THE CLINICAL CHALLENGE
Stroke is characterized as a neurologic deficit attributed to an acute focal injury of the central nervous system (CNS) from a vascular cause.1,2
The definition includes cerebral infarction or acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). AIS is caused by vascular occlusion with interruption of cerebral blood flow (CBF) leading to infarction. Transient ischemic attacks (TIAs) were defined as a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting <1 hour, and without evidence of acute infarction.1,3
Nontraumatic spontaneous ICH is caused by bleeding into the cerebral and cerebellar cortices as well as the into CNS or ventricular system. This chapter discusses AIS, TIAs, and ICH. SAHs and cerebral venous thrombosis (CVT) are discussed in Chapter 16: Headache
The clinical challenge for emergency clinicians is to diagnose an acute stroke, TIA, or hemorrhage accurately and quickly, separating it from other conditions that mimic stroke (false positives) as well as diagnosing masquerading strokes that are called chameleons (false negatives), which initially suggest another diagnosis. Patients with ICH may have focal neurologic symptoms similar to AIS, but frequently present with altered mental status, and may have an unstable airway, extreme hypertension (HTN), new-onset seizures, or elevated intracranial pressure (ICP). All patients with acute stroke require emergent diagnosis, stabilization, and proper therapy. This all needs to happen in a brief period to save the dying brain from infarction or limit harm from an ICH or prevent its expansion. As many of the current therapies are highly time sensitive, including access to interventional radiology or neurosurgical intervention, successful management requires streamlined systems of care to promote optimal patient outcomes.
There are nearly 800,000 strokes that occur per year in the United States, 1 every 40 seconds; 87% are ischemic, 10% are ICHs, and 3% are SAHs. Approximately 600,000 are first strokes and 200,000 are recurrent strokes. The prevalence of stroke in the United States is 2.7%; but varies from 1.3% to 4.7% depending on the state.4
Despite the incidence falling by 32% per 10-year period from 1987 to 2017, it is projected that the prevalence in adults will rise to 4% by 2030 as the population ages4,5
Figure 15.1: Stroke prevalence by age and sex (NHANES, 2015-2018). From Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics—2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254-e743. Data from unpublished National Heart, Lung, and Blood Institute tabulation using NHANES, 2015 to 2018.
In 2018, there were almost 150,000 deaths from stroke, a rate of about 37.1/100,000 people, making it the fifth leading cause of death in the United States. The all-cause mortality rate after stroke is 10.5% at 30 days, 21.2% at 1 year, and 40% at 5 years. The mortality for ICH is especially high, at 44% at 30 days. Two-thirds of stroke deaths were thought to be outside of the hospital setting. Death rates vary significantly based on sex, race/ethnicity, and region of the country (Figure 15.2
), especially in the southeastern United States known as the “Stroke Belt” (Figure 15.3
Most importantly, stroke is the leading cause of adult disability in the United States. There are over 7 million stroke survivors, many of whom require many years of support and care and live with chronic disabilities. The direct and indirect cost of stroke is approximately $50 billion annually, and is projected to increase to nearly $95 billion by 2030.4
The quality adjusted life years (QALYs) lost is about 5 years for the first-ever AIS and 6.2 years for an ICH.6
As a result, stroke trials most often focus on decreasing disability rather than on preventing death.
Globally, stroke is the second leading cause of death and a major cause of disability with a prevalence of over 100 million. The worldwide incidence of stroke is 11.6 million for AIS and 5.3 million for ICHs per year.7,8
The global lifetime risk of stroke is 24.9% for those older than 25 years.
Transient Ischemic Attacks
TIAs have an incidence of 5 million per year. About 2.3% of Americans have experienced a TIA. As with AIS, there is an increasing incidence with age, for males, and for Blacks and Mexican Americans. TIA features associated with subsequent disabling stroke include age older than 60, diabetes, focal symptoms (motor weakness, abnormal speech), and symptom duration over 10 minutes. Up to 30% to 40% of patients with these high-risk features will have a lesion on magnetic resonance imaging (MRI) that amplifies their risk of subsequent disabling stroke.
Recent improvement in the care of patients with TIA has resulted in an overall risk of subsequent disabling stroke of 1.2% at 2 days and 7.4% at 90 days. Currently, the 1-year risk of stroke is 5%, and the 5-year risk is 9.5%.
TIAs are also a marker of cardiovascular disease and carry a 6.2% 1-year and a 12% 5-year risk of stroke, acute coronary syndrome, or death. The 10-year risk for stroke, myocardial infarction, or death is 43%.9
For these reasons, patients with TIAs need to have a rapid follow-up or admission to ensure timely evaluation and treatment.4
Figure 15.2: Death rates by race and sex. Death rates for the American Indian or Alaska Native and Asian or Pacific Islander populations are known to be underestimated. Stroke includes International Classification of Diseases, 10th Revision codes I60 through I69 (cerebrovascular disease). Mortality for NH Asian people includes Pacific Islander people. NH indicates non-Hispanic. From Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics—2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254-e743. Data from unpublished National Heart, Lung, and Blood Institute tabulation using Centers for Disease Control Prevention Wide-Ranging Online Data for Epidemiological Research.
