# US 12,178,592 B2 · Methods for aiding in diagnosing and evaluating a mild traumatic brain injury in a human subject using cardiac troponin I > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,178,592 B2 - Document ID: US12178592B2 - Status: Granted - Kind: B2 - Application number: 17/411,511 - Filed: 2021-08-25 - Published: 2022-02-17 - Granted: 2024-12-31 - Earliest claimed: 2017-05-30 - Assignees: Abbott Laboratories - Applicants: Abbott Laboratories - Inventors: Beth McQuiston; Frederick Korley; Agim Beshiri; Jaime Marino; Saul Datwyler - Web page: https://patentgrep.com/patent/US12178592B2 ## CPC - A61B 5/4064: {Evaluating the brain (for intracranial pressure A61B5/031; for cerebral blood gases A61B5/14553; using EEG A61B5/369)} - G01N 33/54346: {Nanoparticles} - G01N 33/54366: {Apparatus specially adapted for solid-phase testing} - G01N 33/577: involving monoclonal antibodies {binding reaction mechanisms characterised by the use of monoclonal antibodies (G01N33/5302 - G01N33/576 take precedence)} - G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease} - C12Q 1/6883: for diseases caused by alterations of genetic material - G01N 33/533: with fluorescent label - G01N 33/564: for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9} - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 2800/28: Neurological disorders - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N 2800/56: Staging of a disease; Further complications associated with the disease - G01N 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract Disclosed herein are methods that aid in the diagnosis and evaluation of a human subject that has sustained or may have sustained an injury to the head, such as mild or moderate, severe, or moderate to severe traumatic brain injury (TBI), using cTnI. Also disclosed are methods for determining whether to perform a head computerized tomography on a subject by detecting levels of cTnI. Finally, also disclosed are methods of outcome in subjects suffering from a mild TBI. ## Claims ### Claim 1 A method comprising: a) performing at least one assay for cardiac troponin I (cTnI) in at least one sample that is whole blood, serum, plasma, or cerebrospinal fluid obtained from a subject within about 24 hours after an actual or suspected injury to the head; and b) treating the subject for (1) a moderate, severe, or moderate to severe traumatic brain injury (TBI) when the level of cTnI in the sample is higher than a reference level of cTnI, or (2) a mild TBI when the level of cTnI in the sample is lower than a reference level of cTnI; and wherein the subject levels of cTnI are distinct from levels of cTnI in a control subject that has no TBI. ### Claim 2 (depends on 1) The method of claim 1, wherein: (a) the assay is selected from the group consisting of an immunoassay, a clinical chemistry assay, and a point-of-care assay and/or the assay is performed using single molecule detection; (b) the subject has received a Glasgow Coma Scale score before or after the assay is performed, and wherein the reference level is correlated with: (i) a Glasgow Coma Scale score of 3-12 and the subject is suspected of having mild TBI based on the Glasgow Coma Scale score; or (ii) a Glasgow Coma Scale score of 13-15 and the subject is suspected of having a moderate, severe, or moderate to severe TBI based on the Glasgow Coma Scale score; (c) the reference level for cTnI is about 1.94 pg/mL, about 2.54 pg/mL, about 21.23 pg/mL, or about 43.79 pg/mL; (d) the reference level is (i) determined by an assay having a sensitivity of between at least about 85% to 100% and a specificity of between at least about 30% to 100%; (ii) determined by an assay having a sensitivity of at least about 87.5% and a specificity of at least about 31%; or (iii) between at least about 1 pg/mL to about 50 pg/mL; (e) the sample is taken within about 30 minutes, within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours of the actual or suspected injury to the head; or (f) a subject with (1) a moderate, severe, or moderate to severe TBI is treated (a) with one or more therapeutic agents; (b) with one or more surgical procedures; (c) by protecting the subject's airway; (d) with one or more therapies selected from the group consisting of rehabilitation, physical therapy, occupational therapy, cognitive behavioral therapy, anger management, counseling and any combinations thereof; or (e) with any combination of (a)-(d); or (2) a mild TBI is treated (a′) with rest; (b′) by abstaining from physical activities; (c′) by avoiding light; (d′) by wearing protective eyewear when in light; (e′) with one or more therapeutic agents; or (f) with any combination of (a′)-(e′). ### Claim 3 (depends on 1) The method of claim 1, further comprising monitoring the subject assessed as having a mild, moderate, severe, or moderate to severe TBI. ### Claim 4 (depends on 1) The method of claim 1, wherein the assay is performed on the sample obtained from the subject with about 2 hours after an actual or suspected injury to the head to measure or detect a level of cTnI. ### Claim 5 (depends on 1) The method of claim 1, wherein: (a) the reference level for cTnI is about 1.15 pg/mL or about 1.29 pg/mL; (b) the reference level is (i) determined by an assay having a sensitivity of between at least about 85% to 100% and a specificity of between at least about 30% to 100%; (ii) determined by an assay having a sensitivity of at least about 87.5% and a specificity of at least