A. TRANSIENT ISCHEMIC ATTACKDEFINITIONTransient ischemic attack (TIA) refers to a transient neurologic dysfunction caused by focal brain or retinal ischemia, with symptoms typically lasting less than 60 minutes but always less than 24 hours. It is followed by a full recovery of function. PHYSICAL FINDINGS AND CLINICAL PRESENTATION● During an episode, neurologic abnormalities are confi ned

to discrete vascular territory.● Typical carotid artery symptoms (Box 35–1) are ipsilateral

monocular visual disturbance, contralateral homonymous hemianopsia, contralateral hemimotor or sensory dysfunc-tion, and language dysfunction (dominant hemisphere), alone or in combination.

● Typical vertebrobasilar artery symptoms (Box 35–2) are binocular visual disturbance, vertigo, diplopia, dysphagia, dysarthria, and motor or sensory dysfunction involving the ipsilateral face and contralateral body.

CAUSE● Cardioembolic● Large-vessel atherothrombotic disease● Lacunar disease● Hypoperfusion with fi xed arterial stenosis● Hypercoagulable statesDIFFERENTIAL DIAGNOSIS

● Hypoglycemia● Seizures● Anxiety, panic disorder● Migraine

● Subdural hemorrhage● Mass lesions● Vestibular disease

LABORATORY TESTS● Complete blood count (CBC) with platelets● Prothrombin time (PT; international normalized ratio

[INR]) and partial thromboplastin time (PTT)● Glucose● Lipid profi le● Erythrocyte sedimentation rate (ESR; if clinical suspicion for

infectious or infl ammatory process)● Urinalysis● Chest x-ray● Electrocardiography (ECG); consider cardiac enzymes● Other tests as dictated by suspected causeIMAGING STUDIES● Head CT scan to exclude hemorrhage including a subdural

hemorrhage is often performed as the initial diagnostic im-aging modality; however, it is not as sensitive as MRI.

● MRI and MRA. In several studies, MRI with diffusion-weighted imaging has identifi ed early ischemic brain injury in up to 50% of patients with a TIA. MRA of the brain and neck can identify large-vessel intracranial and extracranial stenoses (Fig. 35–1), arteriovenous malformations, and aneurysms

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Chapter 35: Cerebrovascular disease

Chapter 35 Cerebrovascular disease

35

Box 35–1 Characteristics of carotid artery syndrome1. Ipsilateral monocular vision loss (amaurosis fugax)—the

patient often feels as if “a shade” has come down over one eye.

2. Episodic contralateral arm, leg, and face paresis and paresthesias

3. Slurred speech, transient aphasia4. Ipsilateral headache of vascular type5. Carotid bruit may be present over the carotid bifurcation6. Microemboli, hemorrhages, and exudates may be noted

in the ipsilateral retina

Ferri F: Practical Guide to the Care of the Medical Patient, 7th ed. St. Louis, Mosby, 2007.

Box 35–2 Characteristics of vertebrobasilar artery syndrome1. Binocular visual disturbances (blurred vision, diplopia, total

blindness)2. Vertigo, nausea, vomiting, tinnitus3. Sudden loss of postural tone of all four extremities (drop

attacks) with no loss of consciousness4. Slurred speech, ataxia, numbness around lips or face

Ferri F: Practical Guide to the Care of the Medical Patient, 7th ed. St. Louis, Mosby, 2007.

Fig 35–1Irregular high-grade atheromatous stenosis at the origin of the internal carotid artery (large arrow). Shallow atheromatous plaques are seen on the internal (black arrow) and external (white arrow) carotid arteries.(From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger and Allison’s Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. London. Harcourt, 2001.)

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35 Section 2: Brain, peripheral nervous system, muscle

● Carotid Doppler studies identify carotid stenosis● Echocardiography if cardiac source is suspected● Telemetry for hospitalized patients for at least 24 hours;

may consider 24-hour Holter monitoring or event monitor post discharge if arrhythmia is suspected as cause of TIA

● Four-vessel cerebral angiogram if considering carotid endar-terectomy or carotid stent

TREATMENT● Depends on cause● If the time of the onset of symptoms is clear, there are sig-

nifi cant defi cits on neurologic examination, and brain hem-orrhage has been ruled out, then the patient may be a can-didate for thrombolytic therapy, but this option should be discussed with a neurologist or specialist in cerebrovascular disease.

