Practice Essentials

In hemorrhagic stroke, bleeding occurs directly into the brain parenchyma. The usual mechanism is thought to
be leakage from small intracerebral arteries damaged by chronic hypertension. The terms intracerebral
hemorrhage and hemorrhagic stroke are used interchangeably in this article and are regarded as separate
entities from hemorrhagic transformation of ischemic stroke. See the image below.

Axial noncontrast computed tomography scan of the brain of a 60-year-old man with a
history of acute onset of left-sided weakness. Two areas of intracerebral hemorrhage are seen in the right lentiform nucleus,
with surrounding edema and effacement of the adjacent cortical sulci and right sylvian fissure. Mass effect is present upon
the frontal horn of the right lateral ventricle, with intraventricular extension of the hemorrhage.

See Acute Stroke, a Critical Images slideshow, for more information on incidence, presentation, intervention,
and additional resources.
Also, see the Vertigo: 5 Case-Based Diagnostic Puzzles slideshow to help recognize diagnostic clues in vertigo
cases.

Essential update: Inpatient statin use and maintenance may improve outcomes post intracerebral
hemorrhage
In a retrospective multicenter cohort study of 3481 patients with intracerebral hemorrhage over a 10-year
period, Flint et al found that inpatients who received a statin (lovastatin, simvastatin, atorvastatin, pravastatin
sodium) had better 30-day survival rates following the bleeding event and were more likely to be discharged
home or to a rehabilitation center than those who didnt receive a statin while hospitalizeddespite the fact that
the statin users had significantly more severe illness and more comorbidities than non statin users. [1, 2] Moreover,
those whose statins were discontinued during their hospitalization had worse outcomes than those who
remained on statins.
Inpatients treated with a statin had an 18.4% unadjusted 30-day mortality rate compared to 38.7% for those not
treated with a statin during their admission.[1, 2]After adjustment for various factors (age, sex, race/ethnicity,
comorbidities, number of intracerebral hemorrhage cases by hospital, dysphagia), statin users were also more
likely to be alive at 30 days (odds ratio [OR], 4.25; 95% confidence interval [CI], 3.46-5.23; P < .001). Inpatients
treated with statins had a 51.1% rate of discharge to home or to a rehabilitation facility compared to 35.0% for
patients not treated with statins while hospitalized. Furthermore, patients who discontinued statin therapy after
hospital admission had an unadjusted mortality rate of 57.8% compared to 18.9% for patients using a statin
before and during hospitalization; they were also significantly less likely to be alive at 30 days (OR, 0.16; 95%
CI, 0.12-0.21; P < .001).[1, 2]

Signs and symptoms

Patients with intracerebral bleeds are more likely than those with ischemic stroke to have headache, altered
mental status, seizures, nausea and vomiting, and/or marked hypertension. Even so, none of these findings
reliably distinguishes between hemorrhagic and ischemic stroke.
Focal neurologic deficits
The type of deficit depends on the area of brain involved. If the dominant (usually the left) hemisphere is
involved, a syndrome consisting of the following may result:

Right hemiparesis
Right hemisensory loss
Left gaze preference
Right visual field cut
Aphasia
Neglect (atypical)
If the nondominant (usually the right) hemisphere is involved, a syndrome consisting of the following may
result:

Left hemiparesis
Left hemisensory loss
Right gaze preference
Left visual field cut
See Clinical Presentation for more detail.

Diagnosis
Laboratory tests should include a complete blood count (CBC), a metabolic panel, andparticularly in patients
taking anticoagulantscoagulation studies (ie, prothrombin time or international normalized ratio [INR] and an
activated partial thromboplastin time).[3]
Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be obtained on an
emergent basis. Brain imaging aids diagnosing hemorrhage, and it may identify complications such as
intraventricular hemorrhage, brain edema, or hydrocephalus. Either noncontrast computed tomography (NCCT)
scanning or magnetic resonance imaging (MRI) is the modality of choice.
See Workup for more detail.

Management
The treatment and management of patients with acute intracerebral hemorrhage depends on the cause and
severity of the bleeding. Basic life support, as well as control of bleeding, seizures, blood pressure (BP), and
intracranial pressure, are critical. Medications used in the treatment of acute stroke include the following:

Anticonvulsants - To prevent seizure recurrence

Antihypertensive agents - To reduce BP and other risk factors of heart disease
Osmotic diuretics - To decrease intracranial pressure in the subarachnoid space
A potential treatment for hemorrhagic stroke is surgical evacuation of the hematoma. However, the role of
surgical treatment for supratentorial intracranial hemorrhage remains controversial. Outcomes in published
studies are conflicting.
Endovascular therapy using coil embolization, as an alternative to surgical clipping, has been increasingly
employed with great success, although controversy still exists over which treatment is ultimately superior.
See Treatment and Medication for more detail.

Background
The terms intracerebral hemorrhage and hemorrhagic stroke are used interchangeably in this article and are
regarded as separate entities from hemorrhagic transformation of ischemic stroke. Hemorrhagic stroke is less
common than ischemic stroke (ie, stroke caused by thrombosis or embolism); epidemiologic studies indicate
that only 8-18% of strokes are hemorrhagic. [4] However, hemorrhagic stroke is associated with higher mortality
rates than is ischemic stroke. (See Epidemiology.)[5]
Patients with hemorrhagic stroke present with focal neurologic deficits similar to those of ischemic stroke but
tend to be more ill than are patients with ischemic stroke. However, though patients with intracerebral bleeds
are more likely to have headache, altered mental status, seizures, nausea and vomiting, and/or marked
hypertension, none of these findings reliably distinguishes between hemorrhagic and ischemic stroke. (See
Presentation.)[6]

Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be obtained on an
emergent basis (see the image below). Brain imaging aids in excluding ischemic stroke, and it may identify
complications of hemorrhagic stroke such as intraventricular hemorrhage, brain edema, and hydrocephalus.
Either noncontrast computed tomography (NCCT) scanning or magnetic resonance imaging (MRI) is the
modality of choice. For more information, see Ischemic Stroke in Emergency Medicine. (See Workup.)

Axial noncontrast computed tomography scan of the brain of a 60-year-old man with a
history of acute onset of left-sided weakness. Two areas of intracerebral hemorrhage are seen in the right lentiform nucleus,
with surrounding edema and effacement of the adjacent cortical sulci and right sylvian fissure. Mass effect is present upon
the frontal horn of the right lateral ventricle, with intraventricular extension of the hemorrhage.

The treatment of patients with acute stroke depends on the cause and severity of the bleeding. Basic life
support, as well as control of bleeding, seizures, blood pressure (BP), and intracranial pressure, are critical.
Surgical evacuation of the hematoma is a potential therapeutic option, but it remains controversial. (See
Treatment.)
For patient education information, see the Stroke Health Center, as well as Stroke.

Anatomy
Knowledge of cerebrovascular arterial anatomy and the brain regions supplied by the arteries is useful in
determining which vessels are involved in acute stroke. Atypical patterns that do not conform to a vascular
distribution may indicate another diagnosis, such as venous infarction.
The cerebral hemispheres are supplied by 3 paired major arteries: the anterior, middle, and posterior cerebral
arteries. The anterior and middle cerebral arteries are responsible for the anterior circulation and arise from the
supraclinoid internal carotid arteries. The posterior cerebral arteries arise from the basilar artery and form the
posterior circulation, which also supplies the thalami, brainstem, and cerebellum. The angiograms in the
images below demonstrate some portions of the circulation involved in hemorrhagic strokes.

Frontal view of a cerebral angiogram with selective injection of the left internal carotid artery
illustrates the anterior circulation. The anterior cerebral artery consists of the A1 segment proximal to the anterior
communicating artery with the A2 segment distal to it. The middle cerebral artery can be divided into 4 segments: the M1
(horizontal segment) extends to the limen insulae and gives off lateral lenticulostriate branches, the M2 (insular segment),
M3 (opercular branches), and M4 (distal cortical branches on the lateral hemispheric convexities).

Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral
artery (ACA) and sylvian triangle. The pericallosal artery has been described as arising distal to the anterior communicating
artery or distal to the origin of the callosomarginal branch of the ACA. The segmental anatomy of the ACA has been
described as follows: (1) the A1 segment extends from the internal carotid artery (ICA) bifurcation to the anterior
communicating artery, (2) A2 extends to the junction of the rostrum and genu of the corpus callosum, (3) A3 extends into the
bend of the genu of the corpus callosum, and (4) A4 and A5 extend posteriorly above the callosal body and superior portion
of the splenium. The sylvian triangle overlies the opercular branches of the middle cerebral artery, with the apex

representing the sylvian point.

