Hospital Medicine

Stroke

I. Problem/Condition.

Stroke is defined as the sudden loss of neurologic function due to a vascular event. This can include hemorrhage or ischemia as an underlying cause. The key elements in the initial management of stroke include differentiating between hemorrhagic and ischemic stroke, rapid evaluation for thrombolysis or embolectomy to attempt reperfusion of ischemic tissue, and evaluation for any other possible etiologies mimicking stroke. This is followed by attempts to minimize neurologic damage from the stroke, prevent medical complications, evaluate for potential stroke etiologies to guide secondary prevention efforts, and rehabilitation of neurologic deficits.

A. What is the differential diagnosis for the sudden loss of neurologic function?

The major differential includes stroke and its various sub-types, and other conditions that can mimic stroke. Stroke mimics include those conditions that can present with focal neurologic deficits as well as those that present with global alterations to neurologic function and consciousness.

Stroke (a vascular cause for symptoms)

  • Ischemic stroke

    • Thrombotic and thromboembolic stroke - ischemia that develops from obstruction of a vessel from local thrombosis (thrombotic) or from emboli from another arterial source such as the carotid arteries (thromboembolic)

    • Cardioembolic stroke - obstruction of a vessel caused by emboli from the heart, such as thrombus from atrial fibrillation or vegetations from endocarditis

    • Vasculitic stroke - ischemia triggered by inflammation of the blood vessels

    • Lacunar stroke - ischemic strokes involving atherosclerosis of the small penetrating arterioles of the brain, usually involving deep white matter or the brainstem

    • Transient ischemic attack - rapidly resolving episode of focal neurologic deficits (traditionally defined as those lasting less than 24 hours, although may be better defined as an episode of resolved focal neurologic deficits with likely ischemic cause and without evidence of infarction on magnetic resonance imaging (MRI)

  • Hemorrhagic stroke

    • Intracerebral hemorrhage - hemorrhage within the brain parenchyma

    • Subarachnoid hemorrhage - hemorrhage below the arachnoid layer but outside the brain parenchyma and the pial layer, most commonly caused by aneurysmal rupture or trauma.

Stroke mimics

  • Stroke mimics with focal neurologic symptoms

    • Focal seizures

    • Todd's paralysis

    • Intracranial mass (i.e., tumor, abscess)

    • Multiple sclerosis

    • Demyelinating disease

    • Peripheral neuropathy

    • Complicated migraine

    • Conversion disorder

    • Exacerbation or “recrudescence” of symptoms from a previous stroke (secondary to systemic infection, dehydration, metabolic derangements listed below, etc.)

  • Stroke mimics with non-localizing symptoms

    • Hypoglycemia

    • Hypo- and Hypernatremia

    • Hyperammonemia

    • Encephalitis/Meningitis

    • Drug overdose

    • Medication affect

    • Infection

    • Hypoxia or hypercarbia

    • Hypertensive encephalopathy

B. The diagnostic approach to the patient with suspected stroke

N/A

1. Important historical information

The single most important piece of history in a patient presenting with a possible stroke is time of symptom onset. History should also characterize the nature of the neurologic symptoms, evaluate for associated symptoms that suggest stroke mimics, assess for contraindications to acute treatments, and focus on any clues to the etiology of the patient's stroke.

Categorizing features of the stroke

  • Time of onset of symptoms. If unknown or if the patient awoke with symptoms, the last time the patient was seen without symptoms (these questions are important for determining eligibility for any acute interventions).

  • Elicit nature of neurologic symptoms: Weakness? Facial droop? Speech difficulties? Neglect? Sensory changes? Vision changes? Confusion? Altered consciousness?

  • Any symptoms of increased intracranial pressure: Decreased level of consciousness? Worsening neurologic exam?

  • Features suggestive of hemorrhagic stroke: Headache? Nausea and/or vomiting?

    • Specific features suggesting subarachnoid hemorrhage: severe and sudden onset of headache, altered consciousness without focal deficits

  • Risk factors for intracranial hemorrhage: Uncontrolled hypertension? Anticoagulant use? Recent head trauma?

Evaluating for stroke mimics

  • Focal seizures or Todd's paralysis: History of seizures?

  • Mass lesion: History of malignancy? Immunosuppression?

