Intracerebral Hemorrhage
Kinan K. Hreib
Clinical Vignette
A 72-year-old woman with history of hypertension noticed
tingling in the right arm. Within 30 minutes, her right leg
buckled and she fell. Her husband helped her up and she
was able to walk without support. She rested, but within an
hour, she developed speech difficulties and more definite
right-sided weakness.
She was brought to the emergency department (ED) and
was noted to have mild right arm weakness and some word-
finding difficulties. Her blood pressure was 140/80 mm Hg.
She got up to go to the bathroom, walked approximately 10
ft, and collapsed on the floor. She was then globally aphasic,
with left gaze deviation (i.e., paralysis of gaze to the right)
and right hemiplegia. Within 10 minutes, she became grad-
ually unresponsive.
She was intubated for airway protection and taken for
brain CT scanning, which demonstrated a large left putam-
inal hemorrhage. Soon thereafter, she had bilaterally dilated
fixed pupils. The vestibular-ocular reflexes were lost. Within
another 10 minutes, she was determined brain dead.
T he preceding vignette demonstrates the classic presenta-
tion of a primary intracerebral hemorrhage (ICH with a
rapidly evolving focal neurologic deficit). Its progressively
increasing size led to increased intracranial pressure with coma
from downward herniation of the uncus onto the brainstem and
ultimately irreversible neurologic damage. The only means to
prevent ICH is appropriate therapy of its major risk factor,
hypertension.
There are two forms of intrinsic cerebral hemorrhage,
primary ICH, which has a predilection to affect the striatum,
thalamus, midbrain, pons, and cerebellum, and subarachnoid
hemorrhage (Chapter 57). ICH comprises approximately 10%
of all strokes in the Caucasian population and up to 20% in the
Asian population. Over the past several years, improved treat-
ment of hypertension has decreased the number of patients
experiencing ICH.
Hypertension is a major risk factor for intracerebral hemor-
rhages in patients between the ages of 40 and 70. A small pro-
portion of intracerebral hemorrhages in patients older than age
60 years is not directly related to hypertension and is primarily
caused by amyloid angiopathy. Furthermore, the increased use
of oral anticoagulant therapy in the elderly population has led
to higher rates of warfarin-associated ICH. Warfarin anticoagu-
lation increases the risk of intracerebral hemorrhage fivefold,
and some studies have estimated that 18% of intracerebral hem-
orrhages admitted to the hospital are related to its use. Of
interest is that most bleeds in patients on warfarin occur when
the INR is within the recommended therapeutic limits. Second-
ary, less common causes of intracerebral hemorrhages include
primary and metastatic tumors of the brain and in younger
58 
individuals cerebral hemorrhage associated with underlying
arterial venous malformation or cavernous angioma.
PATHOPHYSIOLOGY OF HYPERTENSISVE
PRIMARY ICH
Intracranial hemorrhage is a rapidly evolving process that may
progress over hours or days. The pressure effects of the initial
hemorrhage lead to mechanical disruption and tearing of
surrounding vessels with subsequent gradual expansion of the
hematoma out from the original center. Rebleeding is the most
feared early complication of ICH and occurs in approximately
40% of patients. Rebleeding usually occurs within the first 24
hours but, on occasion, has been reported up to a week later.
The underlying pathological mechanism of primary hyperten-
sive ICH is attributable to either the formation of miliary micro-
aneurysms or primary arteriolar degeneration (lipohyalinosis
and weakening of the blood vessel intima and media wall layers)
(Fig. 58-1). The presence of miliary aneurysms is directly related
to hypertension but is not necessarily the initial site of bleeding,
and cases of hypertensive ICH outside the areas of microaneu-
rysms have been noted. This suggests that degeneration of the
arteriolar smooth muscle wall is likely an important factor in the
evolution of ICH. Hypertensive intracerebral hemorrhages
have a predilection to occur in the basal ganglia and the thala-
mus. The arterioles in these structures are likely more vulner-
able to degenerative changes brought on by diffuse, large
pressure pulses over time.
Although hypertension is considered an important risk factor
for ICH, studies are inconsistent in estimating the exact risk of
ICH in hypertensive patients. It has been noted in some studies
that up to 90% of patients with ICH have evidence of hyperten-
sion at the time of presentation. Other important risk factors
include smoking, alcohol consumption, black race, and low total
serum cholesterol levels. The latter is likely to be an anomaly
of population studies. Patients with ICH and concomitantly low
serum cholesterol levels tend to be older than age 80 years and,
on average, have higher diastolic pressures. The effect of lower
cholesterol levels, particularly LDL, on increasing the incidence
of ICH is likely small and the mechanism remains unclear;
whether it is causative or an epiphenomenon of another process
warrants further investigation.
CLINICAL PRESENTATION
Intraparenchymal hemorrhages vary in presentation depending
on the site of the bleeding (Fig. 58-2). In approximately 60% of
patients, neurologic symptoms develop gradually or stepwise
over a period of hours. To some extent, the location and size of
the hematoma predict clinical outcome.
Headache occurs at presentation in approximately 40% of
patients with ICH. Less commonly, headache develops within a