Frontal projection from a right vertebral artery
angiogram illustrates the posterior circulation. The vertebral arteries join to form the basilar artery. The posterior inferior
cerebellar arteries (PICA) arise from the distal vertebral arteries. The anterior inferior cerebellar arteries (AICA) arise from
the proximal basilar artery. The superior cerebellar arteries (SCA) arise distally from the basilar artery before its bifurcation
into the posterior cerebral arteries.

Pathophysiology
In intracerebral hemorrhage, bleeding occurs directly into the brain parenchyma. The usual mechanism is
thought to be leakage from small intracerebral arteries damaged by chronic hypertension. Other mechanisms
include bleeding diatheses, iatrogenic anticoagulation, cerebral amyloidosis, and cocaine abuse.
Intracerebral hemorrhage has a predilection for certain sites in the brain, including the thalamus, putamen,
cerebellum, and brainstem. In addition to the area of the brain injured by the hemorrhage, the surrounding brain
can be damaged by pressure produced by the mass effect of the hematoma. A general increase in intracranial
pressure may occur.

Subarachnoid hemorrhage
The pathologic effects of subarachnoid hemorrhage (SAH) on the brain are multifocal. SAH results in elevated
intracranial pressure and impairs cerebral autoregulation. These effects can occur in combination with acute
vasoconstriction, microvascular platelet aggregation, and loss of microvascular perfusion, resulting in profound
reduction in blood flow and cerebral ischemia. [7] See the images below.

Noncontrast computed tomography (CT) scanning was performed emergently in a

71-year-old man who presented with acute onset of severe headache and underwent rapid neurologic deterioration requiring

intubation. The noncontrast CT scan (left image) demonstrates diffuse, high-density subarachnoid hemorrhage in the basilar
cisterns and both Sylvian fissures. There is diffuse loss of gray-white differentiation. The fluid-attenuated inversion-recovery
(FLAIR) image (right) demonstrates high signal throughout the cortical sulci and in the basilar cisterns, as well as in the
dependent portions of the ventricles. FLAIR is highly sensitive to acute subarachnoid hemorrhage; the suppression of high
cerebrospinal fluid signal aids in making subarachnoid hemorrhage more conspicuous than do conventional magnetic

resonance imaging sequences.

Computed tomographic angiography examination
and subsequent cerebral angiography were performed in 71-year-old man who presented with acute onset of severe
headache and underwent rapid neurologic deterioration. Multiple aneurysms were identified, including a 9-mm aneurysm at
the junction of the anterior cerebral and posterior communicating arteries seen on this lateral view of an internal carotid

artery injection. Balloon-assisted coil embolization was performed.

Lateral view of a
selective injection of the left internal carotid artery demonstrates a microcatheter passing distal to the aneurysm neck. This
lateral view from an angiogram performed during balloon-assisted coil embolization demonstrates significantly diminished
filling of the aneurysm.

Etiology
The etiologies of stroke are varied, but they can be broadly categorized into ischemic or hemorrhagic.
Approximately 80-87% of strokes are from ischemic infarction caused by thrombotic or embolic cerebrovascular
occlusion. Intracerebral hemorrhages account for most of the remainder of strokes, with a smaller number
resulting from aneurysmal subarachnoid hemorrhage.[8, 9, 10, 11]
In 20-40% of patients with ischemic infarction, hemorrhagic transformation may occur within 1 week after ictus.
[12, 13]

Differentiating between the different types of stroke is an essential part of the initial workup of patients with
stroke, as the subsequent management of each disorder will be vastly different.

Risk factors
The risk of hemorrhagic stroke is increased with the following factors:

Advanced age
Hypertension (up to 60% of cases)
Previous history of stroke
Alcohol abuse
Use of illicit drugs (eg, cocaine, other sympathomimetic drugs)
Causes of hemorrhagic stroke include the following [11, 12, 14, 15, 16] :
Hypertension
Cerebral amyloidosis
Coagulopathies

Anticoagulant therapy
Thrombolytic therapy for acute myocardial infarction (MI) or acute ischemic stroke (can cause
iatrogenic hemorrhagic transformation)

Arteriovenous malformation (AVM), aneurysms, and other vascular malformations (venous and
cavernous angiomas)

Vasculitis

Intracranial neoplasm
Amyloidosis
Cerebral amyloidosis affects people who are elderly and may cause up to 10% of intracerebral hemorrhages.
Rarely, cerebral amyloid angiopathy can be caused by mutations in the amyloid precursor protein and is
inherited in an autosomal dominant fashion.
Coagulopathies
Coagulopathies may be acquired or inherited. Liver disease can result in a bleeding diathesis. Inherited
disorders of coagulation such as factor VII, VIII, IX, X, and XIII deficiency can predispose to excessive
bleeding, and intracranial hemorrhage has been seen in all of these disorders.
Anticoagulant therapy
Anticoagulant therapy is especially likely to increase hemorrhage risk in patients who metabolize warfarin
inefficiently. Warfarin metabolism is influenced by polymorphism in the CYP2C9 genes. Three known variants
have been described.CYP2C9*1 is the normal variant and is associated with typical response to dosage of
warfarin. Variations *2 and *3 are relatively common polymorphisms that reduce the efficiency of warfarin
metabolism.[17]
Arteriovenous malformations
Numerous genetic causes may predispose to AVMs in the brain, although AVMs are generally sporadic.
Polymorphisms in the IL6 gene increase susceptibility to a number of disorders, including AVM. Hereditary
hemorrhagic telangiectasia (HHT), previously known as Osler-Weber-Rendu syndrome, is an autosomal
dominant disorder that causes dysplasia of the vasculature. HHT is caused by mutations inENG, ACVRL1, or
SMAD4 genes. Mutations in SMAD4 are also associated with juvenile polyposis, so this must be considered
when obtaining the patients history.
HHT is most frequently diagnosed when patients present with telangiectasias on the skin and mucosa or with
chronic epistaxis from AVMs in the nasal mucosa. Additionally, HHT can result in AVMs in any organ system or
vascular bed. AVM in the gastrointestinal tract, lungs, and brain are the most worrisome, and their detection is
the mainstay of surveillance for this disease.
Hypertension
The most common etiology of primary hemorrhagic stroke (intracerebral hemorrhage) is hypertension. At least
two thirds of patients with primary intraparenchymal hemorrhage are reported to have preexisting or newly
diagnosed hypertension. Hypertensive small-vessel disease results from tiny lipohyalinotic aneurysms that
subsequently rupture and result in intraparenchymal hemorrhage. Typical locations include the basal ganglia,
thalami, cerebellum, and pons.

Aneurysms and subarachnoid hemorrhage

The most common cause of atraumatic hemorrhage into the subarachnoid space is rupture of an intracranial
aneurysm. Aneurysms are focal dilatations of arteries, with the most frequently encountered intracranial type
being the berry (saccular) aneurysm. Aneurysms may less commonly be related to altered hemodynamics
associated with AVMs, collagen vascular disease, polycystic kidney disease, septic emboli, and neoplasms.
Nonaneurysmal perimesencephalic subarachnoid hemorrhage may also be seen. This phenomenon is thought
to arise from capillary or venous rupture. It has a less severe clinical course and, in general, a better prognosis.
Berry aneurysms are most often isolated lesions whose formation results from a combination of hemodynamic
stresses and acquired or congenital weakness in the vessel wall. Saccular aneurysms typically occur at

vascular bifurcations, with more than 90% occurring in the anterior circulation. Common sites include the
following:

The junction of the anterior communicating arteries and anterior cerebral arteriesmost commonly,
the middle cerebral artery (MCA) bifurcation

The supraclinoid internal carotid artery at the origin of the posterior communicating artery

The bifurcation of the internal carotid artery (ICA)

