535
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→State of the Art
The global incidence of TBI is estimated to be 27 to 69 million a year <ref name="Arti20">Dewan, M. C., Rattani, A., Gupta, S., Baticulon, R. E., Hung, Y. C., Punchak, M., Agrawal, A., Adeleye, A. O., Shrime, M. G., Rubiano, A. M., Rosenfeld, J. V., & Park, K. B. (2019). Estimating the global incidence of traumatic brain injury. Journal of Neurosurgery, 130(4), 1080–1097. https://doi.org/10.3171/2017.10.jns17352</ref> <ref name="Arti21">James, S. L., Theadom, A., Ellenbogen, R. G., Bannick, M. S., Montjoy-Venning, W., Lucchesi, L. R., Abbasi, N., Abdulkader, R., Abraha, H. N., Adsuar, J. C., Afarideh, M., Agrawal, S., Ahmadi, A., Ahmed, M. B., Aichour, A. N., Aichour, I., Aichour, M. T. E., Akinyemi, R. O., Akseer, N., . . . Murray, C. J. L. (2019). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(1), 56–87. https://doi.org/10.1016/s1474-4422(18)30415-0</ref>. Across all severities of TBI, mortality is quite low at 3% <ref name="Arti22">Georges, A., & Das, J. M. (2022). Traumatic Brain Injury [Internet]. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459300/</ref> this was determined in the United States of America, a country where the healthcare system is quite developed. While mortality is low, the long term effects of TBI can be detrimental to a person’s quality of life. Some of the acute symptoms lessen or resolve over time, such as dizziness or nausea. Other consequences do not become apparent until a long period of time has passed, for instance psychiatric conditions.<ref name="Arti23">Seel, R. T., Macciocchi, S., & Kreutzer, J. S. (2010). Clinical Considerations for the Diagnosis of Major Depression After Moderate to Severe TBI. Journal of Head Trauma Rehabilitation, 25(2), 99–112. https://doi.org/10.1097/htr.0b013e3181ce3966</ref>
Currently, the Glasgow coma scale (GCS) is the only standardized way to assess patients with a suspected TBI. The GCS provides a practical method for assessing impairment of conscious level in response to defined stimuli.[[File:The glasgow coma scale.png|thumb|290px|The Glasgow coma scale.<ref name="Arti24">https://smhs.gwu.edu/urgentmatters/news/keep-it-simple-acute-gcs-score-binary-decision</ref>]] Depending on the final score, the TBI can be classified as minor, moderate or severe.
While the GCS score describes the current condition of the patient, its usage has many shortcomings, one of which is the fact that physicians seem to struggle with remembering the exact levels of the scale.<ref name="Arti25">Riechers, R. G., Ramage, A., Brown, W., Kalehua, A., Rhee, P., Ecklund, J. M., & Ling, G. S. (2005). Physician Knowledge of the Glasgow Coma Scale. Journal of Neurotrauma, 22(11), 1327–1334. https://doi.org/10.1089/neu.2005.22.1327</ref> Although there is a dose-response relationship with regard to the severity of the TBI and the severity of the outcome, the GCS does not effectively and uniformly predict mortality rate. <ref name="Arti26">Institute of Medicine (US) Committee on Gulf War and Health: Brain Injury in Veterans and Long-Term Health Outcomes. (2008). Gulf War and Health: Volume 7 (Vol. 7) [Internet]. National Academies Press. https://doi.org/10.17226/12436</ref> <ref name="Arti27">Cho, D. Y., & Wang, Y. C. (1997). Comparison of the APACHE III, APACHE II and Glasgow Coma Scale in acute head injury for prediction of mortality and functional outcome. Intensive Care Medicine, 23(1), 77–84. https://doi.org/10.1007/s001340050294</ref>
Other ways for diagnosing TBI can include various imaging tests like a CT scan or an MRI scan. However, these imaging techniques are often not sensitive/specific enough for milder TBI. According to experts, only 5-10% of mild TBI patients have abnormal CT/MRI scans. The problem with these scans is that they can only detect damage on a macroscopic level, whereas mild TBI manifests primarily at a microscopic level. Therefore, doctors can mistakenly believe that patients with a standard CT or MRI scan have not suffered a TBI.<ref name="Arti28">McKinlay, A., Lin, A., & Than, M. (2018). A comparison of emergency department medical records to parental self-reporting of traumatic brain injury symptoms. Concussion, 3(1), CNC52. https://doi.org/10.2217/cnc-2017-0017</ref> All in all, improvements are needed to objectively and effectively determine whether or not a patient is suffering from a TBI.
== State of the Art ==
Currently, the concentration of GFAP is typically measured in blood plasma (liquid component of blood in which blood cells are absent) or serum (plasma from which the clotting proteins have been removed). Classic methods for the detection of GFAP include ELISA (Enzyme-Linked Immunosorbent Assay).
