On Episode 7 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the August 2021 issue of Stroke: "Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study" and "Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm." She also interviews Drs. Nirav Bhatt and Diogo Haussen about their article "Reliability of Field Assessment Stroke Triage for Emergency Destination Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience."
Dr. Negar Asdaghi:
1) Can preterm birth be associated with increased risk of stroke in adulthood?
2) Can a plant-based diet high in phytoestrogens reduce the risk of aneurysm formation and aneurysmal rupture in postmenopausal women?
3) What is the predictive ability of FAST-ED score in detection of large vessel occlusion?
We will review these questions in today's podcast. You're listening to the Stroke Alert Podcast. Stay with us.
Dr. Negar Asdaghi: From the Editorial Board of Stroke, welcome to the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. The August 2021 issue of Stroke covers a wide range of topics from examining if the presence of spot sign modifies the treatment effect of tranexamic acid in patients with intracerebral hemorrhage to the results of the PRESERVE randomized clinical trial examining whether intensive blood pressure lowering in patients with severe cerebral small vessel disease can be associated with progression of white matter damage as detected by diffusion tensor imaging or MRI studies, which I encourage you to review in addition to our podcast today.
Dr. Negar Asdaghi: Later in today's podcast, I have the pleasure of interviewing Drs. Diogo Haussen and Nirav Bhatt from Emory University on their work on reliability of FAST-ED scale when used by the paramedics in mobile stroke units and learn about the implementation of mobile stroke units in Atlanta. But first with these two articles.
Dr. Negar Asdaghi: Preterm birth, defined as birth prior to 37 weeks of gestation, affects approximately 11% of births worldwide. Today, with the advent of modern neonatal and pediatric care, the majority of preterm babies survive into adulthood. Multiple studies have shown that adult survivors of preterm birth are at increased risk of developing vascular risk factors, such as diabetes and hypertension, and have a higher incidence of ischemic heart disease as compared to their age-matched individuals born at term, though the association between preterm birth and risk of stroke is not well studied.
Dr. Negar Asdaghi: In the current issue of the journal, Dr. Casey Crump from Departments of Family Medicine and Community Health and Population Health Science and Policy at Icahn School of Medicine, Mount Sinai, New York, examined whether preterm birth is associated with an increased risk of stroke and its major subtypes in adulthood. The authors use the prenatal and birth information obtained from the Swedish Birth Register, which contains information for nearly all births in Sweden since 1973. The study cohort included over 2,200,000 singleton live births in Sweden from 1973 to 1994. These years were chosen to allow for sufficient follow-up into adulthood. The study cohort was examined for the earliest diagnosis of stroke from the time the participants turned 18 through September 31, 2015, and the maximum age of included population is 43 years. Stroke was identified using ICD codes from all primary and secondary diagnosis in the Swedish Hospital and Outpatient Registries and all deaths attributed to stroke in the Swedish Death Register.
Dr. Negar Asdaghi: Cosibling analyses assess for potential shared, familial confounding factors, such as genetic and environmental factors, that could contribute to development of stroke. In 28 million person-years of follow-up, 4861, or 0.2% persons, were diagnosed with stroke between 18 to 43 years of age. The authors found that low gestational age at birth was associated with a significantly higher risk of first-time stroke in adulthood. In their adjusted model, as compared to those born at full-term, the hazard ratio for any stroke associated with early preterm, that is birth between 22 to 33 weeks of gestation, was 1.4, and the hazard ratio for late preterm, that is birth between 34 to 36 weeks of gestation, was 1.22, both of which were statistically significant. Interestingly, each additional week of gestation was, on average, associated with a 3% lower risk of first stroke in adulthood.