B. Microaneurysm ruptures,
causing pressure on adjacent
(satellite) vessels.
A. Microaneurysm formed in parenchymal artery of brain as result
of hypertension. Lenticulostriate vessels (shown) most commonly
involved, but similar process may occur in other parts of brain,
especially lobar white matter, thalamus, pons, and cerebellum.
CT scan showing large
putaminal hemorrhage
Figure 58-1  Hypertensive Intracerebral Hemorrhage: Pathogenesis.
few days after the ictus. Intracerebral hemorrhages presenting
with headache are often located at the brain surface or within
the cerebellum. Depression in the level of consciousness and
vomiting occur in 50% of patients, particularly those with large
cerebellar bleeds. Seizures occur at onset in up to 10% and are
seen most commonly with lobar bleeds in the anterior circula-
tion. There are rare incidences of patients with deep hemor-
rhages having seizures. The subsequent risk for seizures in ICH
patients is up to 29% for those with lobar hemorrhages but only
4% for those with deep hemorrhages. Other symptoms seen in
association with ICH include low-grade fever without obvious
infection, cardiac arrhythmias, and dysautonomia, especially
with pontine bleeds. A description of some of the most common
symptoms at different sites of ICH follows.
Deep Supratentorial Hemorrhage
PUTAMINAL HEMORRHAGES
The most common site of ICH is the putamen, and these are
classified into anterior, middle, and posterior lesions. Anterior
putaminal hemorrhage often causes motor weakness due to
compression of the anterior limb of the internal capsule. If the
ICH is on the left, abulia and aphasia are common accompani-
ments. When the lesion occurs on the right, significant behav-
ioral changes can occur, including disinhibition, poor insight
CHAPTER 58  •  Intracerebral Hemorrhage  539
C. Satellite vessels D. Amount of blood extravasated into
rupture. brain tissue depends on tissue turgor
opposed to intravascular blood pressure.
Moderate-sized
intracerebral
hemorrhage involving
left putamen, with
rupture into lateral
ventricle; brain
distorted to opposite
side; scar of healed
hemorrhage on right
side
and judgment, and occasionally violent behavior. Caudate hem-
orrhages are associated with similar behavioral and cognitive
changes. Studies suggest that these behaviors result from frontal
lobe disconnection. Often, deficits from small anterior putam-
inal hemorrhages are reversible.
A hemorrhage within the midputamen, however, results in
severe deficits, often with poor recovery. In this case, ICH
compresses and undercuts nearby cortical structures, causing
global aphasia if involving the left hemisphere and severe neglect
if involving the right. With posterior putaminal hemorrhages, a
combination of sensory-motor deficits, visual field difficulties,
limb ataxia, and behavioral changes often results. Some putam-
inal hemorrhages not extending into the globus pallidus present
with short-lived hemichorea or hemiballismus, although a
variety of other abnormal involuntary movements have been
described. Large or medially located putaminal hemorrhages
and head of the caudate hemorrhages can dissect toward the
ventricle, with resultant intraventricular hemorrhage and the
development of acute obstructive hydrocephalus with rapid
deterioration due to increased intracranial pressure. Primary
intraventricular hemorrhage, in contrast, does not affect sur-
rounding brain tissue, and most cases present as a nonlocalizing
rapidly progressive syndrome of nausea, vomiting, stupor, and
seizure. In less acute cases, the patient presents with headaches,
confusion, and somnolence.
540  SECTION XII  •  Cerebrovascular Diseases

CT scan Pupils Eye Motor and Other

Pathology movements sensory deficits

Caudate Conjugate
nucleus Sometimes Contralateral
deviation to Headache,
(blood in ipsilaterally hemiparesis,
side of lesion; confusion
ventricle) constricted often transient
slight ptosis