{| class="wikitable" style="margin-bottom:0"
!Test Name
!Sample Volume (μL)
!Sample matrix
!Range (pg/mL)
!Precision (CV%)
!Incubation time (min)
!Measuring Technique
!Assay type
!Links
|-
|GFAP CLIA Assay, from Eagle Biosciences
|100
|serum, CSF
|10-640
|Intra-Assay: CV=1%, Inter-Assay: CV=6%
|150
|ELISA
|solid phase enzyme-linked sandwich immunosorbent
|https://eaglebio.com/product/gfap-clia-assay-kit/ https://eaglebio.com/wp-content/uploads/2022/01/gfp31-L01-gfap-clia-assay-kit-package-insert-2022.pdf
|-
|Human GFAP ELISA Kit, from FineTest
|
|serum, plasma, tissue homogenates, other biological fluids
|313-20000
|Intra-Assay: CV<8%, Inter-Assay: CV<10%
|
|ELISA
|sandwich
|https://www.fn-test.com/product/eh0410/ https://www.fn-test.com/content/uploads/product/manuals/elisa/EH0410.pdf
|-
|Human GFAP ELISA Kit, Producer not known, distributed by Mybiosource
|>10
|serum, plasma, tissue homogenates
|625-40000
|Intra-Assay: CV<8%, Inter-Assay: CV<10%
|≈300
|ELISA
|quantitative sandwich enzyme immunoassay
|https://www.mybiosource.com/gfap-human-elisa-kits/glial-fibrillary-acidic-protein/704044 https://cdn.mybiosource.com/tds/protocol_manuals/000000-799999/MBS704044.pdf
|-
|Human GFAP ELISA Kit, from LSBio
|>10
|plasma, serum
|156 - 10000
|Intra-Assay: CV<10%, Inter-Assay: CV<12%
|≈300
|ELISA
|sandwich
|https://www.lsbio.com/elisakits/human-gfap-sandwich-elisa-elisa-kit-ls-f4258/4258?trid=247 https://www.lsbio.com/elisakits/manualpdf/ls-f4258.pdf
|-
|GFAP Human ProcartaPlex™ Simplex Kit, from Thermo
|>25
|plasma, serum, CSF
|8 - 32900
|
|
|ELISA
|sandwich
|https://www.thermofisher.com/order/catalog/product/EPX010-12336-901
|-
|GFAP ELISA Kit, from Aviva Systems Biology
|>2
|Serum, plasma, other biological fluids
|31.25-2000
|Intra-Assay: CV<10%, Inter-Assay: CV<12%
|300
|ELISA
|sandwich enzyme-linked immuno-sorbent
|https://www.avivasysbio.com/gfap-elisa-kit-bovine-okcd02567.html https://www.avivasysbio.com/pub/media/pdf/products/OKCD02567.pdf
|-
|}<div style="margin-bottom:1em"><sub>''Table 1: Commercially available GFAP ELISA test assays.</sub><br/>
As is clear from the above table, the classic ELISA technique is widely available as commercial kits, which makes it a convenient method for biomarker detection in patient samples. Nevertheless, a relatively long detection time (of at least a few hours) and the requirement of a laboratory environment precludes its use in GP surgeries or patients’ homes.<ref name="Arti29">Xu, L., Ramadan, S., Akingbade, O. E., Zhang, Y., Alodan, S., Graham, N., Zimmerman, K. A., Torres, E., Heslegrave, A., Petrov, P. K., Zetterberg, H., Sharp, D. J., Klein, N., & Li, B. (2021). Detection of Glial Fibrillary Acidic Protein in Patient Plasma Using On-Chip Graphene Field-Effect Biosensors, in Comparison with ELISA and Single-Molecule Array. ACS Sensors, 7(1), 253–262. https://doi.org/10.1021/acssensors.1c02232</ref> Classic ELISAs are laboratory-based assay, which are not suited for rapid testing as targeted in the SensUs competition.The same applies to more advanced laboratory assays, such as mass spectrometry and single molecular array (Simoa) technology.
Recently a commercial GFAP test has been developed by Abbott on its i-STAT Alinity biosensor platform. The specifications are listed in the Table below. The i-STAT platform is used in hospitals. However, the i-STAT TBI Plasma test is not intended to be used in point-of-care settings.
{| class="wikitable" style="margin-bottom:0"
!Test Name
!Sample Volume (μL)
!Sample matrix
!Range (pg/mL)
!Precision (CV%)
!Incubation time (min)
!Measuring Technique
!Assay type
!Links
|-
|i-STAT TBI Plasma
|>20
|plasma
|30-10000
|
|15
|cartridge for analyzer
|
|https://www.globalpointofcare.abbott/en/product-details/apoc/istat-tbi-plasma.html https://www.globalpointofcare.abbott/en/product-details/apoc/istat-alinity.html
|-
|}<div style="margin-bottom:1em"><sub>''Table 2: Commercially available GFAP biosensor.</sub><br/>
== Lab protocols ==
During the preparation of the blood samples, one should avoid physical contact with blood by wearing gloves, glasses, and lab coats. Needles and lancets should be used only once and disposed of in a sharps container for decontamination. Furthermore, cuts already present on hands or arms should be covered with plasters to avoid blood-on-blood contact. After completing the samples, gloves should be removed and hands should be washed thoroughly. The waste should be disposed of in specific biohazard waste bins or bags.
== References ==
<references />