about 31%; or (iii) between at least about 0.5 pg/mL to about 30 pg/mL; or (c) the sample is taken within about 5 minutes, within about 10 minutes, within about 12 minutes, within about 15 minutes, within about 20 minutes, within about 30 minutes, within about 60 minutes, or within about 90 minutes after an actual or suspected injury to the head. ### Claim 6 (depends on 2) The method of claim 2, wherein the one or more therapeutic agents is at least one cardioprotective therapy, wherein the at least one cardioprotective therapy comprises a beta-blocker, a diuretic, an Angiotensin-Converting Enzyme (ACE) inhibitor, a calcium channel blocker, a lipid lowering therapy, a statin, a nitrate, an antiplatelet, an anticlotting agent, an anticoagulation agent or combinations thereof. ### Claim 7 A method comprising: a) performing at least one assay for cardiac troponin I (cTnI) in at least one sample that is whole blood, serum, plasma, or cerebrospinal fluid obtained from a subject within about 24 hours after an actual or suspected injury to the head; and b) performing a head computed tomography (CT) scan on the subject when the level of cTnI in the sample is higher than a reference level of cTnI; and wherein the subject levels of cTnI are distinct from levels of cTnI in a control subject that has no traumatic brain injury; and (c) treating the subject for (1) a moderate, severe, or moderate to severe TBI when the level of cTnI in the sample is higher than a reference level of cTnI (a) with one or more therapeutic agents; (b) with one or more surgical procedures; (c) by protecting the subject's airway; (d) with one or more therapies selected from the group consisting of rehabilitation, physical therapy, occupational therapy, cognitive behavioral therapy, anger management, counseling and any combinations thereof; or (e) with any combination of (a)-(d); or (2) a mild TBI when the level of cTnI in the sample is lower than a reference level of cTnI (a′) with rest; (b′) by abstaining from physical activities; (c′) by avoiding light; (d′) by wearing protective eyewear when in light; (e′) with one or more therapeutic agents; or (f) with any combination of (a′)-(e′). ### Claim 8 (depends on 7) The method of claim 7, wherein: (a) the assay is selected from the group consisting of an immunoassay, a clinical chemistry assay, and a point-of-care assay and/or the assay is performed using single molecule detection; (b) the sample is taken from the subject within about 30 minutes, within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours of the actual or suspected injury to the head; (c) the reference level for cTnI is about 1.65 pg/mL, about 2.16 pg/mL, about 14.75 pg/mL, or about 30.43 pg/mL; (d) the reference level is (i) determined by an assay having a sensitivity of between at least about 65% to 100% and a specificity of between at least about 30% to 100%; (ii) determined by an assay having a sensitivity of at least about 85% and a specificity of at least about 33%; or (iii) between at least about 1.0 pg/mL to about 50 pg/mL; or (e) the assay is performed on the sample obtained from the subject with about 2 hours after an actual or suspected injury to the head to measure or detect a level of cTnI. ### Claim 9 (depends on 8) The method of claim 8, wherein: (a) the reference level for cTnI is about 5.8 pg/mL or about 4.7 pg/mL; (b) the reference level is (a) determined by an assay having a sensitivity of between at least about 65% to 100% and a specificity of between at least about 30% to 100%; (b) determined by an assay having a sensitivity of at least about 85% and a specificity of at least about 33%; or (c) between at least about 0.5 pg/mL to about 25 pg/mL; or (c) sample is taken within about 5 minutes, within about 10 minutes, within about 12 minutes, within about 15 minutes, within about 20 minutes, within about 30 minutes, within about 60 minutes, or within about 90 minutes after an actual or suspected injury to the head. ### Claim 10 (depends on 7) The method of claim 7, wherein the method further comprises: (a) not performing a head CT scan on the subject and treating the subject for a mild TBI when the level of cTnI in the sample is lower than a reference level of cTnI; or (b) ruling out the need to perform a head CT scan on the subject when the level of cTnI in the sample is lower than a reference level of cTnI. ### Claim 11 (depends on 10) The method of claim 10, wherein the one or more therapeutic agents is at least one cardioprotective therapy, wherein the at least one cardioprotective therapy comprises a beta-blocker, a diuretic, an Angiotensin-Converting Enzyme (ACE) inhibitor, a calcium channel blocker, a lipid lowering therapy, a statin, a nitrate, an antiplatelet, an anticlotting agent, an anticoagulation agent or combinations thereof. ### Claim 12 A method comprising: a) performing at least one assay for cardiac troponin I (cTnI) in at least a first sample taken at a first time point and a second sample taken at a second time point and obtained from a human subject after an actual or suspected injury to the head; and b) treating the subject for mild, a moderate, severe, or moderate to severe traumatic brain injury (TBI) when the level of cTnI in the sample has increased from the first sample to the second sample; and wherein the sample is whole blood, serum, plasma, or cerebrospinal fluid obtained wherein the first time point is within about 24 hours after the actual or suspected head injury and the