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Prediction of Intraparenchymal Hemorrhage Progression and Neurologic Outcome in Traumatic Brain Injury Patients Using Radiomics Score and Clinical Parameters.

ABSTRACT: (1) Background: Radiomics analysis of spontaneous intracerebral hemorrhages on computed tomography (CT) images has been proven effective in predicting hematoma expansion and poor neurologic outcome. In contrast, there is limited evidence on its predictive abilities for traumatic intraparenchymal hemorrhage (IPH). (2) Methods: A retrospective analysis of 107 traumatic IPH patients was conducted. Among them, 45 patients (42.1%) showed hemorrhagic progression of contusion (HPC) and 51 patients (47.7%) had poor neurological outcome. The IPH on the initial CT was manually segmented for radiomics analysis. After feature extraction, selection and repeatability evaluation, several machine learning algorithms were used to derive radiomics scores (R-scores) for the prediction of HPC and poor neurologic outcome. (3) Results: The AUCs for R-scores alone to predict HPC and poor neurologic outcome were 0.76 and 0.81, respectively. Clinical parameters were used to build comparison models. For HPC prediction, variables including age, multiple IPH, subdural hemorrhage, Injury Severity Score (ISS), international normalized ratio (INR) and IPH volume taken together yielded an AUC of 0.74, which was significantly (p = 0.022) increased to 0.83 after incorporation of the R-score in a combined model. For poor neurologic outcome prediction, clinical variables of age, Glasgow Coma Scale, ISS, INR and IPH volume showed high predictability with an AUC of 0.92, and further incorporation of the R-score did not improve the AUC. (4) Conclusion: The results suggest that radiomics analysis of IPH lesions on initial CT images has the potential to predict HPC and poor neurologic outcome in traumatic IPH patients. The clinical and R-score combined model further improves the performance of HPC prediction.

SUBMITTER: Shih YJ

PROVIDER: S-EPMC9320220 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceIntracerebral hemorrhage progression is associated with unfavorable outcome after traumatic brain injury (TBI). No effective treatments are currently available. This secondary injury process reflects an extreme form of vasogenic edema and blood-brain barrier breakdown. The sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) cation channel is a key underlying mechanism. A phase 2 trial of SUR1-TRPM4 inhibition in contusional TBI is ongoing, and a phase 3 trial is being designed. Targeted identification of patients at increased risk for hemorrhage progression may inform prognostication, trial design (including patient selection), and ultimately treatment response.ObjectiveTo determine whether ABCC8 (SUR1) and TRPM4 genetic variability are associated with intraparenchymal hemorrhage (IPH) progression after severe TBI, based on the putative involvement of the SUR1-TRPM4 channel in this pathophysiology.Design, setting, and participantsIn this genetic association study, DNA was extracted from 416 patients with severe TBI prospectively enrolled from a level I trauma academic medical center from May 9, 2002, to August 8, 2014. Forty ABCC8 and TRPM4 single-nucleotide variants (SNVs) were genotyped (multiplex, unbiased). Data were analyzed from January 7, 2020, to May 3, 2021.Main outcomes and measuresPrimary analyses addressed IPH progression at 6, 24, and 120 hours in patients without acute craniectomy (n = 321). Multivariable regressions and receiver operating characteristic curves assessed SNV and haplotype associations with progression. Spatial modeling and functional predictions were determined using standard software.ResultsOf the 321 patients included in the analysis (mean [SD] age, 37.0 [16.3] years; 247 [76.9%] male), IPH progression occurred in 102. Four ABCC8 SNVs were associated with markedly increased odds of progression (rs2237982 [odds ratio (OR), 2.60-3.80; 95% CI, 1.14-5.90 to 1.80-8.02; P = .02 to P < .001], rs2283261 [OR, 3.37-4.77; 95% CI, 1.07-10.77 to 1.89-12.07; P = .04 to P = .001], rs3819521 [OR, 2.96-3.92; 95% CI, 1.13-7.75 to 1.42-10.87; P = .03 to P = .009], and rs8192695 [OR, 3.06-4.95; 95% CI, 1.02-9.12 to 1.67-14.68]; P = .03-.004). These are brain-specific expression quantitative trait loci (eQTL) associated with increased ABCC8 messenger RNA levels. Regulatory annotations revealed promoter and enhancer marks and strong and/or active brain-tissue transcription, directionally consistent with increased progression. Three SNVs (rs2283261, rs2237982, and rs3819521) in this cohort have been associated with intracranial hypertension. Four TRPM4 SNVs were associated with decreased IPH progression (rs3760666 [OR, 0.40-0.49; 95% CI, 0.19-0.86 to 0.27-0.89; P = .02 to P = .009], rs1477363 [OR, 0.40-0.43; 95% CI, 0.18-0.88 to 0.23-0.81; P = .02 to P = .006], rs10410857 [OR, 0.36-0.41; 95% CI, 0.20-0.67 to 0.20-0.85; P = .02 to P = .001], and rs909010 [OR, 0.27-0.40; 95% CI, 0.12-0.62 to 0.16-0.58; P = .002 to P < .001]). Significant SNVs in both genes cluster downstream, flanking exons encoding the receptor site and SUR1-TRPM4 binding interface. Adding genetic variation to clinical models improved receiver operating characteristic curve performance from 0.6959 to 0.8030 (P = .003).Conclusions and relevanceIn this genetic association study, 8 ABCC8 and TRPM4 SNVs were associated with IPH progression. Spatial clustering, brain-specific eQTL, and regulatory annotations suggest biological plausibility. These findings may have important implications for neurocritical care risk stratification, patient selection, and precision medicine, including an upcoming phase 3 trial design for SUR1-TRPM4 inhibition in severe TBI.

