Which type of stroke correlates with the clinical manifestations of a severe headache?

Large-vessel atherosclerosis can affect intracranial or extracranial arteries.

Atheromas, particularly if ulcerated, predispose to thrombi. Atheromas can occur in any major cerebral artery and are common at areas of turbulent flow, particularly at the carotid bifurcation. Partial or complete thrombotic occlusion occurs most often at the main trunk of the middle cerebral artery and its branches but is also common in the large arteries at the base of the brain, in deep perforating arteries, and in small cortical branches. The basilar artery and the segment of the internal carotid artery between the cavernous sinus and supraclinoid process are often occluded.

Emboli may lodge anywhere in the cerebral arterial tree.

Emboli may originate as cardiac thrombi, especially in the following conditions:

• Atrial fibrillation

• Rheumatic heart disease (usually mitral stenosis)

• Post–myocardial infarction

• Vegetations on heart valves in bacterial or marantic endocarditis

• Prosthetic heart valves

Ischemic stroke can also result from lacunar infarcts. These small (≤ 1.5 cm) infarcts result from nonatherothrombotic obstruction of small, perforating arteries that supply deep cortical structures; the usual cause is lipohyalinosis (degeneration of the media of small arteries and replacement by lipids and collagen). Whether emboli cause lacunar infarcts is controversial.

Lacunar infarcts tend to occur in older patients with diabetes or poorly controlled hypertension.

Less common causes of stroke include vascular inflammation secondary to disorders such as acute or chronic meningitis, vasculitic disorders, and syphilis; dissection of intracranial arteries or the aorta; hypercoagulability disorders (eg, antiphospholipid syndrome, hyperhomocysteinemia); hyperviscosity disorders (eg, polycythemia, thrombocytosis, hemoglobinopathies, plasma cell disorders); and rare disorders (eg, fibromuscular dysplasia, moyamoya disease, Binswanger disease).

Any factor that impairs systemic perfusion (eg, carbon monoxide toxicity, severe anemia or hypoxia, polycythemia, hypotension) increases risk of all types of ischemic strokes. A stroke may occur along the borders between territories of arteries (watershed areas); in such areas, blood supply is normally low, particularly if patients have hypotension and/or if major cerebral arteries are stenotic.

Less commonly, ischemic stroke results from vasospasm (eg, during migraine, after subarachnoid hemorrhage, after use of sympathomimetic drugs such as cocaine or amphetamines) or venous sinus thrombosis (eg, during intracranial infection, postoperatively, peripartum, secondary to a hypercoagulability disorder).

• 1. Kernan WN, Viscoli CM, Furie KL, et al: Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 374 (14):1321–1331, 2016. doi: 10.1056/NEJMoa1506930.

• 2. Morgan JA, Brewer RJ, Nemeh HW, et al: Stroke while on long-term left ventricular assist device support: incidence, outcome, and predictors. ASAIO J 60 (3):284–289, 2014. doi: 10.1097/MAT.0000000000000074.

Symptoms and Signs of Ischemic Stroke

Symptoms and signs of ischemic stroke depend on the part of brain affected. Patterns of neurologic deficits often suggest the affected artery (see table Selected Stroke Syndromes Selected Stroke Syndromes

Deficits may become maximal within several minutes of onset, typically in embolic stroke. Less often, deficits evolve slowly, usually over 24 to 48 hours (called evolving stroke or stroke in evolution), typically in atherothrombotic stroke.

In most evolving strokes, unilateral neurologic dysfunction (often beginning in one arm, then spreading ipsilaterally) extends without causing headache, pain, or fever. Progression is usually stepwise, interrupted by periods of stability.

A stroke is considered submaximal when after it is complete, there is residual function in the affected area, suggesting viable tissue at risk of damage.

Embolic strokes often occur during the day; headache may precede neurologic deficits. Thrombi tend to occur during the night and thus are first noticed on awakening.

A seizure may occur at stroke onset, more often with embolic than thrombotic stroke. Seizures may also occur months to years later; late seizures result from scarring or hemosiderin deposition at the site of ischemia.

Deterioration during the first 48 to 72 hours after onset of symptoms, particularly progressively impaired consciousness, results more often from cerebral edema than from extension of the infarct. Unless the infarct is large or extensive, function commonly improves within the first few days; further improvement occurs gradually for up to 1 year.

Neuroimaging with CT or MRI is done first to exclude intracerebral hemorrhage, subdural or epidural hematoma, and a rapidly growing, bleeding, or suddenly symptomatic tumor. CT evidence of even a large anterior circulation ischemic stroke may be subtle during the first few hours; changes may include effacement of sulci or the insular cortical ribbon, loss of the gray-white junction between cortex and white matter, and a dense middle cerebral artery sign. Within 6 to 12 hours of ischemia, medium-sized to large infarcts start to become visible as hypodensities; small infarcts (eg, lacunar infarcts) may be visible only with MRI.

