American College of Physicians: Internal Medicine — Doctors for Adults ®


Stroke and transient ischemic attack

From the September ACP Observer, copyright 2006 by the American College of Physicians.

Click here for a PDF version of Special Focus: Stroke and transient ischemic attack

Ten years ago, the FDA approved the clot-busting drug tissue-plasminogen activator (tPA) for ischemic stroke treatment, dramatically changing stroke care. It was only one of many advances that have been made in the understanding and management of stroke, ranging from how to reduce risk to the recognition that transient ischemic attack (TIA) was a precursor to imminent acute stroke Ushering those advances from bench to bedside, however, has been slow. Only between 2% and 5% of patients experiencing an ischemic stroke receive tPA, for instance, although stroke experts estimate as many as 50% should.

“This is why the need for designated stroke centers has emerged as a national priority,” explains James C. Grotta, MD, professor and chair of neurology at the University of Texas Medical School in Houston and author of ACP’s PIER module on “Stroke and Transient Ischemic Attack.” (Evidence indicates that more patients in stroke centers receive tPA.)

Part of the reason why tPA usage rates are so low, Dr. Grotta said, is that many patients and their families fail to call 911 or get to a hospital at the first stroke symptom. However, another key reason is physician reluctance to give the medicine, fearing intracranial hemorrhage.

In terms of stroke prevention, Dr. Grotta said, some of the wide gap between evidence and practice is due simply to the fact that so much information is new. Researchers directing a large trial just concluded this year, for instance, that the antithrombotic drug acetylsalicylic acid plus extended-release dipyridamole (Aggrenox) works better than aspirin alone to prevent stroke recurrence. In addition, he said, new evidence is mounting that one alternative therapy—a combination of clopidogrel plus aspirin—should not be used long-term.

Evidence is also growing that the same risk factor reduction efforts that work for heart attack prevention—from aggressive blood pressure lowering to intensive cholesterol reduction—can also stave off stroke.

“A lot of time, internists pay attention to people with cardiac disease, treating them with intensive measures to reduce their risk—but don’t do the same for patients they perceive are at risk for stroke,” Dr. Grotta said.

Another key role for internists is not only to identify those patients at risk for stroke but also to educate them—and, more importantly, their families—about stroke symptoms and the importance of early treatment. Although TIA, often called a “mini stroke,” has been known to presage a full-blown stroke, the newest evidence suggests that the riskiest time is the first few days or weeks afterward.

“We never realized that the risk is so front-loaded,” said Dr. Grotta. “The evidence is definitely emerging that if you see a patient with a TIA, you need to get that patient evaluated emergently.”

This edition of ACP Observer Special Focus is designed to help optimize your ability to diagnose, treat and manage patients with stroke and transient ischemic attack.


Because most risk factors can be modified, identify the following conditions in patients and recommend needed treatment and lifestyle changes:

  • coronary artery disease or peripheral vascular disease, or a family history of either before age 60
  • hypertension
  • diabetes mellitus
  • elevated cholesterol
  • smoking
  • hyperhomocysteinemia
  • carotid bruit
  • history of TIA
  • history of paroxysmal or persistent atrial fibrillation
  • age greater than 50

To substantially reduce stroke risk, recommend the following measures:

  • Avoid hormone replacement therapy in healthy postmenopausal women.
  • Control hypertension. Even a modest reduction in systolic blood pressure can reduce the number of strokes by as much as 36%.
  • Prescribe an ACE inhibitor, especially if the patient is hypertensive, diabetic or has already had a vascular ischemic event.
  • Encourage smoking cessation.
  • Maintain optimal glycemic control in diabetic patients, although no good data confirm that tight control of diabetes reduces risk of stroke.
  • Start warfarin in most patients with atrial fibrillation when sinus rhythm cannot be restored. Avoid warfarin, however, in patients who cannot have adequate prothrombin time (INR) monitoring, cannot receive medications in a predictable fashion or who have an increased risk of bleeding.
  • Start antiplatelet therapy—such as aspirin, clopidogrel or aspirin plus extended-release dipyridamole—in low-risk patients who have atrial fibrillation. Anticoagulant therapy is recommended for prevention of recurrent stroke in patients with nonrheumatic atrial fibrillation and recent non-disabling stroke or TIA.
  • Prescribe statin therapy in patients with coronary artery disease and moderately elevated LDL cholesterol to reduce stroke risk by between 30% and 50%.
  • Refer asymptomatic patients with carotid stenosis for possible carotid endarterectomy if they are younger than age 75, are expected to live more than five years and have a greater than 60% reduction in luminal diameter. Select neurosurgeons or vascular surgeons with a record of low morbidity and mortality. Men benefit more from such surgery than women.

