Stroke

Preface

Stroke is a medical emergency. Rapid bedside diagnosis and interpretation of neuroimaging studies is necessary to identify patients eligible for acute stroke therapies. Identification of the stroke mechanism in conjunction with prompt initiation of appropriate preventative strategies reduces the risk of recurrence. The acute stroke care continuum ­typically concludes with early establishment of rehabilitation and recovery programs. The purpose of this book is to give providers an evidence-based roadmap that they can use at the bedside for the care of patients with acute stroke.

Each chapter is authored by physicians with ­experience and expertise in the front-line evaluation and treatment of patients affected by stroke. The content of each chapter is comprehensive, but not exhaustive, which facilitates utility as both a reference and point-of-care resource. Key references have been included, but limited in number, so as to not interfere with readability. Content included in Tips and Tricks and Science Revisited boxes direct the reader to clinical pearls and the scientific basis supporting key recommendations. An appendix is included for easy access to validated prognostic scales and measures of stroke severity and disability.

We wish to thank Drs. Gross and Mink for the opportunity to edit this book and the staff at Wiley-Blackwell publishing for guiding us through the process of crafting the content outline, inviting expert authors, and final editing. Without their vision and encouragement a project of this magnitude would not have been possible.

We dedicate this book to stroke patients, their families, and their care givers – past, present, and future.

Kevin M. Barrett

James F. Meschia

1

Bedside Evaluation of the Acute Stroke Patient

Bryan J. Eckerle, MD and Andrew M. Southerland, MD, MSc

Department of Neurology, University of Virginia Health System, Charlottesville, Virginia

Introduction

Emanating from the results of the original National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (NINDS rt-PA) trial [1], the management of acute stroke has evolved as a cornerstone of emergency medical care, hospital medicine, and clinical neurology. While the only treatment for acute ischemic stroke approved by the US Food and Drug Administration (FDA) remains intravenous (IV) rt-PA administered within 3 hours of symptom onset, the field continues to expand with a focus on more timely treatment, expanding the pool of patients eligible for treatment, and optimization of methods of reperfusion. These advances include the use of IV rt-PA beyond the 3-hour window, the direct administration of intra-arterial rt-PA, and implementation of a variety of devices aimed at mechanical thrombectomy and other interventional means of cerebrovascular recanalization. However, integrating all of the scientific evidence guiding the acute stroke paradigm is daunting, even for the most seasoned vascular neurologist. According to the National Guideline Clearinghouse, an initiative of the Agency for Healthcare Research and Quality in the De­­partment of Health and Human Services, there are ­currently 225 published guidelines related to acute stroke from various organizations and societies around the world [2]. The current standard of stroke care in the US is guided by the American Heart Association/American Stroke Association’s (AHA/ASA) Get With the Guidelines (GWTG) program [3].

While stroke therapeutics will be discussed in detail elsewhere in this book, the aim of this chapter is to offer a simple, practical approach to the bedside evaluation of the acute stroke patient. As the opinions and recommendations herein draw on experience treating acute stroke, they also reflect the literature and guiding evidence. The chapter will broadly highlight seminal studies, published AHA/ASA guidelines, FDA regulations, and The Joint Commission (TJC) certification requirements for primary/comprehensive stroke centers – links to further resources can be found in the Appendix, Chapter 9. Explored in detail will be the various issues facing neurologists or other physicians in acute stroke scenarios, including an accurate gathering of history, essentials of the acute stroke physical exam, radiological diagnosis, and potential hurdles precluding a treatment decision. While these necessary steps are very much protocol driven, the reality of the acute stroke setting dictates a somewhat simultaneous process in order to achieve the efficient delivery of treatment. Ultimately, the aim of the chapter is to further promote rapid diagnosis and timely management for all acute stroke patients, as the medical community continues to strive for the best possible outcomes from this disabling and deadly disease.

Is it a stroke?

