Biomarkers for Traumatic Brain Injury Proceedings of a Workshop (2023) / Chapter Skim
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3 Exploring the State of the Science for TBI Biomarkers
3 Exploring the State of the Science for TBI Biomarkers
Pages 19-34
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From page 19... ...
. • Multiple measures of physiological deficits that occur after mild TBI, including eye tracking, auditory testing, sleep moni toring, and postural and gait analyses, may serve as biomarkers for diagnosis, prognosis, and monitoring recovery, and they may play a future role in the design of targeted interventions for treatment.
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From page 20... ...
CLASSES OF TBI BIOMARKERS Major classes of TBI biomarkers include those identified through neuroimaging, proteins detectable in blood and other biological fluids, electrophysiological signals, and other physiological indicators such as those measured through eye tracking or gait analysis. This section describes the landscape of current knowledge on the development and use of these types of biomarkers in TBI care and research.
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From page 21... ...
Progress is being made in developing more advanced imaging biomarkers, including a variety of MRI markers, although many do not yet reach level 1 evidence and require additional validation.3 However, Wilde noted that the literature on imaging for TBI is far ahead of clinical practice, reflecting the importance of clinical implementation discussed in the prior session. There has been a dramatic increase in TBI imaging publications since 2015, with T1-weighted MRI and diffusion MRI being two modalities growing the fastest.
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From page 22... ...
However, Wilde noted a recent pilot study using diffusion imaging and machine learning algorithms to predict symptoms after mild TBI (such as concussion) in children.
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From page 23... ...
2. Continued validation of neuroimaging biomarkers for subacute and chronic TBI to understand the underlying injury pathways that correspond to biomarker signatures.
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From page 24... ...
Gill shared data from the CARE Consortium,5 which includes baseline data on protein levels and gene activities measured before an individual plays a collegiate sport, facilitating comparison after concussion. She high 4 This section is based on a presentation by Jessica Gill, Johns Hopkins University.
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From page 25... ...
Gill highlighted the opportunity to identify how fluid biomarkers relate to brain regions and forms of injury, which involves understanding the clearance of the proteins from the brain to the plasma. A study of 700 acute TBI patients used MRI and CT imaging and gadolinium contrast to look at brain meninges after injury and 3–5 days later to examine changes (Gill et al., 2018)
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From page 26... ...
EEG technologies are also portable and do not require sophisticated infrastructure, enabling them to be deployed in austere or military far-forward settings. EEG technologies provide immediate results and enable repeat EEGs to collect longitudinal data.7 More than half a dozen EEG-based biomarkers have been identified for TBI and have assays cleared by the Food and Drug Administration (FDA)
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From page 27... ...
FIGURE 3-1 Comprehensive evaluation for TBI. SOURCE: Presented by Jessica Gill, September 29, 2022.
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From page 28... ...
An indicator such as heart rate variability (HRV) can be easily tracked by a wearable device and combined with data from genomics and transcriptomics, eye tracking, and individual clinical history and analyzed using statistical learning technologies to determine which of the measures are most diagnostically or prognostically useful.
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From page 29... ...
These measures may have potential for improving the understanding of subclinical physiological dysfunction, as well, particularly in areas with functional implications for patients in their everyday lives, such as visual and vestibular issues. Information from these other types of markers may also identify potential targets for interventions aimed at help ing patients return to full function.
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From page 30... ...
. 11 Both saccade and smooth pursuit are types of eye movements, with the key point being that traumatic brain injury is associated with changes in the ability of a patient to perform certain visual functions.
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From page 31... ...
Collecting observable physiological measures through wearables, conducting ecological momentary assessments in real time and real-life contexts, and incorporating options for remote patient monitoring can all be brought to bear in measuring and monitoring outcomes that are meaningful for patients. DISCUSSION Initial discussion centered around the interpretation and generalizability of biomarker results, given small sample sizes used in some s tudies, and the resulting implications for biomarker translation into clinical practice.
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From page 32... ...
It is also important, she said, for the biomarker field not to focus only on specialty services for brain injury but also to solicit feedback that informs the development of markers and assays usable in general locations, such as by emergency medical services and in hospital emergency departments. Master noted that in a primary care setting, providers will feel most comfortable using their existing, familiar clinical assessment tools.
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From page 33... ...
EXPLORING THE STATE OF THE SCIENCE 33 and fluid biomarkers. It will be years before they are ready for clinical use, she noted, but they can be useful in distinguishing subtypes of TBI.
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