Risk Factors for Stroke
The risk factors for stroke include both modifiable and nonmodifiable factors. Eighty-seven percent of strokes are due to modifiable risk factors, and 47% are thought to be due to behavioral factors such as smoking, sedentary lifestyle, and diet. Black Americans, Mexican Americans, and American Indians have a higher risk of stroke compared to White Americans. Women have a higher risk of stroke and fatal strokes not only because they live longer but also due to such factors as pregnancy-associated complications, oral contraception, and hormonal therapy.4
The major modifiable risk factors include HTN, atrial fibrillation (AF), smoking, diabetes, obesity, sedentary lifestyle, and hyperlipidemia. The nonmodifiable risks include age, sex race/ethnicity, prior stroke or TIA, family history, and air pollution.10,11
Management of the major modifiable risk factors decreases not only stroke risk but also cardiovascular risk, all-cause mortality, and cancer risk.12
PATHOPHYSIOLOGY OF ACUTE ISCHEMIC STROKE
The brain receives 20% of the cardiac output, but is only 2% of the total body weight. It has minimal energy reserves, and is highly dependent on continuous supply of oxygen and glucose.13
When CBF is interrupted to a portion of the brain, an AIS occurs and causes brain injury with focal neurologic dysfunction characteristic of the vascular distribution involved. In the case of TIAs, blood flow returns spontaneously, and the symptoms resolve.14
Blood flow can be interrupted by multiple different mechanisms. The most common classification of stroke mechanisms uses the “TOAST” criteria, and includes small vessel occlusions, large artery atherosclerosis, cardioembolism, cryptogenic stroke, and other pathologies.15
The degree of brain injury from a stroke depends on the severity of ischemia (degree of flow restriction) and on the duration of ischemia. As the CBF falls, the brain tissue becomes electrically silent and then suffers membrane failure. The time required to produce irreversible damage is related to the severity
of the ischemia over minutes to hours16,17
). The areas with the most severe ischemia, the core, are irreversibly damaged and die relatively quickly. The surrounding areas with less severe ischemia, the penumbra, are alive, electrically silent, detected on examination, and can be salvaged if reperfusion is rapidly established18
). Surrounding the penumbra is a zone of benign oligemia that eventually survives. Without reperfusion, the core infarct eventually extends to involve the penumbra, which results in a larger final stroke volume.
Figure 15.3: The Stroke Belt.
Rates are spatially smoothed to enhance the stability of rates in counties with small populations. International Classification of Diseases, 10th Revision
codes for stroke: I60 through I69. From National Center for Health Statistics, National Vital Statistics System. Stroke death rates. Accessed April 6, 2020. www.cdc.gov/dhdsp/maps/pdfs/stroke_all.pdf
Secondary injury from ischemia is caused by an acute “excitotoxic” response triggered by membrane failure with release of excitatory amino acids, aspartate and glutamate, from the presynaptic membrane (Figure 15.6
). These excitatory amino acids open calcium channels via N-methyl-D-aspartate (NMDA) receptors, causing calcium/sodium influx, activation of proteolytic enzymes, further membrane and blood-brain barrier failure, and repetition of the cycle. Neuroprotective agents are aimed at interrupting this cycle.
For every minute with a large vessel stroke, the average patient loses 1.9 million neurons, 14 billion synapses, and 7.5 miles of axonal fibers,19
leading to the axiom “Time is brain.” Clock time, as measured by the last known normal, is an unreliable surrogate marker for the underlying progression of these pathophysiologic processes. Variability from patient to patient from ischemic injury is explained by the amount of collateral blood flow and other individual factors. Some patients are fast progressors, whereas others progress to infarction at a slower rate.20
With the development of computed tomography perfusion (CTP) imaging and magnetic resonance (MR) perfusion imaging, obtaining an understanding of the size of the core and penumbra for an individual patient is feasible, especially those with large vessel occlusions (LVOs).21
Figure 15.4: Thresholds of focal cerebral ischemia in awake monkeys. From Jones TH, Morawetz RB, Crowell RM, et al. Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg. 1981;54(6):773-782.
Figure 15.5: The ischemic penumbra. Schematic demonstration of the infarct core, penumbra, benign oligemia, and associated border zones. Dynamic changes in size over time occur depending on the status of the leptomeningeal collaterals and hemodynamic, physiologic, or metabolic factors. The infarct core is nonviable tissue. Penumbra is the ischemic but dysfunctional zone, and remains viable if blood flow is restored. Benign oligemia is underperfused, but functional tissue that remains viable. The threshold level for neuronal dysfunction is a cerebral blood flow (CBF) of approximately 20 mL/100 g/min, and the benign ischemia zone is above this threshold. From Liu CSJ, Dobre MC. Brain MR perfusion imaging: cerebral ischemia. In: Saremi F, ed. Perfusion Imaging in Clinical Practice. Wolters Kluwer; 2016:217-223. Figure 12.1.
