Brigham and Women’s Hospital Researchers Develop Blood Test That Enables Rapid Diagnosis of LVO Stroke in Non-hospital Settings
New technique could allow emergency responders to determine severity of LVO stroke while patient is still in the ambulance
Researchers at Brigham and Women’s Hospital in Massachusetts say they have developed a clinical laboratory test that can quickly determine whether a patient is experiencing one of the deadliest types of strokes, known as an ischemic large vessel occlusion (LVO) stroke. The development team believes this new assay could be deployed as a point-of-care test to enable faster diagnosis of stroke events.
The test combines measurement of two blood plasma biomarkers with an established clinical score used by clinicians and EMS personnel to assess stroke severity. Compared with current approaches, their technique more accurately differentiates LVO strokes from other types of strokes, making it more likely that patients receive appropriate treatment in a timely manner, the researchers said in a Brigham news release.
Dark Daily has long predicted that advances in technology and computing power would make it possible for pathologists and clinical laboratory scientists to combine multiple established biomarkers (individually not associated with the disease state targeted) with other clinical and patient data to create the ability to make an accurate and earlier diagnosis.
The researchers published their findings in the journal Stroke: Vascular and Interventional Neurology titled, “Prospective Validation of Glial Fibrillary Acidic Protein, d‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic Stroke Detection.”
Ultimately, Brigham’s research could “aid in the development of a point‐of‐care diagnostic test capable of guiding prehospital LVO stroke triage,” wrote Joshua Bernstock, MD, PhD, Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital, lead author of the study, and colleagues.
“We have developed a game-changing, accessible tool that could help ensure that more people suffering from stroke are in the right place at the right time to receive critical, life-restoring care,” said Joshua Bernstock, MD, PhD (above), Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital and lead author of the Brigham study that developed the clinical laboratory test that the researchers say can enable emergency caregivers to determine quickly and accurately if a patient is having an ischemic large vessel occlusion (LVO) stroke. (Photo copyright: Brigham and Women’s Hospital.)
Early Identification of LVO Stroke
As explained in the news release, an LVO stroke is a type of ischemic stroke caused by obstruction in a major brain artery. The researchers noted that LVO strokes account for “62% of poststroke disabilities and 96% of poststroke death.”
These strokes are readily treatable using endovascular thrombectomy (EVT), in which the blockages are surgically removed, the news release note. However, the researchers observed that EVT “requires specialized teams and equipment, limiting its availability to comprehensive stroke centers and other EVT‐capable centers.”
This can lead to delays as patients are transferred to those facilities, worsening outcomes and increasing the risk of death, the researchers wrote in Stroke: Vascular and Interventional Neurology. So, early identification of LVO stroke is key to ensuring patients receive timely treatment.
Identifying False Negatives/Positives
One challenge, the news release notes, is that brain bleeds (hemorrhagic stroke) can present similar symptoms, yet require “vastly different” treatment.
“A growing body of work has, therefore, evaluated prehospital stroke assessment scales in an effort to identify LVO strokes in the field,” the researchers wrote. “However, such severity scales lack the sensitivity and specificity required for triaging LVO patients with confidence, resulting in false negatives in patients with LVO as well as false positives in patients with stroke mimics or hemorrhagic stroke.”
As explained by EMS Aware, these assessment scales, such as FAST-ED (field assessment stroke triage for emergency destination) and RACE (rapid arterial occlusion evaluation), attempt to determine the severity of a stroke by assigning scores based on symptoms such as facial palsy, arm weakness, and speech difficulties.
To develop their test, Bernstock and colleagues proposed combining the scales with measurement of two blood proteins:
- Glial fibrillary acidic protein (GFAP), and,
- D-dimer.
In their study, they attempted to validate cutoff values for the biomarkers and scales.
To do so, the researchers analyzed data from 323 patients admitted to a Florida hospital with suspected stroke between May 2021 and August 2022. Each was assigned to one of four diagnostic categories based on clinical data from their medical records, which included results of computed tomography (CT scan) or magnetic resonance angiography (MRA). The diagnostic categories included:
- LVO (29 patients).
- Non-LVO ischemic stroke (48 patients).
- Hemorrhagic stroke (13 patients).
- Transient ischemic attack (12 patients)
- Stroke mimics (220 patients).
The patients were assessed using five stroke severity scales. The researchers used frozen blood samples from the patients to measure the biomarkers. They then used this data to determine the likelihood of LVO stroke and compared the results with the diagnoses as determined by the clinical data.
“Combinations of the blood biomarkers with the scales FAST‐ED or RACE showed the best performance for LVO detection, with a specificity of 94% (for either scale combination) and a sensitivity of 71% for both scales,” the researchers wrote.
Sensitivity was higher in patients who presented within the first six hours from onset of symptoms.
“Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage,” the researchers wrote. However, they also suggested that their algorithm could be adjusted to enable early identification of hemorrhagic stroke.
The researchers noted that they chose biomarker cutoffs to maximize specificity, so “a certain number of LVOs are missed. However, as such patients default into ‘standard‐of‐care’ triaging pathways, such a decision is unlikely to represent much clinical risk.”
Testing in the Field
The Brigham researchers used established biological biomarkers combined with modern computing—in combination with the scores from a field assessment test—to develop their new clinical laboratory test that identifies the type of stroke.
Their next step is to carry out “another prospective trial to measure the test’s performance when used in an ambulance,” the news release states. “They have also designed an interventional trial that leverages the technology to expedite the triage of stroke patients by having them bypass standard imaging and move directly to intervention.”
“In stroke care, time is brain,” Bernstock said. “The sooner a patient is put on the right care pathway, the better they are going to do. Whether that means ruling out bleeds or ruling in something that needs an intervention, being able to do this in a prehospital setting with the technology that we built is going to be truly transformative.”
More research and clinical studies are needed. However, the fact that the Brigham team wants to deploy this approach in ambulances is an indication that there is high clinical value from this approach.
Clinical pathologists and medical laboratory managers will want to watch the ongoing development and deployment of this new assay, whether it is run in near-patient settings or core clinical laboratories in support of patients presenting in emergency departments.
—Stephen Beale
Related Information:
Researchers Develop “Game-Changing” Blood Test for Stroke Detection
New Blood Test Could Spot Dangerous Type of Stroke
Researchers Develop a Blood Test That Can Detect Stroke Quickly
Blood Test a ‘Game Changer’ for Faster Diagnosis, Treatment of LVO Stroke
New Rapid Blood Test Can Accurately Detect Stroke in Six Hours, Save Lives