  • Complicated migraine: Associated headache? History of migraines (either currently or earlier in life)?

  • Conversion disorder: Recent major life changes or stressors?

  • Worsened symptoms from old stroke: Any previous stroke with similar symptoms or documentation of prior stroke or neurologic deficit?

  • Hypoglycemia: History of diabetes? Any oral hypoglycemic agent use? Insulin use?

  • Meningitis or encephalitis: Fevers? Neck pain or stiffness?

  • Illicit drug use? Sedating medication use?

  • Hypercarbia: Associated respiratory symptoms? COPD history?

  • Hypertensive encephalopathy: Hypertension history? Any recent discontinuation of anti-hypertensive agents?

Once the stroke type has been determined, questions should also be directed to finding an etiology for the stroke. For example, it is important to ask about recent neck trauma or neck pain to suggest carotid artery dissection or any IV drug use or fevers to suggest possible endocarditis. This is covered more extensively in the individual stroke sub-type chapters.

2. Useful physical examination maneuvers

In the case of a suspected stroke, the initial neurologic examination should be brief but thorough, as time to reperfusion of ischemic tissue is of the essence. Formal stroke scales such as the modified NIH Stroke Scale (NIHSS) (Lyden et al., 2001) are used to help standardize the assessment of a patient, quantify and communicate the degree of deficits, and assist with prognosis. The modified NIHSS includes 11 high-yield test of neurologic function, including cortical, motor, sensory and cerebellar function as well as cranial nerves. See Table I.

Table I.

Modified NIH Stroke Scale (NIHSS)

In addition to the modified NIHSS examination, further testing may also include the following:

Motor testing

  • In stroke, smaller muscles are generally affected before larger muscles. A typical assessment of strength over-emphasizes these larger muscles. Maneuvers that emphasize small motor function are usually more sensitive in picking up subtle stroke deficits.

    • Rapid finger taps/toe taps - these maneuvers assesses the distal extensors of the extremities.

    • Pronator drift – ask the patient to hold their arms out in extension and supination; assess for pronation and downward drift of the arm.

Speech

  • Dysarthria (defective articulation usually from posterior circulation pathology) needs to be distinguished from aphasia (a language disorder from a left MCA stroke).

  • In Wernicke's aphasia (receptive - found in posterior superior temporal lobe stroke) speech is more fluent but comprehension and repetition are impaired.

  • In Broca's aphasia (expressive - found in posterior inferior frontal lobe stroke) speech is non-fluent, comprehension is better but repetition is still impaired.

Cerebellar testing

  • Gait - Both standard gait and heal-to-toe “tandem” walking to evaluate for ataxia.

3. Laboratory, radiographic and other tests useful in the initial evaluation of suspected stroke

In the emergency room

1. In all patients:

  • Vital signs including oxygen saturation.

  • Computerized tomography (CT) scan of the head without contrast - used to quickly assess for hemorrhagic stroke.

    • If no blood is visualized and the suspicion for subarachnoid hemorrhage remains high, lumbar puncture should be performed.

  • Electrocardiogram

  • Serum glucose (this is the only laboratory test that is absolutely required prior to fibrinolytic therapy, as major glucose abnormalities are a contraindication to t-PA)

  • Serum electrolytes including renal function tests

  • Complete blood count including platelet count

  • Markers for cardiac ischemia

  • Prothrombin time, international normalized ratio, partial thromboplastin time

  • Urinalysis

  • Type and screen

2. In select patients:

  • If within 6 hours of symptom onset of a suspected large vessel ischemic stroke and the patient is a candidate for endovascular therapy, the following should also be ordered:

    • CT perfusion scan of the head.

    • CT angiography of the head and neck.

  • Urine toxicology screen

  • Blood alcohol level

  • Pregnancy test

  • Arterial blood gas

Subsequent testing

  • MRI brain - This test can both confirm the presence of an ischemic stroke and help evaluate for many mimics of stroke. Use of gadolinium-based contrast agents depends on the level of suspicion for mass lesions or other potential enhancing lesions.

  • Electroencephalogram - If suspicion for focal seizures is high.

  • Depending on the type of stroke, further testing to help define etiology and guide secondary prevention efforts such has carotid doppler ultrasound or echocardiogram. This is covered in the stroke sub-type chapters.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Not applicable.