● Acute anticoagulation: no data supporting benefi ts in the acute setting. Heparin is considered for new-onset atrial fi -brillation and atherothrombotic carotid disease causing re-current transient neurologic symptoms, especially in the setting before carotid endarterectomy or carotid stenting. Also, consider basilar artery thrombosis, given concern for progression to brainstem stroke, with high morbidity and mortality.

● First-line treatment has traditionally been aspirin (81 mg/day). Other options include combination of extended-release dipyridamole and immediate-release aspirin (Ag-grenox) or clopidogrel.

● Carotid endarterectomy for carotid artery TIA associated with an ipsilateral stenosis of 70% to 99%: surgery should be done by an experienced surgeon who performs this pro-cedure frequently. Carotid stenting is an option in patients who are not surgical candidates. Trials are underway com-paring stenting with surgery for carotid disease.

● Modifi cation of risk factors, including smoking cessation, blood pressure control, and lipid lowering

B. STROKEDEFINITIONStroke describes acute brain injury caused by decreased blood supply or hemorrhage.PHYSICAL FINDINGS AND CLINICAL PRESENTATION● Motor, sensory, or cognitive defi cits, or a combination, de-

pending on distribution and extent of involved vascular ar-teries (Table 35–1)

● More common manifestations include contralateral motor weakness or sensory loss, as well as language diffi culties (aphasia; predominantly left-sided lesions) and visuospatial neglect phenomena (predominantly right-sided lesions).

● Onset is usually sudden; however, this depends on the spe-cifi c cause.

● Characteristics of cerebral thrombosis and embolism are described in Table 35–2.

CAUSE● Of all strokes, 70% to 80% are caused by ischemic infarcts;

20% to 30% are hemorrhagic.● Ischemic infarcts: 80% are caused by occlusion of large or

small vessels because of atherosclerotic vascular disease (caused by hypertension, hyperlipidemia, diabetes, tobacco abuse), 15% are caused by cardiac embolism, and 5% are from other causes, including hypercoagulable states and vasculitis.

● Small-vessel occlusion is most often caused by lipohyalino-sis precipitated by chronic hypertension.

DIFFERENTIAL DIAGNOSIS● TIA, traditionally defi ned as focal neurologic defi cits lasting less than 24 hours (usually lasting less than 60 minutes)● Migraine, seizure, mass lesion

WORKUP● Thorough history and physical examination, including de-

tailed neurologic and cardiovascular evaluations to identify

TABLE 35–1 Select stroke syndromes

Artery Involved Neurologic Defi cit

Middle cerebral artery Hemiplegia (upper extremity and face are usually more involved than lower extremities)

Hemianesthesia (hemisensory loss)

Hemianopia (homonymous)

Aphasia (if dominant hemisphere is involved)

Anterior cerebral artery Hemiplegia (lower extremities more involved than upper extremities and face)

Primitive refl exes (e.g., grasp and suck)

Urinary incontinence

Vertebral and basilar Ipsilateral cranial nerve fi ndings, cerebellar artery fi ndings

Contralateral (or bilateral) sensory or motor defi cits

Deep penetrating cerebral arteries Usually seen in major hypertensive branches of older patients and diabetics

Four characteristic syndromes (lacunar infarction) are possible:

1. Pure motor hemiplegia (66%)

2. Dysarthria—clumsy hand syndrome (20%)

3. Pure sensory stroke (10%)

4. Ataxic hemiplegia syndrome with pyramidal tract signs

Ferri F: Practical Guide to the Care of the Medical Patient, 7th ed. St. Louis, Mosby, 2007.

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Chapter 35: Cerebrovascular disease 35vascular territory and likely cause. Infectious, toxic, and metabolic causes should be excluded because each may cause clinical deterioration of old stroke symptoms.