Diffusion-weighted MRI (highly sensitive for early ischemia) can be done immediately after initial CT neuroimaging.

For cardiac causes, testing typically includes ECG, telemetry or Holter monitoring, serum troponin, and transthoracic or transesophageal echocardiography.

For vascular causes, testing may include magnetic resonance angiography (MRA), CT angiography (CTA), carotid and transcranial duplex ultrasonography, and conventional angiography. The choice and sequence of testing is individualized, based on clinical findings. MRA, CTA, and carotid ultrasonography all show the anterior circulation; however, MRA and CTA provide better images of the posterior circulation than carotid ultrasonography. MRA is generally preferred to CTA if patients can remain still during MRA (to avoid motion artifact). Usually, CTA or MRA should be done urgently but should not delay IV tPA if it is indicated.

For blood-related causes (eg, thrombotic disorders), blood tests are done to assess their contribution and that of other causes. Routine testing typically includes complete blood count (CBC), platelet count, prothrombin time/partial thromboplastin time (PT/PTT), fasting blood glucose, and lipid profile.

Depending on which causes are clinically suspected, additional tests may include measurement of homocysteine, testing for thrombotic disorders (antiphospholipid antibodies, protein S, protein C, antithrombin III, factor V Leiden), testing for rheumatic disorders (eg, antinuclear antibodies, rheumatoid factor, erythrocyte sedimentation rate), syphilis serologic testing, hemoglobin electrophoresis, and a urine drug screen for cocaine and amphetamines.

• Airway support and ventilatory assistance if decreased consciousness or bulbar dysfunction compromises the airway

• Supplemental oxygen only if needed to maintain oxygen saturation > 94%

• Correction of hyperthermia (temperature > 38° C) by using an antipyretic drug and identifying and treating the cause of hypothermia

• Treatment of hypoglycemia (blood glucose < 60 mg/dL)

• Treatment of hyperglycemia (a reasonable option) to lower blood glucose to 140 to 180 mg/dL while closely monitoring for hypoglycemia

Perfusion of an ischemic brain area may require a high blood pressure (BP) because autoregulation is lost; thus, BP should not be decreased except in the following cases:

• There are signs of other end-organ damage (eg, aortic dissection, acute myocardial infarction, pulmonary edema, hypertensive encephalopathy, retinal hemorrhages, acute renal failure).

• Use of recombinant tissue plasminogen activator (tPA) and/or mechanical thrombectomy is likely.

If BP is ≥ 220 mm Hg systolic or ≥ 120 mm Hg diastolic on 2 successive readings 15 minutes apart, lowering BP by 15% in the 24 hours after stroke onset is reasonable.

For patients who are eligible for acute reperfusion therapy except that BP is > 185/110 mm Hg, BP can be treated to decrease BP to below > 185/110 mm Hg0 t with one of the following:

• Labetalol 10 to 20 mg IV bolus over 1 to 2 minutes (may repeat 1 time)

• Nicardipine 5 mg/hour IV infusion initially (dose is increased by 2.5 mg/hour every 5 to 15 minutes to a maximum of 15 mg/hour)

• Clevidipine 1 to 2 mg/hour IV infusion (titrate by doubling the dose every 2 to 5 minutes until desired BP is reached to a maximum of 21 mg/hour)

Patients with presumed thrombi or emboli may be treated with one or a combination of the following:

• tPA, thrombolysis-in-situ, and/or mechanical thrombectomy

• Antiplatelet drugs

• Anticoagulants

Most patients are not candidates for thrombolytic therapy; they should be given an antiplatelet drug (usually aspirin 325 mg orally) when they are admitted to the hospital. Contraindications to antiplatelet drugs include aspirin-induced or nonsteroidal anti-inflammatory drug (NSAID)-induced asthma or urticaria, other hypersensitivity to aspirin or to tartrazine, acute gastrointestinal bleeding, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and use of warfarin.

Although tPA can cause fatal or other symptomatic brain hemorrhage, patients treated with tPA strictly according to protocols still have a higher likelihood of functional neurologic recovery. Only physicians experienced in stroke management should use tPA to treat patients with acute stroke; inexperienced physicians are more likely to violate protocols, resulting in more brain hemorrhages and deaths. When tPA is given incorrectly (eg, when given despite the presence of exclusion criteria), risk of hemorrhage due to tPA is high mainly for patients who have had stroke; risk of brain hemorrhage is very low (about 0.5%; 95% confidence interval of 0 to 2.0% [ 1 Treatment references Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more

tPA must be given within 4.5 hours of symptom onset—a difficult requirement. Because the precise time of symptom onset may not be known, clinicians must start timing from the moment the patient was last observed to be well.