Dr. Negar Asdaghi: Similar associations were found in men and women and for both hemorrhagic and ischemic strokes. These findings were only partially explained by shared genetic or environmental risks of preterm birth and stroke within families, suggesting important direct effects of preterm birth on risk of stroke. Multiple putative mechanisms that could potentially link preterm birth with increased stroke risk were discussed in the paper as well, including interaction of fetal angiogenesis during the critical developmental period leading to reduced capillary density and increased arterial stiffness, to persistently elevated levels of anti-angiogenic factors, which are correlated with increased blood pressure development and development of hypertension in adulthood. In summary, the study findings suggest that preterm birth should be recognized as a risk factor for stroke later in life, and survivors need early preventive evaluation and long-term clinical follow-up into adulthood to reduce their lifetime risk of stroke.
Dr. Negar Asdaghi: The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women, suggesting estrogen may be protective against aneurysm formation or aneurysmal rupture. However, estrogen-containing hormone replacement therapy is also associated with an increased risk of other significant adverse outcomes, such as increased risk of breast cancer and ischemic stroke, and is not routinely recommended for primary prevention of chronic conditions in postmenopausal women. Isoflavones, a type of phytoestrogen, are plant-based, diet-derived compounds with properties similar to estrogen. Two types of isoflavones, genistein and daidzein, are found in soybeans, chickpeas, and lentils and are thought to be the most potent phytoestrogens that exert estrogenic activities with tissue and receptor specificity. Regular consumption of isoflavones has been shown to alleviate the vasomotor symptoms of estrogen deficiency and associated with reduced incidence of estrogen-dependent diseases in postmenopausal women. Daidzein, once ingested, is converted to its bioactive metabolite, equol, which preferentially binds to estrogen receptor beta, a receptor subtype responsible for the protective effect of estrogen against the formation and rupture of intracranial aneurysms.
Dr. Negar Asdaghi: In the paper titled "Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm," Dr. Tomoki Hashimoto from the Barrow Aneurysm and AVM Research Center, Departments of Neurosurgery and Neurobiology, the Barrow Neurological Institute, and colleagues investigated whether the phytoestrogens daidzein and its bioactive form, equol, are protective against the formation and rupture of intracranial aneurysms in ovariectomized female mice. Intracranial aneurysms were induced by combining systemic hypertension and a single injection of elastase into the CSF at the right basal system. Ovariectomized mice were fed with an isoflavone-free diet. The systemic treatment with equol delivered via an implanted mini-osmotic pump in the treatment group (0.5 mg/kg/day) or vehicle (in the control group) began one week before aneurysm induction and was continued for four weeks thereafter. So, what they found was that equol treatment significantly reduced the incidence of aneurysm formation compared to vehicle, and there was a trend for equol-treated mice to have a lower incidence of aneurysmal rupture than control mice, while there was no difference in the blood pressure noted between the two groups.
Dr. Negar Asdaghi: Furthermore, systemic treatment through equol decreased mRNA expression of proinflammatory cytokines, such as IL-6 and interleukin-1β. Importantly, equol seems to require estrogen receptor beta, as the observed protected effects of equol against aneurysm formation was not duplicated in ovariectomized estrogen receptor beta knockout mice. The authors further demonstrated that dietary daidzein reduced the incidence of aneurysm formation, an effect that was dependent on the conversion of daidzein to equol as the beneficial effect of this dietary supplement was abolished in mice that were fed vancomycin, which prevented the intestinal microbial conversion of daidzein to equol. In summary, this study showed that both dietary oral daidzein or the systemic use of its bioactive metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor beta and subsequent suppression of inflammation. These results indicate a potential therapeutic value of phytoestrogen in prevention of intracranial aneurysm formation and related subarachnoid hemorrhage.