● Cardiac: mandatory ECG, telemetry; serial cardiac enzymes, transthoracic and/or transesophageal echocardiography, Holter monitor or event monitor (should be seriously con-sidered, especially in the setting of suspected embolic cause). Carotid Doppler should be performed in cases of embolic stroke to the anterior or middle cerebral artery region.

LABORATORY TESTS● CBC, platelets, PT (INR), PTT, blood urea nitrogen (BUN),

creatinine, glucose, electrolytes, urinalysis● Additional tests, depending on suspected cause (e.g., coagu-

lopathies in younger patients)IMAGING STUDIES (FIG. 35–2)● CT scan without contrast to distinguish hemorrhage (Fig.

35–3) from infarct (Fig. 35–4)

● MRI (Fig. 35–5) is superior to CT for identifying abnor-malities in the posterior fossa and, in particular, lacunar (small-vessel) infarcts. DWI (Fig. 35–6) is best to determine hyperacute ischemia (positive within 15 to 30 minutes of symptom onset). MRA is recommended to help identify vascular pathology (e.g., extent of intracranial atherosclero-sis or vascular distribution of ischemia)

● In select cases (e.g., hemorrhagic stroke), conventional angi-ography may identify aneurysms or other vascular malfor-mations (Fig. 35–7).

TREATMENT● Depends on several factors, including cause, vascular terri-

tory involved, risk factors, and elapsed time from symptom onset to arrival at hospital

● To prevent pulmonary emboli post stroke above-the-knee elastic stockings, pneumatic boots, or SC heparin if non-hemorrhagic cause and patient is immobile in bed

A B C

Fig 35–2Acute lacunar infarct and small-vessel disease. A, CT and B, T2-weighted MRI show multiple low-density, high-signal foci in both hemispheres. The diffusion-weighted image (C) shows restricted diffusion in the left striatum, which appears as bright and unrestricted diffusion in the other le-sions. This indicates that the former is acute and the latter are old.(From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger and Allison’s Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. London. Harcourt, 2001.)

TABLE 35–2 Characteristics of cerebral thrombosis and embolism

Parameter Thrombosis Embolism

Onset of symptoms Progression of symptoms over hours to days Very rapid (seconds)

History of previous transient ischemic attack Common Uncommon

Time of presentation Often, during night hours while patient is sleeping Patient is usually awake, involved in some type of activity

Typically, patient awakes with a slight neurologic defi cit that gradually progresses in a stepwise fashion

Predisposing factors Atherosclerosis, hypertension, diabetes, arteritis, Atrial fi brillation, mitral stenosis vasculitis, hypotension, trauma to head and neck and regurgitation, endocarditis, mitral valve prolapse

Ferri F: Practical Guide to the Care of the Medical Patient, 7th ed. St. Louis, Mosby, 2007.

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35 Section 2: Brain, peripheral nervous system, muscle

A B C

Fig 35–3Intracranial hemorrhage in a thrombocytopenic patient. A, Unenhanced CT scan. B, T2-weighted fast spin-echo sequence (FSE). C, T2*-weighted gradient-echo sequence (GRE). On CT (A), the high-attenuation occipitoparietal hematoma is surrounded by a low-attenuation rim, indicating clot retraction. The hematoma is of mixed signal intensity on the T2 FSE sequence (B) and could be mistaken for another mass lesion. It is, however, of characteristically low signal on the T2*-weighted GRE (C), which is more sensitive for the detection of hemorrhage.(From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger and Allison’s Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. London. Harcourt, 2001.)

A B

Fig 35–4Embolic stroke. A, CT scan showing a large cortical infarct in the middle cerebral artery in a patient with atrial fi brillation. B, Embolic brain infarct in the right hemisphere (white arrow) treated with heparin, which has caused an intracerebral hemorrhage in the contralateral hemisphere (black arrow).(From Crawford, MH, DiMarco JP, Paulus WJ [eds]: Cardiology, 2nd ed. St. Louis, Mosby, 2004.)

● Carotid endarterectomy (CEA) is recommended for patients with carotid territory stroke associated with 70% to 99% ipsilateral carotid stenosis, performed by an experienced surgeon who has demonstrated low morbidity and mortal-ity results.

● Modifi cation of risk factors (e.g., smoking cessation, exer-cise, diet).

