3346 PART 13 Neurologic Disorders

studies in individual patients taking aspirin is controversial because

of limited data.

In our practices, when considering antithrombotic therapy for

secondary stroke prevention for noncardioembolic strokes and

TIAs, we prescribe aspirin 81 mg/d in aspirin-naive patients after an

initial load of 325 mg. We add either clopidogrel (600-mg load, then

75 mg daily) or ticagrelor (180-mg load, then 90 mg twice daily)

for TIA or minor stroke (NIHSS <5) for 21–30 days, followed by

monotherapy with aspirin alone at 81 mg daily. We treat stroke due

to intracranial atherosclerosis with aspirin 81 mg plus clopidogrel

75 mg daily for 3 months, after which time treatment is continued

with aspirin alone.

ANTICOAGULATION THERAPY AND EMBOLIC

STROKE PREVENTION

Several trials have shown that anticoagulation (international normalized ratio [INR] range, 2–3) in patients with chronic nonvalvular (nonrheumatic) atrial fibrillation (NVAF) prevents cerebral

embolism and stroke and is safe. For primary prevention and for

patients who have experienced stroke or TIA, anticoagulation with

a vitamin K antagonist (VKA) reduces the risk by ~67%, which

clearly outweighs the 1–3% risk per year of a major bleeding complication. VKAs are difficult to dose, their effects vary with dietary

intake of vitamin K, and they require frequent blood monitoring

of the PTT/INR. Several newer oral anticoagulants (OACs) have

recently been shown to be more convenient and efficacious for

stroke prevention in NVAF. A randomized trial compared the oral

thrombin inhibitor dabigatran to VKAs in a noninferiority trial to

prevent stroke or systemic embolization in NVAF. Two doses of

dabigatran were used: 110 mg/d and 150 mg/d. Both dose tiers of

dabigatran were noninferior to VKAs in preventing second stroke

and systemic embolization, and the higher dose tier was superior (relative risk, 0.66; 95% CI, 0.53–0.82; p <.001) and the rate

of major bleeding was lower in the lower dose tier of dabigatran

compared to VKAs. Dabigatran requires no blood monitoring

to titrate the dose, and its effect is independent of oral intake of

vitamin K. Newer oral factor Xa inhibitors have also been found

to be equivalent or safer and more effective than VKAs in NVAF

stroke prevention. In the Apixaban for Reduction in Stroke and

Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE)

trial, patients were randomized between apixaban, 5 mg twice daily,

and dose-adjusted warfarin (INR 2–3). The combined endpoint of

ischemic or hemorrhagic stroke or system embolism occurred in

1.27% of patients in the apixaban group and in 1.6% in the warfarin

group (p <.001 for noninferiority and p <.01 for superiority). Major

bleeding was 1% less, favoring apixaban (p <.001). Similar results

were obtained in the Rivaroxaban Once Daily Oral Direct Factor Xa

Inhibition Compared with Vitamin K Antagonism for Prevention

of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF).

In this trial, patients with NVAF were randomized to rivaroxaban

versus warfarin: 1.7% of the factor Xa group and 2.2% of the warfarin group reached the endpoint of stroke and systemic embolism

(p <.001 for noninferiority); intracranial hemorrhage was also lower

with rivaroxaban. Finally, the factor Xa inhibitor edoxaban was also

found to be noninferior to warfarin. Thus, oral factor Xa inhibitors

are at least a suitable alternative to VKAs, for both primary and

secondary prevention, and likely are superior both in efficacy and

perhaps compliance. Recent FDA approval of a reversal agent for

the Xa inhibitors apixaban and rivaroxaban (andexanet alfa) provides an antidote in the case of major bleeding. Idarucizumab has

been available for reversal of dabigatran. Randomized trials have

not demonstrated the superiority of anticoagulants over antiplatelet

medications for strokes that appear embolic without a clear source.

However, subgroup analyses of these patients who also have moderate or severe left atrial enlargement do show benefit of OACs over

aspirin, and a randomized trial to address this strategy further is

underway.