Figure 15.6: Excitotoxicity. Role of glutamate receptors in excitotoxicity. Although a multiplicity of damaging cellular processes occur as a consequence of the decreased ATP levels that result from impaired oxidative metabolism or from the superoxidative damage from activated neutrophils that invade an ischemic region, only glutamate-mediated processes are depicted here. ATP, adenosine triphosphate; AMPA-R, AMPA receptor; mGluR, NMDA-R, N-methyl-D-aspartate receptor. From Forman SA, Chou J, Strichartz GR, Lo EH. Pharmacology of GABAergic and glutamatergic neurotransmission. In: Golan DE, Tashjian AH, Armstrong EJ, Armstrong AW, eds. Principles of Pharmacology. 3rd ed. Wolters Kluwer; 2012:164-185. Figure 12.10.
The public is encouraged to activate emergency medical services (EMS) if there is concern for an acute stroke because it is the fastest way to get to the emergency department (ED).22
A stroke screening tool is advised for both the dispatchers and the EMS personnel. Stroke screens are based on a brief history or examination checking for common stroke symptoms such as sensorimotor deficits and speech problems. The Los Angeles Prehospital Stroke (LAPSS) and the Cincinnati Prehospital Stroke Screen (CPSS) are reasonable validated stroke screens.23
A Cochran Review recommended the CPSS.24
With the advent of intra-arterial therapy (IAT) for stroke, EMS personnel are being asked to also perform a prehospital stroke severity scale used to detect an LVO and reroute patients to a thrombectomy-capable center (Figure 15.7
Stroke severity scales focus on motor deficits and cortical findings such as aphasia or neglect. Most LVO scales have good accuracy, high sensitivity, and low specificity: The Rapid Arterial Occlusion Evaluation (RACE) scale and the Los Angeles Motor Scale (LAMS) are the most accurate, and the Prehospital Acute Stroke Severity (PASS)
scale was the most easily reconstructed from standard data collection (Table 15.1
Alterations in mental status associated with ICH are more common than with AIS, and should be assessed using the Glasgow Coma Scale (GCS) score.
Figure 15.7: Acute stroke routing protocol. From Jauch EC, Schwamm LH, Panagos PD, et al. Recommendations for regional stroke destination plans in rural, suburban, and urban communities from the prehospital stroke system of care consensus conference: a consensus statement from the American Academy of Neurology, American Heart Association/American Stroke Association, American Society of Neuroradiology, National Association of EMS Physicians, National Association of State EMS Officials, Society of NeuroInterventional Surgery, and Society of Vascular and Interventional Neurology: Endorsed by the Neurocritical Care Society. Stroke. 2021;52(5):e133-e152.
Before evaluating the patient for signs and symptoms of stroke, EMS personnel must evaluate the patient for the “ABCs” (airway, breathing, circulation), address any life-threatening issues, and provide supportive care per their local protocols. Supportive care includes evaluation of the airway, preventing aspiration, and ensuring that the oxygen saturation is over 94%. The blood pressure (BP) should be measured and treated with isotonic fluids if the patient is hypotensive. Extreme elevations in systolic blood pressure (SBP) with ICH and are independently associated with ICH volume, but it is not known if prehospital BP control attenuates ICH expansion. No specific guidelines exist for prehospital treatment of HTN. The patient should also be placed on a monitor and examined for trauma, especially the C-spine if there is a history of associated fall or syncope. A point-of-care glucose measurement is mandatory because hypoglycemia is an easily addressed stroke mimic. Seizures should be managed with benzodiazepines per the EMS protocol in a manner similar to that of any other seizure.
Rapid EMS stroke identification and transport to a thrombolytic-capable center not only improves care for patients with ischemic stroke but also shortens the time to emergency interventions.27
If a patient is clearly outside the 4.5-hour window or has a severe stroke, transportation to a
facility that can provide intra-arterial thrombectomy is reasonable if the delay is not greater than 15 to 20 minutes.28
EMS prenotification of the patient’s arrival is recommended, and bringing a family member, if possible, allows the ED physicians and stroke team to make necessary preparations.
TABLE 15.1 Prehospital Evaluation of Stroke
Sensitivity for Stroke
Specificity for Stroke
1 of 3 new findings: 72% probability AIS
All 3 findings: probability AIS >85%
86% PPV, 98% NPV
96% overall accuracy
Stroke Severity Scales
Sensitivity for LVO
Specificity for LVO
For LAMS ≥4
85% accuracy for LVO
Head, gaze deviation
85% Score ≥ 5
Score ≥ 2
AIS, acute ischemic stroke; CPSS, Cincinnati Prehospital Stroke Screen; LAPSS, Los Angeles Prehospital Stroke Screen; LOC, level of consciousness; LR, likelihood ratio; LVO, large vessel occlusion; NPV, negative predictive value; PASS, Prehospital Acute Stroke Severity scale; PPV, positive predictive value.1
Prospective validation in LA, data from The Stroke Interventionalist 2001 and Hastrup S, Damgaard D, Johnsen SP, Andersen G. Prehospital acute stroke severity scale to predict large artery occlusion: design and comparison with other scales. Stroke. 2016;47(7):1772-1776.