The Canadian CT Head Rule is a validated clinical decision algorithm designed to reduce unnecessary CT scan utilization after head injury
[51,52][36][37] The five high-risk criteria on which the score is based are as follows: GCS (score lower than 15 at 2 h post-injury), skull fracture (open or depressed), signs of basal skull fracture, vomiting 2 or more times, aged 65 years and above.
3. Point-of-Care Cognitive Tests for Mild TBI
Point-of-care cognitive testing assessment methods for mild TBI that do not involve a blood draw are readily available and often employed. The King–Devick is a well-known, inexpensive, easy-to-administer test often used on athletes
[55,56][38][39]. The test takes only minutes to complete and measures rapid number reading and naming, which broadly indicates the state of cognitive function, visual–motor coordination, and language. Symptom checklists such as the Post-Concussion Symptom Scale and the SCAT as well as brief paper-and-pencil tests such as the Standardized Assessment of Concussion are also easy to administer
[57,58][40][41]. The Montreal Cognitive Assessment (MoCA), which contains 12 individual tasks grouped into seven cognitive domains: (1) visuospatial/executive; (2) naming; (3) attention; (4) language; (5) abstraction; (6) memory, and (7) orientation, has also been used to screen TBI patients
[59,60][42][43].
Computerized testing is also being employed, and there is flexibility in the administration of this type of evaluation as it may be done either supervised or unsupervised
[61][44]. The CogState Brief Battery (CBB) is a computerized test that measures four core cognitive domains: processing speed, attention/vigilance, visual learning, and executive function
[62,63][45][46].
4. Blood Biomarkers for Mild TBI
The Food and Drug Administration (FDA) has given clearance to Abbott’s Alinity i TBI test, a commercially available blood test to evaluate and triage concussion patients in an acute setting. What does this really mean for clinical medicine? The FDA previously approved Abbott’s i-STAT TBI Plasma test in 2021
[64,65][47][48]. The purpose of these tests is to screen patients aged 18 years and above who present with an acute head injury and deter-mine without delay in which patients a CT scan of the brain is warranted.
Although the radiation-sparing and expense-saving goals aspired to are commendable and consequential, the execution has suffered hindrances, mostly based on the entrenched nature of CT usage in emergency departments. Despite approval of Abbott’s i-STAT TBI Plasma test, it is unclear whether emergency department physicians have changed their use of head CTs. Resistance to the adaptation of blood biomarkers for concussion evaluation may be a major obstacle. Whether or not Abbott’s Alinity i TBI test or any blood biomarker can transform mild TBI assessment is not yet known
[68,69][49][50].
The handheld point-of-care analyzer needed for Abbot’s i-STAT TBI Plasma test is expensive and may not be on hand in many hospitals
[70,71][51][52]. Further, a study by Larcher et al. found that its results for some blood measures had a level of imprecision that should cause caution in interpretation
[72][53].
While there are robust data in the medical literature, a huge investment in medical education might be necessary to alter standard emergency department practice patterns. Convenience is also critical. The CT scanner is already situated in the hospital, and the radiology staff remains on-site with scan interpretation accessible in person or by virtual means. There is no new investment in equipment or personnel needed. The results are intuitively reassuring; if the radiologist clears the scan, the patient can be discharged.
What is the new hope presented with the recent approval of Abbott’s Alinity i TBI test? The new test can be performed on Abbott’s Alinity i laboratory instrument, as an alternative to the previous i-STAT TBI Plasma test. The Alinity i instrument is in wide use in hospitals within and beyond the USA for its ability to measure a variety of hormones, antigens, and other compounds using a chemiluminescent microparticle immunoassay
[74][54].
The two biomarkers measured in the simple Alinity i TBI blood test are glial fibrillary acidic protein (GFAP), the key intermediate filament protein in astrocytes, and ubiquitin C-terminal hydrolase L1 (UCH-L1), a neuronal enzyme that marks proteins for degradation. Both of these are released by the brain into the peripheral blood when the brain is injured
[75,76,77][55][56][57].
