Acute Stroke

Strokes are classified as either ischemic (approximately 85% of cases) or hemorrhagic (approximately 15% of cases). Important guidelines from the American Heart Association/American Stroke Association (AHA/ASA) for the care of patients with stroke include the following:

• Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke

• 2021 Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack

• 2022 Guideline for the Management of Patients with Spontaneous Intracerebral Hemorrhage

Ischemic Stroke

Ischemic stroke is a cerebrovascular occlusion that causes ischemic neuronal injury. The source of occlusion is typically either embolism or thrombosis. See the AHA/ASA guidelines for the early management of acute ischemic stroke in patients.

Causes

Leading causes:

• atherosclerosis (of the aortic arch, cervical arteries, large intracranial arteries, and small cerebral vessels)

• cardioembolism (due to atrial fibrillation, low ejection fraction leading to ventricular thrombus, and “paradoxical” systemic venous embolism through a patent foramen ovale)

Less-common causes:

• cervical artery dissection

• endocarditis

• vasculitis (systemic vs. primary central nervous system)

• reversible cerebral vasoconstriction syndrome (RCVS, or Call-Fleming syndrome)

• hypercoagulable states (e.g., systemic malignancy, antiphospholipid antibody syndrome

• hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura, nephrotic syndrome)

• global hypoperfusion

• vascular compression (herniation syndromes)

Workup

When a patient presents with symptoms suggestive of acute ischemic stroke, the primary and urgent goal is to determine whether they can safely receive intravenous (IV) tissue plasminogen activator (tPA) or benefit from other forms of arterial revascularization. Because these interventions are time sensitive, the immediate workup should be focused and efficient and include the following:

• Neurologic assessment: All patients with suspected ischemic stroke should undergo a careful and focused neurologic assessment and evaluation using the National Institutes of Health Stroke Scale, a standardized physical examination template that quantifies the severity of the deficit.

• Focused history and physical examination: The purpose of the focused history is to identify absolute and relative contraindications to tPA (see table below for full list). The evaluation should focus on the following:

  • last-seen well time

  • current use of anticoagulant/antiplatelet agents

  • current platelet count and international normalized ratio (INR)

  • previous strokes

  • prior intracranial bleeding or other major bleeding

  • recent surgery

  • current blood pressure

  • NIH Stroke Scale evaluation

• Noncontrast CT: This is required immediately to distinguish intracerebral hemorrhage from ischemic stroke. CT has high sensitivity for identifying acute intracranial hemorrhage but may not show early ischemic changes during the acute period. If imaging demonstrates hemorrhage, tPA is obviously contraindicated.

• Other studies (not necessarily during the acute period):

  • MRI: This is highly sensitive for identifying both acute intracranial hemorrhage and acute ischemic changes, but it is slower, more expensive, and more susceptible to motion artifact than CT; MRI may be contraindicated in some patients (e.g., patients with pacemakers or metal implants).

  • vessel imaging: Imaging of the head and neck vessels may be useful to detect areas of stenosis, dissections, or occlusions. Vessel imaging may also guide intervention when intra-arterial therapy is being considered. Options for vessel imaging include CT of the head and neck vessels with arterial contrast (CTA) or magnetic resonance angiogram (MRA), which does not require contrast. Ultrasound of the neck vessels may be useful for assessment of the carotid arteries but does not provide good imaging of the intracranial and posterior neck vessels. In select cases, catheter-based angiography is performed.

  • echocardiogram: When a cardioembolic source is suspected, transthoracic echocardiography is performed to evaluate for vegetation, mural thrombus, and presence of patent foramen ovale. Transesophageal echocardiography is performed when atrial appendage clot is suspected.

  • heart rhythm monitoring: Ambulatory noninvasive electrocardiogram (ECG) monitoring is often recommended after discharge if a cause of stroke has not been identified; some studies suggest up to 16% of patients have newly detected atrial fibrillation detected only by Holter monitor.

