Diagnosis and Management
The differential diagnosis of ischemic stroke and TCIs includes diabetic and convulsive seizures, migraine, vertigo, and neoplasms. Although the presentation of stroke is usually characteristic, the diagnosis should be differentiated from that of other conditions that may mimic strokes, such as multiple sclerosis, subdural hematoma, cranial nerve palsy, encephalitis, hypoglycemia, seizures, brain tumor, hypertensive encephalopathy, syncope, migraine, and functional disorder.
Obtaining a detailed history from the patient, including the time and duration of onset, is important. Also, an assessment of risk factors is critical for treating a patient with suspected stroke. Nonmodifiable risk factors include age older than 60 years, male sex, and family history or prior history of stroke or TCIs. Modifiable risk factors include diabetes mellitus, hypertension, hyperlipidemia, cardiac arrhythmias, smoking, alcohol use, illicit drug use, migraine, and hypercoagulable states.
The clinical severity of a stroke can be determined using the US National Institutes of Health Stroke Scale (NIHSS), which assesses level of consciousness, gaze, visual fields, facial strength, motor function of the arms and legs, ataxia, sensation, language, dysarthria, and inattention, giving a specified number of points to each impairment found. A scale of 0–42 is used for the assessment, with 0 representing normal function and 42 representing the most severe functional impairment.
Patients presenting with TCI within 72 hours of the event should be hospitalized if they have a known source of embolic phenomena that is treatable, such as cardiac valvular disease, evidence of acute infarction on initial imaging, and significant concurrent morbidities. Individuals who are not hospitalized should be instructed to undergo diagnostic workup within 48 hours and warned to return to the emergency department if symptoms recur.
For practical purposes, diagnostic studies may be separated into those done in an acute care setting, such as in the emergency department, and those done in a more subacute setting, such as in a stable inpatient or stable outpatient clinic. Emergent testing assesses the patient’s clinical stability and the possibility of conditions that mimic stroke or conditions that could contribute to stroke; the tests should include blood glucose, complete blood count, blood chemistry, coagulation studies such as PT/aPTT (prothrombin time/activated partial thromboplastin time), international normalized ratio, troponins, and electrocardiogram. Ideally, all suspected cases of stroke and TCI should be evaluated with urgent noncontrast computed tomography (CT) of the brain, because contrast and blood appear similar on CT, and this similarity can result in misinterpretation of the image. Noncontrast CT is very sensitive for the presence of intracranial hemorrhage and remains the imaging modality of choice for emergent initial evaluation of stroke. However, enhancement in CT imaging has also improved its diagnostic capability in the evaluation of early cerebral ischemia.
Investigation of the systemic arteries and the heart is essential in determining the cause of cerebral ischemia. Differences between upper limb pulse rates and blood pressure (BP) may indicate serious subclavian disease. Multiple bruits may suggest widespread arterial disease but may be present without significant occlusion. Evidence of a cardioembolic source should be pursued aggressively, especially in younger normotensive persons with cerebral ischemia and in older patients, for whom atrial fibrillation is included in the differential diagnosis. Electrocardiography and telemetry or Holter monitoring should be routinely performed to exclude cardiac dysrhythmia and occult MI. Echocardiography is often helpful in excluding intracardiac thrombi; transesophageal Doppler echocardiography is most sensitive in this regard. Lumbar puncture is required in the evaluation of stroke or TIA only in rare instances, for example, if meningovascular syphilis, meningitis, or subarachnoid hemorrhage is a serious consideration.
Imaging studies for evaluation of cerebral ischemia
Updates in imaging techniques have now provided numerous options for the clinician in assessing the presence or absence of tissue injury, tissue at risk, and the anatomy of the regional circulation.
Multimodal computed tomography In multimodal CT, 3 CT modes are combined: non-contrast CT, CT perfusion imaging, and CT angiography. This type of imaging can rule out hemorrhage, permit early detection of acute infarction, and allow assessment of the site of occlusion, infarct core, and salvageable brain tissue. In addition, the angiography mode can assess collateral circulation.
Magnetic resonance imaging and magnetic resonance angiography Magnetic resonance imaging (MRI) is more sensitive than noncontrast CT in detecting an evolving stroke within hours of its onset. Diffusion-weighted imaging (DWI) MRI with apparent diffusion coefficient (ADC) mapping is useful in the evaluation of early cerebral ischemia and regional blood flow to determine the presence or absence of acute infarction. MRI perfusion-weighted imaging (PWI) assesses transit time of the contrast agent. Magnetic resonance angiography (MRA) can be used to detect vascular stenosis and/or occlusion. Multimodal MRI, which combines DWI with PWI, is useful in predicting outcomes in patients with TCI. To date, DWI appears to be the imaging modality of choice in the evaluation of a TCI.
Helical computed tomography angiography This type of angiography can rapidly and non-invasively image the large cerebral arteries with very high specificity and sensitivity.
Carotid duplex ultrasonography This imaging modality may be used to evaluate the patency of the extracranial carotid arteries.
Transcranial doppler ultrasonography This type of ultrasonography is used for evaluation of the intracranial arteries (see more in the section Carotid Occlusive Disease).
Cerebral arteriography Although it is the gold standard for angiographic technique, cerebral arteriography has high morbidity and is usually required only if the cause of the TCI is unclear or if intra-arterial thrombolysis or surgical intervention is being strongly considered.
The goals of treating ischemic stroke are to restore blood flow to the brain and to salvage ischemic brain tissue that has not already infarcted. Achieving these goals involves ensuring the patient’s medical stability and determining whether the patient is eligible for thrombolytic therapy. There is a narrow window in which to accomplish these objectives, ideally within 3 hours of symptom onset.
