Chapter 26. Stroke

Stroke continues to be a major cause of morbidity and mortality in adult populations worldwide. Over 750,000 patients are newly diagnosed with stroke each year in the United States alone, and this entity remains the third most frequent cause of death among adults.1 This disease is a leading cause of disability in the adult population. More than 50% of stroke sufferers will be left with permanent disability, 25% will require some assistance with activities of daily living, and 25% of patients will remain in an institutional setting 6 months poststroke.2

The management of acute stroke had been strictly supportive until 1995 when the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group published their trial of recombinant tissue plasminogen activator (rt-PA) in the treatment of acute ischemic stroke.3 The availability of an effective therapy triggered a renewed interest in treatment of acute ischemic infarction as well as the development of specialized “stroke centers” in an attempt to improve outcome in patients with cerebral ischemic infarction. These interventions have improved the outcomes in acute ischemic infarction; however, the 30-day mortality following acute stroke is still unacceptably high at 15–30%.4 Clearly, more interventions are needed in this devastating disease. New hope has been instilled with the advent of interventional neuroradiology.

It is now even more important for the emergency physician to be able to recognize acute ischemic infarction, order appropriate imaging studies, initiate intravenous (IV) thrombolytic therapy and rapidly consult neurologists and interventional neuroradiologists. This paradigm is akin to the treatment of ST-elevation myocardial infarction (STEMI). This chapter will review (1) basic neurologic syndromes as localized by their arterial distributions (i.e., anterior cerebral artery [ACA], middle cerebral artery [MCA], posterior cerebral artery [PCA], basilar artery, etc.) as an effort to simplify recognition of large-vessel infarctions, (2) new imaging modalities, (3) initial medical management, and (4) interventional management.

Computed tomography (CT) scans do not “rule out” acute ischemic infarctions. This is an unfortunate reality that forces the non-neurologist to perform a detailed neurologic examination. Identifying these patterns can assist in the identification of stroke syndromes that can be treated with thrombolytic therapy, as opposed to stroke syndromes that do not follow vascular territories such as hemorrhages, venous infarctions (extremely rare), or stroke mimics such as extreme ranges of blood sugar, seizures, or tumors. The history of a sudden onset of neurologic deficit and the time of onset are paramount to making the diagnosis and treatment decisions.

The presentation of acute stroke follows distinctive anatomic patterns that are predictive of the involved arterial territory. Here are anatomic structures and associated syndromes as supplied by each major vessel:

• ACA: The first segment (A1) of the ACA gives rise to the recurrent artery of Huebner that supplies the caudate head, anterior limb of the internal capsule, and anterior aspect of the putamen and globus pallidus (there is some variability). Infarcts to these structures can result in confusion, and arm and face weakness. The remainder of the ACA supplies the medial surface of the cerebral hemisphere and the superior aspect of the frontal and parietal lobes. Infarcts in these territories may result in lack of initiative, abulia, paratonia (“gegenhalten”) (anterior frontal lobes), contralateral leg paralysis (superior aspect of the motor cortex—the precentral gyrus), and to a lesser extent arm paralysis (in particular, the shoulder). In bilateral frontal infarction, akinetic mutism, paraplegia, incontinence, and apathy with amnesia may result. Lower extremity contralateral sensory loss may be present if the postcentral gyrus is affected. Other nuances may occur in ACA territory strokes, but these are out of the scope of this review.
• MCA: The MCA is the most common site of ischemic stroke and the largest branch of the internal carotid artery (ICA). It supplies the majority of the lateral surface of the cerebral hemisphere and the deep structures of the frontal, insular, and parietal lobes. The lenticular striate arteries arise off the M1 segment and supply the corona radiata, external capsule, claustrum, putamen, part of the globus pallidus, body of the caudate nucleus, and superior aspect of the anterior and posterior limbs of the internal capsule. The clinical picture of the MCA territory infarction depends on the site of occlusion. Contralateral face, arm, and leg weakness manifests when the precentral gyrus (primary motor cortex) is affected. Contralateral face, arm, and leg sensory loss occurs when the postcentral gyrus (primary sensory cortex) is affected. Gaze preference to the affected side may occur when the frontal eye fields are affected. In the dominant hemisphere, the various aphasias occur when Wernicke's, Broca's, or communicating fibers are affected. Complicated sensory syndromes such as alexia with agraphia (left angular gyrus), and combinations of finger agnosia, acalculia, right–left disorientation, and agraphia (Gerstmann syndrome) may also be encountered in posterior MCA territory infarctions. Neglect, denial (agnosagnosia), apraxias, sudden confusional states, and agitated delirium may also occur with parietal lobe infarctions. Contralateral visual field cuts (homonymous hemianopsia, or homonymous inferior quadrantanopsia) may occur if the parietal radiations are affected. Clinical manifestations of infarcts to the lenticulostriate territory include hemiplegia and less often dysarthria alone or upper limb clumsiness. Of course, other nuances to MCA territory ischemic infarctions exist that are out of the scope of this review.
• PCA: The PCAs are the terminal branches of the basilar artery; however, 25% of the time they have an embryonic origin off the ICA (aka fetal PCA). The PCA supplies the occipital lobes and the inferomedial portions of the temporal lobes. Numerous small branches off the P1 segments and sometimes the top of the basilar artery supply the mesencephalon, thalamus, and adjacent structures. Proximal PCA occlusion may simulate MCA occlusion when it causes hemiparesis, hemianopsia, hemispatial neglect aphasia, and sensory loss. Cortical signs may be pseudolocalizers in the event of thalamic involvement. The PCA gives a splenial branch (splenium of the corpus callosum) that makes anastamosis with the ACA. Infarction of the splenium can result in alexia without agraphia, “pure word blindness,” and sometimes color anomia and/or object/photograph anomia. The cortical branches of the PCA are the anterior temporal, posterior temporal, parieto-occipital, and calcarine arteries. These supply the inferior aspect of the temporal lobe and the parietal radiations, and terminate with the calcarine branch that supplies the visual cortex. Cortical PCA branch occlusion almost always presents with a contralateral visual field cut. Involvement of the calcarine artery may be associated with ipsilateral eye pain. Involvement of bilateral PCAs may result in cortical blindness. Patients are often unaware of their “cortical blindness” (Anton's syndrome).
• Vertebral and basilar arteries: The vertebral arteries give rise to the posterior inferior cerebellar arteries (PICAs) that supply the inferior cerebellum and inferior vermis. Infarcts here result in ataxia. The vertebral arteries then merge in what is referred to as the vertebral–basilar junction (VBJ) to give rise to the basilar artery. The basilar artery gives rise to the anterior inferior cerebellar arteries (AICAs), which when infarcted result in ataxia and possible hearing loss if the labyrinthine artery arises off the AICA. The superior cerebellar artery (SCA) is near the top of the basilar artery and supplies the superior vermis and the superior aspect of the cerebellar hemispheres. Infarcts here can vary from limb ataxia to truncal ataxia or both. The mid and the top segments of the basilar artery give off perforating branches into the brainstem (medulla and pons) and thalamus/midbrain, respectively. The top of the basilar branches has overlap with the perforating branches that arise off the P1 segments of the PCAs. These perforating vessels allow for the plethora of “posterior circulation syndromes” (Table 26-1).

Differentiating an acute ischemic stroke from a hemorrhage is nearly impossible by history and physical exam alone. This is the reason why a CT scan must be done. Acute ischemic stroke cannot be “ruled out” by CT scan. It is hemorrhage that can be ruled out. Once hemorrhage has been excluded and the remainder of the inclusion/exclusion criteria satisfied, thrombolytic therapy may be administered. It is important to note that acute ischemic stroke is usually not visible on a CT scan in its early stages (typically less than 6 hours).

Imaging has progressed in several fronts. Magnetic resonance imaging (MRI) has the diffusion-weighted imaging (DWI) sequence where acute ischemic stroke can be seen within minutes of infarction. CT scanning remains more commonly available and has the advantage of being quick. To this end, progress in CT scanning includes CT angiography (CTA) and CT perfusion (CTP). MRI advances also include the perfusion sequences.