• additional workup: Young patients or patients without apparent risk factors warrant additional workup for unusual causes of stroke, including evaluation for a hypercoagulable state.

Treatment

The purpose of acute treatment in ischemic stroke is to salvage viable tissue and to improve brain function. Initial stroke symptoms reflect the area of core infarction in addition to surrounding tissue with low perfusion (penumbra). This area of low perfusion surrounding the core area of infarction can be preserved if reperfusion is achieved rapidly. Otherwise, the area eventually becomes incorporated into the area of infarct. Therefore, revascularization interventions (e.g., tPA), when indicated, should be attempted as soon as safely possible.

(Source: Acute Ischemic Stroke. N Engl J Med 2007.)

tPA revascularization: Before giving tPA, a CT scan must be obtained to rule out hemorrhage. The time-sensitive decision regarding the use of tPA does not depend on MRI; CT is sufficient to rule out hemorrhage. If a patient presents early with no contraindications to therapy, IV tPA may be given to try to dissolve the clot.

• The Food and Drug Administration (FDA) has approved use of tPA within 3 hours after the stroke event.

• In contrast, AHA/ASA guidelines extend treatment beyond 4.5 hours in selected patients, based on results of a placebo-controlled study. In this study, treatment with IV alteplase in patients with an unknown time of stroke onset, acute stroke symptoms, and MRI features suggestive of recent cerebral infarction resulted in a higher likelihood of no or minimal neurologic deficit at 90 days.

• The benefit of tPA decreases and the risk increases with time, such that the earlier tPA is administered, the higher the likelihood of a positive neurologic outcome (“time is brain”). It is important to understand and inquire about potential contraindications before administering tPA.

• The following risk-benefit statistics are important to share with patients and family members when counseling about tPA therapy:

  • benefit: absolute increase of 11-13 percentage points in the odds of neurologic improvements at 90 days

  • risk: 6% risk for intracerebral hemorrhage, possibly causing neurologic deterioration or death

(Source: Intravenous Thrombolytic Therapy for Acute Ischemic Stroke. N Engl J Med 2011.)

Intra-arterial mechanical thrombectomy: Current evidence supports the use of intra-arterial mechanical thrombectomy (with a stent-retriever device) in patients with proximal large-vessel occlusions of the anterior circulation (intracranial internal carotid, middle cerebral, anterior cerebral) who present within 6 hours after their last-seen well time. Mechanical thrombectomy within 6 to 16 hours of onset or last-seen well time is also recommended in selected patients with acute ischemic stroke who have large-vessel occlusion and other eligibility criteria.

• Visualization of the cerebral vessels is required, either by CT angiography, MRA, or digital subtraction angiography.

• Mechanical thrombectomy should only be performed at stroke centers with experienced operators. Consideration of mechanical thrombectomy should not delay or influence the decision to give IV tPA (per AHA/ASA guidelines). Mechanical thrombectomy can follow IV tPA administration.

Complications of Acute Ischemic Stroke

• hemorrhagic transformation of the infarct bed (bleeding into the friable, newly infarcted tissue)

• malignant cerebral edema (swelling of the infarcted tissue): When severe, this can cause shifting and herniation of the brain. Suboccipital craniotomy (for large posterior-fossa infarcts) and decompressive hemicraniectomy (for large middle-cerebral-artery infarcts) can be considered.

• Depending on the etiology, appropriate secondary-stroke prevention can be chosen (e.g., aspirin, anticoagulation, blood-pressure [BP] control, lipid-lowering agents).

Secondary Prevention of Ischemic Stroke

Recommendations for prevention of secondary stroke depend on the etiology of the initial ischemic stroke or transient ischemic attack. The AHA/ASA guidelines for secondary prevention of stroke recommend a diagnostic workup focused on determining the etiology (if possible) and management strategies based on risk factors.