Dr. Negar Asdaghi: Early recognition of stroke-like symptoms, combined with increased utilization of revascularization therapies, have greatly improved the clinical outcomes of patients with acute ischemic stroke, but have similarly resulted in an ever-growing demand on the stroke systems of care. In the era of endovascular thrombectomy, a prehospital scoring tool with predictive abilities for detection of a target vessel occlusion can greatly assist in the appropriate triage, transfer, and activation of the endovascular team for eligible patients, all the while preventing the inevitable fatigue that accompanies the overuse of the system by properly triaging out those who have a lower likelihood of needing endovascular therapy. For any scoring system used in the prehospital setting, the need for precision needs to be balanced with notions such as ease of administration, time consumption, and reproducibility, as decisions made in the field are invariably fast and frequently made in unstable situations. The Field Assessment Stroke Triage for Emergency Destination, or the FAST-ED scale, is one such stroke scale that meets many of the above-stated criteria in patients with stroke-like presentations to predict a possible large vessel occlusion.
Dr. Negar Asdaghi: In the paper titled "Reliability of FAST-ED Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience," Drs. Nirav Bhatt and Diogo Haussen and colleagues, from the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, and the Department of Neurology at Emory University School of Medicine in Atlanta, report on the reliability of the FAST-ED score in the prehospital setting when used by the paramedics in a mobile stroke unit. I'm joined now by Drs. Bhatt and Haussen to discuss this paper. Good afternoon, Nirav and Diogo. Thank you very much for joining us.
Dr. Nirav Bhatt: Thank you so much for the invitation. I'm very happy to be here.
Dr. Diogo Haussen: Thank you very much. It is a great pleasure to join you.
Dr. Negar Asdaghi: Right. In this paper, the FAST-ED score was administered by the paramedics in a mobile stroke unit. So Nirav, to get us started, please tell us about the concept of a mobile stroke unit, how long it's been implemented in Atlanta, and what it means for patients with stroke-like symptoms who would possibly have a large vessel occlusion.
Dr. Nirav Bhatt: The mobile stroke unit, or the MSU, is an ambulance equipped with a CT scanner and state-of-the-art telemedicine capabilities and is operated by the Grady Emergency Medical Services that covers majority of Metro Atlanta and many of its suburbs, caring for a population of a little over 500,000. It was specifically incorporated to expedite care amongst patients with suspected strokes and went into operations on 30th May, 2018, Monday through Saturday, 12 hours a day, 8 a.m. through 8 p.m. It is operated by a group consisting of an EMT driver, a paramedic, an emergency medicine registered nurse, and a CT technician. So, when a patient has symptoms suspicious for a stroke, the MSU is activated either through 911 dispatch or by an ALS ambulance crew evaluating a possible stroke alert patient in the field. After the initial stroke triage performed by the MSU crew, if there is a persistent suspicion for stroke, the patient is transferred to the MSU and a noncontrast CT scan of the brain is immediately performed.
Dr. Nirav Bhatt: These CT images are transmitted via the telemedicine platform and are available for review by the vascular neurologist and neuroradiologist in real time. With the help of telemedicine technology, a remotely located vascular neurologist then examines the patient. So, with the help of telemedicine and CT scanner, it allows the remotely located vascular neurologist to identify patients who may qualify for IV alteplase, which is then administered in the MSU to qualifying patients, and these patients get subsequently transported to a stroke treatment center. Now, if the neurological exam is concerning for a large vessel occlusion and the non-contrast CT scan does not show corresponding early ischemic changes, these patients get transferred specifically to a comprehensive stroke center for consideration of thrombectomy. At our centers, some of these patients get directly transported to the neuro-angio suite for further imaging and possible thrombectomy. Thus, the MSU serve a very important goal of expediting critical neurological care for a stroke patient, not only by administering IV alteplase in the field to qualifying patients, but also early triage and transport of qualifying patients to the neuro-angio-suite and with earlier activation of neuroangiosuite.
Dr. Negar Asdaghi: Perfect, Nirav. An important and a growing concept, bringing treatment to patients and helping with triaging them appropriately, as you mentioned, which I'm sure we'll see more of in the United States and across the world. Now, Diogo, over to you. Can you tell us about the FAST-ED score, its components, then about the reliability of FAST-ED score in the prehospital setting prior to your current study?
