Methods for aiding in the hyperacute diagnosis and determination of traumatic brain injury using early biomarkers on at least two samples from the same human subject

Inventors

McQuiston, Beth • Rogers, Justin • Datwyler, Saul • Marino, Jaime

Assignees

Abbott Laboratories

Abstract

Disclosed herein are methods that aid in the hyperacute diagnosis and evaluation of a human subject that has sustained or may have sustained an injury to the head, such as mild, moderate, severe, or moderate to severe traumatic brain injury (TBI), using an early biomarker, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or a combination thereof. Also disclosed here are methods that aid in the hyperacute determination of whether a human subject that has sustained an injury or may have sustained to the head would benefit from and thus receive a head computerized tomography (CT) scan based on the levels of UCH-L1. These methods involve detecting changes of levels of an early biomarker, such as ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or a combination thereof, in samples taken from a human subject at a time point within about 2 hours, such as about 10, 12, or 20 minutes, after the subject has sustained or may have sustained an injury to the head and a second time point about 3 hours to about 6 hours after the first sample is taken.

Core Innovation

The invention provides a method for hyperacute diagnosis and evaluation after an actual or suspected injury to the head. At least one assay for ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or a combination thereof is performed in at least a first sample and a second sample obtained from a human subject. The sample is whole blood, serum, plasma, or cerebrospinal fluid, and the first time point is within about 2 hours after the actual or suspected head injury, with the second time point within about 3 to about 6 hours after the first sample is taken.

The method classifies the injury as mild versus moderate, severe, or moderate to severe traumatic brain injury (TBI) based on whether the level of UCH-L1 increases or decreases by at least about 40 pg/mL from the first sample to the second sample and/or whether the level of GFAP increases or decreases by at least about 1 pg/mL from the first sample to the second sample. When these change criteria are met for UCH-L1 and/or GFAP, the subject is treated for moderate, severe, or moderate to severe TBI, whereas when the criteria are not met, the subject is treated for mild TBI.

In one embodiment, the method uses the same biomarker change criteria to determine whether to perform a head computed tomography (CT) scan. A head CT scan is performed when UCH-L1 increases or decreases by at least about 40 pg/mL and/or when GFAP increases or decreases by at least about 1 pg/mL between the first and second samples, and the scan decision is incorporated into the subsequent treatment selection. The disclosed approach can also correlate with Glasgow Coma Scale (GCS) score categories as additional clinical context.

Claims Coverage

Two independent claims are identified. The claims cover serial biomarker assays for UCH-L1 and/or GFAP at first and second time points, threshold-based classification of TBI severity with corresponding treatment selection, and in one independent claim, biomarker-change-based head CT decisions. Dependent features further specify sample type, assay modality, and assay performance.

Across the independent claims, the method relies on serial measurement of UCH-L1 and/or GFAP from whole blood, serum, plasma, or cerebrospinal fluid obtained within specified first and second time points, and applies threshold-based biomarker change criteria to determine TBI severity category and select treatment; one claim additionally ties the same criteria to whether a head CT scan is performed.

Stated Advantages

Documented Applications