Despite rapid advances in neuroimaging over the past 20 years, the bedrock of the evaluation of the acute stroke patient remains sound clinical diagnosis. The physician is frequently asked to see a patient in urgent consultation for treatment of acute stroke in the absence of a firmly established diagnosis. Even with the advent of highly advanced ­neuroimaging techniques, stroke remains a clinical diagnosis; as opposed to an infarct, which is an imaging or tissue-based diagnosis. Stroke is, by definition, the acute onset of a persistent focal neurological deficit or constellation of deficits referable to a specific cerebrovascular territory. The absence of abrupt onset of symptoms all but precludes acute stroke as the diagnosis. Symptoms that do not all fit into a specific vascular territory suggest either a diagnosis other than stroke or the ­possibility of multifocal ischemia as may be seen in cardioembolism. Additionally, stroke typically produces negative symptoms –that is to say, loss of strength, sensation, vision, or other neurological function. Presence of positive symptoms (pares­thesias, involuntary movements, visual pheno­mena) is uncommon in stroke, unless the patient with a cortical stroke is having a concurrent ­seizure or occasionally a triggered migraine – as in cervical artery dissection.

Ischemic stroke subtypes in specific vascular territories tend to produce fairly predictable constellations of signs and symptoms, or syndromes [4]. Rapid recognition of these syndromes is crucial in early diagnosis and timely treatment of acute stroke or, often of equal importance, the elimination of stroke as a potential diagnosis. In terms of broadly defined clinical stroke syndromes, one can consider large vessel versus small vessel presentations. Generally speaking, large vessel strokes tend to occur in the setting of atherosclerotic and/or embolic disease, whereas small vessel (lacunar) strokes tend to present in the setting of chronic small vessel occlusive disease related primarily to chronic hypertension and diabetes. The clinical manifestations of commonly encountered large vessel syndromes are described in Table 1.1.

Table 1.1 Large vessel stroke syndromes (laterality assumes left hemispheric dominance)

The syndromes above reflect classical neuroanatomy and may vary depending on individual variations in the circle of Willis or collateral vascular supply.

Cortical syndromes

Between large vessel and cardioembolic disease, there are several classic cortical syndromes that when presenting acutely are most often the result of an ischemic stroke. The classic hallmark of a left hemispheric cortical syndrome involves aphasia. Aphasia is defined as an acquired abnormality of language in any form. By and large, aphasia presents as a deficit of verbal language, but truly involves any medium of communication (e.g. reading and writing, or sign language in the hearing impaired). Specific linguistic properties that may be affected by aphasia include volume of speech, vocabulary, cadence, syntax, and phonics. Often, subtle aphasia is difficult to distinguish from encephalopathy and it is important for the bedside clinician to test specific domains of language – fluency, repetition, comprehension, naming, reading, and writing – in order to make the correct diagnosis.

Specific types of aphasia most often encountered in stroke patients (Table 1.2) classically include expressive/motor/nonfluent (Broca’s) and receptive/ sensory/fluent (Wernicke’s) types. Strokes causing expressive aphasia localize to the posterior inferior frontal lobe, or frontal operculum, whereas receptive aphasias commonly originate from lesions in the posterior superior temporal/inferior parietal lobe. Both of these types commonly affect naming and repetition. Broca’s patients are best identified by difficulties with word finding, speech initiation, volume of speech, and in making paraphasic errors (e.g. hassock instead of hammock). Wernicke’s patients have clearly impaired comprehension with non­sensical speech, but preserved speech volume and cadence. The transcortical aphasias mirror motor and sensory types except in preservation of repetition, due to lack of injury to the arcuate ­fasciculus linking Broca’s and Wernicke’s areas. Figure 1.1 ­displays the aphasia box showing the overlap ­between the commonly encountered aphasias.

  TIPS AND TRICKS

A common false localizer for aphasia is left thalamic stroke, which may present with a mixed aphasia of nonspecific character.

In the bedside evaluation of the stroke patient, ­differentiating between aphasia subtypes is less ­relevant than differentiating aphasia from ence­phalopathy. As most all aphasia emanates from dominant hemispheric injury, commonly middle cerebral artery (MCA) occlusion, one should consider the abrupt onset of aphasia indicative of stroke until proven otherwise.

  TIPS AND TRICKS

Aphasia differs from delirium (acute confusional state) in that attention is usually preserved in isolated aphasia. Moreover, the aphasic patient is often visibly aware of and frustrated by their deficits, as opposed to the poorly attentive patient with encephalopathy.

