Exploring Serum Biomarkers for Mild Traumatic Brain Injury

Papa, Linda; Edwards, Damyan; Ramia, Michelle M.

doi:10.1201/b18126-29

Cited by 12 publications

(6 citation statements)

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“…Nor does this table include any review articles. The application of MRS to mTBI was reviewed elsewhere [ 31 , 38 , 81 , 149 ].…”

Section: Application Of Mri To Wm Injury In Mtbimentioning

confidence: 99%

White matter changes in patients with mild traumatic brain injury: MRI perspective

Narayana¹

2017

Concussion

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This review focuses on white matter (WM) changes in mild traumatic brain injury (mTBI) as assessed by multimodal MRI. All the peer reviewed publications on WM changes in mTBI from January 2011 through September 2016 are included in this review. This review is organized as follows: introduction to mTBI, the basics of multimodal MRI techniques that are potentially useful for probing the WM integrity, summary and critical evaluation of the published literature on the application of multimodal MRI techniques to assess the changes of WM in mTBI, and correlation of MRI measures with behavioral deficits. The MRI–pathology correlation studies based on preclinical models of mTBI are also reviewed. Finally, the author's perspective of future research directions is described.

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“…Nor does this table include any review articles. The application of MRS to mTBI was reviewed elsewhere [ 31 , 38 , 81 , 149 ].…”

Section: Application Of Mri To Wm Injury In Mtbimentioning

confidence: 99%

White matter changes in patients with mild traumatic brain injury: MRI perspective

Narayana¹

2017

Concussion

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“…The term mild TBI often misrepresents the patient's burden with functional, emotional, and cognitive long-term sequelae, as half of mTBI patients with a negative cranial computed tomography (CCT) complain functional limitations 12 months after the brain impact, and up to one third suffer from cognitive dysfunction [8][9][10][11][12]. Nearly 90% of CCT or routine MRI brain scans remain negative despite major clinical health concerns with the inability to return to work after mTBI [13][14][15][16][17], which emphasizes the need for additional diagnostic tools to identify patients earlier who are at risk for unfavorable outcome or even posttraumatic dementia. Current state-of-the-art CCT and MRI techniques are limited in recognizing the full complexity of the mTBI neuropathology, and thus more sensitive, yet still realistic clinical measures to detect early compromised brain metabolism that might help to predict longterm cognitive deficits are required [16,18].…”

Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

Eisele¹,

Hill-Strathy²,

Michels³

et al. 2020

Neurodegener Dis

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Introduction: Traumatic brain injury (TBI) is the most relevant external risk factor for dementia and a major global health burden. Mild TBI (mTBI) contributes to up to 90% of all TBIs, and the classification “mild” often misrepresents the patient’s burden who suffer from neuropsychiatric long-term sequelae. Magnetic resonance spectroscopy (MRS) allows in vivo detection of compromised brain metabolism although it is not routinely used after TBI. Objective: Thus, we performed a systematic review and meta-analysis to elucidate if MRS has the potential to identify changes in brain metabolism in adult patients after a single mTBI with a negative routine brain scan (CCT and/or MRI scan) compared to aged- and sex-matched healthy controls (HC) during the acute or subacute postinjury phase (≤90 days after mTBI). Methods: A comprehensive literature search was conducted from the first edition of electronic databases until January 31, 2020. Group analyses were performed per metabolite using a random-effects model. Results: Four and 2 out of 5,417 articles met the inclusion criteria for the meta-analysis and systematic review, respectively. For the meta-analysis, 50 mTBI patients and 51 HC with a mean age of 31 and 30 years, respectively, were scanned using N-acetyl-aspartate (NAA), a marker for neuronal integrity. Glutamate (Glu), a marker for disturbed brain metabolism, choline (Cho), a marker for increased cell membrane turnover, and creatine (Cr) were used in 2 out of the 4 included articles. Regions of interests were the frontal lobe, the white matter around 1 cm above the lateral ventricles, or the whole brain. NAA was decreased in patients compared to HC with an effect size (ES) of –0.49 (95% CI –1.08 to 0.09), primarily measured in the frontal lobe. Glu was increased in the white matter in 22 mTBI patients compared to 22 HC (ES 0.79; 95% CI 0.17–1.41). Cho was decreased in 31 mTBI patients compared to 31 HC (ES –0.31; 95% CI –0.81 to 0.19). Cr was contradictory and, therefore, potentially not suitable as a reference marker after mTBI. Conclusions: MRS pinpoints changes in posttraumatic brain metabolism that correlate with cognitive dysfunction and, thus, might possibly help to detect mTBI patients at risk for unfavorable outcome or posttraumatic neurodegeneration early.

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“…In situations where the time for MRI must for clinical reasons be extended beyond the acute phase, hemorrhagic lesions depicted in particular on SWI sequence seem to have higher prognostic value than other MR sequences. It is notable that conventional MRI sequences may still be insensitive to microstructural damage to axons and injury to white matter tracts of clinical significance can still be missed with this imaging modality ( 96 ).…”

Section: Neuroimagingmentioning

confidence: 99%

Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

2017

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Traumatic brain injury (TBI) is a multidimensional and highly complex disease commonly resulting in widespread injury to axons, due to rapid inertial acceleration/deceleration forces transmitted to the brain during impact. Axonal injury leads to brain network dysfunction, significantly contributing to cognitive and functional impairments frequently observed in TBI survivors. Diffuse axonal injury (DAI) is a clinical entity suggested by impaired level of consciousness and coma on clinical examination and characterized by widespread injury to the hemispheric white matter tracts, the corpus callosum and the brain stem. The clinical course of DAI is commonly unpredictable and it remains a challenging entity with limited therapeutic options, to date. Although axonal integrity may be disrupted at impact, the majority of axonal pathology evolves over time, resulting from delayed activation of complex intracellular biochemical cascades. Activation of these secondary biochemical pathways may lead to axonal transection, named secondary axotomy, and be responsible for the clinical decline of DAI patients. Advances in the neurocritical care of TBI patients have been achieved by refinements in multimodality monitoring for prevention and early detection of secondary injury factors, which can be applied also to DAI. There is an emerging role for biomarkers in blood, cerebrospinal fluid, and interstitial fluid using microdialysis in the evaluation of axonal injury in TBI. These biomarker studies have assessed various axonal and neuroglial markers as well as inflammatory mediators, such as cytokines and chemokines. Moreover, modern neuroimaging can detect subtle or overt DAI/white matter changes in diffuse TBI patients across all injury severities using magnetic resonance spectroscopy, diffusion tensor imaging, and positron emission tomography. Importantly, serial neuroimaging studies provide evidence for evolving axonal injury. Since axonal injury may be a key risk factor for neurodegeneration and dementias at long-term following TBI, the secondary injury processes may require prolonged monitoring. The aim of the present review is to summarize the clinical short- and long-term monitoring possibilities of axonal injury in TBI. Increased knowledge of the underlying pathophysiology achieved by advanced clinical monitoring raises hope for the development of novel treatment strategies for axonal injury in TBI.

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Exploring Serum Biomarkers for Mild Traumatic Brain Injury

Cited by 12 publications

References 1 publication

White matter changes in patients with mild traumatic brain injury: MRI perspective

White matter changes in patients with mild traumatic brain injury: MRI perspective

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

Current Opportunities for Clinical Monitoring of Axonal Pathology in Traumatic Brain Injury

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