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Brigham and Women’s Hospital Researchers Develop Blood Test That Enables Rapid Diagnosis of LVO Stroke in Non-hospital Settings

Oct 23, 2024 | Laboratory Management and Operations, Laboratory News, Laboratory Pathology, Laboratory Resources, Laboratory Testing

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:

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:

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

Prospective Validation of Glial Fibrillary Acidic Protein, d‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic 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

University of Warwick Researchers Identity Blood Protein Biomarkers That Can Predict Dementia Onset Years in Advance

May 29, 2024 | Digital Pathology, International Laboratory News, Laboratory Instruments & Laboratory Equipment, Laboratory Pathology, Laboratory Resources, Laboratory Testing, Precision Medicine

With further study, this research may provide clinical laboratories with a new proteomic biomarker for dementia screenings that identifies risk more than 10 years before symptoms appear

Researchers at the University of Warwick in the UK and Fudan University in Shanghai, China, identified four protein biomarkers in blood that they say can predict dementia up to 15 years before diagnosis. They say these biomarkers may lead to clinical laboratory blood tests that offer alternatives to costly brain scans and lumbar punctures for diagnosis of dementia.

The scientists “used the largest cohort of blood proteomics and dementia to date,” according to a University of Warwick news release. This included taking blood from 52,645 “healthy” people without dementia who participated in the UK Biobank—a population-based study cohort, the new release noted.

“The proteomic biomarkers are [easy] to access and non-invasive, and they can substantially facilitate the application of large-scale population screening,” said neurovegetative disease specialist Jin-tai Yu, MD, PhD, a professor at Fudan University and co-author of the study, in the news release.

The scientists published their findings in the journal Nature Aging titled, “Plasma Proteomic Profiles Predict Future Dementia in Healthy Adults.”

“The advent of proteomics offers an unprecedented opportunity to predict dementia onset,” the researchers wrote.

“This is a well-conducted study that adds to what we know about changes in blood that occur very early in diseases that cause dementia, which will be important for early diagnosis in the future,” said Tara Spires-Jones, PhD, in a post from the Science Media Center in the UK. “However,” she added, “it is important to note that these are still scientific research studies and that there are currently no blood tests available for routine use that can diagnose dementia with certainty.

Jones, who was not involved in the study, is President of the British Neuroscience Association (BNA) and group leader of the UK Dementia Research Institute at the University of Edinburgh.

“Based on this study, it does seem likely that blood tests will be developed that can predict risk for developing dementia over the next 10 years, although individuals at higher risk often have difficulty knowing how to respond,” Suzanne Schindler, MD, PhD (above), told Reuters. Schindler, an Associate Professor of Neurology at Washington University in St. Louis, was not involved in the research. Clinical laboratories may soon have a new blood test for dementia. (Photo copyright: VJDementia.)

Predicting Onset of Dementia with 90% Accuracy

The researchers analyzed 52,645 blood samples from the UK Biobank (UKBB). The samples were collected between 2006 and 2010 from healthy individuals who at that time were without dementia.

By March 2023, 1,417 of the study participants had developed Alzheimer’s disease or some other form of dementia. The researchers looked at 1,463 proteins and identified four that were present in high levels among those people:

“Individuals with higher GFAP levels were 2.32 times more likely to develop dementia,” the researchers wrote in Nature Aging. “Notably, GFAP and LTBP2 were highly specific for dementia prediction. GFAP and NEFL began to change at least 10 years before dementia diagnosis.”

When adding known risk factors such as age, sex, and genetics, the researchers said they could predict onset of dementia with 90% accuracy, according to the University of Warwick news release.

“Our findings strongly highlight GFAP as an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis, with implications for screening people at high risk for dementia and for early intervention,” the researchers wrote.

The news release also noted that smaller studies had already identified some of the proteins as potential biomarkers, “but this new research was much larger and conducted over several years.”

Further Validation Needed

Amanda Heslegrave, PhD, of the UK Dementia Research Institute, University College London described the UKBB as “an excellent resource” in the Science Media Center (SMC) post. However, she noted, it’s “a highly curated biobank and may not capture all populations that we need to know the risk for. The new biomarkers identified will need further validation before being used as screening tools.”

Another expert raised additional questions about the University of Warwick/Fudan University study in the SMC post.

“These results may help researchers understand the biological systems involved in the development of dementia,” said David Curtis, MD, PhD, of the UCL Genetics Institute at University College London. “However in my view the strengths of the reported associations are not really strong enough to say that these would form a useful test for predicting who will get dementia in the future.”

Conversely, Curtis pointed to other studies suggesting that phosphorylated tau (p-tau) proteins are better candidates for developing a simple blood test.

P-tau “provides a very good indicator of whether the pathological processes leading to Alzheimer’s disease are present in the brain,” he said. “When effective treatments for Alzheimer’s disease are developed it will be very helpful indeed to have simple blood tests—such as measuring phosphorylated tau—available in order to identify who could benefit.”

At least two blood tests based on the p-tau217 variant—from ALZpath and C2N—are currently available to US clinicians as laboratory developed tests (LDT).

In “University of Gothenburg Study Findings Affirm Accuracy of Clinical Laboratory Blood Test to Diagnose Alzheimer’s Disease,” Dark Daily reported on a study from the University of Gothenburg in Sweden which found that the ALZpath test was as good or better than lumbar punctures and brain scans as a diagnostic tool for Alzheimer’s.

UK Biobank

The UK Biobank continues to be used by researchers both in the UK and abroad because of the full sets of data on large numbers of patients over many years. There are few other sources of such data elsewhere in the world. The UK Biobank is a large-scale biomedical database and research resource. It contains de-identified genetic, lifestyle and health information, and biological samples from 500,000 UK participants.

On its website, the UK Biobank states, “It is the most comprehensive and widely-used dataset of its kind and is globally accessible to approved researchers who are undertaking health-related research that is in the public interest, whether they are from academic, commercial, government or charitable settings.”

Thus, clinical laboratory managers and pathologists can expect a continuing stream of published studies that identify biomarkers associated with different health conditions and to see where the data used in these analyses came from the UK’s biobank.

—Stephen Beale

Related Information:

Protein Biomarkers Predict Dementia 15 Years Before Diagnosis, According to New Study

Plasma Proteomic Profiles Predict Future Dementia in Healthy Adults

Proteins May Predict Who Will Get Dementia 10 Years Later, Study Finds

Expert Reaction to Study of Potential Protein Biomarkers for Dementia Risk

Two New p-Tau217 Blood Tests Join a Crowded Field

Plasma p-Tau-217 Assays Work Well, But No Home Run for Diagnosis

Dementia Can Be Predicted More than a Decade Before Diagnosis with These Blood Proteins

Dementia Predicted 10 Years Before Diagnosis

Early Blood Test to Predict Dementia Is Step Closer as Biological Markers Identified

Validating Blood Tests as A Possible Routine Diagnostic Assay of Alzheimer’s Disease

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