second time point is within about 3 to about 6 hours, and further wherein the subject levels of cTnI are distinct from levels of cTnI in a control subject that has no TBI. ### Claim 13 The method of 12, wherein: (a) the first sample is taken from the subject within about 30 minutes, within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours of the actual or suspected injury to the head; (b) the assay is selected from the group consisting of an immunoassay, a clinical chemistry assay, and a point-of-care assay and/or the assay is performed using single molecule detection; or (c) a subject with (1) a moderate, severe, or moderate to severe TBI is treated (a) with one or more therapeutic agents; (b) with one or more surgical procedures; (c) by protecting the subject's airway; (d) with one or more therapies selected from the group consisting of rehabilitation, physical therapy, occupational therapy, cognitive behavioral therapy, anger management, counseling and any combinations thereof; or (e) with any combination of (a)-(d); or (2) a mild TBI is treated (a′) with rest; (b′) by abstaining from physical activities; (c′) by avoiding light; (d′) by wearing protective eyewear when in light; (e′) with one or more therapeutic agents; or (f) with any combination of (a′)-(e′). ### Claim 14 (depends on 13) The method of claim 13, wherein the one or more therapeutic agents is at least one cardioprotective therapy, wherein the at least one cardioprotective therapy comprises a beta-blocker, a diuretic, an Angiotensin-Converting Enzyme (ACE) inhibitor, a calcium channel blocker, a lipid lowering therapy, a statin, a nitrate, an antiplatelet, an anticlotting agent, an anticoagulation agent or combinations thereof. ### Claim 15 A method comprising: a) performing at least one assay for cardiac troponin I (cTnI) in at least a first sample taken at a first time point and a second sample taken at a second time point and obtained from a human subject after an actual or suspected injury to the head; and b) treating the subject for mild, a moderate, severe, or moderate to severe traumatic brain injury (TBI) when the level of cTnI in the sample has increased from the first sample to the second sample; and wherein the sample is whole blood, serum, plasma, or cerebrospinal fluid obtained wherein the first time point is within about 24 hours after the actual or suspected head injury and the second time point is within about 1 to about 4 hours, and further wherein the subject levels of cTnI are distinct from levels of cTnI in a control subject that has no TBI. ### Claim 16 The method of 15, wherein: (a) the first sample is taken from the subject within about 30 minutes, within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours of the actual or suspected injury to the head; (b) the assay is selected from the group consisting of an immunoassay, a clinical chemistry assay, and a point-of-care assay and/or the assay is performed using single molecule detection; (c) the amount of cTnI in the first sample or second sample is from about 1.0 to about 50 pg/mL; or (d) a subject with (1) a moderate, severe, or moderate to severe TBI is treated (a) with one or more therapeutic agents; (b) with one or more surgical procedures; (c) by protecting the subject's airway; (d) with one or more therapies selected from the group consisting of rehabilitation, physical therapy, occupational therapy, cognitive behavioral therapy, anger management, counseling and any combinations thereof; or (e) with any combination of (a)-(d); or (2) a mild TBI is treated (a′) with rest; (b′) by abstaining from physical activities; (c′) by avoiding light; (d′) by wearing protective eyewear when in light; (e′) with one or more therapeutic agents; or (f) with any combination of (a′)-(e′). ### Claim 17 (depends on 16) The method of claim 16, wherein the one or more therapeutic agents is at least one cardioprotective therapy, wherein the at least one cardioprotective therapy comprises a beta-blocker, a diuretic, an Angiotensin-Converting Enzyme (ACE) inhibitor, a calcium channel blocker, a lipid lowering therapy, a statin, a nitrate, an antiplatelet, an anticlotting agent, an anticoagulation agent or combinations thereof. ### Claim 18 A method comprising: a) performing at least one assay for cardiac troponin I (cTnI) in at least a first sample taken at a first time point and a second sample taken at a second time point and obtained from a human subject after an actual or suspected injury to the head; and b) treating the subject for mild, a moderate, severe, or moderate to severe traumatic brain injury (TBI) when the level of cTnI in the sample has increased by at least about 20% from the first sample to the second sample; and wherein the sample is whole blood, serum, plasma, or cerebrospinal fluid wherein the first time point is within about 24 hours after the actual or suspected head injury and the second time point is within about 0 to about 4 hours, and further wherein the subject levels of cTnI are distinct from levels of cTnI in a control subject that has no TBI. ### Claim 19 The method of 18, wherein: (a) the first sample is taken from the subject within about 30 minutes, within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours of the actual or suspected injury to the head; or (b) the assay is selected from the group consisting of an immunoassay, a clinical chemistry assay, and a point-of-care assay and/or the assay is performed using single molecule detection.