Genetic causes of aneurysms
Intracranial aneurysms may result from genetic disorders. Although rare, several families have been described
that have a predispositioninherited in an autosomal dominant fashionto intracranial berry aneurysms. A
number of genes, all categorized as ANIB genes, are associated with this predisposition.
Presently,ANIB1 through ANIB11 are known.
Autosomal dominant polycystic kidney disease (ADPKD) is another cause of intracranial aneurysm. Families
with ADPKD tend to show phenotypic similarity with regard to intracranial hemorrhage or asymptomatic berry
aneurysms.[18]
Loeys-Dietz syndrome (LDS) consists of craniofacial abnormalities, craniosynostosis, marked arterial tortuosity,
and aneurysms and is inherited in an autosomal dominant manner. Although intracranial aneurysms occur in
LDS of all types, saccular intracranial aneurysms are a prominent feature of LDS type IC, which is caused by
mutations in the SMAD3 gene.[19]
Ehlers-Danlos syndrome is a group of inherited disorders of the connective tissue that feature hyperextensibility
of the joints and changes to the skin, including poor wound healing, fragility, and hyperextensibility. However,
Ehlers-Danlos vascular type (type IV) also is known to cause spontaneous rupture of hollow viscera and large
arteries, including arteries in the intracranial circulation.
Patients with Ehlers-Danlos syndrome may also have mild facial findings, including lobeless ears, a thin upper
lip, and a thin, sharp nose. The distal fingers may appear prematurely aged (acrogeria). In the absence of a
suggestive family history, it is difficult to separate Ehlers-Danlos vascular type from other forms of EhlersDanlos. Ehlers-Danlos vascular type is caused by mutations in the COL3A1 gene; it is inherited in an
autosomal dominant manner.
See Genetic and Inflammatory Mechanisms in Stroke, as well as Blood Dyscrasias and Stroke. Information on
metabolic diseases and stroke can be found in the following articles:

Methylmalonic Acidemia
Homocystinuria/Homocysteinemia
Fabry Disease
MELAS Mitochondrial Encephalomyopathy, Lactic Acidosis, Strokelike Episodes
Hyperglycemia/Hypoglycemia

Hemorrhagic transformation of ischemic stroke

Hemorrhagic transformation represents the conversion of a bland infarction into an area of hemorrhage.
Proposed mechanisms for hemorrhagic transformation include reperfusion of ischemically injured tissue, either
from recanalization of an occluded vessel or from collateral blood supply to the ischemic territory or disruption
of the blood-brain barrier. With disruption of the blood-brain barrier, red blood cells extravasate from the
weakened capillary bed, producing petechial hemorrhage or frank intraparenchymal hematoma. [11, 12, 20] (For more
information, seeReperfusion Injury in Stroke.)
Hemorrhagic transformation of an ischemic infarct occurs within 2-14 days postictus, usually within the first
week. It is more commonly seen following cardioembolic strokes and is more likely with larger infarct size. [11, 13,
21]
Hemorrhagic transformation is also more likely following administration of tissue plasminogen activator (tPA)
in patients whose noncontrast computed tomography (CT) scans demonstrate areas of hypodensity.[20, 22, 23] See
the image below.

Noncontrast computed tomography scan (left) obtained in a 75-year-old man who

was admitted for stroke demonstrates a large right middle cerebral artery distribution infarction with linear areas of
developing hemorrhage. These become more confluent on day 2 of hospitalization (middle image), with increased mass
effect and midline shift. There is massive hemorrhagic transformation by day 6 (right), with increased leftward midline shift
and subfalcine herniation. Obstructive hydrocephalus is also noted, with dilatation of the lateral ventricles, likely due to
compression of the foramen of Monroe. Intraventricular hemorrhage is also noted layering in the left occipital horn. Larger
infarctions are more likely to undergo hemorrhagic transformation and are one contraindication to thrombolytic therapy.

Epidemiology
Occurrence in the United States
Each year in the United States, approximately 795,000 people experience new or recurrent stroke. Of these,
approximately 610,000 represent initial attacks, and 185,000 represent recurrent strokes. Epidemiologic studies
indicate that approximately 87% of strokes in the United States are ischemic, 10% are secondary to
intracerebral hemorrhage, and another 3% may be secondary to subarachnoid hemorrhage. [8, 24]
A 2010 retrospective review from a stroke center found that 40.9% of the 757 patients in the study had suffered
hemorrhagic strokes.[25] The researchers speculate that improved availability and implementation of computed
tomography (CT) scanning may have unmasked a previous underestimation of the actual percentage of
hemorrhagic strokes, or increased use of antiplatelet agents and warfarin may have led to a higher incidence of
hemorrhage. Alternatively, this higher rate may represent referral bias of patients with intracerebral
hemorrhages to medical centers with neurosurgical capabilities.
The incidence of stroke varies with age, sex, ethnicity, and socioeconomic status. For example, American Heart
Association (AHA) researchers found that rates of intracerebral hemorrhage are higher in Mexican Americans,
Latin Americans, blacks, Native Americans, Japanese people, and Chinese people than they are in whites. [8]
Flaherty et al found that excess risk of intracranial hemorrhage in African Americans is largely attributable to
higher hemorrhage rates in young and middle-aged persons, particularly for deep cerebral and brainstem
locations. Hypertension is the predominant risk factor.[26]

International occurrence
According to the World Health Organization (WHO), 15 million people suffer stroke worldwide each year. Of
these, 5 million die and another 5 million are left permanently disabled. [27]
The global incidence of stroke has at least a modest variation from nation to nation, suggesting the importance
of genetics and environmental factors, such as disparities in access to health care in developing countries. The
age-adjusted incidence of total strokes per 1000 person-years for people 55 years or older has been reported
in the range of 4.2 to 6.5. The highest incidences have been reported in Russia, Ukraine, and Japan.
In a prospective, population-based registry study from Italy, the crude annual incidence rate of intracerebral
hemorrhage was 36.9 per 100,000 population. When standardized to the 2006 European population, the rate
was 32.9 per 100,000 population; standardized to the world population, the rate was 15.9 per 100,000
population.[28]
Overall, the incidence of acute stroke has demonstrated a constant decline over the past several decades,
most notably during the 1970s-1990s, although in recent years the rate trend has begun to plateau. However,
the increased survival among stroke victims will place an increased demand on health-care systems globally. [11,
29]

Stroke subtypes also vary greatly in different parts of the world and between different races. For example, the
proportion of hemorrhagic strokes may be higher in certain populations, such as the Chinese population, in
which it has been reported to be up to 39.4%, and the Japanese, in which it is reportedly up to 38.7%. [4, 29]

Prognosis

The prognosis in patients with hemorrhagic stroke varies depending on the severity of stroke and the location
and the size of the hemorrhage. Lower Glasgow Coma Scale (GCS) scores are associated with poorer
prognosis and higher mortality rates. A larger volume of blood at presentation is also associated with a poorer
prognosis. Growth of the hematoma volume is associated with a poorer functional outcome and increased
mortality rate.
The intracerebral hemorrhage score is the most commonly used instrument for predicting outcome in
hemorrhagic stroke. The score is calculated as follows:

GCS score 3-4: 2 points

GCS score 5-12: 1 point
GCS score 13-15: 0 points
Age 80 years: Yes, 1 point; no, 0 points
Infratentorial origin: Yes, 1 point; no, 0 points
Intracerebral hemorrhage volume 30 cm 3: 1 point
Intracerebral hemorrhage volume < 30 cm 3: 0 points
Intraventricular hemorrhage: Yes, 1 point; no, 0 points
In a study by Hemphill et al, all patients with an Intracerebral Hemorrhage Score of 0 survived, and all of those
with a score of 5 died; 30-day mortality increased steadily with the Score. [30]
Other prognostic factors include the following:

Nonaneurysmal perimesencephalic stroke has a less severe clinical course and, in general, a better
prognosis

The presence of blood in the ventricles is associated with a higher mortality rate; in one study, the
presence of intraventricular blood at presentation was associated with a mortality increase of more than 2-fold

Patients with oral anticoagulation-associated intracerebral hemorrhage have higher mortality rates and
poorer functional outcomes
In studies, withdrawal of medical support or issuance of Do Not Resuscitate (DNR) orders within the first day of
hospitalization predict poor outcome independent of clinical factors. Because limiting care may adversely
impact outcome, American Heart Association/American Stroke Association (AHA/ASA) guidelines suggest that
new DNR orders should probably be postponed until at least the second full day of hospitalization. Patients with
DNRs should be given all other medical and surgical treatment, unless the DNR explicitly says otherwise. [3]
For more information, see Motor Recovery in Stroke.

History
Obtaining an adequate history includes determining the onset and progression of symptoms, as well as
assessing for risk factors and possible causative events. Such risk factors include the following:

Previous transient ischemic attack (TIA) and stroke

Hypertension
Diabetes
Smoking
Arrhythmia and valvular disease
Illicit drug use
Use of anticoagulants
Risk factors for thrombosis
A history of trauma, even if minor, may be important, as extracranial arterial dissections can result in ischemic
stroke.

