Acute Stroke

Acute Stroke

Christopher A. Lewandowski

Edward P. Sloan


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).

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

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


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 (Figure 15.4). 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 (Figure 15.5). 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.

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


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).25 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).26 Alterations in mental status associated with ICH are more common than with AIS, and should be assessed using the Glasgow Coma Scale (GCS) score.

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.



When a patient with an acute stroke symptom presents, multiple simultaneous processes need to occur to minimize time from door to treatment. A team approach within the context of an established system of care including a stroke team is advised. The exact order of the evaluation may vary among institutions. These systems should also prepare for rapid management of adverse events.

Diagnosis of Acute Ischemic Stroke

The diagnosis of AIS is dependent on the history, physical findings, and appropriate imaging. Classically, an acute stroke has a sudden onset of symptoms with focal neurologic findings attributed to a vascular distribution. Standard neurologic examination is reviewed in Chapter 2: The Neurologic Examination. There are five syndromes that the emergency physician should become very familiar with29 (Table 15.2).

The National Institute of Health Stroke Scale (NIHSS) is a highly reproducible stroke severity scale that was developed and validated for research purposes,30 but was found to be highly useful in clinical care. It does not represent a complete neurologic examination. The stroke scale evaluates
the 11 domains with a standard scoring system. It correlates to the size of the stroke, the risk of post lytic hemorrhage, the likelihood of an LVO, and allows for patient monitoring over time (see Table 15.3). In general, a stroke scale of 0 to 5 is considered mild, 6 to 15 moderate, 16 to 20 severe, and over 20 very severe strokes. The NIHSS gives higher scores to dominant hemispheric strokes compared to same-size strokes on nondominant hemispheres, and it is less sensitive for posterior circulation stroke.

Stroke outcomes are frequently measured by the modified Rankin Score (mRS), which reflects a patient’s functional status (see Table 15.4). The mRS is also used to estimate the patient’s baseline functional status before the stroke. Most thrombectomy trials only included patients with a baseline mRS of 0 to 2. Both scales require brief training and certification to ensure reliability and reproducibility.

Non-contrast computed tomography (NCCT) or MRI is the first step in imaging the patient with acute stroke.22 The NCCT is most frequently used because it is readily available and is highly reliable in demonstrating an acute ICH. A negative NCCT finding with symptoms of an AIS makes the diagnosis. The ability of the NCCT to detect an AIS is limited in the early hours; it is about 50% sensitive and 80% specific. Diffusion-weighted imaging (DWI) on MRI is highly sensitive for AIS, and can detect the cytotoxic edema of infarcted tissue within 20 minutes of the first symptoms. The NCCT can be followed by a computed tomography angiogram (CTA) of the head and neck to diagnose an LVO and a CTP to determine the size of the penumbra. The CTA is nearly 100% sensitive and 80% to 100% specific for LVO. The CTP is now aided by postprocessing software that can identify tissue destined to infarct (the core) with a 100% sensitivity and a 91%

specificity, and can identify the volume of the ischemic tissue.31 The difference between these is the mismatch volume, and is considered to be the penumbra.

Transient Ischemic Attacks

The initial evaluation of a TIA is identical to that of an acute stroke. Seventy-five percent of TIAs resolve within 1 hour. When the patient returns to normal, the time of last known well also resets for purposes of acute treatment. The differential diagnosis of sudden focal neurologic deficits is quite large (Table 15.5). It is important to ensure a complete workup for the cause of the TIA as soon as possible, preferably within 24 to 48 hours. The ABCD2 score32 is commonly used for risk stratification after a TIA to prioritize patients in need of an urgent evaluation (Table 15.6). This score may be skewed toward classic, clear-cut TIAs and away from TIAs with more atypical or isolated symptoms, that is, nonconsensus TIAs. In a 16-year study, the 90-day stroke risk after a TIA was 11.6% for classic TIAs and 10.6% for nonconsensus TIAs, with a 10-year risk of any major vascular of 27.1% and 31%, respectively. The nonconsensus group was more likely to have posterior circulation stenosis (odds ratio [OR] = 2.21; 95% CI: 1.59-3.1) and was less likely to follow up with a doctor.33

AIS Management

The ED approach is to first stabilize the patient and address any immediate life threats. Airway and ventilation need to be secured if the patient is unconscious or has significant bulbar impairment. Oxygen levels should be maintained above 94% O2 saturation, but higher levels have not been shown to be beneficial; 100% O2 or a non-rebreather mask should not be used unless specifically indicated. Low BP is much more detrimental than is high BP, and needs immediate attention and treatment. High BPs are common in the acute phase and typically decline during the initial evaluation and with IV fluids. An evaluation of the C-spine and for signs of major trauma is also indicated. This should be followed by a focused examination to determine the severity of the stroke. The NIHSS can be performed in 5 to 7 minutes. Simultaneously, team members should be placing intravenous (IV) lines and obtaining blood samples. Blood tests should include glucose (point of care), troponin, complete blood count (CBC), platelets, international normalized ratio (INR), prothrombin time (PT), partial thromboplastin time (PTT), and electrolytes. An electrocardiogram (ECG) and chest x-ray should be deferred until imaging is completed to avoid delays in treatment. The initial history should be focused and concentrate on the time last known normal, as compared to the time symptoms were discovered, and exclusion criteria for thrombolysis. All patients with acute stroke should start with an NCCT. Patients with AIS having an NIHSS score of 6 or more
should undergo a CTA of the head and neck. If the onset of symptoms is over 6 hours, then CTP should be added. MRI with DWI and a magnetic resonance angiogram (MRA) can also be used for the initial imaging as long as the time to treatment is not delayed.