Before treatment with tPA, the following are required:

• Brain hemorrhage must be excluded by CT

• Systolic BP must be < 185 mm Hg

• Diastolic BP must be < 110 mm Hg

• Blood glucose must be > 50 mg/dL

Antihypertensive drugs (IV nicardipine, IV labetalol, IV clevidipine) may be given as above. Blood pressure should be kept < 180/105 mm Hg for at least 24 hours after treatment with tPA.

Dose of tPA is 0.9 mg/kg IV (maximum dose 90 mg); 10% is given by rapid IV injection over 1 minute, and the remainder by constant infusion over 60 minutes. Vital signs are closely monitored for 24 hours after treatment. Any bleeding complications are aggressively managed. Anticoagulants and antiplatelet drugs are not used within 24 hours of treatment with tPA.

Thrombolysis-in-situ (angiographically directed intra-arterial thrombolysis) of a thrombus or embolus can sometimes be used for major strokes if symptoms began < 6 hours ago, particularly for strokes that are due to large occlusions in the middle cerebral artery and cannot be treated with IV recombinant tPA. Clots in the basilar artery may be intra-arterially lysed up to 12 hours after stroke onset, sometimes even later depending on the clinical circumstances. This treatment, although standard of care in some large stroke centers, is often unavailable in other hospitals.

Mechanical thrombectomy (angiographically directed intra-arterial removal of a thrombus or embolus by a stent retriever device) is standard of care in large stroke centers for patients with recent large-vessel occlusion in the anterior circulation. It should not be used instead of IV recombinant tPA within 4.5 hours of onset of symptoms in eligible patients with acute ischemic stroke. Devices used to remove thrombi are being improved, and recent models reestablish perfusion in 90 to 100% of patients.

Oral antiplatelet drugs are used in acute stroke treatment. The following may be used:

• Aspirin 100 to 325 mg within 48 hours of stroke onset

• Dual antiplatelet therapy: Aspirin plus clopidogrel (eg, 300 to 600 mg orally once, then 75 mg orally once a day) within 24 hours of stroke onset for patients at high risk of a transient ischemic attack (TIA, ABCD2 score ≥ 4) or minor stroke

The ABCD2 score is calculated by adding the following

• A (age): ≥ 60 = 1

• B (blood pressure): Systolic blood pressure ≥ 140 and/or diastolic blood pressure > 90 = 1

• C (clinical features): Weakness = 2, speech disturbance without weakness = 1

• D (TIA duration): ≥ 60 min = 2, 10 to 59 min = 1, < 10 minutes = 0

• D2 (diabetes) = 1

Risk of stroke within 2 days based on the ABCD2 score is about

• For a score of 6 to 7: 8%

• For a score of 4 to 5: 4%

• For a score of 0 to 3: 1%

Anticoagulation with heparin or low molecular weight heparin is used for stroke caused by cerebral venous thrombosis and sometimes for stroke caused by cervical artery dissection. Anticoagulation can also be used in patients at high risk of recurrent cardiac emboli (eg, those with cardiac thrombi or mechanical valves).

Usually, anticoagulation is avoided in the acute stage because risk of hemorrhage (hemorrhagic transformation) is higher, especially with large infarcts.

Supportive care is continued during convalescence:

• Controlling hyperglycemia and fever can limit brain damage after stroke, leading to better functional outcomes.

• Screening for dysphagia before patients begin eating, drinking, or receiving oral drugs can help identify patients at increased risk of aspiration; it should be done by a speech-language pathologist or other trained health care practitioner.

• Enteral nutrition if needed should be started within 7 days of admission after an acute stoke.

• Intermittent pneumatic compression (IPC) for deep venous thrombosis prophylaxis is recommended for immobile stroke patients without contraindications.

• Low molecular weight heparin may be given to immobile stroke patients without contraindications.

Long-term management also focuses on prevention of recurrent stroke (secondary prevention). Modifiable risk factors (eg, hypertension, diabetes, smoking, alcoholism, dyslipidemia, obesity) are treated. Reducing systolic BP may be more effective when the target BP is < 120 mm Hg rather than the typical level (< 140 mm Hg).