Contralateral
Putamen Aphasia
Conjugate hemiparesis
(small Normal (if lesion
deviation to and
hemorrhage) on left
side of lesion hemisensory side)
loss

In presence Contralateral
Putamen of herniation, Conjugate hemiparesis Decreased
(large pupil dialated deviation to and conscious-
hemorrhage) on side of side of lesion hemisensory ness
lesion loss

Both lids Slight

Constricted, retracted; eyes contralateral Aphasia
poorly positioned
Thalamus hemiparesis, (if lesion
reactive downward but greater on
to light and medially; hemisensory left side)
bilaterally cannot look loss
upward

Occipital
lobar Normal Normal Mild, transient Contralateral
white hemiparesis hemianopsia
matter

No horizontal
Constricted, movements;
Pons reactive to vertical Quadriplegia Coma
light movements
preserved

Slight deviation to
Slight opposite side; Ipsilateral
constriction movements toward limb ataxia; Gait ataxia,
Cerebellum on side of side of lesion im- no vomiting
lesion paired, or sixth hemiparesis
cranial nerve palsy

Figure 58-2  Intracerebral Hemorrhage: Clinical Manifestations Related to Site.

THALAMIC HEMORRHAGES
Clinically, thalamic ICHs are classified into posterior–inferior,
posterior–lateral, and dorsal–medial. Somnolence is one of the
most common presentations of medial–posterior and inferior
thalamic bleeds and can be profound as a result of bilateral
disruption of the rostral reticular activating system. If the
hemorrhage dissects anteriorly, often persistent hypokinetic
behavior results from disconnection of the frontal lobe. With
inferior–lateral thalamic hemorrhage, there is weakness and
clumsiness and, occasionally, tremors and choreoathetoid move-
ments. Tremors are likely related to disruption of projections
from the cerebellum and dentate nucleus. Disruption of the
fibers of the ansa lenticularis are likely responsible for the cho-
reoathetoid movements.
More lateral thalamic hemorrhages involving the ventral
posteromedial and ventral posterolateral thalamic nuclei
primarily cause unilateral sensory symptoms but occasionally
motor involvement when the hemorrhage extends laterally to
involve the internal capsule. Eye movement abnormalities, small
pupils, ptosis, chorea, and dystonia also occur. Hematomas
involving the dorsal-medial thalamic area present with promi-
nent memory problems and behavioral changes thought to
relate to dissociated frontal cortex, cingulate gyrus, and amyg-
dalar connections. Speech and language deficits are the least
consistent symptoms of thalamic hemorrhages. Paraphasia,
naming difficulties, or a perceived inability to comprehend, with
preservation of repetition, is typical of thalamic aphasia. In
patients with right thalamic hemorrhage, deficits mimic cortical
lesions with neglect or hemi-inattention, vivid visual, and, less
often, auditory hallucinations can occur in the days following
thalamic ICH.