Hemorrhagic versus ischemic stroke

Symptoms alone are not specific enough to distinguish ischemic from hemorrhagic stroke. However,
generalized symptoms, including nausea, vomiting, and headache, as well as an altered level of
consciousness, may indicate increased intracranial pressure and are more common with hemorrhagic strokes
and large ischemic strokes.
Seizures are more common in hemorrhagic stroke than in the ischemic kind. Seizures occur in up to 28% of
hemorrhagic strokes, generally at the onset of the intracerebral hemorrhage or within the first 24 hours.

Focal neurologic deficits

The neurologic deficits reflect the area of the brain typically involved, and stroke syndromes for specific
vascular lesions have been described. Focal symptoms of stroke include the following:

Weakness or paresis that may affect a single extremity, one half of the body, or all 4 extremities
Facial droop
Monocular or binocular blindness
Blurred vision or visual field deficits
Dysarthria and trouble understanding speech
Vertigo or ataxia
Aphasia

Subarachnoid hemorrhage
Symptoms of subarachnoid hemorrhage may include the following:

Sudden onset of severe headache

Signs of meningismus with nuchal rigidity
Photophobia and pain with eye movements
Nausea and vomiting
Syncope - Prolonged or atypical
The most common clinical scoring systems for grading aneurysmal subarachnoid hemorrhage are the Hunt and
Hess grading scheme and the World Federation of Neurosurgeons (WFNS) grading scheme, which
incorporates the Glasgow Coma Scale. The Fisher Scale incorporates findings from noncontrast computed
tomography (NCCT) scans.

Physical Examination
The assessment in patients with possible hemorrhagic stroke includes vital signs; a general physical
examination that focuses on the head, heart, lungs, abdomen, and extremities; and a thorough but expeditious
neurologic examination.[3] However, intracerebral hemorrhage may be clinically indistinguishable from ischemic
stroke. (Though stroke is less common in children, the clinical presentation is similar.)

Hypertension (particularly systolic blood pressure [BP] greater than 220 mm Hg) is commonly a prominent
finding in hemorrhagic stroke. Higher initial BP is associated with early neurologic deterioration, as is fever.[3]
An acute onset of neurologic deficit, altered level of consciousness/mental status, or coma is more common
with hemorrhagic stroke than with ischemic stroke. Often, this is caused by increased intracranial pressure.
Meningismus may result from blood in the subarachnoid space.
Examination results can be quantified using various scoring systems. These include the Glasgow Coma Scale
(GCS), the Intracerebral Hemorrhage Score (which incorporates the GCS; see Prognosis), and the National
Institutes of Health Stroke Scale.

Focal neurologic deficits

The type of deficit depends upon the area of brain involved. If the dominant hemisphere (usually the left) is
involved, a syndrome consisting of the following may result:

Right hemiparesis
Right hemisensory loss
Left gaze preference
Right visual field cut
Aphasia
Neglect (atypical)
If the nondominant (usually the right) hemisphere is involved, a syndrome consisting of the following may
result:

Left hemiparesis
Left hemisensory loss
Right gaze preference
Left visual field cut
Nondominant hemisphere syndrome may also result in neglect when the patient has left-sided hemi-inattention
and ignores the left side.
If the cerebellum is involved, the patient is at high risk for herniation and brainstem compression. Herniation
may cause a rapid decrease in the level of consciousness and may result in apnea or death.
Specific brain sites and associated deficits involved in hemorrhagic stroke include the following:

Putamen - Contralateral hemiparesis, contralateral sensory loss, contralateral conjugate gaze paresis,
homonymous hemianopia, aphasia, neglect, or apraxia
Thalamus - Contralateral sensory loss, contralateral hemiparesis, gaze paresis, homonymous
hemianopia, miosis, aphasia, or confusion
Lobar - Contralateral hemiparesis or sensory loss, contralateral conjugate gaze paresis, homonymous
hemianopia, abulia, aphasia, neglect, or apraxia
Caudate nucleus - Contralateral hemiparesis, contralateral conjugate gaze paresis, or confusion
Brainstem - Quadriparesis, facial weakness, decreased level of consciousness, gaze paresis, ocular
bobbing, miosis, or autonomic instability
Cerebellum Ipsilateral ataxia, facial weakness, sensory loss; gaze paresis, skew deviation, miosis, or
decreased level of consciousness
Other signs of cerebellar or brainstem involvement include the following:
Gait or limb ataxia
Vertigo or tinnitus
Nausea and vomiting
Hemiparesis or quadriparesis
Hemisensory loss or sensory loss of all 4 limbs
Eye movement abnormalities resulting in diplopia or nystagmus
Oropharyngeal weakness or dysphagia

Crossed signs (ipsilateral face and contralateral body)

Many other stroke syndromes are associated with intracerebral hemorrhage, ranging from mild headache to
neurologic devastation. At times, a cerebral hemorrhage may present as a new-onset seizure.

Diagnostic Considerations
Intracerebral hemorrhage may be clinically indistinguishable from ischemic stroke, and a thorough history and
physical examination are important. An acute onset of neurologic deficit, altered level of consciousness/mental
status, or coma is more common with hemorrhagic stroke than with ischemic stroke. A history of trauma, even if
minor, may be important, as extracranial arterial dissections can result in ischemic stroke.
Seizures are more common in hemorrhagic stroke than in ischemic stroke and occur in up to 28% of
hemorrhagic strokes, generally at the onset of the intracerebral hemorrhage or within the first 24 hours.
Postictal (Todd) paralysis and hyperosmolality should also be considered.
Other problems to consider are as follows:

Hyponatremia or hypernatremia
Migraine headache
Hyperosmolar hyperglycemic nonketotic coma

Differential Diagnoses

Encephalitis
Headache, Migraine
Hypernatremia
Hyperosmolar Hyperglycemic Nonketotic Coma
Hypertensive Emergencies
Hypoglycemia
Hyponatremia
Labyrinthitis Ossificans
Meningitis
Neoplasms, Brain
Stroke, Ischemic
Subarachnoid Hemorrhage
Subdural Hematoma
Transient Ischemic Attack
Proceed to Workup
READ MORE ABOUT HEMORRHAGIC STROKE ON MEDSCAPE

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RELATED NEWS AND ARTICLES

Middle Cerebral Artery Stroke

Cost of Stroke Care Does Not

Decrease Over Long Term
Magnetic Resonance Imaging in

Decreased Risk of Secondary

Acute Stroke
Brain
Herniation With Intracranial

Acute Management of Stroke

Pressure Monitoring in Patients With
Haemorrhagic Stroke

FDA Advisors Cool on Watchman

Approval Amid Ischemic-Stroke Data

Approach Considerations
Laboratory tests should include a complete blood count, a metabolic panel, andparticularly in patients taking
anticoagulantscoagulation studies (ie, prothrombin time or international normalized ratio [INR] and an
activated partial thromboplastin time).[3]
Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be obtained on an
emergent basis. Brain imaging aids diagnosing hemorrhage, and it may identify complications such as
intraventricular hemorrhage, brain edema, or hydrocephalus. Either noncontrast computed tomography (NCCT)
scanning or magnetic resonance imaging (MRI) is the modality of choice.
Computed tomography (CT)-scan studies can also be performed in patients who are unable to tolerate a
magnetic resonance examination or who have contraindications to MRI, including pacemakers, aneurysm clips,
or other ferromagnetic materials in their bodies. Additionally, CT-scan examination is more easily accessible for
patients who require special equipment for life support. See the image below.

Noncontrast computed tomography scan of the brain (left) demonstrates an acute

hemorrhage in the left gangliocapsular region, with surrounding white matter hypodensity consistent with vasogenic edema.
T2-weighted axial magnetic resonance imaging scan (middle image) again demonstrates the hemorrhage, with surrounding
high-signal edema. The coronal gradient-echo image (right) demonstrates susceptibility related to the hematoma, with
markedly low signal adjacent the left caudate head. Gradient-echo images are highly sensitive for blood products.