Extracranial carotid endarterectomy or stenting is indicated for patients with recent nondisabling, submaximal stroke attributed to an ipsilateral carotid obstruction of 70 to 99% of the arterial lumen or to an ulcerated plaque if life expectancy is at least 5 years. In other symptomatic patients (eg, patients with TIAs), endarterectomy or stenting with antiplatelet therapy is indicated for carotid obstruction of ≥ 60% with or without ulceration if life expectancy is at least 5 years. These procedures should be done by surgeons and interventionists who have a successful record with the procedure (ie, morbidity and mortality rate of < 3%) in the hospital where it will be done. If carotid stenosis is asymptomatic, endarterectomy or stenting is beneficial only when done by very experienced surgeons or interventionists, and that benefit is likely to be small. For many patients, carotid stenting with an emboli-protection device (a type of filter) is preferred to endarterectomy, particularly if patients are < 70 years and have a high surgical risk. Carotid endarterectomy and stenting are equally effective for stroke prevention. In the periprocedural period, myocardial infarction is more likely after endarterectomy, and recurrent stroke is more likely after stenting.

Extracranial vertebral angioplasty and/or stenting can be used in certain patients with recurrent symptoms of vertebrobasilar ischemia despite optimal medical treatment and a vertebral artery obstruction of 50 to 99%.

Intracranial major artery angioplasty and/or stenting is considered investigational for patients with recurrent stroke or TIA symptoms despite optimal medical treatment and a 50 to 99% obstruction of a major intracranial artery.

Endovascular closure of a patent foramen ovale does not appear to be more effective for preventing strokes than medical management, but studies are ongoing.

Oral antiplatelet drugs are used to prevent subsequent noncardioembolic (atherothrombotic, lacunar, cryptogenic) strokes (secondary prevention). The following may be used:

• Aspirin 81 or 325 mg once a day

• Clopidogrel 75 mg once a day

• The combination product aspirin 25 mg/extended-release dipyridamole 200 mg 2 times a day

In patients taking warfarin, antiplatelet drugs additively increase risk of bleeding and are thus usually avoided; however, aspirin is occasionally used simultaneously with warfarin in certain high-risk patients. Clopidogrel is indicated for patients who are allergic to aspirin. If ischemic stroke recurs or if a coronary artery stent becomes blocked while patients are taking clopidogrel, clinicians should suspect impaired metabolism of clopidogrel (ineffective conversion of clopidogrel to its active form because cytochrome P-450 2C19 [CYP2C19] activity is reduced); a test to determine CYP2C19 status (eg, genetic testing for CYP450 polymorphisms) is recommended. If impaired metabolism is confirmed, aspirin or the combination product aspirin/extended-release dipyridamole is a reasonable alternative.

Clopidogrel plus aspirin, if started during acute treatment, is given for only a short time (eg, < 3 months) because it has no advantage over aspirin alone in long-term secondary stroke prevention and results in more bleeding complications. Clopidogrel plus aspirin before and for ≥ 30 days after stenting is indicated, usually for ≤ 6 months; if patients cannot tolerate clopidogrel, ticlopidine 250 mg 2 times a day can be substituted.

Oral anticoagulants are indicated for secondary prevention of cardioembolic strokes (as well as primary prevention). Adjusted-dose warfarin (a vitamin K antagonist) with a target international normalized ratio (INR) of 2 to 3 is used for certain patients with nonvalvular or valvular atrial fibrillation. A target INR of 2.5 to 3.5 is used if patients have a mechanical prosthetic cardiac valve. Efficacious alternatives to warfarin for patients with nonvalvular atrial fibrillation include the following new anticoagulants:

• Dabigatran (a direct thrombin inhibitor) 150 mg 2 times a day in patients without severe renal failure (creatinine clearance < 15 mL/minute) and/or liver failure (elevated INR)

• Apixaban (a direct factor Xa inhibitor) 5 mg 2 times a day in patients ≥ 80 years, in patients with serum creatinine ≥ 1.5 mg/dL and creatinine clearance ≥ 25 mL/minute, or as an alternative to aspirin in patients who cannot take warfarin

• Rivaroxaban (a direct factor Xa inhibitor) 20 mg once a day for patients without severe renal failure (creatinine clearance < 15 mL/minute)

Statins are used to prevent recurrent strokes; lipid levels must be decreased by substantial amounts. Atorvastatin 80 mg once a day is recommended for patients with evidence of atherosclerotic stroke and LDL (low-density lipoprotein) cholesterol ≥ 100 mg/dL. A reasonable LDL cholesterol target is a 50% reduction or a level of < 70 mg/dL. Other statins (eg, simvastatin, pravastatin) may be also used.

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• 2. Powers WJ, Rabinstein AA, Ackerson T, et al: 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49 (3):e46–e110, 2018. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.

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• 8. Hao Q, Tampi M, O'Donnell M, et al: Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: Systematic review and meta-analysis. BMJ 2018 363:k5108, 2018. doi: 10.1136/bmj.k5108.