Stroke Diagnosis via ProBNP and NDKA Biomarker Measurement
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Solution Overview
Problem
Current methods for diagnosing stroke, particularly ischemic stroke, have low sensitivity and specificity, and existing marker panels are cumbersome or insufficient for early detection in emergency settings, necessitating the development of alternative or complementary diagnostic approaches.
Innovation Solution
The method involves measuring levels of proBNP(1-108) and nucleoside diphosphate kinase A (NDKA) in biological samples, using specific antibodies and calibrators, to determine the occurrence of stroke or transient ischemic attack, potentially combined with markers for cardiovascular diseases to improve diagnostic accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If CT is used for stroke diagnosis, then the diagnostic method is widely available and relatively simple, but the sensitivity for detecting ischemic stroke is less than 33%
Solution Approach 1:
The patent replaces the mechanical imaging system (CT scanner) with a biochemical detection system measuring proBNP(1-108) and NDKA markers in blood samples. This substitution achieves superior sensitivity (92% at 93% specificity) without requiring complex imaging equipment, making the diagnostic method both highly accurate and practically deployable in emergency settings.
2Measurement precision
If MRI is used for stroke diagnosis, then the sensitivity for detecting ischemic stroke improves to 84%, but the equipment cost and availability in emergency rooms become problematic
Solution Approach 1:
The patent employs a disposable blood sample-based biochemical assay instead of expensive, complex MRI equipment. The method uses standard laboratory equipment to measure proBNP(1-108) and NDKA markers, achieving MRI-comparable sensitivity (92% at 93% specificity) with significantly lower infrastructure requirements and cost, making it readily available in emergency room settings.
3Measurement precision
If a panel of 5 markers (S-100b, BNGF, vWF, MMP-9, MCP-1) is used for diagnosing ischemic stroke, then the sensitivity reaches 92% at 93% specificity, but the procedure becomes cumbersome especially in the emergency room
Solution Approach 1:
The patent extracts and measures only the two most critical and discriminatory markers (proBNP(1-108) and NDKA) from the panel of five markers. This extraction approach maintains high diagnostic accuracy (92% sensitivity at 93% specificity within 6 hours) while dramatically simplifying the procedure to just two measurements, making it practical for emergency room use.
4Ease of operation
If individual markers like S-100b or NSE are used for stroke detection, then the diagnostic procedure remains simple, but the discriminatory power is insufficient to be of clinical value
Solution Approach 1:
The patent combines two complementary markers (proBNP(1-108) and NDKA) that detect different aspects of stroke pathology. proBNP(1-108) reflects cardiac strain and neurogenic inflammation, while NDKA indicates neuronal damage. This combination achieves high discriminatory power (92% sensitivity at 93% specificity) while maintaining procedural simplicity with just two measurements.
Data Source
AI summary
The present invention relates to a method for the in vitro diagnosis of stroke and transient ischemic attack (TIA) in an individual, comprising the following steps: (a) measuring the level of proBNP(1 -108), or of fragments of proBNP(1 -108) comprising a RAPRSP sequence (SEQ ID NO: 1 ), in a biological sample of the individual; (b) measuring the level of nucleoside diphosphate kinase A (NDKA) in a biological sample of the individual; (c) comparing the level of proBNP(1 -108), or of fragments of proBNP(1 -108), and the level of NDKA, with one or several cut-off values; (d) determining therefrom whether a stroke or a TIA has occurred in the individual.