Intravenous thrombolysis Thrombolytic and antithrombotic agents are the primary drugs used in the treatment of ischemic stroke, and recombinant tissue plasminogen activator (rtPA) is the fibrinolytic agent of choice. In the US National Institute of Neurological Diseases and Stroke (NINDS) rtPA Stroke Study, the administration of rtPA within 3 hours of acute ischemic stroke was associated with improved function at 3 months but not with earlier neurologic improvement or lower mortality. The European Cooperative Acute Stroke Study III (ECASS III) demonstrated the benefit of rtPA initiated up to 4½ hours after the onset of stroke. However, the exclusion criteria for patients treated 3–4½ hours from symptom onset (age older than 80 years, severe stroke, diabetes mellitus with a previous infarct, and any anticoagulant use) were more restrictive than for those treated at 3 hours or less. Most studies indicate that the sooner rtPA is initiated, the more likely it is to be beneficial. The most serious complication of administering rtPA is symptomatic intracranial hemorrhage, which occurs in 6.4% of treated patients and has a mortality rate of 50%.
Mechanical (endovascular) thrombectomy Unfortunately, patients with a large cerebral artery occlusion and a large clot burden are less likely to benefit from rtPA and are at high risk of a neurologically disabling outcome. More proximal occlusions are also more resistant to thrombolysis, as are those occlusions resulting from clots with less favorable composition. Furthermore, because some patients fail to meet the eligibility criteria for intravenous rtPA, thrombectomy techniques were developed with clot-retrieving devices to improve canalization of the artery and arrest the ischemic stroke. Therefore, as part of the initial imaging evaluation of acute ischemic stroke, noninvasive vascular study, such as CT angiography, should be performed to assess the patient’s candidacy for endovascular intervention.
Mechanical thrombectomy (MT) performed with first-generation stent retrievers such as the Merci and Penumbra failed to show an improvement in patient outcomes. However, second-generation stent retrievers such as Solitaire and Trevo achieved significantly higher recanalization rates with correspondingly improved outcomes. Five clinical trials with second-generation stent retrieval devices (ESCAPE, EXTEND-IA, MR CLEAN, REVASCAT, and SWIFT PRIME) showed the efficacy of MT when compared with standard medical care in patients with acute ischemic stroke caused by occlusion of the large arteries of the proximal anterior circulation. Anatomic success with recanalization, functional independence, and major neurologic recovery was significantly better in those patients receiving MT. However, mortality at 90 days, risk of intracranial hemorrhage, and risk of parenchymal hematoma involving greater than 30% of the infarct territory did not differ between the 2 study populations. These data have resulted in a paradigm shift in the early treatment of ischemic stroke; mechanical thrombectomy with second-generation stent retrieving devices is now highly recommended in eligible patients. Mechanical thrombectomy should be performed at centers with surgeons skilled in the use of stent-retrieving devices, and initiation of MT should be within 6 hours of stroke onset.
Investigational reperfusion techniques Currently under investigation are other methods of reperfusion, such as intra-arterial thrombolysis (SYNTHESIS expansion trial), use of alternative fibrinolytic agents, combined intravenous and intra-arterial thrombolysis (IMS III trial), stenting, and combined use of fibrinolytics and glycoprotein IIb/IIIa antagonists, but none of these techniques have yet demonstrated improved outcomes.
The cornerstone of stroke management is to prevent future events, especially because most stroke patients do not receive the acute care treatment previously discussed. In addition to thrombolytic drugs and mechanical thrombectomy, the management of stroke includes antithrombotic therapy with antiplatelet agents, initiation of statins, and control of BP after the acute phase is over.
Antithrombotic therapy Although aspirin, clopidogrel, and aspirin/extended-release dipyridamole combination are acceptable drug choices for secondary stroke prevention, aspirin is the only antiplatelet agent that is effective in the early treatment of ischemic stroke. Two large clinical trials showed a benefit of treatment with aspirin over placebo in short-term mortality and recurrent stroke risk when aspirin is initiated within 48 hours of ischemic stroke onset. Early use of combination antiplatelet agents such as aspirin with clopidogrel for acute ischemic stroke may be beneficial, but the available evidence is not consistent and is limited to the specific populations studied. Heparin and related agents are not effective in reduction of mortality or recurrent stroke in patients with cardioembolic or noncardioembolic stroke; in fact, they are associated with higher mortality and a worse outcome. However, use of heparin may be considered in the acute care setting for stroke resulting from postoperative atrial fibrillation in patients with mechanical heart valves or in those with cervicocephalic arterial dissections.
Statins Initiation or continuation of statins early after presentation is critically important. Studies have shown that long-term intensive use of statins after stroke reduces risk of recurrent ischemic stroke and other cardiovascular events. In addition, numerous reports support the beneficial effects of statin administration during the acute phase of ischemic stroke.
Blood pressure control Hypertension is the most important risk factor for stroke. Treatment with antihypertensives in the prevention of recurrent ischemic stroke is supported by data from multiple randomized clinical trials and from 2 meta-analyses of a total of 24 clinical trials with over 70,000 patients. Current guidelines from the 2014 American Heart Association/American Stroke Association (AHA/ASA) recommend continued treatment with antihypertensive drugs in patients with hypertension prior to the stroke event and initiation of antihypertensive treatment for patients with newly diagnosed hypertension. Antihypertensive therapy is not recommended in patients with blood pressures lower than 120/70 mm Hg as there may be risk of harm in individuals with systolic blood pressures lower than 120 mm Hg. Although blood pressure reduction is critical in preventing recurrent ischemic stroke and other ischemic cardiovascular events, care must be taken to maintain blood pressure at a level that will not compromise cerebral perfusion.
For further discussion of hypertension, see Chapter 3 in this volume.
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Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.