With CTA, it is now possible to identify large-vessel occlusions in the brain within seconds. In addition, part of the etiologic workup of the stroke can be attained simultaneously by performing a CTA of the neck. Now, carotid stenosis and intracranial vessel integrity (occlusion, vasculopathy, dissection, or stenosis) can be determined within minutes of performing the initial head CT.

Perfusion studies have been referred to as “physiologic imaging.” In simple terms, perfusion imaging can determine a delay in the arrival of contrast (blood) to the vascular bed in question. If there is a delay to a certain territory, say the right MCA, for example, one can spend more time analyzing the vasculature leading to and including the right MCA in the hopes of identifying (1) a treatable source, for example, carotid stenosis and (2) the actual clot/occlusion causing the stroke (Figure 26-1).

Physiologic imaging has further progressed with analysis of the concept of “mismatch.” Infarcted or otherwise dead tissue can be demonstrated on MRI DWI. Perfusion defects may be equal to the amount of tissue already dead, or they can be greater giving rise to a new definition of penumbra: underperfused territory that is at risk of dying (Figures 26-2 and 26-3).

The NINDS trial in 1995 provided evidence that intervention is possible in the setting of ischemic stroke. By administering IV rt-PA within 3 hours, 30% of patients improved to near-normal exams at 3 months with a 6% risk of intracranial hemorrhage (ICH). However, only a small percentage of patients are candidates for IV rt-PA. Even in the subgroup receiving thrombolytic therapy, appropriate supportive care can significantly reduce morbidity.

The Abc's

While the majority of patients with acute ischemic stroke will not require intubation or ventilatory support, endotracheal intubation should be considered in those patients who are obtunded or those who have lost airway protective reflexes. Also, many patients will have impaired mobility of their oropharynx, placing them at risk for aspiration. As pneumonia has been shown to be an important cause of death after cerebrovascular events,5 it is prudent to keep these patients NPO until their swallowing ability has been evaluated.

Blood pressure (BP) management immediately following acute ischemic stroke remains somewhat controversial. Hypertension is common in the immediate poststroke period and is felt to be a protective response—an attempt to provide adequate perfusion to the ischemic penumbra that surrounds the area of acute infarct. There is some evidence demonstrating a correlation between hypertension in the first 24 hours after stroke and increased mortality.6,7 There is also evidence that rapid reduction of BP may contribute to morbidity after acute stroke.8 It is generally believed that extreme hypertension contributes to poor outcome in the setting of stroke, but there is no evidence that clearly defines the upper limits of BP that should be considered a trigger for therapy. This is not the case in those patients receiving thrombolytic therapy, where there are clearly defined limits (systolic BP [SBP] <185 mm Hg and diastolic BP [DBP] <110 mm Hg) beyond which the risk of ICH is increased.9

The current American Heart Association/American Stroke Association (AHA/ASA) guidelines for management of hypertension in acute stroke are as follows:

1. Aggressive management of BP should be considered in all patients who demonstrate evidence of severe end-organ damage from hypertension in addition to acute stroke. This includes patients with hypertensive encephalopathy, acute renal failure, aortic dissection, acute myocardial infarction (MI), or acute congestive heart failure.

2. If a patient will be undergoing thrombolytic therapy or other reperfusion intervention, BP should be lowered to an SBP of less than 185 mm Hg and a DBP of less than 110 mm Hg.

3. In those who are not candidates for intervention, a less aggressive approach is recommended. Antihypertensive agents should be held until SBP remains above 220 mm Hg or DBP remains above 120 mm Hg.

