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Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury.

ABSTRACT: Patient outcomes are variable following severe traumatic brain injury (TBI); however, the biological underpinnings explaining this variability are unclear. Mitochondrial dysfunction after TBI is well documented, particularly in animal studies. The aim of this study was to investigate the role of mitochondrial polymorphisms on mitochondrial function and patient outcomes out to 1 year after a severe TBI in a human adult population. The Human MitoChip V2.0 was used to evaluate mitochondrial variants in an initial set of n=136 subjects. SNPs found to be significantly associated with patient outcomes [Glasgow Outcome Scale (GOS), Neurobehavioral Rating Scale (NRS), Disability Rating Scale (DRS), in-hospital mortality, and hospital length of stay] or neurochemical level (lactate:pyruvate ratio from cerebrospinal fluid) were further evaluated in an expanded sample of n=336 subjects. A10398G was associated with DRS at 6 and 12 months (p=0.02) and a significant time by SNP interaction for DRS was found (p=0.0013). The A10398 allele was associated with greater disability over time. There was a T195C by sex interaction for GOS (p=0.03) with the T195 allele associated with poorer outcomes in females. This is consistent with our findings that the T195 allele was associated with mitochondrial dysfunction (p=0.01), but only in females. This is the first study associating mitochondrial DNA variation with both mitochondrial function and neurobehavioral outcomes after TBI in humans. Our findings indicate that mitochondrial DNA variation may impact patient outcomes after a TBI potentially by influencing mitochondrial function, and that sex of the patient may be important in evaluating these associations in future studies.

SUBMITTER: Conley YP

PROVIDER: S-EPMC3880110 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury.

Conley Yvette P YP Okonkwo David O DO Deslouches Sandra S Alexander Sheila S Puccio Ava M AM Beers Sue R SR Ren Dianxu D

Journal of neurotrauma 20131114 1

Patient outcomes are variable following severe traumatic brain injury (TBI); however, the biological underpinnings explaining this variability are unclear. Mitochondrial dysfunction after TBI is well documented, particularly in animal studies. The aim of this study was to investigate the role of mitochondrial polymorphisms on mitochondrial function and patient outcomes out to 1 year after a severe TBI in a human adult population. The Human MitoChip V2.0 was used to evaluate mitochondrial variant ...[more]

PMID: 23883111

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Project description:ImportanceThe development and expansion of intracranial hematoma are associated with adverse outcomes. Use of tranexamic acid might limit intracranial hematoma formation, but its association with outcomes of severe traumatic brain injury (TBI) is unclear.ObjectiveTo assess whether prehospital administration of tranexamic acid is associated with mortality and functional outcomes in a group of patients with severe TBI.Design, setting, and participantsThis multicenter cohort study is an analysis of prospectively collected observational data from the Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) study in the Netherlands. Patients treated for suspected severe TBI by the Dutch Helicopter Emergency Medical Services between February 2012 and December 2017 were included. Patients were followed up for 1 year after inclusion. Data were analyzed from January 10, 2020, to September 10, 2020.ExposuresAdministration of tranexamic acid during prehospital treatment.Main outcomes and measuresThe primary outcome was 30-day mortality. Secondary outcomes included mortality at 1 year, functional neurological recovery at discharge (measured by Glasgow Outcome Scale), and length of hospital stay. Data were also collected on demographic factors, preinjury medical condition, injury characteristics, operational characteristics, and prehospital vital parameters.ResultsA total of 1827 patients were analyzed, of whom 1283 (70%) were male individuals and the median (interquartile range) age was 45 (23-65) years. In the unadjusted analysis, higher 30-day mortality was observed in patients who received prehospital tranexamic acid (odds ratio [OR], 1.34; 95% CI, 1.16-1.55; P < .001), compared with patients who did not receive prehospital tranexamic acid. After adjustment for confounders, no association between prehospital administration of tranexamic acid and mortality was found across the entire cohort of patients. However, a substantial increase in the odds of 30-day mortality persisted in patients with severe isolated TBI who received prehospital tranexamic acid (OR, 4.49; 95% CI, 1.57-12.87; P = .005) and after multiple imputations (OR, 2.05; 95% CI, 1.22-3.45; P = .007).Conclusions and relevanceThis study found that prehospital tranexamic acid administration was associated with increased mortality in patients with isolated severe TBI, suggesting the judicious use of the drug when no evidence for extracranial hemorrhage is present.

Project description:Background and aims: Severe traumatic brain injury is a leading cause of acquired persistent disabilities, and represents an important health and economic burden. However, the determinants of long-term outcome have rarely been systematically studied in a prospective longitudinal study of a homogeneous group of patients suffering exclusively from severe TBI Methods: Prospective observational study of an inception cohort of adult patients with severe traumatic brain injury in the Parisian area (PariS-TBI). Outcome was assessed with face-to-face interview 8 years after Traumatic Brain Injury, focusing on impairments, activity limitations, and participation restriction. Results: Five hundred and four patients were included between 2005 and 2007. At 8-year follow-up, 261 patients were deceased, 128 were lost to follow-up, 22 refused to participate, and 86 were finally evaluated. Age, gender, initial injury severity did not significantly differ between evaluated patients and lost to follow-up, but the latter were more frequently students or unemployed. Mean age was 41.9 (SD 13.6), 79% were male, median initial Glasgow Coma Scale Score was 6. The most frequent somatic complaints concerned balance (47.5%), motricity (31%), and headaches (36%), but these were less frequent than cognitive complaints (Memory 71%, Slowness 68%, Concentration 67%). According to the Hospital Anxiety and Depression Scale (HADS), 25 % had a score >8 for anxiety and 23.7% for depression. According to the Extended Glasgow Outcome Scale, 19.8% remained severely disabled, 46.5% moderately disabled, 33.7% had a good recovery. Older age, longer education duration, lower functional status upon intensive care discharge, and more severe 8-year dysexecutive problems were significantly associated with a lower Extended Glasgow Outcome Scale score in multivariable analysis. At 8 years, 48.7% of patients were employed in a productive job. Of those, 38% declared a salary loss since traumatic brain injury. Unemployment was significantly associated with lower 1-year GOSE score and more severe 8-year dysexecutive problems. Conclusions: These results from an inception cohort study highlight the fact that long-term outcome after severe TBI is determined by a complex combination of injury-related, demographic and neuropsychological factors. Long after the injury, persisting impairments still interfere with social integration, and participation.

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Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury.

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Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury.

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