CT angiography and contrast-enhanced CT scanning may be considered for helping identify patients at risk for
hematoma expansion. Extravasation of contrast within the hematoma indicates high risk.
When clinical or radiologic findings suggest an underlying structural lesion, useful techniques include CT
angiography, CT venography, contrast-enhanced CT scanning, contrast-enhanced MRI, magnetic resonance
angiography (MRA), or magnetic resonance venography.[3]
Conventional angiography is the gold standard in evaluating for cerebrovascular disease and for providing lessinvasive endovascular interventions. This modality can be performed to clarify equivocal findings or to confirm
and treat disease seen on MRA, CTA, transcranial Doppler, or neck ultrasonograms. However, Zhu et al found
that in patients with spontaneous intracranial hemorrhage, angiographic yield was significantly lower in patients
older than 45 years and those who had preexisting hypertension. [31]
Although the traditional approach to excluding underlying vascular abnormalities in patients with spontaneous
intracerebral hemorrhage is to use digital subtraction angiography (DSA) in the acute and subacute phases,
Wong et al found that MRA was able to detect most structural vascular abnormalities in the subacute phase in
most patients. Consequently, they recommend MRA as the screening test.
Proceed to Treatment & Management
READ MORE ABOUT HEMORRHAGIC STROKE ON MEDSCAPE

RELATED REFERENCE TOPICS

RELATED NEWS AND ARTICLES

Middle Cerebral Artery Stroke

Cost of Stroke Care Does Not

Decrease Over Long Term
Magnetic Resonance Imaging in

Decreased Risk of Secondary

Acute Stroke
Brain Herniation With Intracranial

Acute Management of Stroke

Pressure Monitoring in Patients With
Haemorrhagic Stroke

FDA Advisors Cool on Watchman

Approval Amid Ischemic-Stroke Data

Approach Considerations
The treatment and management of patients with acute intracerebral hemorrhage depends on the cause and
severity of the bleeding. Basic life support, as well as control of bleeding, seizures, blood pressure (BP), and
intracranial pressure, are critical. Medications used in the treatment of acute stroke include the following:

Anticonvulsants - To prevent seizure recurrence

Antihypertensive agents - To reduce BP and other risk factors of heart disease
Osmotic diuretics - To decrease intracranial pressure in the subarachnoid space
Management begins with stabilization of vital signs. Perform endotracheal intubation for patients with a
decreased level of consciousness and poor airway protection. Intubate and hyperventilate if intracranial
pressure is elevated, and initiate administration of mannitol for further control. Rapidly stabilize vital signs, and
simultaneously acquire an emergent computed tomography (CT) scan. Glucose levels should be monitored,
with normoglycemia recommended.[3] Antacids are used to prevent associated gastric ulcers.
No effective targeted therapy for hemorrhagic stroke exists yet. Studies of recombinant factor VIIa (rFVIIa)
have yielded disappointing results. Evacuation of hematoma, either via open craniotomy or endoscopy, may be
a promising ultra-early-stage treatment for intracerebral hemorrhage that may improve long-term prognosis.
A combined analysis of INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) 1
and 2 suggested that in patients with intracerebral hemorrhage, intensive BP reduction early in their treatment
lessens the absolute growth of hematomas, with the effect being especially pronounced in patients who have
undergone prior antithrombotic therapy.[32]
The study involved 1310 patients who had undergone repeat 24-hour CT scans, including 665 who received
intensive BP reduction therapy (target BP < 140 mm Hg systolic) and 645 controls (target BP < 180 mm Hg
systolic).[32] A total of 235 patients in the intensive reduction and control groups had received antithrombotic
medication prior to intracerebral hemorrhage.
The investigators found that, in patients who had not had prior antithrombotic therapy, hematoma volume
increased 1.1 mL on repeat CT scan in those who underwent intensive BP reduction, compared with 2.4 mL in
controls.[32] In patients who had previously taken antithrombotics, however, the difference between the intensivereduction and control groups was much greater, with the increase in hematoma volume being 3.4 mL in the
intensive-reduction patients and 8.1 mL in the controls.

Management of Seizures
Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage; these seizures are often
nonconvulsive.[33, 34] According to American Heart Association/American Stroke Association (AHA/ASA) 2010
guidelines for the management of spontaneous intracerebral hemorrhage, patients with clinical seizures or
electroencephalographic (EEG) seizure activity accompanied by a change in mental status should be treated
with antiepileptic drugs.[3]
Patients for whom treatment is indicated should immediately receive a benzodiazepine, such as lorazepam or
diazepam, for rapid seizure control. This should be accompanied by phenytoin or fosphenytoin loading for
longer-term control.

Prophylaxis
The utility of prophylactic anticonvulsant medication remains uncertain. In prospective and population-based
studies, clinical seizures have not been associated with worse neurologic outcome or mortality. Indeed, 2
studies have reported worse outcomes in patients who did not have a documented seizure but who received
antiepileptic drugs (primarily phenytoin).[3]
The 2010 AHA/ASA guidelines do not offer recommendations on prophylactic anticonvulsants, but suggest that
continuous EEG monitoring is probably indicated in patients with intracranial hemorrhage whose mental status
is depressed out of proportion to the degree of brain injury

Prophylactic anticonvulsant therapy has been recommended in patients with lobar hemorrhages to reduce the
risk of early seizures. One large, single-center study showed that prophylactic antiepileptic drugs significantly
reduced the number of clinical seizures in these patients. [33]
In addition, AHA/ASA guidelines from 2012 suggest that prophylactic anticonvulsants may be considered for
patients with aneurysmal subarachnoid hemorrhage. In such cases, however, anticonvulsant use should
generally be limited to the immediate post-hemorrhagic period. Routine long-term use is not recommended, but
it may be considered in patients with a prior seizure history, intracerebral hematoma, intractable hypertension,
or infarction or aneurysm at the middle cerebral artery.[35]

Blood Pressure Control

No controlled studies have defined optimum BP levels for patients with acute hemorrhagic stroke, but greatly
elevated BP is thought to lead to rebleeding and hematoma expansion. Stroke may result in loss of cerebral
autoregulation of cerebral perfusion pressure.
Intensive BP reduction (target BP < 140 mm Hg systolic) early in the treatment of patients with intracerebral
hemorrhage appears to lessen the absolute growth of hematomas, particularly in patients who have received
previous antithrombotic therapy, according to a combined analysis of the Intensive Blood Pressure Reduction in
Acute Cerebral Hemorrhage Trials 1 and 2 (INTERACT).[32]
Suggested agents for use in the acute setting are beta blockers (eg, labetalol) and angiotensin-converting
enzyme inhibitors (ACEIs) (eg, enalapril). For more refractory hypertension, agents such as nicardipine and
hydralazine are used. Avoid nitroprusside because it may raise intracranial pressure.
The 2010 AHA/ASA guidelines acknowledge that evidence for the efficacy of managing BP in hemorrhagic
stroke is currently incomplete. With that caveat, the AHA/ASA recommendations for treating elevated BP are as
follows[3] :

If systolic BP is over 200 mm Hg or mean arterial pressure (MAP) is over 150 mm Hg, then consider
aggressive reduction of BP with continuous IV infusion; check BP every 5 minutes

If systolic BP is over 180 mm Hg or MAP is over 130 mm Hg and intracranial pressure may be
elevated, then consider monitoring intracranial pressure and reducing BP using intermittent or continuous
intravenous medications, while maintaining a cerebral perfusion pressure of 60 mm Hg or higher

If systolic BP is over 180 or MAP is over 130 mm Hg and there is no evidence of elevated intracranial
pressure, then consider modest reduction of BP (target MAP of 110 mm Hg or target BP of 160/90 mm Hg)
using intermittent or continuous intravenous medications to control it, and perform clinical reexamination of
the patient every 15 minutes

In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140
mm Hg is probably safe
For patients with aneurysmal subarachnoid hemorrhage, the 2012 AHA/ASA guidelines recommend lowering
BP below 160 mmHg acutely to reduce rebleeding.[35]
The ongoing Antihypertensive Treatment in Acute Cerebral Hemorrhage-II (ATACH-II) phase 3 randomized
clinical trial is designed to determine whether the likelihood of death or disability at 3 months after spontaneous
supratentorial intracerebral hemorrhage is lower when systolic BP has been reduced to 180 mm Hg or below or
to 140 mm Hg or below. In ATACH-II, intravenous nicardipine is started within 3 hours of stroke onset and
continued for the next 24 hours.