New guidelines for ischemic stroke prevention were published in the March 1, 2006, issue of Stroke.


Ask patients about cerebrovascular symptoms, such as weakness, paresthesia, vertigo, or a loss of sensation, speech or vision in one eye or one visual field.

Aphasia, visual field defect or contralateral neglect suggests a cortical lesion, while pure motor or sensory symptoms involving the face, arm and leg usually indicate a subcortical location. Cranial nerve involvement, diplopia, vertigo, imbalance, and bilateral motor or sensory symptoms—especially perioral tingling—imply posterior circulation involvement. A complaint of a sudden “worst headache of my life,” usually without focal symptoms or signs, suggests subarachnoid hemorrhage.

To differentiate ischemic from hemorrhagic stroke and to determine the extent and location of ischemic lesions, perform a cranial CT or MRI within 30 minutes of emergency department arrival. TIA and stroke both require the same urgent diagnostic evaluation.

Use electrocardiography to document atrial fibrillation. Use carotid ultrasonogram if patients have atherosclerotic risk factors and could be candidates for carotid endarterectomy. Avoid routine testing for antiphospholipid antibodies.

Always consider other underlying diseases that can present with acute neurological dysfunction. These include seizure, hypoglycemia, complicated migraine, toxic or metabolic insult unmasking previous central nervous system injury, brain tumor, or subdural hematoma or functional illness.


Request a neurology consultation to help determine the cause of the stroke, assess its severity and decide on appropriate therapy or if the diagnosis is unclear.

Hospitalize all patients with a suspected stroke for at least 24 hours in a dedicated stroke unit if possible, and arrange for the patient to be managed by a multidisciplinary stroke team. Admit patients to an intensive care unit if they exhibit signs of respiratory or cardiovascular instability or decreased consciousness.

Because there is a significant risk of stroke in patients who present with TIA, also hospitalize high-risk patients with TIA. Patients are at highest risk for completed stroke when they are older than age 60, show signs of weakness or speech disturbance, have diabetes, or had a TIA that lasted longer than 10 minutes.

The risk of stroke following TIA is greatest for those patients with large vessel stenosis. For these patients, order a carotid ultrasound (or alternative vascular imaging) and an echocardiogram to exclude a cardiac source of emboli, and observe them with frequent neurologic evaluations for at least 24 hours.

Drug therapy

Because thrombolytic therapy may reverse neurologic dysfunction in patients with acute stroke, begin intravenous tPA within three hours of suspected ISCHEMIC stroke onset. Note that tpa is not indicated in patients with evidence of intracranial hemorrhage. Use only tPA. Streptokinase is ineffective and harmful, and other thrombolytics have not been tested intravenously for stroke.

The percentage of patients who recover complete independence following a stroke increases from 35% to 50% after tPA therapy, and all types of ischemic stroke respond to intravenous tPA therapy. The risk of tPA-induced hemorrhage is less than that due to hemorrhage from severe untreated stroke.

Before administering tPA, perform the following diagnostic studies:

  • To rule out intracerebral hemorrhage, perform a non-contrast head CT or an MRI with gradient echo sequence.
  • EKG
  • hematocrit, platelet count and glucose measurement
  • INR and partial thromboplastin time if the patient is taking anticoagulants.

Give a total tPA dose of 0.9 mg/kg—10% in the first minute as a bolus and the remainder as an infusion over one hour—to a maximum dose of 90 mg. At the same time, withhold aspirin and anticoagulants for 24 hours, monitor the patient closely in a stroke or intensive care unit for changes in vital signs or neurologic status, and control blood pressure to 180/110 mm Hg. If blood pressure rises to above 185/110 mm Hg, treat with one to two doses of IV labetalol 10–20 mg, or IV nicardipine 5 mg/h. If these measures are unsuccessful, do not give tPA.