Project description:BACKGROUND AND PURPOSE:Intracerebral hemorrhage is a considerable source of morbidity and mortality. This 3-center study describes outcomes of pediatric intracerebral hemorrhage and identifies 2-year neurological outcome predictors. METHODS:Children 29 days to 18 years of age presenting with intracerebral hemorrhage from March 2007 to May 2015 were enrolled prospectively. Exclusion criteria included trauma; intracranial tumor; hemorrhagic transformation of arterial ischemic stroke or cerebral sinovenous thrombosis; isolated subdural, epidural, or subarachnoid hemorrhage; and abnormal baseline neurological function. Intracerebral hemorrhage and total brain volumes were measured on neuroimaging. The Pediatric Stroke Outcome Measure assessed outcomes. RESULTS:Sixty-nine children were included (median age: 9.7 years; interquartile range: 2.2-14). Six children (9%) died during hospitalization. Outcomes in survivors were assessed at early follow-up in 98% (median 3.1 months; interquartile range: 3.1-3.8) and at later follow-up in 94% (median: 2.1 years; interquartile range: 1.3-2.8). Over a third had a significant disability at 2 years (Pediatric Stroke Outcome Measure >2). Total Pediatric Stroke Outcome Measure score improved over time (P=0.0003), paralleling improvements in the sensorimotor subscore (P=0.0004). Altered mental status (odds ratio, 13; 95% confidence interval, 3.9-46; P<0.001), hemorrhage volume ?4% of total brain volume (odds ratio, 17; 95% confidence interval, 1.9-156; P=0.01), and intensive care unit length of stay (odds ratio, 1.1; 95% confidence interval, 1.0-1.2; P=0.002) were significantly associated with poor 2-year outcome. CONCLUSIONS:Over one third of children experienced significant disability at 2 years. Improvements in outcomes were driven by recovery of sensorimotor function. Altered mental status, hemorrhage volume ?4% of total brain volume, and intensive care unit length of stay were independent predictors of significant disability at 2 years.

Project description:BackgroundIdentifying patients at risk of secondary neurologic deterioration (SND) after moderate traumatic brain injury (moTBI) is a challenge, as such patients will need specific care. No simple scoring system has been evaluated to date. This study aimed to determine clinical and radiological factors associated with SND after moTBI and to propose a triage score.MethodsAll adults admitted in our academic trauma center between January 2016 and January 2019 for moTBI (Glasgow Coma Scale [GCS] score, 9-13) were eligible. SND during the first week was defined either by a decrease in GCS score of >2 points from the admission GCS in the absence of pharmacologic sedation or by a deterioration in neurologic status associated with an intervention, such as mechanical ventilation, sedation, osmotherapy, transfer to the intensive care unit (ICU), or neurosurgical intervention (for intracranial mass lesions or depressed skull fracture). Clinical, biological, and radiological independent predictors of SND were identified by logistic regression (LR). An internal validation was performed using a bootstrap technique. A weighted score was defined based on beta (β) coefficients of the LR.ResultsA total of 142 patients were included. Forty-six patients (32%) showed SND, and 14-day mortality rate was 18.4%. Independent variables associated with SND were age above 60 years (odds ratio [OR], 3.45 [95% confidence interval {CI}, 1.45-8.48]; P = .005), brain frontal contusion (OR, 3.22 [95% CI, 1.31-8.49]; P = .01), prehospital or admission arterial hypotension (OR, 4.86 [95% CI, 2.03-12.60]; P = .006), and a Marshall computed tomography (CT) score of 6 (OR, 3.25 [95% CI, 1.31-8.20]; P = .01). The SND score was defined with a range from 0 to 10. The score included the following variables: age >60 years (3 points), prehospital or admission arterial hypotension (3 points), frontal contusion (2 points), and Marshall CT score of 6 (2 points). The score was able to detect patients at risk of SND, with an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI, 0.65-0.82). A score of 3 had a sensitivity of 85%, a specificity of 50%, a VPN of 87%, and a VPP of 44 % to predict SND.ConclusionsIn this study, we demonstrate that moTBI patients have a significant risk of SND. A simple weighted score at hospital admission could be able to detect patients at risk of SND. The use of the score may enable optimization of care resources for these patients.

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Prediction of Intraparenchymal Hemorrhage Progression and Neurologic Outcome in Traumatic Brain Injury Patients Using Radiomics Score and Clinical Parameters.

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