A. Initial management of suspected stroke - Initial assessment

  • Initial efforts should focus on ABCs. If a patient has respiratory compromise or needs cardiovascular support, this needs to be addressed immediately. If a patient has a severely depressed level of consciousness (GCS<7) or loss of airway reflexes, intubation and mechanical ventilation should be initiated.

  • Next, the patient needs rapid evaluation for hemorrhage. At most institutions, this is done with a non-contrasted head CT. Subsequent steps depend on the results of that imaging. See below for a brief summary and the stroke sub-type chapters for more extensive information.

B. Initial management of stroke - intracerebral hemorrhage

  • Admission to the intensive care unit (ICU)

  • Initial and ongoing assessment for herniation and increased intracranial pressure

  • Neurosurgical consultation (or transfer to a facility where neurosurgery is available on-call), especially if cerebellar or other infratentorial hemorrhage, for potential surgical intervention.

  • Rapid correction of any coagulopathies with fresh-frozen plasma, vitamin K, protamine, platelet infusion, recombinant factor replacements

  • Aggressive blood pressure control to systolic < 140 with labetalol and nicardipine

  • Minimization of potential complications (i.e., aspiration pneumonia, deep vein thrombosis [DVT])

  • Evaluation for a potential etiology of the patient's hemorrhage

C. Initial management of stroke - subarachnoid hemorrhage

  • Admission to the ICU

  • Neurosurgical consultation (or transfer to a experienced referral center)

  • Consider placement of intraventricular catheter to closely monitor intracranial pressure (ICP) as well as to treat or prevent obstructive hydrocephalus

  • Maintenance of euvolemia

  • Blood pressure control to goal systolic <130 (unless there is suspicion for vasospasm in which case the blood pressure goal would be higher)

  • Efforts to minimize vasospasm (ie. nimodipine)

  • Seizure prophylaxis (in practice, patients are usually only treated with antiepileptics if they've actually had a seizure)

  • Definitive treatment of aneurysm to prevent rebleeding (surgical clipping vs. endovascular intervention)

D. Initial management of suspected stroke - ischemic stroke

  • If the patient presents within 4.5 hours of the onset of symptoms, consider thrombolytics. If the patient presents within 6 hours and has a large vessel occlusion, consider embolectomy.

  • Decide patient's risk for neurologic decompensation and the level of monitoring required during hospitalization:

    • Cerebellar strokes, large brainstem strokes and large hemispheric strokes are at higher risk for rapid decompensation with worsening edema and warrant closer monitoring, potentially in the intensive care unit.

    • If not available, these patients may need to be transferred to facilities with available on-call neurosurgical evaluation.

  • Admission for:

    • Neurologic monitoring

    • Efforts to minimize infarction

    • Minimization of associated complications (i.e., aspiration pneumonia, DVT)

    • Initiation of secondary prevention efforts (both general and etiology-specific)

    • Initiation of rehabilitation

E. Thrombolytics and other interventions in acute stroke

tPA

  • The two major trials that guide our use of tPA are the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study which demonstrated benefits in a selected population of ischemic stroke patients if administered within 3 hours of the onset of symptoms, and the European Cooperative Acute Stroke Study 3 (ECASS 3), which expanded the window to 4.5 hours for a subset of patients (see below for additional criteria).

    • In the NINDS tPA study, 39% of patients who received tPA had a modified Rankin Scale of 0-1 (minimal or no disability) at 3 months as compared to 26% of the placebo group. However, the risk of intracranial hemorrhage in the tPA group was about 6% (compared to 0.6% in the placebo group), with half of those cases being fatal. Both the tPA and the control arm had similar mortality rates at 3-months

    • The key difference between the NINDS trial and previous trials in the strict inclusion and exclusion criteria in patient selection. Deviance from current recommendations (largely derived from that study's protocol) increase the risk of intracerebral hemorrhage with tPA.

  • Selection criteria include:

    • Symptoms most likely caused by ischemic stroke that are not clearing spontaneously and are not minor. Caution should be taken of major deficits.

    • No head trauma, previous stroke or myocardial infarction (MI) in previous 3 months.

    • No GI or urinary tract hemorrhage in the last 21 days, no major surgery in the last 14 days and no arterial puncture at a non-compressible site in the last 7 days.