Do not give thrombolytics if:

  • mean arterial pressure is >130 mm Hg
  • Systolic blood pressure is >185 m Hg
  • Diastolic blood pressure is >110 mm Hg

Use easily titrated drugs—such as intravenous labetalol or nicardipine—to reach the above blood pressure goals in patients who are otherwise good candidates for thrombolytics.

Because aggressive blood pressure lowering in acute ischemic stroke is associated with worse outcomes in patients not receiving TPA, treat blood pressure only if systolic blood pressure exceeds 220 mm Hg; mean arterial pressure is greater than 140 mm Hg; or there is evidence of coronary or renal insufficiency or a suspicion of aortic dissection.

Start adjunctive antiplatelet therapy (aspirin, 160-325 mg/d) for most patients with acute ischemic stroke, but delay starting it until 24 hours after tPA therapy.

Do not provide anticoagulation with heparin or low-molecular-weight heparin in most ischemic strokes except for subcutaneous heparin for prophylaxis against deep venous thrombosis. However, consider heparin therapy in certain emergency situations, such as suspected cerebral venous thrombosis; basilar occlusion or stenosis in patients who are not candidates for rtPA therapy; and suspected extracranial arterial dissection or atherosclerotic occlusion.

Antithrombotic therapy may help retard thrombosis in these situations and may decrease risk for subsequent stroke.

Other drugs to avoid include glycerol as an osmotic therapy for brain edema and steroids for brain edema following stroke. No trials prove the benefit of mannitol to reduce elevated intracranial pressure.

Non-drug therapy

Adjunctive measures can prevent complications and improve prognosis, and include the following:

  • Treat temperature elevation above 38 degrees.
  • Give supplemental oxygen to maintain more than 95% oxygen saturation.
  • Control blood glucose levels to less than 150-170 mg/dL, and avoid glucose-containing solutions.
  • Give intravenous normal saline to maintain euvolemia.
  • Insert bladder catheter if necessary.
  • Until you assess swallowing, make sure patients consume nothing by mouth. Place a nasogastric feeding tube if the patient is at risk for aspiration with standard oral feeding.

Consider carotid endarterectomy for eligible patients with TIA or nondebilitating stroke and without excessive cardiopulmonary risk, depending on the degree of stenosis. Carotid endarterectomy reduces the rate of recurrent ipsilateral stroke in symptomatic patients with stenosis more than medical therapy alone.

Recommend carotid endarterectomy if a stroke or TIA in the past six months was due to internal carotid stenosis of more than 70%, or if the stenosis is 50-69% and the patient is likely to live at least five years. The greatest benefit occurs if the surgery is performed within two weeks following a stroke, although the risks are greatest then too.

As an alternative to carotid endarterectomy, consider stenting. The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), sponsored by the National Institute of Neurological Disorders and Stroke, is exploring that option. (Go online for more information.)

If the stroke is complicated, request specialist consultation. Obtain a rehabilitation consultation to maximize long-term function after stroke, including physical and occupational therapy, speech and swallowing assessment, and psychiatry evaluation. Start physical, occupational and speech therapy as well as rehab planning within the first 48 hours.

Secondary prevention

Focus on secondary stroke prevention. Stroke risk is between 4% and 8% in the first month after TIA and can be modified with antiplatelet therapy. Prescribe aspirin, 50-325 mg/d. Even better—but more expensive—is aspirin, 25 mg, plus extended-release dipyridamole (Aggrenox), 200 mg/bid. For patients who cannot tolerate aspirin, clopidogrel, 75 mg/d, has similar efficacy. Do not combine aspirin and clopidogrel; it increases the risk of life-threatening and other major bleeding.

Fully anticoagulate for secondary stroke prevention when the cause of the stroke or TIA is cardioembolism. High-risk cardioembolic etiologies of stroke and TIA include atrial fibrillation, left atrial appendage thrombus, left ventricular thrombus and dilated cardiomyopathy with a significant reduction in ejection fraction.