Dr. Diogo Haussen: So, the landmark trials published in 2015 defined mechanical thrombectomy as this very effective and powerful treatment of large vessel occlusion stroke patients, and the clinical and the public health impact of this treatment are certainly highly dependent on the rapid triage of these folks into the appropriate destination. So, this involves the prompt identification of patients with severe symptoms by the emergency medical system personnel, and obviously the transportation of them for a thrombectomy capable center. So, some scales had been proposed earlier on, and the FAST-ED was then developed, and it aimed to help with the identification of patients with a higher probability of having a large vessel occlusion stroke. So, in 2017, we validated the scale on stroke patients that had undergone contrast-enhanced vascular images, which had not been done before, in this publication led by Fabricio Lima and Raul Nogueira in Stroke, in the Stroke journal.
Dr. Diogo Haussen: So, this paper demonstrated that FAST-ED had higher accuracy than RACE and CPSS. The main limitation at the time was the fact that the FAST-ED score derived from the NIH Stroke Scale and, therefore, had to be validated in the field. The FAST-ED scale stands for the important features that are involved with stroke care and recognition and triage, such as facial palsy, arm weakness, speech changes, and time. Then we complimented this with findings of critical dysfunction illustrated by eye deviation and also denial/neglect. So, the FAST-ED has the following scoring system: So, facial palsy scored from zero to one; arm weakness from zero to two; speech changes, which is aphasia, from zero to two; time is just for documentation, but not for really any decision-making in terms of the scale itself. So, eye deviation goes from zero to two, and denial/neglect from zero to two, and again, was designed based on the items of the NIH Stroke Scale with higher predictive value for large vessel occlusion strokes. I think Nirav is going to discuss a little bit more about why we chose those cutoffs, but they're all designed in a specific way.
Dr. Negar Asdaghi: Perfect. So a quick score that can be administered easily by different healthcare personnel. So, please tell us, before we go back to Nirav, about your paper's methodology. What were you hoping to expand on the existing knowledge with this paper?
Dr. Diogo Haussen: I'm just going to repeat a few things, but our mobile stroke unit is equipped obviously with a CT machine and is staffed by an EMT driver and emergency medicine registered nurse, a paramedic, and a CT technician. So, a remote evaluation of patients by a vascular neurologist is then performed through this video-based telemedicine platform. The MSU, as he mentioned, is routinely accompanied by an Advanced Life Support–staffed ambulance, which responds to the suspected stroke calls, and sometimes then calls in or calls off the potential of our stroke code. And as part of this MSU evaluation, the FAST-ED is then administered by the MSU paramedic via the FAST-ED smartphone application that was designed. And then an independent NIH is performed by the registered nurse within the MSU. So, subsequently, the patient is transferred into the MSU itself and a non-conscious CT is performed. Once the scan is completed, the patient is evaluated by the vascular neurologist in a two-way video conference where the FAST-ED is then estimated by the physician.
Dr. Diogo Haussen: So, all patients are then transferred to the comprehensive stroke center, where further evaluation, including vascular imaging, is performed. The vascular imaging data was formerly read by neuroradiology and then followed by an independent read by the vascular neurologist for the identification of large vessel occlusion strokes, which we define in this paper as an intracranial occlusion off the internal carotid, the M1 or the M2 branches of the middle cerebral artery or the basilar artery. The study encompassed our initial experience, which was from May of 2018 till August of 2019. And we have some other goals, but the initial experience was planned to allow us to investigate, once again, this most important feature, which is the potential reliability of the estimation of the FAST-ED score by paramedics in the field.
Dr. Negar Asdaghi: Perfect. Thank you for this background, Diogo. Now Nirav, we're ready to hear about the study results.