If aphasia is the hallmark of dominant (left) ­hemisphere cortical injury, then hemispatial neglect is the hallmark of injury in the nondominant (right) hemisphere. Accordingly, abrupt onset of ­hemineglect should raise concern for acute stroke by occlusion of the right MCA. Examining the patient with neglect at the bedside is challenging, primarily due to difficulties in teasing out primary contra­lateral motor weakness and numbness. The most sensitive bedside test for subtle neglect is ­double simultaneous stimulation to look for extinction of ­contralateral sensory modalities. In other words, when presented with bilateral stimuli, the neglectful patient will preferentially identify the ipsilateral stimulus, often in the absence of a primary sensory deficit (see National Institutes of Health Stroke Scale (NIHSS) item 11, in the Appendix, Chapter 9). Extinction may include not only tactile sensation but also other sensory modalities, such as vision or hearing. Motor neglect is typified by preferential use of the ipsilateral limbs when formal confrontational testing reveals no actual hemiparesis. The tactful bedside clinician, when asking the patient to raise both limbs, may observe a delay in or absence of activation of the contralateral side.

Table 1.2 The aphasias

Figure 1.1 The graphical aphasia box.

Making the evaluation of the neglectful patient more difficult still is the frequent accompaniment of agnosia. These patients may lack awareness of their deficit (anosagnosia) and may seem apathetic to the gravity of their situation. Other nondominant hemispheric phenomena may include stereoagnosia (inability to identify an object by touch), agraphesthesia (deficit of dermal kinesthesia tested by tracing numbers or letters on the palm or finger pad), and aprosodia (analogue of aphasia affecting expression or comprehension of the emotional aspects of ­language, i.e. pitch, rhythm, intonation). Practically speaking, testing for these more esoteric deficits is not commonly part of the acute stroke evaluation, but may be helpful in confirming suspicion of nondominant hemispheric ischemia.

  TIPS AND TRICKS

Agnostic patients presents a unique challenge regarding consent for IV rt-PA as they may refute the need for treatment. One proposed method is to provide a thought experiment. Ask the patient hypothetically, If you were to have a devastating stroke, would you in that instance want to be treated knowing the risks and benefits of tPA as discussed? An answer in the affirmative places the treating physician on more solid ethical ground in the acute setting [5].

Another cortical syndrome of clinical importance for bedside stroke diagnosis is visual field loss. Simplistically, the abrupt onset of homonymous hemianopsia is a posterior cerebral artery (PCA) or posterior MCA territory stroke until proven otherwise. Often, visual field cuts present as part of the collage of larger stroke syndromes, but may present in isolation with pure occipital lobe ischemia. Strokes affecting the optic radiations typically cause contralateral quandrantanopsias; temporal lobe ischemia involving the inferior optic radiations (i.e. Meyer’s loop) typically affects the superior visual quadrant, as opposed to parietal lesions affecting the superior optic radiations and the inferior visual quadrant. Clinically, patients often do not recognize visual field loss unless confronted, but historical clues may include bumping into walls or merging into traffic. Rather than recognizing a lateralized deficit in both visual fields, patients more commonly complain of peripheral vision loss in the contalateral eye (easily teased out by confrontational testing at the bedside – see item 3 in the NIHSS). Treating patients with thrombolysis for isolated visual field loss is an ­individualized decision. While the NIHSS score indi­cates minor severity in these situations, a visual field deficit may nonetheless be severely disabling, ­parti­cularly for patients who require good vision for employment or those that already have vision problems at baseline. As in all scenarios, an objective conversation with the stroke patient regarding risk and benefits of therapy will often guide one’s hand.

  TIPS AND TRICKS

Lesions posterior to the optic chiasm (e.g. cerebral infarct) generate visual field defects that respect the vertical midline (i.e. hemianopsias), whereas those anterior the chiasm (e.g. branch retinal artery occlusion) respect the horizontal midline (i.e. altitudinal defect). Branch retinal artery occlusions may present as a monocular quadrantanopia.

Small vessel (lacunar) syndromes

Lacunar strokes include five classical syndromes, with some having multiple possible anatomic localizations (Table 1.3).