For patients who cannot take anticoagulant medications, clopidogrel plus aspirin was compared to aspirin alone in the Atrial

Fibrillation Clopidogrel Trial with Irbesartan for Prevention of

Vascular Events (ACTIVE-A). Clopidogrel combined with aspirin

was more effective than aspirin alone in preventing vascular events,

principally stroke, but increased the risk of major bleeding (relative

risk, 1.57; p <.001). Left atrial appendage occlusion followed by

antiplatelet therapy was found to be noninferior to oral Xa inhibitors in patients at moderate to high risk of bleeding in a single trial.

If confirmed, this may be a safer strategy than management with

aspirin alone for these patients at high risk of atrial fibrillation–

related stroke.

The decision to use anticoagulation for primary prevention is

based primarily on risk factors (Table 427-3). The history of a TIA

or stroke tips the balance in favor of anticoagulation regardless of

other risk factors. Intermittent atrial fibrillation carries the same

risk of stroke as chronic atrial fibrillation, and several ambulatory

studies of seemingly “cryptogenic” stroke have found evidence

of intermittent atrial fibrillation in nearly 20% of patients monitored for a few weeks. Interrogation of implanted pacemakers also

confirms an association between subclinical atrial fibrillation and

stroke risk. Therefore, for patients with otherwise cryptogenic

embolic stroke (no evidence of any other cause for stroke), ambulatory monitoring for 3–4 weeks is a reasonable strategy to determine

the best prophylactic therapy.

Because of the high annual stroke risk in untreated rheumatic heart disease with atrial fibrillation, primary prophylaxis

against stroke has not been studied in a double-blind fashion.

These patients generally should receive long-term anticoagulation.

Dabigatran and the oral Xa inhibitors have not been studied in this

population.

Anticoagulation also reduces the risk of embolism in acute MI.

Most clinicians recommend a 3-month course of anticoagulation

when there is anterior Q-wave infarction, substantial left ventricular dysfunction, congestive heart failure, mural thrombosis, or atrial

fibrillation. OACs are recommended long term if atrial fibrillation

persists.

Stroke secondary to thromboembolism is one of the most serious

complications of prosthetic heart valve implantation. The intensity

of anticoagulation and/or antiplatelet therapy is dictated by the type

of prosthetic valve and its location. Dabigatran may be less effective

than warfarin, and the oral Xa inhibitors have not been studied in

this population.

If the embolic source cannot be eliminated, anticoagulation

should in most cases be continued indefinitely. Many neurologists

recommend combining antiplatelet agents with anticoagulants for

patients who “fail” anticoagulation (i.e., have another stroke or

TIA), but the evidence basis for this is lacking.

It is our practice to prescribe apixaban 5 mg twice daily for nonvalvular atrial fibrillation with CHA2

DS2

-VASc score of ≥2, aspirin

81 mg plus clopidogrel 75 mg daily for patients who cannot take

oral anticoagulation, and VKAs for valvular atrial fibrillation or

mechanical heart valve.

ANTICOAGULATION THERAPY AND

NONCARDIOGENIC STROKE

Data do not support the use of long-term VKAs for preventing

atherothrombotic stroke for either intracranial or extracranial cerebrovascular disease. The Warfarin-Aspirin Recurrent Stroke Study

(WARSS) found no benefit of warfarin sodium (INR 1.4–2.8) over

aspirin, 325 mg, for secondary prevention of stroke but did find

a slightly higher bleeding rate in the warfarin group; a European

study confirmed this finding. The Warfarin and Aspirin for Symptomatic Intracranial Disease (WASID) study (see below) demonstrated no benefit of warfarin (INR 2–3) over aspirin in patients

with symptomatic intracranial atherosclerosis and found a higher

rate of bleeding complications. The first of several trials testing

factor Xa medications for prevention of embolic stroke of unknown

source failed to show benefit compared to treatment with antiplatelet medications. The oral factor Xa inhibitor apixaban was found to

be noninferior to subcutaneous dalteparin for patients with cancer

3347 Ischemic Stroke CHAPTER 427

and venous thromboembolism; many oncologists are using Xa

inhibitors to prevent second stroke in patients with malignancy.

