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Longitudinal Metabolite Changes after Traumatic Brain Injury: A Prospective Pediatric Magnetic Resonance Spectroscopic Imaging Study.

ABSTRACT: The aims of this study were to evaluate longitudinal metabolite changes in traumatic brain injury (TBI) subjects and determine whether early magnetic resonance spectroscopic imaging (MRSI) changes in discrete brain regions predict 1-year neuropsychological outcomes. Three-dimensional (3D) proton MRSI was performed in pediatric subjects with complicated mild (cMild), moderate, and severe injury, acutely (6-17 days) and 1-year post-injury along with neurological and cognitive testing. Longitudinal analysis found that in the cMild/Moderate group, all MRSI ratios from 12 regions returned to control levels at 1 year. In the severe group, only cortical gray matter regions fully recovered to control levels whereas N-acetylaspartate (NAA) ratios from the hemispheric white matter and subcortical regions remained statistically different from controls. A factor analysis reduced the data to two loading factors that significantly differentiated between TBI groups; one included acute regional NAA variables and another consisted of clinically observed variables (e.g., days in coma). Using scores calculated from the two loading factors in a logistic regression model, we found that the percent accuracy for classification of TBI groups was greatest for the dichotomized attention measure (93%), followed by Full Scale Intelligence Quotient at 91%, and the combined memory Z-score measure (90%). Using the acute basal ganglia NAA/creatine (Cr) ratio alone achieved a higher percent accuracy of 94.7% for the attention measure whereas the acute thalamic NAA/Cr ratio alone achieved a higher percent accuracy of 91.9% for the memory measure. These results support the conclusions that reduced NAA is an early indicator of tissue injury and that measurements from subcortical brain regions are more predictive of long-term cognitive outcome.

SUBMITTER: Holshouser B

PROVIDER: S-EPMC6479249 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Longitudinal Metabolite Changes after Traumatic Brain Injury: A Prospective Pediatric Magnetic Resonance Spectroscopic Imaging Study.

Holshouser Barbara B Pivonka-Jones Jamie J Nichols Joy G JG Oyoyo Udo U Tong Karen K Ghosh Nirmalya N Ashwal Stephen S

Journal of neurotrauma 20181220 8

The aims of this study were to evaluate longitudinal metabolite changes in traumatic brain injury (TBI) subjects and determine whether early magnetic resonance spectroscopic imaging (MRSI) changes in discrete brain regions predict 1-year neuropsychological outcomes. Three-dimensional (3D) proton MRSI was performed in pediatric subjects with complicated mild (cMild), moderate, and severe injury, acutely (6-17 days) and 1-year post-injury along with neurological and cognitive testing. Longitudinal ...[more]

PMID: 30351247

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Project description:Novel and non-routine tasks often require information processing and behavior to adapt from moment to moment depending on task requirements and current performance. This ability to adapt is an executive function that is referred to as cognitive control. Patients with moderate-to-severe traumatic brain injury (TBI) have been reported to exhibit impairments in cognitive control and functional magnetic resonance imaging (fMRI) has provided evidence for TBI-related alterations in brain activation using various fMRI cognitive control paradigms. There is some support for greater and more extensive cognitive control-related brain activation in patients with moderate-to-severe TBI, relative to comparison subjects without TBI. In addition, some studies have reported a correlation between these activation increases and measures of injury severity. Explanations that have been proposed for increased activation within structures that are thought to be directly involved in cognitive control, as well as the extension of this over-activation into other brain structures, have included compensatory mechanisms, increased demand upon normal processes required to maintain adequate performance, less efficient utilization of neural resources, and greater vulnerability to cognitive fatigue. Recent findings are also consistent with the possibility that activation increases within some structures, such as the posterior cingulate gyrus, may reflect a failure to deactivate components of the default mode network (DMN) and that some cognitive control impairment may result from ineffective coordination between the DMN and components of the salience network. Functional neuroimaging studies examining cognitive control-related activation following mild TBI (mTBI) have yielded more variable results, with reports of increases, decreases, and no significant change. These discrepancies may reflect differences among the various mTBI samples under study, recovery of function in some patients, different task characteristics, and the presence of comorbid conditions such as depression and posttraumatic stress disorder that also alter brain activation. There may be mTBI populations with activation changes that overlap with those found following more severe injuries, including symptomatic mTBI patients and those with acute injuries, but future research to address such dysfunction will require well-defined samples with adequate controls for injury characteristics, comorbid disorders, and severity of post-concussive symptoms.

Project description:Background and Objectives: The annual global incidence of traumatic brain injury (TBI) is over 10 million. An estimated 29% of TBI patients with negative computed tomography (CT-) have positive magnetic resonance imaging (MRI+) findings. Judicious use of serum biomarkers with MRI may aid in diagnosis of CT-occult TBI. The current manuscript aimed to evaluate the diagnostic, therapeutic and risk-stratification utility of known biomarkers and intracranial MRI pathology. Materials and Methods: The PubMed database was queried with keywords (plasma OR serum) AND (biomarker OR marker OR protein) AND (brain injury/trauma OR head injury/trauma OR concussion) AND (magnetic resonance imaging/MRI) (title/abstract) in English. Seventeen articles on TBI biomarkers and MRI were included: S100 calcium-binding protein B (S100B; N = 6), glial fibrillary acidic protein (GFAP; N = 3), GFAP/ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1; N = 2), Tau (N = 2), neurofilament-light (NF-L; N = 2), alpha-synuclein (N = 1), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor peptide (AMPAR; N = 1). Results: Acute GFAP distinguished CT-/MRI+ from CT-/MRI- (AUC = 0.777, 0.852 at 9-16 h). GFAP discriminated CT-/diffuse axonal injury (DAI+) from controls (AUC = 0.903). Tau correlated directly with number of head strikes and inversely with white matter fractional anisotropy (FA), and a cutoff > 1.5 pg/mL discriminated between DAI+ and DAI- (sensitivity = 74%/specificity = 69%). NF-L had 100% discrimination of DAI in severe TBI and correlated with FA. Low alpha-synuclein was associated with poorer functional connectivity. AMPAR cutoff > 0.4 ng/mL had a sensitivity of 91% and a specificity of 92% for concussion and was associated with minor MRI findings. Low/undetectable S100B had a high negative predictive value for CT/MRI pathology. UCH-L1 showed no notable correlations with MRI. Conclusions: An acute circulating biomarker capable of discriminating intracranial MRI abnormalities is critical to establishing diagnosis for CT-occult TBI and can triage patients who may benefit from outpatient MRI, surveillance and/or follow up with TBI specialists. GFAP has shown diagnostic potential for MRI findings such as DAI and awaits further validation. Tau shows promise in detecting DAI and disrupted functional connectivity. Candidate biomarkers should be evaluated within the context of analytical performance of the assays used, as well as the post-injury timeframe for blood collection relative to MRI abnormalities.

Dataset Information

Longitudinal Metabolite Changes after Traumatic Brain Injury: A Prospective Pediatric Magnetic Resonance Spectroscopic Imaging Study.

Publications

Longitudinal Metabolite Changes after Traumatic Brain Injury: A Prospective Pediatric Magnetic Resonance Spectroscopic Imaging Study.

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