Sex differences in outcomes from mild traumatic brain injury eight years post-injury

Starkey, Nicola J.; Duffy, Brittney; Jones, Kelly; Theadom, Alice; Barker‐Collo, Suzanne; Feigin, Valery

doi:10.1371/journal.pone.0269101

Cited by 15 publications

(16 citation statements)

References 59 publications

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“…This pattern may reflect differences in demarcating change across measures (reliable change scores were only available for BTACT and BSI) or that factors independent of cognitive and psychiatric decline can also adversely affect functional independence. In contrast with previous findings, 8,[28][29][30][31] this study did not observed greater rates of decline among those with a history of comorbid health conditions, and future studies are needed to identify factors not currently considered that may influence worse longer-term outcomes after TBI.…”

Section: Discussioncontrasting

confidence: 99%

Long-term Multidomain Patterns of Change After Traumatic Brain Injury

Brett¹,

Temkin²,

Barber³

et al. 2023

Neurology

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Background:Traumatic brain injury (TBI) may be a chronic condition carrying risk for future sequelae; few prospective studies examine long-term post-injury outcomes. We examined prevalence of functional, cognitive, and psychiatric change outcomes from 1–7 years post-injury.Methods:TRACK-TBI LONG participants were prospectively enrolled within 24-hours of injury and followed to 1-year post-injury; a subset participated in long-term follow-up from 2-7 years post-injury. Reliable change thresholds for the Brief Test of Adult Cognition by Telephone General Composite (cognition) and Brief Symptom Inventory-18 (psychiatric) were derived from orthopedic trauma controls (OTCs). Multiple assessments were completed (post-injury baseline assessment and two or three visits 2-7 years post-injury) within a sample subset. Change was assessed for functional outcome (Glasgow Outcome Scale-Extended[GOSE]) and self/informant report of decline. Prevalence ratios for outcomes classified as stable, improved, declined were reported individually and collectively. Fisher’s-exact test and log-binomial regression models examined factors associated with decline and improvement.Results:Of the sample (N=1264; mild TBI, GCS 13-15 [mTBI] n=917, moderate-severe TBI GCS 3-12 [msTBI] n=193, or OTC n=154), ‘stable’ was the most prevalent outcome. Functional outcome showed the highest rates of decline, regardless of TBI severity (mild=29%; moderate/severe=23%). When measures were considered collectively, rates of decline included mTBI(21%), msTBI(26%), OTC(15%). Age and pre-injury employment status were associated with functional decline (per 10-years; RR=1.16[95% CI=1.07, 1.25], p<.001; higher in retired/disabled/not working vs. full-time/part-time; RR=1.81[1.33, 2.45], respectively) in the mTBI group. Improvement in functional recovery 2-7 years post-injury was associated with higher BSI scores (per 5 points; RR=1.11[1.04, 1.18], p=.002) and GOSE score of 5-7 (GOSE=8 as reference; RR=2.64[1.75, 3.97], p<.001). Higher BSI scores and identifying as Black (RR=2.28[1.59, 3.25], p<.001) was associated with greater likelihood of improved psychiatric symptoms in mTBI (RR=1.21[1.14, 1.29], p<.001). Greater likelihood of cognitive improvement was observed among those with higher educational attainment in msTBI (per 4-years; RR=2.61[1.43, 4.79], p=.002).Conclusionsand Relevance: Function across domains at 1-year post-injury, a common recovery benchmark, undergo change across the subsequent 6-years. Results support consideration of TBI as a chronic, evolving condition and suggest continued monitoring, rehabilitation, and support is required to optimize long-term independence and quality of life.

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Section: Discussioncontrasting

confidence: 99%

Long-term Multidomain Patterns of Change After Traumatic Brain Injury

Brett¹,

Temkin²,

Barber³

et al. 2023

Neurology

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“…Although males represent at least 60% of all TBI cases, females with the same TBI severity experience worse symptoms than males. [69][70][71]…”

Section: Discussionmentioning

confidence: 99%

Hippocampal vulnerability to hyperhomocysteinemia worsens pathological outcomes of mild traumatic brain injury in rats

Tchantchou

Hsia

Puché

et al. 2023

J Cent Nerv Syst Dis

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Background Mild traumatic brain injury (mTBI) generally resolves within weeks. However, 15-30% of patients present persistent pathological and neurobehavioral sequelae that negatively affect their quality of life. Hyperhomocysteinemia (HHCY) is a neurotoxic condition derived from homocysteine accumulation above 15 μM. HHCY can occur in diverse stressful situations, including those sustained by U.S. active-duty service members on the battlefield or during routine combat practice. Mild-TBI accounts for more than 80% of all TBI cases, and HHCY exists in 5-7% of the general population. We recently reported that moderate HHCY exacerbates mTBI-induced cortical injury pathophysiology, including increased oxidative stress. Several studies have demonstrated hippocampus vulnerability to oxidative stress and its downstream effects on inflammation and cell death. Objective This study aimed to assess the deleterious impact of HHCY on mTBI-associated hippocampal pathological changes. We tested the hypothesis that moderate HHCY aggravates mTBI-induced hippocampal pathological changes. Methods HHCY was induced in adult male Sprague-Dawley rats with a high methionine dose. Rats were then subjected to mTBI by controlled cortical impact under sustained HHCY. Blood plasma was assessed for homocysteine levels and brain tissue for markers of oxidative stress, blood-brain barrier integrity, and cell death. Endothelial cell ultrastructure was assessed by Electron Microscopy and working memory performance using the Y maze test. Results HHCY increased the hippocampal expression of nitrotyrosine in astroglial cells and decreased tight junction protein occludin levels associated with the enlargement of the endothelial cell nucleus. Furthermore, HHCY altered the expression of apoptosis-regulating proteins α-ii spectrin hydrolysis, ERK1/2, and AKT phosphorylation, mirrored by exacerbated mTBI-related hippocampal neuronal loss and working memory deficits. Conclusion Our findings indicate that HHCY is an epigenetic factor that modulates mTBI pathological progression in the hippocampus and represents a putative therapeutic target for mitigating such physiological stressors that increase severity.

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“…LinearSVCs were applied to differentiate mTBI patients from controls and mTBI patients with complete or incomplete recovery using the dMRI maps, sex and age. Sex and age were included as they have previously been shown to affect both the quantitative metrics obtained with DTI (FA and MD), as well as outcome after mild TBI [51][52][53][54] . The linearSVCs were either trained on the voxel-or ROI-wise FA and MD images 1) non-harmonized, 2)…”

Section: Machine Learningmentioning

confidence: 99%