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Sex differences in outcome after mild traumatic brain injury.

ABSTRACT: The objective of this study was to estimate the independent association of sex with outcome after mild traumatic brain injury (mTBI). We performed an analysis of a subset of an established cohort involving 1425 mTBI patients presenting to an academic emergency department (ED). The associations between sex and three outcomes determined 3 months after the initial ED visit were examined: post-concussive symptom (PCS) score (0, 1-5, 6-16, and >16), the number of days to return of normal activities (0, 1-7, and >7), and the number of days of work missed (0, 1-7,and >7). Logistic regression analyses were used to determine the relationship between sex and each outcome after controlling for 12 relevant subject-level variables. Of the 1425 subjects, 643 (45.1%) were female and 782 (54.9%) were male. Three months after mTBI, males had significantly lower odds of being in a higher PCS score category (odds ratio [OR] 0.62, 95% confidence interval [CI]: 0.50, 0.78); this association appeared to be more prominent during child-bearing years for females. Males and females did not significantly differ with respect to the odds of poorer outcome as defined by the number of days to return of normal activities or the number of days of work missed. Female sex is associated with significantly higher odds of poor outcome after mTBI, as measured by PCS score, after control for appropriate confounders. The observed pattern of peak disability for females during the child-bearing years suggests disruption of endogenous estrogen or progesterone production. Attempts to better understand how mTBI affects production of these hormones acutely after injury and during the recovery period may shed light on the mechanism behind poorer outcome among females and putative therapeutic interventions.

SUBMITTER: Bazarian JJ

PROVIDER: S-EPMC2867588 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Sex differences in outcome after mild traumatic brain injury.

Bazarian Jeffrey J JJ Blyth Brian B Mookerjee Sohug S He Hua H McDermott Michael P MP

Journal of neurotrauma 20100301 3

The objective of this study was to estimate the independent association of sex with outcome after mild traumatic brain injury (mTBI). We performed an analysis of a subset of an established cohort involving 1425 mTBI patients presenting to an academic emergency department (ED). The associations between sex and three outcomes determined 3 months after the initial ED visit were examined: post-concussive symptom (PCS) score (0, 1-5, 6-16, and >16), the number of days to return of normal activities ( ...[more]

PMID: 19938945

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Project description:The long-term effects of mild TBI (mTBI) are not well understood, and there is an ongoing debate about whether there are sex differences in outcomes following mTBI. This study examined i) symptom burden and functional outcomes at 8-years post-injury in males and females following mTBI; ii) sex differences in outcomes at 8-years post-injury for those aged <45 years and ≥45 years and; iii) sex differences in outcomes for single and repetitive TBI. Adults (≥16 years at injury) identified as part of a population-based TBI incidence study (BIONIC) who experienced mTBI 8-years ago (N = 151) and a TBI-free sample (N = 151) completed self-report measures of symptoms and symptom burden (Rivermead Post-Concussion Symptom Questionnaire, Hospital Anxiety and Depression Scale, Post-traumatic Stress Disorder Checklist), and functional outcomes (Participation Assessments with Recombined Tools, Work Limitations Questionnaire). The mTBI group reported significantly greater post-concussion symptoms compared to the TBI-free group (F(1,298) = 26.84, p<.01, ηp2 = .08). Females with mTBI were twice as likely to exceed clinical cut-offs for post-concussive (X2 (1)>5.2, p<.05, V>.19) and PTSD symptoms (X2(1) = 6.10, p = .014, V = .20) compared to the other groups, and reported their health had the greatest impact on time-related work demands (F(1,171) = 4.36, p = .04, ηp2 = .03. There was no interaction between sex and age on outcomes. The repetitive mTBI group reported significantly greater post-concussion symptoms (F(1,147) = 9.80, p<.01, ηp2 = .06) compared to the single mTBI group. Twice the proportion of women with repetitive mTBI exceeded the clinical cut-offs for post-concussive (X2(1)>6.90, p<.01, V>.30), anxiety (X2(1)>3.95, p<.05, V>.23) and PTSD symptoms (X2(1)>5.11, p<.02, V>.26) compared with males with repetitive TBI or women with single TBI. Thus, at 8-years post-mTBI, people continued to report a high symptom burden. Women with mTBI, particularly those with a history of repetitive mTBI, had the greatest symptom burden and were most likely to have symptoms of clinical significance. When treating mTBI it is important to assess TBI history, particularly in women. This may help identify those at greatest risk of poor long-term outcomes to direct early treatment and intervention.