Table 1.3 The lacunar syndromes

Table 1.4 The midbrain and medullary syndromes

pure motor – contralateral hemiparesis; localizes to posterior limb of internal capsule, corona ­radiata, or basis pontis (ventral pons); secondary to occlusion of lenticulostriates branches of the MCA or perforating arteries from the basilar

pure sensory – contralateral hemisensory deficit; localizes to ventroposterolateral nucleus of the thalamus secondary to lenticulostriates or small thalamoperforators from the PCA

sensorimotor – contralateral paresis and numbness; localizes to thalamus and adjacent posterior limb of internal capsule (thalamocapsular)

dysarthria – clumsy hand – slurred speech and weakness of contralateral hand usually most ­evident when writing or performing other fine motor tasks (may also include supranuclear facial weakness, tongue deviation, and dysphagia), localizes to basis pontis between upper third and lower two-thirds

ataxic hemiparesis – contralateral mild to moderate hemiparesis and limb ataxia out of proportion to the degree of weakness, usually affecting the leg more than the arm, localizes to posterior limb of internal capsule or basis pontis

there is a rare sixth lacunar syndrome presenting with contralateral hemichorea or hemiballismus from a small infarct in the basal ganglia or subthalamic nucleus.

  TIPS AND TRICKS

Lacunar strokes typically present with fluctuating symptoms in the acute period. The so-called capsular warning syndrome often presents with oscillating sensorimotor deficits over a 24 to 48-hour period representing a small lenticulostriate perforator artery in the process of occlusion. In too many cases, tPA treatment is withheld due to rapidly improving symptoms in the hyperacute period only to find the patient with a dense hemiparesis the following morning secondary to completed small vessel stroke.

Brainstem syndromes

There are several vertebrobasilar brainstem syndromes that should be recognizable in the acute stroke setting. These are often caused by occlusion of a small brainstem-penetrating artery stemming from a larger parent vessel, and can therefore be related to either large artery atherosclerosis or small vessel occlusive disease. Less commonly, a microembolus may find its way into one of these perforators, but this is difficult to distinguish without a source of embolus. Named midbrain and medullary syndromes are described in Table 1.4.

Pontine syndromes (see Table 1.1 – basilar territory stroke) are often caused by occlusion of deep or circumferential pontine penetrating branch arteries in the presence of a patent basilar artery. A hallmark of deep pontine infarcts is an abnormality of horizontal gaze and dysarthria. A chief comp­laint is horizontal diplopia, and presenting signs may include ipsilateral lateral gaze palsy from involvement of the abucens nucleus (CN VI) or as an internuclear ophthalmoplegia (INO) from injury to the medial longitudinal fasciculus that yokes conjugate horizontal gaze – although the latter is consistently seen in paramedian midbrain syndromes as well. Due to proximity of the abducens nucleus to CN VII, these patients may also have a peripheral pattern of facial weakness involving upper and lower facial muscles ipsilateral to the infarct. Involvement of more ventral portions of the pons (i.e. corticospinal and corticopontocerebellar tracts) causes contra­lateral hemiparesis or ataxia.

  TIPS AND TRICKS

If a patient presents with neck pain and/or Horner’s syndrome, particularly in young adults, consider cervical artery dissection. Vertebral artery dissection often presents with ipsilesional lateral medullary syndrome and/or cerebellar stroke due to posterior inferior cerebellar artery (PICA) territory infarction. Distal carotid artery dissection may cause lower cranial nerve palsies, but this is a false localizer for brainstem stroke.

  TIPS AND TRICKS

Be vigilant of the locked-in patient; that is a patient who may appear comatose but yet has voluntary blinking or vertical eye movements allowing bedside communication. Locked-in syndrome is caused by bilateral ventral pontine injury with preserved rostral brainstem function including spared level of consciousness from an intact reticular activating system and vertical gaze centers in the midbrain. Similar to top of the basilar syndrome mentioned above, recognizing a devastating pattern of brainstem dysfunction in the acute stroke setting requires immediate evaluation of the basilar artery for possible reperfusion therapy.

Stroke versus TIA?

Transient ischemic attacks (TIA) occur in approximately 15% of patients before an eventual stroke, with the highest risk in the first days to weeks following an event [6,7]. While TIAs do not always come to medical attention, their presentation in the acute stroke setting ostensibly complicates the treatment decision in patients who may be exhibiting some improvement. The majority of TIAs resolve in less than 60 minutes whereas the majority of true strokes reach peak deficit in the same time frame. A 2009 scientific statement from the American Heart Asso­ciation/American Stroke Association discourages the use of traditional time-based definitions of TIA in favor of a tissue-based definition (i.e. the presence or absence of lesions on diffusion-weighted MR imaging) [8]. The fact that 30–50% of TIAs will result in diffusion-weighted abnormalities on brain MRI emphasizes the importance of making a clinical diagnosis in the acute setting. The diagnosis of a TIA requires absolute resolution of symptoms, whereas a persistent deficit should continue to raise concern for a treatable stroke. If a patient returns completely to their neurological baseline (100%), then the clock starts over and any recurrent deficits may be considered a new event (i.e. reopening the treatment window). Evaluation of TIA in the acute stroke setting also requires some assessment of risk. A common practice at US stroke centers is to admit patients ­following TIA in order to expedite the urgent workup of causative mechanisms, including noninvasive vascular imaging and cardiac evaluation. The ABCD2 score has been established as a validated clinical tool to aid in risk assessment and management decisions [9] (Table 1.5). The AHA/ASA statement referenced above provides the following recommendation as a possible algorithm in the acute setting:

Table 1.5 The ABCD2 score

It is reasonable to hospitalize patients with TIA if they present within 72 hours of the event and any of the following criteria are present:

a. ABCD2 score of ≥3

b. ABCD2 score of 0 to 2 and uncertainty that diagnostic workup can be completed within 2 days as an outpatient

c. ABCD2 score of 0 to 2 and other evidence that indicates the patient’s event was caused by focal ischemia.

Stroke mimics

Of the many judgments required of the stroke ­physician at the bedside during an emergency, ­perhaps the most difficult is consideration of the stroke mimic. As treatment with rt-PA clearly is not without risk it is important that the physician be able to rapidly differentiate a stroke mimic from symptoms due to retinal, hemispheric, or brainstem ischemia. The following paragraphs highlight frequently encountered stroke mimics and how to more reliably differentiate them from ischemic stroke in the bedside evaluation.

Following a seizure, postictal focal neurological deficit can appear identical to any cortical stroke syndrome, and without a reliable history or ­eyewitness can be nearly impossible to diagnose prospectively. One would hope that the seizure patient would be able to provide a telling history but this often is not the case, particularly in encephalopathic or aphasic patients when the ictal event is unwitnessed. The most commonly encountered postictal phenomenon is Todd’s paralysis (postictal hemiparesis), but the bedside physician should be aware that almost any focal cortical neurological deficit can be witnessed following a seizure depending on the anatomic location of the seizure focus. Examples include postictal aphasia, sensory disturbance, and neglect. While seizure at the outset of symptoms is a relative contraindication to rt-PA, it should be noted that focal seizures can often herald ischemic stroke onset, particularly of cardioembolic origin. In cases of high suspicion for stroke, attention should be made to the bedside exam and head CT for diagnostic confirmation before ruling out treatment options.

  TIPS AND TRICKS

Gaze preference may help differentiate seizure versus stroke – in a large MCA stroke, eyes will deviate towards the lesion, i.e. away from the side of paralysis. In an ongoing seizure, eyes will deviate away from the ictus, i.e. towards the side of focal motor tonic–clonic activity. Gaze may reverse preference in the postictal state, looking away from Todd’s paralysis.

Another common mimic that can be difficult to diagnose is migraine with aura. The migraine patient, of course, typically will have an associated headache most often following the onset of focal neurological symptoms. However, this is not always the case. Older individuals, in particular, are prone to migraine equivalents without head pain, making the diagnosis even more difficult as this population is typically also at a higher risk for stroke. Like ­seizures, migraine equivalents can mimic almost any focal cortical neurological deficit due to the spreading cortical depression that is characteristic of migraine pathology. A history of migraine, as well as the presence of commonly associated symptoms of nausea, anorexia, photophobia, phonophobia, and positive visual phenomenon, can be helpful. Other clues include a temporal marching quality of symptoms (i.e. from face to arm to leg) and positive symptoms such as parasthesias. However, it should be emphasized that the ­diagnosis of migraine in the acute stroke patient, particularly in persons with legitimate vascular risk factors, remains a diagnosis of exclusion. Hemorrhagic strokes and some less common causes of ischemic stroke, such as reversible cerebral vasoconstriction syndrome and carotid dissection, may be associated with acute headache at the time of the event.

Metabolic derangements that may mimic stroke include hyper- or hypoglycemia, electrolyte dis­turbances, or infection. It is widely held that any metabolic stress on the body can cause stroke reactiva­­tion or anamnestic syndrome. In this case, symptoms of a prior stroke from which a patient has recovered can re-emerge as the metabolic stress on the brain increases. A history of identical symptoms during a prior ischemic event or evidence of chronic infarction in a relevant vascular territory on ­noncontrast head CT can help make this diagnosis. Generally, neurological symptoms