Intracranial Pressure Control

Elevated intracranial pressure may result from the hematoma itself, from surrounding edema, or from both. The
frequency of increased intracranial pressure in patients with intracerebral hemorrhage is not known.
Elevate the head of the bed to 30. This improves jugular venous outflow and lowers intracranial pressure. The
head should be midline and not turned to the side. Provide analgesia and sedation as needed. Antacids are
used to prevent gastric ulcers associated with intracerebral hemorrhage.
More aggressive therapies, such as osmotic therapy (ie, mannitol, hypertonic saline), barbiturate anesthesia,
and neuromuscular blockage, generally require concomitant monitoring of intracranial pressure and BP with an
intracranial pressure monitor to maintain adequate cerebral perfusion pressure of greater than 70 mm Hg. A

randomized, controlled study of mannitol in intracerebral hemorrhage failed to demonstrate any difference in
disability or death at 3 months.[36]
Hyperventilation (partial pressure of carbon dioxide [PaCO 2] of 25 to 30-35 mm Hg) is not recommended,
because its effect is transient, it decreases cerebral blood flow, and it may result in rebound elevated
intracranial pressure.[5] Glucocorticoids are not effective and result in higher rates of complications with poorer
outcomes.

Hemostatic Therapy
The use of hemostatic therapy with rFVIIa to stop ongoing hemorrhage or prevent hematoma expansion has
generated much interest. However, research to date has failed to support this off-label use of rFVIIa. [37, 38, 39]
A preliminary study of treatment rFVIIa demonstrated reduced mortality and improved functional outcomes.
Unfortunately, the results of a subsequent randomized trial that was larger than the preliminary study revealed
no overall benefit from treatment; hemostatic therapy with rFVIIa reduced growth of the hematoma but did not
improve survival or functional outcome.[40]
Diringer et al found that a higher dose of rFVIIa was associated with a small increase in the risk of arterial
thromboembolic events in patients who presented less than 3 hours after spontaneous intracerebral
hemorrhage. Arterial events were also associated with the presence of cardiac or cerebral ischemia at
presentation, with advanced age, and with antiplatelet use. [41]
The investigators also found that with the use of 20 or 80 mcg/kg rFVIIa, the rates of venous events were
similar to those with placebo.

Treatment of Anticoagulation-associated Intracranial Hemorrhage

Patients on warfarin have an increased incidence of hemorrhagic stroke. Morbidity and mortality for warfarinassociated bleeding is high, with over one half of patients dying within 30 days. Most episodes occur with a
therapeutic international normalized ratio (INR), but overanticoagulation is associated with an even greater risk
of bleeding.
The need to reverse warfarin anticoagulation is a true medical emergency, and reversal must be accomplished
as quickly as possible to prevent further hematoma expansion. Options for reversal therapy include the
following:

Intravenous vitamin K
Fresh frozen plasma (FFP)
Prothrombin complex concentrates (PCC)
rFVIIa

FFP versus PCC

Because vitamin K requires more than 6 hours to normalize the INR, it should be administered with either FFP
or PCC. FFP is the standard of care in the United States [42] ; however, FFP needs to be given in a dose of 15-20
mL/kg and therefore requires a large-volume infusion. PCC contains high levels of vitamin K-dependent
cofactors and thus involves a smaller-volume infusion than FFP and more rapid administration. [43, 44] However,
PCC is associated with high rates of thrombotic complications.
No randomized, controlled trial has studied the safety and efficacy of FFP versus PCC for reversing the effects
of warfarin in patients with intracranial hemorrhage. The International Normalised ratio normalisation in patients
with Coumarin-related intracranial Haemorrhages (INCH) trial, a prospective, randomized, controlled,
multicenter trial comparing the 2 agents, began recruiting subjects in 2009. [45]

FVIIa
Based upon the available medical evidence, the use of FVIIa is currently not recommended over other agents.
The PCC available in the United States contains only low levels of FVII, however, and Sarode et al have
described successful, rapid reversal of vitamin K antagonistrelated coagulopathy using a combination of lowdose FVIIa with PCC, although they note the need for caution in patients at high risk for thrombosis. [42]

Patients on heparin (either unfractionated or low molecular weight heparin [LMWH]) who develop a
hemorrhagic stroke should immediately have anticoagulation reversed with protamine. [5] The dose of protamine
is dependent upon the dose of heparin that was given and the time elapsed since that dose.
Patients with severe deficiency of a specific coagulation factor who develop spontaneous intracerebral
hemorrhage should receive factor replacement therapy.[3]

Reversal of antiplatelet therapy and platelet dysfunction

There is controversy about whether patients on antiplatelet medications (eg, aspirin, aspirin/dipyridamole
[Aggrenox], clopidogrel) should be given desmopressin (DDAVP) and/or platelet transfusions. Patients with
renal failure and platelet dysfunction may also benefit from the administration of desmopressin (DDAVP). The
2010 AHA/ASA guideline for management of spontaneous intracerebral hemorrhage recommends platelet
transfusions only when such hemorrhaging complicates severe thrombocytopenia. [3]

Invasive Therapy
A potential treatment for hemorrhagic stroke is surgical evacuation of the hematoma. However, the role of
surgical treatment for supratentorial intracranial hemorrhage remains controversial. Outcomes in published
studies are conflicting. The international multicenter Trial in Intracerebral Haemorrhage (STICH), which
compared early surgery with initial conservative treatment, failed to demonstrate a surgery-related benefit. [46]
In contrast, a meta-analysis of trials for surgical treatment of spontaneous supratentorial intracerebral
hemorrhage found evidence for improved outcome with surgery if any of the following applied [47] :

Surgery undertaken within 8 hours of ictus

Volume of the hematoma 20-50 mL
Glasgow coma score 9-12
Patient age 50-69 years
In addition, evidence suggests that a subset of patients with lobar hematoma but no intraventricular
hemorrhage may benefit from intervention.[48] A study in this group of patients (STICH II) has been completed,
but results are still pending.[49]
In patients with cerebellar hemorrhage, surgical intervention has been shown to improve outcome if the
hematoma is greater than 3 cm in diameter. It can be lifesaving in the prevention of brainstem compression.

Endovascular treatment of aneurysms

Endovascular therapy using coil embolization, as an alternative to surgical clipping, has been increasingly
employed in recent years with great success (see the following images), although controversy still exists over
which treatment is ultimately superior.

A cerebral angiogram was performed in a 57-year-old man with a family history of

subarachnoid hemorrhage and who was found on previous imaging to have a left distal internal carotid artery (ICA)
aneurysm. The lateral projection from this angiogram demonstrates a narrow-necked aneurysm arising off the posterior
aspect of the distal supraclinoid left ICA, with an additional nipplelike projection off the inferior aspect of the dome of the

aneurysm. There is also a mild, lobulated dilatation of the cavernous left ICA.
Followup cerebral angiogram after coil embolization in a 57-year-old man with a left distal internal carotid artery aneurysm. Multiple
coils were placed with sequential occlusion of the aneurysm, including the nipple at its inferior aspect. A small amount of
residual filling is noted at the proximal neck of the aneurysm, which may thrombose over time.

The International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling
reported that independent survival was higher at 1 year with endovascular coiling and that the survival benefit
continued for at least 7 years.[50] This randomized, multicenter, international trial included 2143 patients. The
investigators also noted that the risk of late rebleeding was small in both groups but higher in the endovascular
coiling group, reconfirming the higher long-term anatomic cure rate of surgery.[50, 51]
More recently, the Barrow Ruptured Aneurysm Trial (BRAT), which included 358 patients, demonstrated
superior functional outcome at 1 year with endovascular coil embolization than with microsurgical clipping for
acutely ruptured intracerebral aneurysm. Further, in contrast to the ISAT results, no patient in the endovascular
embolization group suffered a recurrent hemorrhage.[52] Outcomes at 3-year follow-up of the BRAT patients
continued to favor coil embolization, though the difference no longer reached statistical significance. [53]
Endovascular treatment of aneurysms may be favored over surgical clipping under the following
circumstances[54] :

The aneurysm is in a location that is difficult to access surgically, such as the cavernous internal
carotid artery (ICA) or the basilar terminus

The aneurysm is small-necked and located in the posterior fossa

The patient is elderly

The patient has a poor clinical grade

The following factors militate against endovascular treatment:

Wide-based aneurysms or those without an identifiable neck

Aneurysms with a vessel extending off the aneurysm dome
Severely atherosclerotic or tortuous vessels that limit the endovascular approach
Although vasospasm may be treated with intra-arterial pharmaceutical agents, such as verapamil or
nicardipine, balloon angioplasty can be used for opening larger vessels (see the images below). The
combination of the 2 treatments appears to provide safe and long-lasting therapy for severe, clinically
significant vasospasm.[55]

Frontal view from a cerebral angiogram in a 41-year-man who presented 7 days earlier
with subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA) aneurysm (which was treated with
surgical clipping). There is significant narrowing of the proximal left ACA, left M1 segment, and left supraclinoid internal

carotid artery, indicating vasospasm.