Dr. Nirav Bhatt: So, in the first 15 months of operation of the mobile stroke unit, we analyzed data on 173 eligible patients. We had an almost equal distribution of our patients in terms of gender. We had 52.6% females, and the majority of our patients were Black. We found that FAST-ED scores matched perfectly between paramedics and vascular neurologists 56% of the time, and there was only a zero to one point difference in 91% of the cases. Cases in which the discrepancy of the FAST-ED score between the paramedic and vascular neurologist was two points or higher were less than 9%. Overall, the intraclass correlation of FAST-ED score between the paramedic and the vascular neurologist was 0.94, indicating excellent interrater reliability.
Dr. Negar Asdaghi: Thank you. You found a higher interrater reliability between the paramedics and vascular neurologists for scores of three or above on the FAST-ED scale. Higher FAST-ED scales also were more specific in terms of detection of a target vessel occlusion. How should your results be interpreted in our day-to-day practice, Nirav?
Dr. Nirav Bhatt: That is correct. When vascular neurologists recorded a FAST-ED score greater than or equal to three, paramedics also recorded a FAST-ED score greater than or equal to three in 87.5% of the instances, and when a vascular neurologist recorded a FAST-ED score of greater than or equal to four, the paramedics also recorded a FAST-ED score of greater than or equal to four in 92% of the instances. This is suggestive that when the patients presented with a moderate to a severe stroke, that EMS paramedics were highly reliable in identifying the neurological severity of these patients. This provides a sound basis for more widespread utilization of FAST-ED as a simple and reliable tool that can be utilized by paramedics to identify stroke severity in the field.
Dr. Negar Asdaghi: Thank you, Nirav. Simple indeed. I know Diogo briefly alluded to this, but can you also tell us a little more about how FAST-ED compares to the other prehospital scoring systems in terms of their interrater reliability and LVO prediction? And what should be our takeaway message from your paper?
Dr. Nirav Bhatt: Yes, absolutely. So, just to give you an example, the Los Angeles Motor Scale, LAMS, tests for facial droop, arm drift, and grip strength, but does not really test for cortical signs. We know that a lot of patients with subcortical strokes will have those features, meaning facial droop, arm drift, and decreased grip strength. Similarly, while RACE is very similar to FAST-ED, it tests for leg weakness in addition to what FAST-ED does. It also puts a lot more emphasis on the facial droop as compared to FAST-ED. And with that, I want to draw your attention to a study that we cited in our paper where these scales were compared head to head, and while the accuracies of all the prehospital scales were found to be acceptable, the accuracy of RACE and LAMS were slightly higher than that of FAST-ED. However, it should be noted that in almost 35% of the cases, a complete FAST-ED score could not be reconstructed largely due to data and availability regarding patients' neglect.
Dr. Nirav Bhatt: This percentage for data and availability for RACE was even higher, meaning we have to consider the feasibility of these scales when we recommend the widespread adoption of these scales into our communities. Overall, the takeaway from this entire study is we strongly believe that there needs to be a system in place for prehospital stroke triage in order to identify and transport the patients to the right destination rapidly. However, the choice of individual scales should be made after consideration of the geographical characteristics of a particular community, and also that experience and that comfort with the level of training required for reliable performance of each of these scales by the EMS personnel.
Dr. Negar Asdaghi: Thank you so much, Nirav. More to come on this, I'm sure, in the future. Thank you for joining us on the podcast today.
Dr. Nirav Bhatt: Thank you so much. It was our pleasure.
Dr. Negar Asdaghi: Thank you, Drs. Nirav Bhatt and Diogo Haussen. Thank you for joining us on the podcast today, and we look forward to covering more of your work in the future. This concludes our podcast for the August 2021 issue of Stroke. Please be sure to check out the August table of contents for the full list of publications, including a special report on the safety of the mobile stroke units and a descriptive review of the amount of radiation exposure to the public, patients, and staff from these mobile units. With that, as our work to save every brain cell from ischemic and hemorrhagic damage continues, we invite you to stay alert with Stroke Alert.
Dr. Negar Asdaghi: This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.