It is our practice to prescribe aspirin for secondary stroke prevention in noncardiogenic cerebral embolism except for stroke

associated with cancer (apixaban 5 mg twice daily) and the antiphospholipid syndrome (warfarin with target INR 2–3).

TREATMENT

Carotid Atherosclerosis

Carotid atherosclerosis can be removed surgically (endarterectomy)

or mitigated with endovascular stenting with or without balloon

angioplasty. Anticoagulation has not been directly compared with

antiplatelet therapy for carotid disease.

SURGICAL THERAPY

Symptomatic carotid stenosis was studied in the North American

Symptomatic Carotid Endarterectomy Trial (NASCET) and the

European Carotid Surgery Trial (ECST). Both showed a substantial

benefit for surgery in patients with stenosis of ≥70%. In NASCET,

the average cumulative ipsilateral stroke risk at 2 years was 26%

for patients treated medically and 9% for those receiving the same

medical treatment plus a carotid endarterectomy. This 17% absolute reduction in the surgical group is a 65% relative risk reduction

favoring surgery (Table 427-4). NASCET also showed a significant,

although less robust, benefit for patients with 50–70% stenosis.

ECST found harm for patients with stenosis <30% treated surgically.

A patient’s risk of stroke and possible benefit from surgery are

related to the presence of retinal versus hemispheric symptoms,

degree of arterial stenosis, extent of associated medical conditions

(of note, NASCET and ECST excluded “high-risk” patients with significant cardiac, pulmonary, or renal disease), institutional surgical

morbidity and mortality, timing of surgery relative to symptoms,

and other factors. A recent meta-analysis of the NASCET and ECST

trials demonstrated that endarterectomy is most beneficial when

performed within 2 weeks of symptom onset. In addition, benefit is

more pronounced in patients >75 years, and men appear to benefit

more than women.

In summary, a patient with recent symptomatic hemispheric

ischemia, high-grade stenosis in the appropriate internal carotid

artery, and an institutional perioperative morbidity and mortality

rate of ≤6% generally should undergo carotid endarterectomy. If

the perioperative stroke rate is >6% for any particular surgeon,

however, the benefits of carotid endarterectomy are questionable.

The indications for surgical treatment of asymptomatic carotid

disease have been clarified by the results of the Asymptomatic

Carotid Atherosclerosis Study (ACAS) and the Asymptomatic

Carotid Surgery Trial (ACST). ACAS randomized asymptomatic

patients with ≥60% stenosis to medical treatment with aspirin

or the same medical treatment plus carotid endarterectomy. The

surgical group had a risk over 5 years for ipsilateral stroke (and any

perioperative stroke or death) of 5.1%, compared to a risk in the

medical group of 11%. Although this demonstrates a 53% relative

risk reduction, the absolute risk reduction is only 5.9% over 5 years,

or 1.2% annually (Table 427-4). Nearly one-half of the strokes in

the surgery group were caused by preoperative angiograms. ACST

randomized asymptomatic patients with >60% carotid stenosis to

endarterectomy or medical therapy. The 5-year risk of stroke in the

surgical group (including perioperative stroke or death) was 6.4%,

compared to 11.8% in the medically treated group (46% relative risk

reduction and 5.4% absolute risk reduction).

In both ACAS and ACST, the perioperative complication rate

was higher in women, perhaps negating any benefit in the reduction

of stroke risk within 5 years. It is possible that with longer follow-up,

a clear benefit in women will emerge. At present, carotid endarterectomy in asymptomatic women remains particularly controversial.

In summary, the natural history of asymptomatic stenosis is an

~2% per year stroke rate, whereas symptomatic patients experience

a 13% per year risk of stroke. Whether to recommend carotid

revascularization for an asymptomatic patient is somewhat controversial and depends on many factors, including patient preference,

degree of stenosis, age, gender, and comorbidities. Medical therapy

for reduction of atherosclerosis risk factors, including cholesterollowering agents and antiplatelet medications, is generally recommended for patients with asymptomatic carotid stenosis. As with

atrial fibrillation, it is imperative to counsel the patient about TIAs

so that therapy can be revised if symptoms develop.