Angiographic view in a 41-year-man who
presented 7 days earlier with subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA) aneurysm
(which was treated with surgical clipping). Superimposed road map image demonstrates placement of a wire across the left
M1 segment and balloon angioplasty. The left proximal ACA and supraclinoid internal carotid artery (ICA) were also
angioplastied, and intra-arterial verapamil was administered. Follow-up image on the right after treatment demonstrates
resolution of the left M1 segment and distal ICA, which are now widely patent. Residual narrowing is seen in the left proximal
ACA.

Ventriculostomy
Placement of an intraventricular catheter for cerebrospinal fluid drainage (ie, ventriculostomy) is often used in
the setting of obstructive hydrocephalus, which is a common complication of thalamic hemorrhage with thirdventricle compression and of cerebellar hemorrhage with fourth-ventricle compression. Ventriculostomies are
associated with a risk of infection, including bacterial meningitis.

Prevention of Hemorrhagic Stroke

Antihypertensives
The 2010 AHA/ASA guidelines for spontaneous ICH recommend that after acute intracerebral hemorrhage,
patients without medical contraindications should have BP well controlled, especially for hemorrhage in typical
hypertensive vasculopathy locations.[3] In addition, the guidelines strongly recommend maintenance of BP below
140/90 mm Hg to prevent a first stroke. In patients with hypertension plus either diabetes or renal disease, the
treatment goal is BP below 130/80 mm Hg.[56]
BP-lowering medications include thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme
inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). For patients with diabetes, the use of ACEIs and
ARBs to treat hypertension is a class I-A recommendation (strongest and best-documented), according to the
2011 AHA/ASA primary prevention guidelines.[3] Beta blockers are considered second-line agents given their
inferiority in preventing vascular events, despite producing similar reductions in BP. (Adverse effects of ACEIs
include cough [10%], which is less common with ARBs.)
Although statin therapy is recommended for primary prevention of ischemic stroke (class I-A recommendation),
[56]
especially if other risk factors are present, some studies have found an increased risk of intracerebral
hemorrhage with statin use. However, a meta-analysis of 31 randomized, controlled trials of statin therapy
found that active statin therapy was not associated with a significant increase in intracerebral hemorrhage. [57]
In the Heart Outcomes Prevention Evaluation (HOPE) study, the addition of the ACEI ramipril to all other
medical therapy, including antiplatelet agents, reduced the relative risk of stroke, death, and myocardial
infarction by 32% compared with placebo.[58] Only 40% of the efficacy of ramipril could be attributed to its BPlowering effects. Other postulated mechanisms included endothelial protection.
Whether the beneficial effect of ramipril represents a class effect of ACEIs or whether it is a property unique to
ramipril is unclear.
In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a regimen based on perindopril, an
ACEI, was superior to placebo.[59] Although this drug alone was not superior to placebo, the combination of
perindopril with indapamide (a thiazide diuretic) substantially reduced the recurrence of stroke. [59]Much of the
effect in reducing stroke recurrence was attributable to the lowering of BP, in contrast to findings for ramipril
from the HOPE study.
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed slight
superiority of chlorthalidone (a thiazide diuretic) over lisinopril (an ACEI) in terms of stroke occurrence. [60]

The Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE) demonstrated that an ARB
(losartan) was superior to a beta blocker (atenolol) in reducing the occurrence of stroke. [61]
The Morbidity and Mortality after Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention
(MOSES) study found that the ARB eprosartan was superior to the calcium channel blocker nitrendipine in the
secondary prevention of stroke and transient ischemic attack (TIA). [62] This was true despite comparable BP
reductions. The absolute annual difference in stroke and TIA risk was approximately 4%. The study was
relatively small, and most events were TIAs.

Lifestyle interventions
Smoking cessation, a low-fat diet (eg, Dietary Approaches to Stop Hypertension [DASH] or Mediterranean
diets), weight loss, and regular exercise should be encouraged as strongly as pharmacologic treatment. Written
prescriptions for exercise and medications for smoking cessation (ie, nicotine patch, bupropion, varenicline)
increase the likelihood of success with these interventions.
Reducing sodium intake and increasing consumption of foods high in potassium to reduce BP may also help in
primary prevention.[56] High alcohol intake should be reduced, as drinking more than 30 drinks per month has
been tied to increased risk of intracerebral hemorrhage.
Exercise
A Finnish study showed that the likelihood of stroke in men with the lowest degree of physical fitness (maximal
oxygen uptake [VO2max] < 25.2 mL/kg/min) was more than 3 times greater than in men with the highest degree of
physical fitness (VO2max>35.3 mL/kg/min).[63] level of physical fitness was a more powerful risk factor than lowdensity lipoprotein cholesterol level, body mass index, and smoking, and it was nearly comparable to
hypertension as a risk factor.
The 2011 AHA/ASA guidelines for the primary prevention of stroke, which address hemorrhagic and ischemic
stroke, emphasize exercise and other lifestyle modifications. The guidelines endorse the 2008 Physical Activity
Guidelines for Americans, which include a recommendation of at least 150 minutes per week of moderateintensity aerobic physical activity.[56]

Consultations
Emergent neurosurgical or neurologic consultation is often indicated; local referral patterns may vary. The need
for invasive intracranial pressure monitoring and for emergent cerebral angiography should be assessed by the
neurosurgeon. Patients in whom the hemorrhages cause is unclear and who would otherwise be candidates
for surgery should be considered for angiographic evaluation. Also seeStroke Team Creation and Primary
Stroke Center Certification.

Medication Summary
Medications used in the treatment of acute stroke include anticonvulsants such as diazepam, to prevent
seizure recurrence; antihypertensive agents such as labetalol, to reduce blood pressure (BP) and other risk
factors for heart disease; and osmotic diuretics such as mannitol, to decrease intracranial pressure in the
subarachnoid space.
As previously mentioned, the treatment and management of patients with acute intracerebral hemorrhage
depends on the cause and severity of the bleeding. However, there is currently no effective targeted therapy for
hemorrhagic stroke.

Anticonvulsants, Other
Class Summary
Benzodiazepines are commonly used to control seizure activity and recurrence. Agents such as lorazepam and
diazepam are often used acutely, in combination with either phenytoin or fosphenytoin loading.
View full drug information

Diazepam (Diastat, Diazemuls, Valium)

Diazepam controls active seizures by modulating the postsynaptic effects of gamma-aminobutyric acid type A
(GABA-A) transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic
system, the thalamus, and hypothalamus, to induce a calming effect. It also acts as an effective adjunct for the
relief of skeletal muscle spasm caused by upper motor neuron disorders.
Diazepam should be augmented by longer-acting anticonvulsants, such as phenytoin or phenobarbital,
because it rapidly distributes to other body fat stores.
View full drug information

Lorazepam (Ativan)

Lorazepam is a short-acting acting benzodiazepine with a moderately long half-life. It has become the drug of
choice in many centers for treating active seizures.

Anticonvulsants, Hydantoins
Class Summary
Anticonvulsants prevent seizure recurrence and terminate clinical and electrical seizure activity. These agents
are used routinely to avoid seizures that may be induced by cortical damage.
According to the American Heart Association/American Stroke Association (AHA/ASA) 2010 guidelines for
management of spontaneous intracranial hemorrhage, treatment with antiepileptic drugs is indicated for those

patients with clinical seizures or with electroencephalographic (EEG) seizure activity accompanied by a change
in mental status.[3] Prophylactic use of anticonvulsants is controversial and should be used judiciously, if at all.
View full drug information

Phenytoin (Dilantin)

Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity, as well as in the
brainstem centers responsible for the tonic phase of grand mal seizures. All doses should be individualized.
The antiepileptic effect of phenytoin is not immediate. Concomitant administration of an intravenous
benzodiazepine will usually be necessary to control status epilepticus. In addition, a larger dose before retiring
should be administered if the dose cannot be divided equally.
View full drug information

Fosphenytoin (Cerebyx)

Fosphenytoin is a diphosphate ester salt of phenytoin that acts as water-soluble prodrug of phenytoin.
Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
To avoid the need to perform molecular-weight-based adjustments when converting between fosphenytoin and
phenytoin sodium doses, express the dose as phenytoin sodium equivalents. Although fosphenytoin can be
administered intravenously or intramuscularly, the intravenous route is the route of choice and should be used
in emergency situations.
The antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate.
Concomitant administration of an intravenous benzodiazepine will usually be necessary to control status
epilepticus.