In all instances, it is recommended that the agent of choice be easily titratable to prevent rapid sustained declines in BP. The current guidelines recommend labetalol 10 mg IV repeated every 10–20 minutes to a maximum dose of 200 mg, labetalol 10 mg IV followed by a 2–8 mg/min infusion, or nicardipine infusion starting at 5 mg/h and titrated to desired BP or a maximum dose of 15 mg/h.10 Hypotension is uncommon in patients with acute stroke. If it develops, the cause should be actively sought—aortic dissection, acute MI, etc. Cardiac dysrhythmias, blood loss, or volume depletion should all be considered. Therapy should be directed at the underlying cause and may include volume replacement and pressors if hypotension persists. Certainly patients may sustain ischemic infarction in the setting of arterial stenosis and hypotension. Neurovascular imaging is warranted (CTA or MRA of the head and neck).

Management of Glucose

Hyperglycemia is a common phenomenon immediately poststroke and has been shown to be associated with worsened outcome. The correlation is strongest in the population without diabetes mellitus. Hyperglycemia in the critically ill is often referred to as stress hyperglycemia and is characterized by elevation in catecholamines, cortisol, growth hormone, glucagon, gluconeogenesis, insulin levels, insulin resistance, and insulin-like growth factor-1 (IGF-1) protein. There is evidence that hyperglycemia worsens outcome and increases the risk of ICH in patients receiving rt-PA.11 While current evidence demonstrates worsened outcome in the setting of hyperglycemia poststroke, there is no solid evidence to guide the means of therapy or the level to which glucose control should be maintained. The majority of randomized controlled trials (RCTs) available that deal with glucose control are studies that looked at insulin therapy in patients in the intensive care unit (ICU) setting for illnesses other than stroke. These studies indicate variable benefit from tight glycemic control and demonstrated a significant risk of hypoglycemia with worsened outcome in patients in the treatment arm.12 The largest RCT looking specifically at tight glucose control in stroke patients is the GIST-UK trial. The methods for maintaining infusion and monitoring glucose were highly labor intensive, and the results were neutral with effect on morbidity and mortality.13 The current AHA/ASA guidelines are to begin intervention for serum glucose levels of >140–185 mg/dL and to try to maintain levels between 80 and 140 mg/dL. Therapy can involve repeated boluses of insulin or IV infusion.10 In all instances, careful monitoring is needed and hypoglycemia should be avoided as this also has been shown to have a negative effect on patient outcome.

The goal of the treatment of acute ischemia is rapid reperfusion in patients who present within the therapeutic window. Every ischemic stroke patient must be evaluated quickly. Time is brain. Early stroke treatment is associated with better outcome.14 Treatment of the symptoms of ischemic infarction begins as soon as the diagnosis is made, in other words, once the CT scan excludes the hemorrhage. Give aspirin. Aspirin has been shown in numerous trials to reduce the frequency of subsequent ischemic events.15 Per rectum aspirin may be safely administered in patients with swallowing or face weakness.

With the publication of the NINDS trial in 1995, thrombolytic therapy entered the spotlight. The study demonstrated significant benefit of therapy, but also demonstrated a 6% risk of ICH in the treatment arm. Significant controversy ensued among the emergency medicine community. Did the benefit of lytics outweigh the risk? Could rt-PA be safely used in the community setting? Can thrombolytic therapy safely be initiated in the absence of a neurologist? A plethora of research ensued.

As of 2010, thrombolytic therapy is widely accepted and is widely used throughout the United States and Europe. However, not all hospitals have initiated protocols for the use of rt-PA in this setting. This may be due to a lack of neurology coverage in many areas of the country—it is estimated that 20% of the population is served by emergency departments that lack immediate access to a neurologist. The literature supports the use of thrombolytics even in the absence of an onsite neurologist. Teleneurology is becoming increasingly popular and has been shown to be safe and efficacious.16,17 Also, in spite of subtleties in stroke presentation, accuracy of diagnosis by emergency physicians has been demonstrated18 and thrombolytic treatment can be safely initiated using a standard protocol, even in the absence of a neurologist.19 Current evidence-based medicine indicates that rt-PA can be safely used in the community setting, so long as strict adherence to protocols is maintained. The rate of ICH remains at 6% in most studies, but has been noted to be lower (1.7%) in the SITS-MOST observational study.20 The current AHA/ASA guidelines10 for the use of rt-PA in the setting of acute ischemic stroke recommend treatment for patients who fit the following profile: Patients must have a measurable neurologic deficit that is not clearing spontaneously and is not minor and isolated. In those with more severe deficits—National Institutes of Health Stroke Scale (NIHSS) >22—caution is advised, because while there may be some benefit to therapy, there is a significant increase in the incidence of ICH. Contraindications to rt-PA therapy are listed in Table 26-2.