ENDOVASCULAR THERAPY

Balloon angioplasty coupled with stenting is being used with

increasing frequency to open stenotic carotid arteries and maintain

their patency. These techniques can treat carotid stenosis not only

at the bifurcation but also near the skull base and in the intracranial

segments. The Stenting and Angioplasty with Protection in Patients

at High Risk for Endarterectomy (SAPPHIRE) trial randomized

high-risk patients (defined as patients with clinically significant

coronary or pulmonary disease, contralateral carotid occlusion,

restenosis after endarterectomy, contralateral laryngeal-nerve palsy,

prior radical neck surgery or radiation, or age >80) with symptomatic carotid stenosis >50% or asymptomatic stenosis >80% to

either stenting combined with a distal emboli-protection device or

endarterectomy. The risk of death, stroke, or MI within 30 days and

ipsilateral stroke or death within 1 year was 12.2% in the stenting

group and 20.1% in the endarterectomy group (p = .055), suggesting that stenting is at the very least comparable to endarterectomy

as a treatment option for this patient group at high risk of surgery.

However, the outcomes with both interventions may not have been

better than leaving the carotid stenoses untreated, particularly for

the asymptomatic patients, and much of the benefit seen in the

stenting group was due to a reduction in periprocedure MI. Two

randomized trials comparing stents to endarterectomy in lower-risk patients have been published. The Carotid Revascularization

Endarterectomy versus Stenting Trial (CREST) enrolled patients

with either asymptomatic or symptomatic stenosis. The 30-day

risk of stroke was 4.1% in the stent group and 2.3% in the surgical

group, but the 30-day risk of MI was 1.1% in the stent group and

2.3% in the surgery group, suggesting relative equivalence of risk

between the procedures. At median follow-up of 2.5 years, the

combined endpoint of stroke, MI, and death was the same (7.2%

stent vs 6.8% surgery) and remained so at 10-year follow-up. The

rate of restenosis at 2 years was also similar in both groups. The

International Carotid Stenting Study (ICSS) randomized symptomatic patients to stents versus endarterectomy and found a different

result: at 120 days, the incidence of stroke, MI, or death was 8.5%

in the stenting group versus 5.2% in the endarterectomy group

(p = .006). At median follow-up of 5 years, these differences were

no longer significant except a small increase in nondisabling stroke

in the stenting group but no change in the average disability. In

meta-analysis, carotid endarterectomy (CEA) is less morbid in

older patients (aged ≥70) than is stenting. Investigation is ongoing

in asymptomatic patients to compare medical therapy to stenting

and CEA. This will likely answer how well medical patients do

with more modern medical therapy (statins, close blood pressure

control, and lifestyle modification).

BYPASS SURGERY

Extracranial-to-intracranial (EC-IC) bypass surgery has been

proven ineffective for atherosclerotic stenoses that are inaccessible

to conventional CEA. In patients with recent stroke, an associated

carotid occlusion, and evidence of inadequate perfusion of the brain

as measured with positron emission tomography, no benefit from

EC-IC bypass was found in a trial stopped for futility.

PATENT FORAMEN OVALE (PFO)

In patients with PFO and/or atrial septal aneurysm with an embolic

stroke and no other cause identified, three randomized trials

using various endovascular closure devices individually and in

meta-analysis report a significant (1% per year) reduction in second

3348 PART 13 Neurologic Disorders

stroke compared to antiplatelet agents. If the neurological opinion

is that no other source of stroke is identified and consultation with a

cardiologist knowledgeable about PFO closure supports intervention,

we recommend endovascular PFO closure.

INTRACRANIAL ATHEROSCLEROSIS

The WASID trial randomized patients with symptomatic stenosis

(50–99%) of a major intracranial vessel to either high-dose aspirin

(1300 mg/d) or warfarin (target INR, 2.0–3.0), with a combined

primary endpoint of ischemic stroke, brain hemorrhage, or death

from vascular cause other than stroke. The trial was terminated

early because of an increased risk of adverse events related to

warfarin anticoagulation. With a mean follow-up of 1.8 years, the

primary endpoint was seen in 22.1% of patients in the aspirin group

and 21.8% of the warfarin group. Death from any cause was seen in

4.3% of the aspirin group and 9.7% of the warfarin group; 3.2% of

patients on aspirin experienced major hemorrhage, compared to

8.3% of patients taking warfarin.