● Judicious control of blood pressure. Patients with chronic hypertension may extend the area of infarction if the blood pressure is lowered into the normal range. It is best not to lower blood pressure too aggressively in the acute setting unless it is markedly elevated. Adequate hydration and bed rest (e.g., head of bed down in pressure depen-dent ischemia vs. head of bed up if patient is an aspiration risk). Adequate glycemic control is also recommended (e.g., sliding scale insulin).

● In patients presenting less than 3 hours after onset of a non-hemorrhagic stroke—thrombolytic therapy in a specialized stroke center is benefi cial in select populations.

● If atrial fi brillation, cardiac mural thrombus (or both) is found on echocardiography, heparin may be considered.

● If a subarachnoid or intracerebral hemorrhage is found on CT, MRA or cerebral angiography, or both, may be indicated to identify aneurysm. If no aneurysm is found and the clot is expanding, neurosurgical evacuation of the clot may be attempted, but outcomes are generally poor.

● In select cases of patients presenting more than 3 hours but less than 6 hours after the stroke, an interventional neurora-diologist or neurosurgeon may be able to offer direct injec-tion of a clot-busting agent (e.g., intra-arterial tissue-type plasminogen activator, t-PA) or direct extraction of the clot (e.g., U.S. Food and Drug Administration [FDA]–approved

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Chapter 35: Cerebrovascular disease 35

A B

Fig 35–5Acute right posterior cerebral artery infarct. A, The T2-weighted fast spin-echo sequence (FSE) shows high signal in the right thalamus (arrow) and occipital lobe (double arrows). B, The changes are much more striking on the diffusion-weighted image, which shows a higher lesion-to-background contrast. The diffusion is restricted in the acutely infarcted tissue and appears bright.(From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger and Allison’s Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. London. Harcourt, 2001.)

A B C

Fig 35–6Diffusion and perfusion imaging in acute ischemic stroke. A, Diffusion image of a large left middle cerebral infarct. B, Index regional cerebral blood fl ow (rCBF) in the same patient showing a large nonperfused area on the left. Perfusion is also compromised in the contralateral hemisphere (dias-chisis). C, Normal index rCBF for comparison. The patient underwent a left-sided craniectomy, resulting in restored perfusion on the right (not shown).(From Crawford, MH, DiMarco JP, Paulus WJ [eds]: Cardiology, 2nd ed. St. Louis, Mosby, 2004.)

A B

C

Fig 35–7Cerebral arteriovenuous malformation (AVM). Shown are arterial (A) and venous (B) phases of digital subtraction angiography in a patient with a cerebral AVM. The AVM is fed by branches of the anterior and middle cerebral arteries and the venous drainage is predominantly superfi cial into the superior sagittal and transverse sinuses. C, Three-dimensional surface-shaded reconstruction of a CT angiogram in the same patient.(Courtesy of Dr. Moore, National Hospital, Queen Square, England.)

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35 Section 2: Brain, peripheral nervous system, muscle

Merci Retrieval System). However, this remains investiga-tional and has yet to be well studied in the setting of a controlled trial. Intracranial angioplasty/stenting may also be a consideration.

● Antiplatelet therapy (aspirin, dipyridamole-aspirin, clopi-dogrel, or ticlopidine) reduces the risk of subsequent stroke.

● If patient presents with fi rst TIA or stroke and was not on a prior antiplatelet agent, aspirin (325 mg vs. 81 mg each day) is usually chosen initially. If a TIA occurs while on aspirin, the patient should be switched to dipyridamole-aspirin.

● Warfarin is usually reserved for patients with cardioembolic stroke, as well as for patients with atrial fi brillation.

C. SUBARACHNOID HEMORRHAGEDEFINITIONSubarachnoid hemorrhage (SAH) is the presence of active bleeding into the subarachnoid space, usually secondary to a spontaneous ruptured aneurysm or after head trauma.PHYSICAL FINDINGS AND CLINICAL PRESENTATION● Patients typically present with sudden onset of a severe

headache, with maximal intensity at onset. Additional fi nd-ings may include nuchal rigidity, nausea, and vomiting.