5. Potential Expanded Use of Point-of-Care Biomarker TBI Testing
Persons who have suffered a TBI and reach an emergency department or other facility equipped with the analyzer within the delimited time period are considered candidates for Abbott’s new Alinity i TBI test. The biomarker levels in these patients could serve as a source of valuable data, whether or not the CT scan is obtained in tandem. The presence or levels of GFAP and UCH-L1 cannot reliably discriminate between patients who will improve rapidly versus those with prolonged recovery time who may continue to experience troubling neurologic symptoms [113][58]. Currently, there is no test with that capability [114,115][59][60]. This poses a challenge, especially as a majority of TBI patients have no follow-up scheduled. A positive blood test might suggest that follow-up care is indicated, but wescholars propose that TBI biomarker data obtained where healthcare is provided such as the Alinity i TBI test can give the medical community so much more. Analysis and integration of data aggregated in emergency departments performing TBI biomarker testing could produce a massive database that would allow the development of a predictive model so that those at the highest risk for poor recovery could be targeted for early intervention. Sports provide a unique advantage in data collection with an opportunity to obtain preseason baseline tests so that within-player change in plasma biomarkers with TBI could be accurately captured [116][61].
In addition, the lack of effective treatment for mild TBI beyond rehabilitation and symptomatic relief makes the idea of applying the Alinity i TBI test data to acquire a more complete understanding of damage development very appealing [117,118][62][63]. This type of understanding is necessary if a breakthrough is to come, whether through the repurposing of current drugs or the application of new gene-expression-altering technologies to interrupt a program of neuronal destruction set in motion by the head injury [119][64] (Figure 2).
![](/media/common/202311/graphabstrtbibiomarker-65528b886ec3a.jpg)
FigureFigure 2. 2 Depicts tThe blood biomarkers utilized in the Alinity i TBI test and delineates the major issues involved in mild TBI diagnosis and management.
Yet another consideration in biomarker use in TBI is the lack of any validated assessment for those under age 18. The absence of representation of the pediatric concussion patient is a major gap since the developing brain is particularly susceptible to injury and prolonged sequelae [122,123][65][66]. In older persons, baseline levels of biomarkers are higher, and discriminative capability may be less or of shorter duration after injury [115,124,125][60][67][68]. In persons with Alzheimer’s disease, GFAP levels may be elevated [126][69]. The need to devise age-appropriate TBI biomarker tests is clear.
The value of the Alinity I test in TBI patients who present after the recommended testing window is somewhat in question. Although biomarker levels lose their ability to distinguish who should receive imaging, that does not preclude using the data to develop a model that will give us prognostic information concerning the chance that long-term neurologic consequences will occur [64,127,128][47][70][71].
6. Conclusions
There is not a clear consensus on diagnostic assessments for TBI, and CT scans are often used because of their availability in acute settings. As described, CT scans are useful for visualizing the presence and location of hemorrhages but are not as sensitive as MRIs for axonal injury visualization. It is also unclear how clinically useful these neuroimaging techniques are for long-term prognosis and quality of life. Since delaying the diagnosis of mild TBI can lead not only to prolonged recovery time, but also to premature return-to-activity and dangerous repeat concussion, it is important to refine blood biomarkers and apply them in real world settings
[272].
Abbott’s Alinity i TBI test may be beneficial in evaluating common biomarkers released upon brain injury such as GFAP and UCH-L1. The newfound increasing availability of Abbott’s Alinity i laboratory instrument contrary to the previous i-STAT TBI Plasma test demonstrates the potential cost-effectiveness of the test and its usefulness in detecting lasting brain damage. This development brings a new opportunity for TBI research to grow and make useful conclusions for long-term physiological and neurocognitive prognosis. The ultimate goal would be to use aggregate data to pinpoint those mild TBI patients with the highest risk of long-term debilitating neurologic problems and then implement mitigating actions to avert these consequences. Finally,
wescholars may be able to move beyond blood biomarkers to even less invasive salivary biomarkers of concussion. This is in early stages of study with interest in using salivary microRNA measures to evaluate mild TBI
[373] [474]
.