Intracranial stenting of intracranial atherosclerosis was found to

be dramatically harmful compared to aspirin in the Stenting and

Aggressive Medical Management for Preventing Recurrent Stroke

in Intracranial Stenosis (SAMMPRIS) trial. This trial enrolled newly

symptomatic TIA or minor stroke patients with associated 70–99%

intracranial stenosis to primary stenting with a self-expanding stent

or to medical management. Both groups received clopidogrel, aspirin, statin, and aggressive control of blood pressure. The endpoint

of stroke or death occurred in 14.7% of the stented group and 5.8%

of the medically treated groups (p = .002). This low rate of second

stroke was significantly lower than in the WASID trial and suggests

that aggressive medical management had a marked influence on

secondary stroke risk. A concomitant study of balloon-expandable

stenting was halted early at 125 patients because of the negative

SAMMPRIS results and due to harm. Therefore, routine use of

intracranial stenting is harmful, and medical therapy is superior for

intracranial atherosclerosis.

Dural Sinus Thrombosis Limited evidence exists to support

short-term use of anticoagulants, regardless of the presence of

intracranial hemorrhage, for venous infarction following sinus

thrombosis. The long-term outcome for most patients, even those

with intracerebral hemorrhage, is excellent.

■ FURTHER READING

Goyal M et al: Endovascular thrombectomy after large-vessel

ischaemic stroke: A meta-analysis of individual patient data from

five randomised trials. Lancet 387:1723, 2016.

Grotta JC et al: Prospective, multicenter, controlled trial of mobile

stroke units. N Engl J Med 385:971, 2021.

January CT et al: 2019 AHA/ACC/HRS focused update of the 2014

AHA/ACC/HRS guideline for the management of patients with atrial

fibrillation: A report of the American College of Cardiology/American

Heart Association Task Force on Clinical Practice Guidelines and the

Heart Rhythm Society. J Am Coll Cardiol 74:104, 2019.

Larsson SC et al: Prognosis of carotid dissecting aneurysms: Results

from CADISS and a systematic review. Neurology 88:646, 2017.

Osmancik P et al: Left atrial appendage closure versus direct oral

anticoagulants in high-risk patients with atrial fibrillation. J Am Coll

Cardiol 75:3122, 2020.

Powers WJ et al: 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: A guideline for healthcare

professionals from the American Heart Association/American Stroke

Association. Stroke 50:e344, 2019.

Saver JL et al: Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: A meta-analysis. JAMA

316:1279, 2016.

Sprint Research Group et al: A randomized trial of intensive versus

standard blood-pressure control. N Engl J Med 373:2103, 2015.

Torbey MT et al: Evidence-based guidelines for the management of

large hemispheric infarction: A statement for health care professionals

from the Neurocritical Care Society and the German Society for Neuro-intensive Care and Emergency Medicine. Neurocrit Care 22:146,

2015.

Intracranial hemorrhage is a form of stroke (see Chap. 426). Compared to ischemic stroke, patients with intracranial hemorrhage are

more likely to present with headache; however, brain imaging is

required to distinguish these entities. CT imaging of the head is highly

sensitive and specific for intracranial hemorrhage and determines the

location(s) of bleeding. Hemorrhages are classified by their location

and the underlying vascular pathology. Hemorrhage directly into the

brain parenchyma, also known as intracerebral hemorrhage (ICH), and

arteriovenous malformations (AVMs) of the brain will be considered

here. Other categories of hemorrhage include bleeding into subdural

and epidural spaces, usually caused by trauma (Chap 443), and subarachnoid hemorrhage due to trauma or the rupture of an intracranial

aneurysm (Chap. 429).

■ DIAGNOSIS

Intracranial hemorrhage is often identified on noncontrast CT imaging of the brain during the acute evaluation of stroke. Because CT is

more widely available and may be logistically easier to perform than

MRI, CT imaging is generally the preferred method for acute stroke

evaluation (Fig. 428-1). The location of the hemorrhage narrows the

differential diagnosis to a few entities. Table 428-1 lists the causes and

anatomic spaces involved in hemorrhages.