• Management of vascular risk factors: In addition to diagnosing and treating symptomatic carotid stenosis and atrial fibrillation, it is important to diagnose and treat hypertension, diabetes, hyperlipidemia, and etiologies of cardioembolic stroke with specific treatments and indications (e.g., endocarditis, patent foramen ovale in select patients) and systemic diseases that may initially manifest with stroke. Smoking is also an important vascular risk factor.

• Management of lifestyle risk factors: Smoking cessation as well as promoting a healthy diet (e.g., transition to low-salt and Mediterranean diets) and physical activity are important interventions for secondary prevention.

(Source: Secondary Prevention after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med 2012.)

Hemorrhagic Stroke

Fifteen percent of strokes are due to hemorrhagic stroke, either intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH).

Intracerebral Hemorrhage (ICH)

ICH is a neurologic emergency. Causes of ICH include the following:

• hypertension

• trauma

• bleeding diatheses

• amyloid angiopathy

• illicit drug use

• rarer causes (e.g., bleeding into tumors, aneurysm rupture, other vascular malformations)

Workup: The AHA/ASA ICH guidelines recommend workup of patients with ICH focus on the factors summarized in the following table:

(Source: 2022 Guideline for the Management of Patients with Spontaneous Intracerebral Hemorrhage: A Guideline from the American Heart Association/American Stroke Association. Stroke 2022.)

Management: The AHA/ASA ICH guidelines include the following management recommendations:

• admission to intensive care unit (ICU) or dedicated stroke unit

• focused history, physical examination, routine laboratory tests to evaluate for etiology, comorbidities, and risk factors

• immediate imaging

  • CT or MRI to confirm diagnosis of spontaneous ICH

  • cerebral vascular imaging (e.g., CT angiography, MRA) to assess for aneurysms, vascular malformation, and active extravasation of contrast (this so-called “spot sign” indicates ongoing bleeding that may predict expansion of the hemorrhage).

  • intra-arterial digital subtraction angiography (particularly in the setting of spontaneous intraventricular hemorrhage with no detectable parenchymal hemorrhage) to exclude a macrovascular cause

  • cerebral venography with CTA to assess for macrovascular causes or cerebral venous thromboses (particularly in patients <70 years with lobar spontaneous ICH and patients 45-70 years with deep/posterior fossa without history of hypertension)

• reversal of coagulopathy (if possible): coagulation agents include vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and/or platelets, depending on why the patient is coagulopathic

  • For patients with vitamin K-associated ICH and INR>2.0: To quickly correct INR and limit hematoma expansion, PCCs are preferable to FFP.

  • To prevent later increase in INR, IV vitamin K should be given after coagulation factor replacement

  • IV protamine may be considered to partially reverse anticoagulant effect of low molecular weight heparin and unfractionated heparin.

  • For patients on direct oral anticoagulants (DOACs): If taken within the previous few hours, consider activated charcoal to prevent DOAC absorption.

  • To reverse anticoagulation with dabigatran (a direct thrombin agent) use idarucizumab; if idarucizumab is not available, consider PCCs or hemodialysis.

  • PCCs may be useful for reversal of rivaroxaban and apixaban (factor Xa inhibitors).

  • For patients on aspirin: Unless emergency surgery is planned for spontaneous ICH, platelet transfusions should not be administered due to potential harm.

• management of hypertension: In the INTERACT2 trial, rates of hematoma growth, death, and major disability did not differ between standard-of-care BP control (<180 mm Hg systolic BP) and intensive management (<140 mm Hg systolic BP), but the intensive-control group had better functional outcomes as measured by the Rankin scale. (See related NEJM JW summary.) In the ATACH-2 trial, treatment of participants with ICH to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg, with no significant between-group difference in the ordinal distribution of the modified Rankin scale score at 3 months.

  • For patients with spontaneous ICH of mild-to-moderate severity and presenting systolic BP (SBP) between 150 and 220 mm Hg and no contraindication to acute BP treatment: Aiming to lower SBP to target of 140 mm Hg with the goal of maintaining SBP between 130 and 150 mmHg is safe and can improve functional outcome; acute lowering to SBP<130 mmHg is potentially harmful.