Older age is not in and of itself a contraindication to thrombolytic therapy. Prior suggestions that rt-PA should be withheld in patients older than 80 years have been questioned, and data analysis has shown that there is some benefit to treatment in this age group. Overall, these patients still have poorer outcomes than younger patients when suffering an acute stroke, but the incidence of ICH among this population is not higher than in younger patients treated with thrombolytics.21,22

The recommended dose of rt-PA in the setting of acute stroke is 0.9 mg/kg with a maximum dose of 90 mg. The initial 10% of the dose is administered as an IV bolus given over 1 minute and the remaining is infused over 60 minutes. It is markedly important to obtain a weight on all patients in whom thrombolysis is considered. Overestimation of weight and subsequent overdosing of rt-PA is one of the more common violations of protocol and is thought to contribute significantly to the incidence of ICH in this patient population.23 Another frequently noted protocol violation is failure to adequately control BP. Frequent monitoring of BP should be initiated in these patients, and antihypertensives should be administered if the SBP is 180 mm Hg or higher and the DBP is 105 mm Hg or higher.

The decision to treat patients with thrombolytics is time dependent. In the initial NINDS trial, there was a significant increase in the incidence of ICH in patients receiving rt-PA more than 3 hours after symptom onset. For years, the “3-hour window” has been the gold standard. Over the past 5 years, multiple studies have asked the following question: Is it possibly safe to expand this therapeutic window? The most definitive is the European Cooperative Acute Stroke Study (ECASS) III trial, published in September 2008. The trial was multicentered, randomized, and placebo controlled and enrolled patients with stroke onset 3–4.5 hours prior to receiving therapy. There was a significant improvement in neurologic outcome at 90 days in the treatment group. The incidence of ICH was also larger in the treatment arm, with symptomatic ICH occurring in 2.7% of those receiving lytics. There was no significant difference in mortality between the groups.24 As a result of this trial, the AHA/ASA guidelines for the use of thrombolytics in acute stroke have been revised. It is now a Class IB recommendation for lytics to be used in patients for up to 4.5 hours after the onset of symptoms.25 As failure to present within the 3-hour window is one of the most common reasons why thrombolytic therapy is not provided to stroke patients, the new time window is likely to increase the number of patients receiving therapy, and will contribute to improved outcome among patients with acute ischemic stroke.

Even so, there will be patients who are not candidates for IV thrombolysis or those who present with a greater delay after symptom onset. These patients need no longer all fall into the category of “supportive care only.” Over the past 15 years, an entire specialty, interventional neuroradiology, has developed, and now there are a multitude of techniques that have been added to the therapeutic armamentarium.

Indications for the interventional management of acute ischemic infarction parallel those for IV thrombolysis with a few important variations: (1) time window is increased to 6 hours; (2) inclusion criteria now include the presence of an occluded vessel by CTA; and (3) anticoagulation is not a contraindication. Absolute contraindications are hemorrhage and hypoattenuation of the region in question on CT (in other words, the region of brain where the deficits localize is already infracted). Patients may receive IV rt-PA and then undergo intra-arterial (IA) thrombolysis safely26 or receive IA thrombolysis in the 3- to 6-hour window safely.27 In patients who are anticoagulated or have recently received surgery, mechanical thrombectomy is an option employing devices such as Mechanical Embolus Removal in Cerebral Ischemia (MERCI) thrombectomy device28 and Penumbra Aspiration System.29 The aforementioned studies have demonstrated efficacy and safety in interventional thrombolysis and thrombectomy in patients with acute cerebral ischemia. This is different from demonstration of efficacy in the medical treatment of acute cerebral ischemia. Although level 1 evidence for the interventional treatment of stroke is pending, there are numerous reports of success in the literature.