■ EMERGENCY MANAGEMENT

Close attention should be paid to airway management because a reduction in the level of consciousness is common and often progressive.

The initial blood pressure should be maintained until the results of the

428 Intracranial Hemorrhage

Wade S. Smith, J. Claude Hemphill, III,

S. Claiborne Johnston

FIGURE 428-1 Hypertensive hemorrhage. Transaxial noncontrast computed

tomography scan through the region of the basal ganglia reveals a hematoma

involving the left putamen in a patient with rapidly progressive onset of right

hemiparesis.

3349 Intracranial Hemorrhage CHAPTER 428

presentation or who are deeply comatose with possible elevated intracranial pressure (ICP). In patients who have ICP monitors in place,

current recommendations are that maintaining the cerebral perfusion

pressure (mean arterial pressure [MAP] minus ICP) at 50–70 mmHg

is reasonable, depending on the individual patient’s cerebral autoregulation status (Chap. 307). Blood pressure should be lowered with

nonvasodilating IV drugs such as nicardipine, labetalol, or esmolol.

Patients with cerebellar hemorrhages with depressed mental status or

radiographic evidence of hydrocephalus should undergo urgent neurosurgical evaluation; these patients require close monitoring because

they can deteriorate rapidly. Based on the clinical examination and CT

findings, further imaging studies may be necessary, including MRI or

conventional x-ray angiography. Stuporous or comatose patients with

clinical and imaging signs of herniation are generally treated presumptively for elevated ICP with tracheal intubation and sedation, administration of osmotic diuretics such as mannitol or hypertonic saline, and

elevation of the head of the bed while surgical consultation is obtained

(Chap. 307). Reversal of coagulopathy and consideration of surgical

evacuation of the hematoma (detailed below) are two other principal

aspects of initial emergency management.

■ INTRACEREBRAL HEMORRHAGE

ICH accounts for ~10% of all strokes, and ~35–45% of patients die

within the first month. Incidence rates are particularly high in Asians

and blacks. Hypertension, coagulopathy, sympathomimetic drugs

(cocaine, methamphetamine), and cerebral amyloid angiopathy (CAA)

cause most of these hemorrhages. Advanced age, heavy alcohol, and

low-dose aspirin use in those without symptomatic cardiovascular

disease increase the risk, and cocaine or methamphetamine use is one

of the most important causes in the young.

Hypertensive ICH • PATHOPHYSIOLOGY Hypertensive ICH

usually results from spontaneous rupture of a small penetrating artery

deep in the brain. The most common sites are the basal ganglia (especially the putamen), thalamus, cerebellum, and pons. The small arteries in these areas seem most prone to hypertension-induced vascular

injury. When hemorrhages occur in other brain areas or in nonhypertensive patients, greater consideration should be given to other causes

such as hemorrhagic disorders, neoplasms, vascular malformations,

vasculitis, and CAA. The hemorrhage may be small, or a large clot

may form and compress adjacent tissue, causing herniation and death.

Blood may also dissect into the ventricular space, which substantially

increases morbidity and may cause hydrocephalus.

Most hypertensive ICHs initially develop over 30–90 min, whereas

those associated with anticoagulant therapy may evolve for as long

as 24–48 h. It is now recognized that about a third of patients even

with no coagulopathy may have significant hematoma expansion

with the first day. Within 48 h, macrophages begin to phagocytize the

hemorrhage at its outer surface. After 1–6 months, the hemorrhage

is generally resolved to a slitlike cavity lined with a glial scar and

hemosiderin-laden macrophages.

CLINICAL MANIFESTATIONS ICH generally presents as the abrupt

onset of a focal neurologic deficit. Seizures are uncommon. Although

clinical symptoms may be maximal at onset, more commonly, the focal

deficit worsens over 30–90 min and is associated with a diminishing

level of consciousness and signs of increased ICP such as headache

and vomiting.

The putamen is the most common site for hypertensive hemorrhage,

and the adjacent internal capsule is usually damaged (Fig. 428-1).