  • For patients with ICH presenting with SBP >220 mm Hg: Consider aggressive reduction of BP with a continuous IV infusion and frequent BP monitoring.

• glucose management (avoid both hyper- and hypoglycemia)

• treatment of fever (may be reasonable based on animal studies, although no conclusive evidence exists from human studies)

• management of seizures:

  • Treat clinical seizures or electrographic seizures on electroencephalograph (EEG) with antiepileptic drugs.

  • Prophylactic antiepileptic medications are not indicated for ICH without evidence of seizures as they convey no benefit in relation to functional outcomes, long-term seizure control, or mortality. Note: A short course of prophylactic antiepileptic drug therapy is used in patients with subdural hematoma.

• intracranial pressure (ICP) monitoring: Consider in patients with Glasgow Coma Score (GCS) ≤8, clinical evidence of transtentorial herniation, or intraventricular hemorrhage or hydrocephalus. Cerebral perfusion pressure goal is usually 50-70 mm Hg.

• minimally invasive hematoma evacuation with endoscopic or sterotactic aspiration with or without thrombolytic use: Consider for patients with supratentorial ICH 20-30 mL in volume with GCS 5-12 to reduce mortality (as compared to medical management alone). Consider minimally evasive hematoma evaluation over conventional craniotomy in this patient subset.

• referral for neurosurgery: Limited evidence supports surgery for ICH except in the following specific situations:

  • Patients with cerebellar hemorrhage and neurologic deterioration from brain-stem compression, hydrocephalus, or both should undergo surgical removal of hemorrhage as soon as possible (with concomitant administration of hyperosmolar therapy such as mannitol).

  • In deteriorating patients with supratentorial hematoma evacuation, surgery might be lifesaving, but efficacy is not established. The Surgical Treatment for Ischemic Heart Failure (STICH) trial showed no benefit from early decompressive surgery.

  • In patients with supratentorial ICH with coma, midline shift, or elevated ICP refractory to medical management, decompressive craniotomy with or without hematoma evacuation might reduce mortality.

• other (nonacute) management:

  • prevention of venous thromboembolism: Patients with ICH are at high risk for venous thromboembolism. In nonambulatory patients, intermittent compression boots are recommended on day of diagnosis. In addition, low initiating low-dose unfractionated heparin or low molecular weight heparin prophylaxis at 24-48 hours from ICH onset may be reasonable to consider to balance risks for thrombosis and hematoma expansion. Compression stockings alone are not beneficial for venous thromboembolism prophylaxis.

  • assessment and management of dysphagia: Some patients require feeding tube placement.

Subarachnoid Hemorrhage

The most common cause of subarachnoid hemorrhage (SAH) is aneurysm rupture or trauma. Other causes include vascular malformations.

Presentation: SAH begins abruptly with the primary symptom of a sudden severe headache, classically described as a thunderclap or “the worst headache of my life.” Usually, no important focal neurologic signs appear at presentation unless bleeding occurs into the brain at the same time.

Severe headache may be associated with:

• brief loss of consciousness

• seizure

• nausea

• vomiting

• focal neurologic deficit

• stiff neck

Diagnosis: A patient’s first or worst headache or one that starts abruptly (thunderclap) should trigger suspicion for SAH and prompt workup, including imaging with CT of the head. Lumbar puncture (LP) should be performed in any patient with suspected SAH and negative results on head CT. Misdiagnosis can occur in the absence of the classic signs and symptoms of SAH. The most common incorrect alternative diagnoses are migraine and tension-type headaches.

(Source: Aneurysmal Subarachnoid Hemorrhage. N Engl J Med 2006.)

Treatment: In the critical care setting, the main goals of treatment are:

• prevent rebleeding

• secure the vascular malformation

• prevent and manage vasospasm

• treat other medical and neurologic complications

(Source: Aneurysmal Subarachnoid Hemorrhage. N Engl J Med 2006.)

(Source: Subarachnoid Hemorrhage. N Engl J Med 2017.)