● Transient loss of consciousness occurs in 45% of patients.● Focal neurologic defi cits may be present.● Funduscopic examination may reveal subhyaloid hemor-

rhage.

CAUSE● Key distinction is aneurysmal (nontraumatic cause in more

than 60% of cases, most commonly after rupture of saccular “berry” aneurysms) versus nonaneurysmal (traumatic) SAH

● Others: arteriovenous malformation (AVM), angioma, fusi-form or mycotic aneurysm, dissecting and tumor-related aneurysms

DIFFERENTIAL DIAGNOSIS● Intraparenchymal hemorrhage (see Fig. 35–3)● Subarachnoid extension of an extracranial arterial dissec-tion or intracerebral hemorrhage● Meningoencephalitis (e.g., hemorrhagic meningoenceph-alitis caused by herpes simplex virus, HSV [see Fig. 46–11])● Headache associated with sexual activity (e.g., coital or postcoital headache; usually acute onset of severe headache around time of orgasm)

WORKUP● CT scanning (Fig. 35–8) is the initial test of choice, no con-

trast is necessary. Sensitivity is 90% or higher in the fi rst 12 to 24 hours. If CT is negative and there is a high clinical suspicion for SAH, lumbar puncture must be considered, because there is an approximately 7% (or 1 in 14) chance of having a SAH. Spinal fl uid is considered positive if there is xanthochromia and if there is a constant amount of red cells in each lumbar puncture (LP) tube. LP performed less than 12 hours after onset of headache may be falsely negative for xanthochromia.

● Electrocardiography (ECG): nonspecifi c ST and T wave changes, “cerebral T waves.”

A B

C

Fig 35–8Subarachnoid hemorrhage. A, CT scan shows blood in the right sylvian fi ssure and in the interhemispheric fi ssure. B, This appears as high signal intensity on the fl uid-attenuated inversion recovery (FLAIR) MRI, as opposed to the normal cerebrospinal fl uid, which appears dark. C, A three-dimensional TOF MR angiogram shows a right middle cerebral artery aneurysm (double arrows), which has bled, and an incidental ophthalmic artery aneurysm (single arrow); both were confi rmed with digital subtraction angiography.(From Grainger RG, Allison DJ, Adam A, Dixon AK [eds]: Grainger and Allison’s Diagnostic Radiology: A Textbook of Medical Imaging, 4th ed. London. Harcourt, 2001.)

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Chapter 35: Cerebrovascular disease 35LABORATORY TESTS● PT (INR), PTT, platelet count at a minimum for clotting

abnormalityIMAGING STUDIES● CT scan followed by cerebral angiography if hemorrhage is

confi rmed● May also use transcranial Doppler (TCD) as a baseline later

to assess more adequately for vasospasmTREATMENT● Intubation as necessary● Bed rest, isotonic fl uids● Short-acting analgesics (e.g., morphine 1 to 4 mg IV) and

sedation (e.g., midazolam 1 to 5 mg IV); avoid oversedation and watch neurologic examination closely.

● Seizure prophylaxis controversial (consider phenytoin)● Vasospasm prophylaxis (nimodipine)● Blood pressure (BP) control; lower BP for unprotected aneu-

rysms versus higher BP if protected (postcoiling, clipping)● Stool softeners

● Neurosurgical or interventional neuroradiologic referral mandatory if aneurysm or AVM demonstrated by angiogra-phy; also, invasive intracranial pressure (ICP) monitoring, ventriculostomy may be required on an emergent basis (e.g., deteriorating level of consciousness, development of hydro-cephalus); elevated ICP is associated with a worse patient outcome, particularly if ICP does not respond to treatment.

● Hypertonic saline (HS) solutions can be used in various concentrations (e.g., 7.5%, 10%, 23.5%) to treat elevated ICP and augment cerebral blood fl ow (CBF).

● Vasospasm occurs in 20% to 30% of patients and peaks at about 1 week; monitor closely for this. Consider TCD monitoring in high-risk patients. Triple-H therapy for pre-vention of vasospasm includes hemodilution, hypertension (consider pressors), and hypervolemia. Intra-arterial papav-erine, balloon angioplasty, or both may be necessary in some cases.

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