outcomes are lacking. Thus, we generated a model to investigate how PTE after moderate-to-severe (ms)TBI affects TBI-associated impairments, limits activities and participation, and influences SWL. Of 5108 participants with msTBI enrolled into the National Institute for Disability, Independent Living, and Rehabilitation Research TBI Model Systems between 2010 and 2018 and with seizure-event data available at year-1 post-TBI, 1214 had complete outcome data and 1003 had complete covariate data used for analysis. We constructed a conceptual framework illustrating hypothesized interrelationships between year-1 PTE, driving status, functional independence measure (FIM), depression and anxiety, as well as year-2 participation, and SWL. We performed univariate and multivariable linear and logistic regressions. A covariate-adjusted structural equation model (SEM), using the lavaan package (R), assessed the conceptual framework's suitability in establishing PTE links with outcomes 1-2 years post-injury. Multiple parameters were evaluated to assess SEM fit. Year-1 PTE was correlated with year-1 FIM motor (standardized coefficient, β&lt;sub&gt;std&lt;/sub&gt; = -0.112, &lt;i&gt;p&lt;/i&gt; = 0.007) and showed a trend level association with year-1 FIM cognition (β&lt;sub&gt;std&lt;/sub&gt; = -0.070, &lt;i&gt;p&lt;/i&gt; = 0.079). Individuals with year-1 PTE were less likely to drive independently at year 1 (β&lt;sub&gt;std&lt;/sub&gt; = -0.148, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In addition, FIM motor (β&lt;sub&gt;std&lt;/sub&gt; = 0.323, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), FIM cognition (β&lt;sub&gt;std&lt;/sub&gt; = 0.181, &lt;i&gt;p&lt;/i&gt; = 0.012), and anxiety (β&lt;sub&gt;std&lt;/sub&gt; = -0.135, &lt;i&gt;p&lt;/i&gt; = 0.024) influenced driving status. FIM cognition was associated with year-1 depression (β&lt;sub&gt;std&lt;/sub&gt; = 0.386, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and year-1 anxiety (β&lt;sub&gt;std&lt;/sub&gt; = 0.396, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), whereas year-1 FIM motor (β&lt;sub&gt;std&lt;/sub&gt; = 0.186, &lt;i&gt;p&lt;/i&gt; = 0.003), depression (β&lt;sub&gt;std&lt;/sub&gt; = -0.322, &lt;i&gt;p&lt;/i&gt; = 0.011), and driving status (β&lt;sub&gt;std&lt;/sub&gt; = 0.233, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) directly affected year-2 objective life participation metrics. Moreover, year-1 depression (β&lt;sub&gt;std&lt;/sub&gt; = -0.382, &lt;i&gt;p&lt;/i&gt; = 0.001) and year-2 participation (β&lt;sub&gt;std&lt;/sub&gt; = 0.160, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) had direct effects on year-2 SWL. SWL was influenced indirectly by year-1 variables, including functional impairment, anxiety, and driving status-factors that impacted year-2 participation directly or indirectly, and consequently year-2 SWL, forming a complex relationship with year-1 PTE. A sensitivity analysis SEM showed that the number of MH disorders was associated with participation and SWL (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), an","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"399-416"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932019","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":"Traumatic Brain Injury and Alzheimer's Disease Biomarkers: A Systematic Review of Findings from Amyloid and Tau Positron Emission Tomography.","authors":"Kaitlyn M Dybing, Cecelia J Vetter, Desarae A Dempsey, Soumilee Chaudhuri, Andrew J Saykin, Shannon L Risacher","doi":"10.1089/neu.2024.0055","DOIUrl":"10.1089/neu.2024.0055","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of β-amyloid (Aβ) and/or tau to examine individuals with a history of TBI who are at increased risk for AD due to age. A comprehensive literature search was conducted on January 9, 2023, and 26 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about participants' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both Aβ and tau, results were widespread but inconsistent. The regions that showed the most compelling evidence for increased Aβ deposition were the cingulate gyrus and cuneus/precuneus. Evidence for elevated tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions in both Aβ- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older individuals at risk for AD.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"333-348"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing the Effect of Repetitive Head Impact Exposure and mTBI on Adolescent Collision Sports Players' Brain with Diffusion Magnetic Resonance Imaging.","authors":"Maryam Tayebi, Eryn Kwon, Josh McGeown, Leigh Potter, Davidson Taylor, Paul Condron, Miao Qiao, Patrick McHugh, Jerome Maller, Poul Nielsen, Alan Wang, Justin Fernandez, Miriam Scadeng, Vickie Shim, Samantha Holdsworth","doi":"10.1089/neu.2024.0064","DOIUrl":"10.1089/neu.2024.0064","url":null,"abstract":"<p><p>Athletes in collision sports frequently sustain repetitive head impacts (RHI), which, while not individually severe enough for a clinical mild traumatic brain injury (mTBI) diagnosis, can compromise neuronal organization by transferring mechanical energy to the brain. Although numerous studies target athletes with mTBI, there is a lack of longitudinal research on young collision sport participants, highlighting an unaddressed concern regarding cumulative RHI effects on brain microstructures. Therefore, this study aimed to investigate the microstructural changes in the brains' of high school