Beta Blockers, Alpha Activity

Class Summary
Beta blockers are used to reduce BP and risk factors for heart disease. They are first-line agents for acute BP
reduction in hemorrhagic stroke, but they are second-line agents for stroke prevention. Selective beta blockers
obstruct access to beta-1 receptors more than they do to beta-2 receptors; nonselective beta blockers obstruct
access to beta-1 and beta-2 receptors.
View full drug information

Labetalol (Trandate)

Labetalol blocks beta1-, alpha-, and beta2-adrenergic receptor sites to decrease BP. It is administered as a 520 mg intravenous bolus over 2 minutes, then as a continuous infusion at 2 mg/min (not to exceed 300
mg/dose).

Beta Blockers, Beta-1 Selective

Class Summary
Beta blockers are used to reduce BP and risk factors for heart disease. They are first-line agents for acute BP
reduction in hemorrhagic stroke, but they are second-line agents for stroke prevention. Selective beta blockers
obstruct access to beta-1 receptors more than they do to beta-2 receptors; nonselective beta blockers obstruct
access to beta-1 and beta-2 receptors.
View full drug information

Esmolol (Brevibloc)

Esmolol is an ultra-short-acting agent that selectively blocks beta-1 receptors with little or no effect on beta-2
receptor types. This drug is particularly useful in patients with elevated arterial pressure, especially if surgery is
planned, and its short half-life of 8 minutes allows for titration and quick discontinuation, if necessary.
Esmolol is also useful in patients at risk for experiencing complications from beta blockade, particularly those
with reactive airway disease, mild to moderate left-ventricular dysfunction, and/or peripheral vascular disease.

Vasodilators
Class Summary
Vasodilators lower BP through direct vasodilation and relaxation of the vascular smooth muscle. They are used
more for BP lowering in refractory situations.
View full drug information

Hydralazine (Apresoline)

Hydralazine decreases systemic resistance through direct vasodilation of arterioles and is used to treat
hypertensive emergencies. The use of a vasodilator will reduce the stroke volume ratio (SVR), which, in turn,
may allow forward flow, improving cardiac output. Hydralazine is typically not a first-line agent, because of its
side-effect profile.

Calcium Channel Blockers

Class Summary
Calcium channel blockers are used to lower BP by relaxing the blood vessels and increasing the amount of
blood and oxygen that is delivered to the heart, while reducing the hearts workload. In acute situations,
intravenous calcium channel blockers are frequently used to control BP. These are first-line agents for longterm BP control in stroke patients (along with thiazides, ACEIs, and angiotensin receptor blockers [ARBs]).
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Nicardipine (Cardene, Cardene IV, Cardene SR)

Nicardipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves
myocardial oxygen delivery and reduces myocardial oxygen consumption.

Angiotensin-converting Enzyme Inhibitors

Class Summary
ACEIs prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower
aldosterone secretion. These are first-line agents for emergent and long-term BP control in hemorrhagic stroke
patients.
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Enalapril (Vasotec)

Enalapril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in
increased levels of plasma renin and a reduction in aldosterone secretion. It helps to control BP and
proteinuria.
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Ramipril (Altace)

Ramipril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in
increased levels of plasma renin and a reduction in aldosterone secretion.
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Lisinopril (Zestril)

Lisinopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower
aldosterone secretion.

Angiotensin Receptor Blockers

Class Summary
ARBs may be used as an alternative to ACEIs in patients who develop adverse effects, such as a persistent
cough.
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Losartan (Cozaar)

Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more
complete inhibition of the renin-angiotensin system than ACEIs do. In addition, it does not affect the response
to bradykinin and is less likely to be associated with cough and angioedema.
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Candesartan (Atacand)

Candesartan blocks vasoconstriction and the aldosterone-secreting effects of angiotensin II. It may induce a
more complete inhibition of the renin-angiotensin system than ACEIs do. In addition, it does not affect response
to bradykinin and is less likely to be associated with cough and angioedema.
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Valsartan (Diovan)

Valsartan produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1
receptor and may lower BP by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine
release, arginine vasopressin release, water intake, and hypertrophic responses.

Diuretics, Thiazide
Class Summary
Thiazide diuretics inhibit sodium and chloride reabsorption in the distal tubules of the kidney, resulting in
increased urinary excretion of sodium and water.
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Hydrochlorothiazide (Microzide)

Hydrochlorothiazide inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium
and water, as well as potassium and hydrogen ions.
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Chlorthalidone (Diuril)

Chlorthalidone inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium and
water, as well as potassium and hydrogen ions.

Diuretics, Osmotic Agents

Class Summary
Osmotic diuretics, such as mannitol, may be used to decrease intracranial pressure in the subarachnoid space.
As water diffuses from the subarachnoid space into the intravascular compartment, pressure in the
subarachnoid compartment may decrease.
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Mannitol (Osmitrol)

Mannitol reduces cerebral edema with the help of osmotic forces. It also decreases blood viscosity, resulting in
reflex vasoconstriction and lowering of intracranial pressure.

Analgesics, Other
Class Summary
Because hyperthermia may exacerbate neurologic injury, these agents may be given to reduce fever and
relieve pain.
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Acetaminophen (Tylenol, FeverAll, Aspirin Free Anacin)

Acetaminophen reduces fever, maintains normothermia, and reduces headache.

Hemostatics
Class Summary
Vitamin K is used to promote the formation of clotting factors. Phytonadione can overcome the competitive
block produced by warfarin and other related anticoagulants. A fresh frozen plasma (FFP) infusion followed by
oral vitamin K should be given without delay in the emergency department to manage warfarin-related
intracranial hemorrhage.
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Vitamin K1 (phytonadione; vitamin K, Mephyton, AquaMephyton)

Phytonadione can overcome the competitive block produced by warfarin and other related anticoagulants.
Vitamin K3 (menadione) is not effective for this purpose. There is a delay of the clinical effect for several hours
while liver synthesis of the clotting factors is initiated and plasma levels of clotting factors II, VII, IX, and X are
gradually restored.

Phytonadione should not be administered prophylactically and is used only if evidence of anticoagulation
exists. The required dose varies with the clinical situation, including the dose and duration of action of the
anticoagulant ingested. Intravenous phytonadione is recommended for life-threatening bleeding, including
intracerebral hemorrhage complicating warfarin therapy, although it carries a small risk of anaphylaxis.

Blood Components
Class Summary
These agents are indicated for the correction of abnormal hemostatic parameters.
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Fresh frozen plasma

Plasma, the fluid component of blood, contains the blood's soluble clotting factors. FFP is created by
separating plasma from a unit of blood and freezing it for use in patients with blood-product deficiencies.
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Platelets

Platelets are fragments of large bone marrow cells found in the blood that play a role in blood coagulation. A
single random donor unit of platelets per 10 kg is administered in adults when the platelet count drops below
50,000/L.
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Prothrombin complex concentrate (Bebulin VH, Profilnine SD)

Prothrombin complex concentrate (PCC) is a mixture of vitamin K-dependent clotting factors found in normal
plasma that replaces deficient clotting factors, provides an increase in plasma levels of factor IX, and can
temporarily correct a coagulation defect in patients with factor IX deficiency. PCC is usually reserved for
situations in which volume overload is a concern.

Antidotes, Other
Class Summary
Protamine is used to neutralize the effects of anticoagulants.
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Protamine

Protamine sulfate forms a salt with heparin and neutralizes its effects. The dosage administered is dependent
on the amount of time that has passed since heparin was given.

Vasopressin-Related
Class Summary
These agents improve bleeding time and hemostasis.
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Desmopressin acetate (DDAVP, Stimate)

Desmopressin releases von Willebrand protein from endothelial cells. It improves bleeding time and
hemostasis in patients with mild and moderate von Willebrand disease without abnormal molecular forms of
von Willebrand protein. It is effective in uremic bleeding. Tachyphylaxis usually develops after 48 hours, but the
drug can be effective again after several days.