Neurometabolites alteration in the acute phase of mild traumatic brain injury (mTBI): an in vivo proton magnetic resonance spectroscopy (1H-MRS) study

Rationale and Objectives: Magnetic resonance spectroscopy is a noninvasive imaging technique that allows for reliable assessment of microscopic changes in brain cytoarchitecture, neuronal injuries, and neurochemical changes resultant from traumatic insults. We aimed to evaluate the acute alteration of neurometabolites in complicated and uncomplicated mild traumatic brain injury (mTBI) patients in comparison to control subjects using proton magnetic resonance spectroscopy (1H magnetic resonance spectroscopy). Material and Methods: Forty-eight subjects (23 complicated mTBI [cmTBI] patients, 12 uncomplicated mTBI [umTBI] patients, and 13 controls) underwent magnetic resonance imaging scan with additional single voxel spectroscopy sequence. Magnetic resonance imaging scans for patients were done at an average of 10 hours (standard deviation 4.26) post injury. The single voxel spectroscopy adjacent to side of injury and noninjury regions were analysed to obtain absolute concentrations and ratio relative to creatine of the neurometabolites. One-way analysis of variance was performed to compare neurometabolite concentrations of the three groups, and a correlation study was done between the neurometabolite concentration and Glasgow Coma Scale. Results: Significant difference was found in ratio of N-acetylaspartate to creatine (NAA/Cr + PCr) (χ2(2) = 0.22, P < .05) between the groups. The sum of NAA and N-acetylaspartylglutamate (NAAG) also shows significant differences in both the absolute concentration (NAA + NAAG) and ratio to creatine (NAA + NAAG/Cr + PCr) between groups (χ2(2) = 4.03, P < .05and (χ2(2) = 0.79, P < .05)). NAA values were lower in cmTBI and umTBI compared to control group. A moderate weak positive correlation were found between Glasgow Coma Scale with NAA/Cr + PCr (ρ = 0.36, P < .05 and NAA + NAAG/Cr + PCr (ρ = 0.45, P < .05)), whereas a moderate correlation was seen with NAA + NAAG (ρ = 0.38, P < .05). Conclusion: Neurometabolite alterations were already apparent at onset of both complicated and uncomplicated traumatic brain injury. The ratio of NAA and NAAG has potential to serve as a biomarker reflecting injury severity in a quantifiable manner as it discriminates between the complicated and uncomplicated cases of mTBI

Diffusion tensor imaging parameters in mild traumatic brain injury and its correlation with early neuropsychological impairment: a longitudinal study

We explored the prognostic value of diffusion tensor imaging (DTI) parameters of selected white matter (WM) tracts in predicting neuropsychological outcome, both at baseline and 6 months later, among well-characterized patients diagnosed with mild traumatic brain injury (mTBI). Sixty-one patients with mTBI (mean age=27.08; standard deviation [SD], 8.55) underwent scanning at an average of 10 h (SD, 4.26) post-trauma along with assessment of their neuropsychological performance at an average of 4.35 h (SD, 7.08) upon full Glasgow Coma Scale recovery. Results were then compared to 19 healthy control participants (mean age=29.05; SD, 5.84), both in the acute stage and 6 months post-trauma. DTI and neuropsychological measures between acute and chronic phases were compared, and significant differences emerged. Specifically, chronic-phase fractional anisotropy and radial diffusivity values showed significant group differences in the corona radiata, anterior limb of internal capsule, cingulum, superior longitudinal fasciculus, optic radiation, and genu of corpus callosum. Findings also demonstrated associations between DTI indices and neuropsychological outcome across two time points. Our results provide new evidence for the use of DTI as an imaging biomarker and indicator of WM damage occurring in the context of mTBI, and they underscore the dynamic nature of brain injury and possible biological basis of chronic neurocognitive alterations

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index.

peer reviewedPrognosis of prolonged Disorders of Consciousness (pDoC) is influenced by patients' clinical diagnosis and Coma Recovery Scale-Revised (CRS-R) total score. We compared the prognostic accuracy of a novel Consciousness Domain Index (CDI) with that of clinical diagnosis and CRS-R total score, for recovery of full consciousness at 6-, 12-, and 24-months post-injury. The CDI was obtained by a combination of the six CRS-R subscales via an unsupervised machine learning technique. We retrospectively analyzed data on 143 patients with pDoC (75 in Minimally Conscious State; 102 males; median age = 53 years; IQR = 35; time post-injury = 1-3 months) due to different etiologies enrolled in an International Brain Injury Association Disorders of Consciousness Special Interest Group (IBIA DoC-SIG) multicenter longitudinal study. Univariate and multivariate analyses were utilized to assess the association between outcomes and the CDI, compared to clinical diagnosis and CRS-R. The CDI, the clinical diagnosis, and the CRS-R total score were significantly associated with a good outcome at 6, 12 and 24 months. The CDI showed the highest univariate prediction accuracy and sensitivity, and regression models including the CDI provided the highest values of explained variance. A combined scoring system of the CRS-R subscales by unsupervised machine learning may improve clinical ability to predict recovery of consciousness in patients with pDoC

Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study.

peer reviewedBACKGROUND AND PURPOSE: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality. METHODS: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury. RESULTS: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors. CONCLUSIONS: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC

Multicenter prospective study on predictors of short-term outcome in disorders of consciousness

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Scoping Review on the Diagnosis, Prognosis, and Treatment of Pediatric Disorders of Consciousness.

peer reviewed[en] BACKGROUND AND OBJECTIVES: Comprehensive guidelines for diagnosis, prognosis, and treatments of disorders of consciousness (DoCs) in pediatric patients have not yet been released. We aim to summarize available evidence for DoCs with >14 days duration, to support the future development of guidelines for children aged 6 months to 18 years. METHODS: This scoping review was reported based on PRISMA-ScR guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3-blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated. RESULTS: On November 9, 2022, 2167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the last 5 years. Overall, 2161 individuals met the inclusion criteria; female patients were 527 of 1554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports, and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%), and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near Coma Scale, Level of Cognitive Functioning Assessment Scale and Post-Acute Level of Consciousness scale. Electroencephalography, event related potentials, structural computerized tomography and Magnetic Resonance Imaging were the most frequently used instrumental techniques. In 29/53 (54.7%) cases DoC improvement was observed, which was associated to treatment with amantadine. DISCUSSION: The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence, and have limited validity, and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to diagnosis, prognosis and treatment of pediatric DoCs