Contralateral hemiparesis is therefore the sentinel sign. When mild,

the face sags on one side over 5–30 min, speech becomes slurred, the

arm and leg gradually weaken, and the eyes deviate away from the side

of the hemiparesis. The paralysis may worsen until the affected limbs

become flaccid or extend rigidly. When hemorrhages are large, drowsiness gives way to stupor as signs of upper brainstem compression

appear. Coma ensues, accompanied by deep, irregular, or intermittent

respiration, a dilated and fixed ipsilateral pupil, and decerebrate rigidity. In milder cases, edema in adjacent brain tissue may cause progressive deterioration over 12–72 h.

TABLE 428-1 Causes of Intracranial Hemorrhage

CAUSE LOCATION COMMENTS

Head trauma Intraparenchymal: frontal

lobes, anterior temporal

lobes; subarachnoid;

extra-axial (subdural,

epidural)

Coup and contrecoup injury

during brain deceleration

Hypertensive

hemorrhage

Putamen, globus pallidus,

thalamus, cerebellar

hemisphere, pons

Chronic hypertension

produces hemorrhage from

small (~30–100 μm) vessels in

these regions

Transformation

of prior ischemic

infarction

Basal ganglion,

subcortical regions, lobar

Occurs in 1–6% of ischemic

strokes with predilection for

large hemispheric infarctions

Metastatic brain

tumor

Lobar Lung, choriocarcinoma,

melanoma, renal cell

carcinoma, thyroid, atrial

myxoma

Coagulopathy Any Risk for ongoing hematoma

expansion

Drug Any, lobar, subarachnoid Cocaine, amphetamine

Arteriovenous

malformation

Lobar, intraventricular,

subarachnoid

Risk is ~2–3% per year

for bleeding if previously

unruptured

Aneurysm Subarachnoid,

intraparenchymal, rarely

subdural

Mycotic and nonmycotic

forms of aneurysms

Amyloid angiopathy Lobar Degenerative disease

of intracranial vessels;

associated with dementia,

rare in patients <60 years

Cavernous angioma Intraparenchymal Multiple cavernous angiomas

linked to mutations in KRIT1,

CCM2, and PDCD10 genes

Dural arteriovenous

fistula

Lobar, subarachnoid Produces bleeding by venous

hypertension

Dural sinus

thrombosis

Along sagittal sinus,

posterior temporal/

inferior parietal

Sagittal sinus thrombosis

can cause hemispheric

parasagittal hemorrhage

with edema; vein of Labbé

occlusion from transverse

sinus occlusion produces

posterior temporal/inferior

parietal hemorrhage

Capillary

telangiectasias

Usually brainstem Rare cause of hemorrhage

CT scan are reviewed and demonstrate ICH. In theory, a higher blood

pressure should promote hematoma expansion, but it remains unclear

if lowering of blood pressure reduces hematoma growth. Recent clinical trials have shown that systolic blood pressure (SBP) can be safely

lowered acutely and rapidly to <140 mmHg in patients with spontaneous ICH whose initial SBP was 150–220 mmHg. The INTERACT2

trial was a large phase 3 clinical trial to address the effect of acute

blood pressure lowering on ICH functional outcome. INTERACT2

randomized patients with spontaneous ICH within 6 h of onset and a

baseline SBP of 150–220 mmHg to two different SBP targets (<140 and

<180 mmHg). In those with the target SBP <140 mmHg, 52% had an

outcome of death or major disability at 90 days compared with 55.6% of

those with a target SBP <180 mmHg (p = .06). There was a significant

shift to improved outcomes in the lower blood pressure arm, whereas

both groups had a similar mortality. ATACH2 was a similarly designed

clinical trial that assessed the same blood pressure targets but demonstrated no difference in outcome between groups. Current U.S. and

European guidelines emphasize that blood pressure lowering to a target

SBP is likely safe and possibly beneficial. However, these guidelines

were completed prior to publication of the ATACH2 results; thus, the

specific optimal target remains a point of debate. It is unclear whether

these clinical trial results apply to patients who have higher SBP on