rugby players due to repeated head impacts and to establish a correlation between clinical symptoms, cumulative effects of RHI exposure, and changes in the brain's microstructure. We conducted a longitudinal magnetic resonance imaging (MRI) study on 36 male high school rugby players across a season using 3D T1-weighted and multi-shell diffusion MRI sequences, comparing them with 20 matched controls. Players with concussions were separately tracked up to 6 weeks post-injury with three-times scans within this period. The Sport Concussion Assessment Tool (SCAT5) symptom scale assessed mTBI symptoms, and mouthguard-embedded kinematic sensors recorded head impacts. No significant volumetric changes in subcortical structures were found post-rugby season. However, there were substantial differences in mean diffusivity (MD) and axial diffusivity (AD) between the rugby players and controls across widespread brain regions. Diffusion metrics, especially AD, MD, and radial diffusivity of certain brain tracts, displayed strong correlations with SCAT5 symptom severity. Repeated head impacts during a rugby season may adversely affect the structural organization of the brain's white matter. The observed diffusion changes, closely tied to SCAT5 symptom burden, stress the profound effects of seasonal head impacts and highlight individual variability in response to repetitive head impact exposure. To better manage sports-related mTBI and guide return-to-play decisions, comprehensive studies on brain injury mechanisms and recovery post-mTBI/RHI exposure are required.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"349-366"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882429","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":"Identifying Growth Hormone Deficiency in Brain-Injured Patients: The Quality of Life Scale-99.","authors":"Stephen Barnard, Ramtilak Gattu, Vijaykumar M Baragi, Opada Alzohaili, Randall Benson","doi":"10.1089/neu.2024.0114","DOIUrl":"10.1089/neu.2024.0114","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is frequently associated with hypopituitarism. The hypothalamic-pituitary axis appears to be susceptible to the same forces that cause injury to the parenchyma of the brain. Following even a mild TBI (mTBI), patients may suffer transient or permanent decreases in anterior pituitary hormones, including somatotropin (growth hormone [GH]), gonadotropins (luteinizing hormone and follicle-stimulating hormone), thyrotropin, and adrenocorticotropic hormone, with the most frequent long-term deficiency being GH deficiency (GHD). GHD is common after mTBI and is often the cause of persistent post-concussive symptoms a year or more post-injury. GHD is known to cause physical and cognitive fatigue, cognitive inefficiency, metabolic changes, and a range of psychological symptoms. Confusing the picture is that some symptoms of GHD are also common to brain injury itself. To facilitate the detection of GHD when comorbid with TBI, we utilized a new symptom inventory, the Quality-of-Life Scale-99 (QoLS-99), and administered it to a cohort of chronic TBI subjects with and without GHD, distinguished using the insulin tolerance test (ITT). Between 2018 and 2023, 371 patients completed the QoLS-99, of which 263 underwent GH testing with the ITT. Of these 263 patients, 136 (52%) were diagnosed with GHD. A retrospective comparison of QoLS-99 scores found that loss of libido (<i>p</i> < 0.006), a reliance on sleep aids (<i>p</i> < 0.011), and feeling overweight (<i>p</i> < 0.015) were the strongest univariate predictors of GHD. Most survey items did not elicit a significant difference in response between the GHD groups, and for those that did, effect sizes were mild to moderate. Still, initial findings demonstrate strong predictive value in a subset of survey items (i.e., GHD symptoms) that are most discriminating in the sample of patients with TBI. A multivariate prediction model using this subset of questions was able to differentiate GHD status in patients with TBI, correctly identifying 88% of GHD cases with a 37% false positive rate. Based on these findings, we recommend that clinicians inquire about libido, insomnia, and body image as potential markers for GHD. Furthermore, given the amenability of patients with GHD to growth hormone replacement therapy, we strongly encourage clinicians and basic scientists to develop interventions for the large and underserved population of patients with TBI with comorbid GHD.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"379-390"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836984","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":"Revisiting Subject-Specific Analyses in Neuroimaging Data Using \"Z-Score\" Methods.","authors":"Andrew R Mayer, Andrew B Dodd, Josef M Ling, Edward J Bedrick","doi":"10.1089/neu.2024.0434","DOIUrl":"10.1089/neu.2024.0434","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e461-e462"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785349","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":"Authors' Response to \"Revisiting Subject-Specific Analyses in Neuroimaging Data Using \"Z-Score\" Methods\".","authors":"Sarah I Gimbel, Lars Hungerford, Elizabeth W Twamley, Mark L Ettenhofer","doi":"10.1089/neu.2024.0546","DOIUrl":"10.1089/neu.2024.0546","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e463-e464"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785412","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}