Wait between 48 and 96 hours to start such anticoagulation after an established suspected cardioembolic stroke, and repeat brain imaging to exclude hemorrhagic changes in the infarct. Use weight-adjusted heparin without bolus dosing at first.

Anticoagulate more urgently with heparin to a partial thromboplastin time of 60 to 70 seconds in “crescendo” TIA. Anticoagulate (usually after 48 hours) with warfarin to an INR of between 2.0 and 3.0 once patients are stable in cases of atrial fibrillation, the sick sinus syndrome, recent anterior myocardial infarction, mural thrombus, left ventricular aneurysm or akinetic segment mechanical valve. Consider warfarin therapy in patients with cerebrovascular symptoms due to a confirmed hypercoagulable state and consider short-term anticoagulation (three to six months) in patients with cervicocephalic arterial dissection.

Discontinue hormone replacement therapy, and recommend the following risk-factor modifications for secondary prevention:

  • smoking cessation
  • optimal glycemic control in patients with diabetes
  • long-term blood pressure control, using an ACE inhibitor or an angiotensin receptor blocker

And all TIA and stroke patients benefit from a statin.


Perform frequent neurologic examinations (daily during the first week and monthly after hospital discharge), stress secondary prevention measures and risk factor reduction, and consider intensive therapist-based rehabilitation to improve balance, endurance, mobility and aerobic capacity. Formal training of caregivers during rehabilitation improves outcomes and reduces caregiver burden as well.

Local injections with botulinum toxin type A can reduce spasticity of patients' wrists or fingers. To prevent hip fracture, which is more common in stroke patients than in the general population, initiate measures to reduce fall risk and prescribe a bisphosphonate in those with osteoporosis.

Identify and treat post-stroke depression with either tricyclics or serotonin reuptake inhibitors, which have fewer side effects.

This information comes from the PIER module "Stroke and Transient Ischemic Attack."

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.


Stroke warning signs

Make sure patients know these warning signs:

  • Sudden numbness or weakness of the face, arm or leg, especially on one side of the body
  • Sudden confusion, trouble speaking or understanding
  • Sudden trouble seeing in one or both eyes
  • Sudden trouble walking, dizziness, loss of balance or coordination
  • Sudden, severe headache with no known cause

Source: American Stroke Association


The new age of stroke centers

Strokes can be deadly and devastating, but one way to improve the odds that patients may survive and recover is to make sure they receive immediate medical treatment in a certified stroke center.

“It’s like having a trauma center for stroke,” said Mark J. Alberts, MD, professor of neurology at Chicago's Northwestern University Medical School and director of the stroke program at Northwestern Memorial Hospital. “The idea is to identify stroke patients as soon as they call 911 and then to triage them to the nearest stroke center facility.”

Such facilities, he said, have the protocols and infrastructure to be able to administer the drug tPA swiftly and safely to appropriate patients, to accurately diagnose and treat stroke patients, and to prevent complications.

Other protocols and specialists on site able to prevent complications treat stroke patients with the most appropriate medical or surgical therapies. There are abundant data that dedicated stroke units are very helpful for reducing complications and improving outcomes.

Dr. Alberts has been the lead author on several key articles promoting the stroke center concept. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has adopted the concept and to date has certified about 250 primary stroke centers in hospitals across the country.

Several states, including New York, Massachusetts and Florida, have their own programs and have approved another 250 stroke centers. (Information on JCAHO’s program and a list of certified centers are online.)

According to Dr. Alberts, there is emerging evidence that patients who go to a stroke center facility are more likely to receive tPA and—once they get tPA—have better outcomes. “And there is emerging data that patients treated at stroke center facilities and by stroke neurologists have better outcomes in terms of fewer in-hospital complications," he added. "They are more likely to go home or to rehab as opposed to dying or going to a nursing home.”

The next goal of stroke experts, Dr. Alberts said, is to certify comprehensive stroke centers, which would be even more specialized with the staff and expertise to provide interventional stroke care, including stents and endovascular surgery. More information about comprehensive stroke centers was in the July 2005 issue of Stroke.


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