    • No history of intracranial hemorrhage

    • Blood pressure less than 185 mmHg systolic and less than 100 mmHg diastolic.

    • No active bleeding, acute trauma or fracture on exam.

    • No oral anticoagulants or, if taken, international normalized ratio (INR) less than 1.7. If on heparin in the last 48 hours, aPTT must be in the normal range. Platelets greater than 100,000.

    • Blood glucose greater than 50 or greater than 400 mg/dL

    • No seizures with post-ictal neurologic deficits

    • CT without evidence of multilobal infarction (hypodensity greater than 1/3 of cerebral hemisphere)

    • Patient and/or family members understand the risk and benefits of treatment

  • Differences for the 4.5 hour window – the ECASS-3 study population additionally required:

    • Age less than 80 years old

    • No oral anticoagulant use (regardless of INR)

    • A National Institute of Health (NIH) stroke score below 25

    • No history of prior stroke AND diabetes

  • After tPA administration, the patient should be admitted to the ICU or a specialized stroke unit for frequent vital sign monitoring and neurologic function assessments. Blood pressure should be tightly controlled <185 systolic with labetalol or nicardipine. Any suspicion of intracranial hemorrhage should prompt an emergent head CT scan. A head CT at 24 hours should be checked before any antiplatelet agents or anticoagulants are started to look for hemorrhagic transformation.

Endovascular Reperfusion techniques

  • For patients who present with a large vessel occlusion within 6 hours of symptom onset, consider embolectomy (in addition to tPA if within 4.5 hours).

  • Multiple trials in 2015 showed benefit of mechanical embolectomy in addition to tPA for patients with large vessel occlusions (MR CLEAN, EXTEND-IA, ESCAPE, SWIFT-PRIME; see references below), and is now considered the standard of care.

    For this reason, “stroke protocol” CT scans now include a non-contrast head CT, CT perfusion, and CT angiography in order to determine if there is a large vessel occlusion. Of note, administration of t-PA should not be delayed in order to perform the extra two sequences.

F. Management of a worsening neurologic exam

  • First and foremost, elevated ICP and impending herniation must be ruled-out. If new pupil asymmetry or Cushing's triad (hypertension, bradycardia, respiratory variations), treat immediately for elevated ICP before further work-up:

    • Elevate head position to 30-60 degrees

    • Intubate and hyperventilate (goal pH of 7.25-7.30)

    • Administer hyperosmolar agents (i.e., mannitol boluses and 3% hypertonic saline infusion)

    • Consider anesthetic agents (i.e., barbituates or propofol)

    • Transfer to the ICU

    • Consider potential neurosurgical interventions (i.e., intraventricular catheter, neurosurgical decompression)

  • Once the patient has stabilized, then a CT scan of the head without contrast to further investigate etiology.

  • Potential causes:

    • Increasing edema (which generally peaks 2-4 days after stroke)

    • Enlarging hemorrhagic stroke

    • Hemorrhagic conversion in ischemic stroke (generally managed the same as other hemorrhagic stroke)

    • Recurrent stroke

    • Hypotension and cerebral hypoperfusion

    • Seizure (especially if hemorrhagic stroke)

    • Metabolic derangements or infection (i.e. electrolyte abnormalities, urinary tract infection)

    • Delirium

G. Common mistakes in the initial management of stroke

  • Do not underestimate the danger of a cerebellar stroke. The posterior fossa has little room to accommodate edema and swelling, and these strokes can rapidly lead to herniation. If a cerebellar stroke is suspected but not yet confirmed (i.e. dysmetria of exam), admit the patient to a unit where frequent neurologic checks can be done and consider transfer to a facility with neurosurgical evaluation is rapidly available.

  • The 3-hour and 4.5-hour windows are the outer-limits as to when IV t-PA can be administered for ischemic stroke. The risk of hemorrhagic conversion increases as time passes within these windows, so administer thrombolytics as soon as possible if indicated.

  • The 6-hour time window is currently the outer-limit as to when mechanical embolectomy can be attempted for patients with large vessel occlusions. Mechanical embolectomy in addition to IV tPA is now the gold standard for acute stroke management. CT “stroke protocol” now includes non-contrast head CT, CT perfusion, and CT angiography, in order to determine candidacy for neurointerventional embolectomy.

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