Project description:Neural and cognitive deficits after mild traumatic brain injury (mTBI) are paralleled by changes in resting state functional correlation (FC) networks that mirror post-traumatic pathophysiology effects on functional outcomes. Using functional magnetic resonance images acquired both acutely and chronically after injury (∼1 week and ∼6 months post-injury, respectively), we map post-traumatic FC changes across 136 participants aged 19-79 (52 females), both within and between the brain's seven canonical FC networks: default mode, dorsal attention, frontoparietal, limbic, somatomotor, ventral attention, and visual. Significant sex-dependent FC changes are identified between (A) visual and limbic, and between (B) default mode and somatomotor networks. These changes are significantly associated with specific functional recovery patterns across all cognitive domains (p < 0.05, corrected). Changes in FC between default mode, somatomotor, and ventral attention networks, on the one hand, and both temporal and occipital regions, on the other hand, differ significantly by age group (p < 0.05, corrected), and are paralleled by significant sex differences in cognitive recovery independently of age at injury (p < 0.05, corrected). Whereas females' networks typically feature both significant (p < 0.036, corrected) and insignificant FC changes, males more often exhibit significant FC decreases between networks (e.g., between dorsal attention and limbic, visual and limbic, default-mode and somatomotor networks, p < 0.0001, corrected), all such changes being accompanied by significantly weaker recovery of cognitive function in males, particularly older ones (p < 0.05, corrected). No significant FC changes were found across 35 healthy controls aged 66-92 (20 females). Thus, male sex and older age at injury are risk factors for significant FC alterations whose patterns underlie post-traumatic cognitive deficits. This is the first study to map, systematically, how mTBI impacts FC between major human functional networks.

Project description:BackgroundExtracranial complications after traumatic brain injury (TBI) are common. Their influence on outcome is uncertain. Furthermore, the role of sex on the development of extracranial complications following TBI remains poorly investigated. We aimed to investigate the incidence of extracranial complications after TBI with particular focus on sex-related differences with regard to complications and their influence on outcome.MethodsThis retrospective, observational study was conducted in a level I universitary swiss trauma center. Consecutive patients with TBI admitted to the intensive care unit (ICU) between 2018 and 2021 were included. Patients' and trauma characteristics, in-hospital complications (i.e., cardiovascular, respiratory, renal, metabolic, gastrointestinal, hematological, and infectious) as well as functional outcome 3 months after trauma were analyzed. Data was dichotomized by sex or by outcome. Univariate as well as multivariate logistic regression was performed to reveal possible associations between sex, outcome and complications.ResultsOverall, 608 patients were included (male n = 447, 73.5%). Extracranial complications occurred most frequently in cardiovascular, renal, hematological and infectious systems. Men and women suffered similarly from extracranial complications. While men needed correction of coagulopathies more often (p = 0.029), women suffered more frequently from urogenital infections (p = 0.001). Similar results were found in a subgroup of patients (n = 193) with isolated TBI. A multivariate analysis did not show extracranial complications to be independent predictors of unfavorable outcome.ConclusionExtracranial complications following TBI occur frequently during the ICU-stay, can affect almost all organ systems but are not independent predictors of unfavorable outcome. The results suggest that sex-specific strategies for early recognition of extracranial complications might not be needed in patients with TBI.

Project description:Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers' diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.

Project description:Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using 23Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with 23Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up 1H and 23Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from 23Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

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Sex differences in outcome after mild traumatic brain injury.

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Sex differences in outcome after mild traumatic brain injury.

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