SUPERFICIAL LOBAR HEMORRHAGES
After the putamen, the most common site of primary ICH is
one of four locations in the cerebral cortex. The parietal and
occipital areas are most frequently involved. In general, hyper-
tension is an important risk factor for all ICH regardless of
location, but whether blood pressure plays a lesser role in the
contribution of lobar versus subcortical hemorrhages remains
inconclusive. Primary amyloid angiopathy frequently underlies
nonhypertensive intracerebral lobar hemorrhage. Other less
common causes include vascular malformations, primary and
metastatic malignancies, sympathomimetic drugs, anticoagu-
lants, irreversible antiplatelet and fibrinolytic agents, and sinus
thrombosis with venous infarctions and bleeds.
Lobar hemorrhages often present with headaches and vomit-
ing. Seizures at the onset of lobar hemorrhage are common,
particularly those within the posterior parietal or frontal lobe.
Functionally, patients with lobar hemorrhage may have better
outcomes than those with deep hemorrhages. However, prog-
nosis depends on hematoma size, level of consciousness at pre-
sentation, and presence of intraventricular blood. Mortality
rates range from 12 to 30% in superficial lobar hemorrhages
compared to 25–42% in deep basal ganglionic and thalamic
hemorrhages and up to 97% in pontine hemorrhages.
• Frontal hematomas. Intracranial hemorrhages in the supe-
rior aspect of the frontal lobe are usually small and cause
weakness in the contralateral leg. Inferior frontal hemor-
rhages are larger, causing a depressed level of conscious-
ness, hemiplegia, hemisensory deficits, and horizontal
gaze paresis. Language output can also be affected. Apathy
and abulia occur with superior mesial lesions and may be
prominent.
• Parietal hematomas. With right hemispheric hemorrhages,
often the most striking clinical presentation is a cortical
neglect syndrome, while left hemispheric hemorrhages
produce various degrees of aphasia. Extension into subcorti-
cal areas often occurs with weakness, and hemianopsia is
frequently seen. More medial hemorrhages result in down-
ward pressure on the upper brainstem and can cause obtunda-
tion or coma.
• Occipital hematomas. Although headaches are prominent
in many lobar hemorrhages, those occurring with occipital
hemorrhage are particularly severe. The most obvious
neurologic deficit is a homonymous hemianopsia but some
patients present with other visual changes, including flashes
of bright lights and palinopsia (afterimages). Other deficits
indicative of more anteriorly located hemorrhage include
visual extinction, dysgraphia, and dyslexia. Occipital hemato-
mas are the least likely to be related to hypertension.
• Temporal hematomas. Neurologic deficits in temporal
hematomas differ depending on the side involved. Fluent
aphasia, often associated with paraphasia and poor compre-
hension, is the most prominent deficit from isolated left
temporal lobe hemorrhage. In contrast, right temporal hem-
orrhages are often associated with relatively minor problems,
most commonly confusion. Other neurologic symptoms
depend on whether there is extension into the surrounding
subcortical areas or adjacent frontal lobe.
CHAPTER 58  •  Intracerebral Hemorrhage  541
Infratentorial Hemorrhages
CEREBELLAR HEMORRHAGE
Clinical Vignette
A 58-year-old woman with substantial history of arterial
hypertension presented to the ED with a 1-hour duration
of acute-onset headache, gait unsteadiness, and left arm
incoordination. On examination, the patient was alert and
oriented but had left-sided dysmetria, gait ataxia, and left
CN-VI and CN-VII palsies. Her BP was 200/110 mm Hg.
Urgent head CT showed a 3-cm cerebellar hemorrhage
with slight compression of the fourth ventricle. Antihyper-
tensive treatment aiming for a MAP of 100–120 mm Hg was
initiated.
Within 30 minutes after the CT scan, the patient’s level of
consciousness deteriorated, necessitating intubation. She
was brought immediately to the operating room for evacu-
ation of the hematoma and responded well. One month
later, her examination was remarkable for only mild clumsi-
ness of the left arm and a slightly wide-based gait.
As in the preceding vignette, patients with cerebellar hemor-
rhages can deteriorate rapidly, even “in front of one’s eyes,” but
can still respond exceptionally well with expeditious surgical
intervention. Most cerebellar hemorrhages are associated with
hypertension. However, approximately 10% of primary cerebel-
lar hemorrhages are caused by AVM, tumors, blood dyscrasias
and the use of warfarin anticoagulation. Headache, spinning
vertigo, nausea, vomiting, and, most commonly, unsteady gait
characterize the typical presentation. Some headaches are occip-
ital, but many involve the orbital and supraorbital areas. The
most reliable symptoms of a hemispheric cerebellar hemorrhage
include headache, vomiting, nystagmus, ipsilateral limb ataxia
with, at times, ipsilateral peripheral CN-VI and CN-VII palsies
and horizontal nystagmus.
The less common vermian hemorrhages often resemble a
pontine hemorrhage and can progress rapidly to coma, making
it difficult to identify specific early clinical signs that can dif-
ferentiate one from the other. Cranial nerve palsies are related
to involvement of adjacent pontine structures or stretching sec-
ondary to increased cerebellar pressure. In hypertensive bleeds
involving the vermis or the cerebellar hemispheres, the superior
cerebellar artery is most often involved.
Unlike supratentorial bleeds, in which a small hemorrhage is
often well tolerated, infratentorial ICH within the posterior
fossa often leads to rapid neurologic deterioration and death.
Close monitoring in an ICU for 36–48 hours, when the risk of
deterioration is at its highest, is therefore recommended for
most patients. Rebleeding, rupture into the fourth ventricle, and
accelerated hemorrhagic edema, alone or in combination, often
lead to a devastating outcome. Hemorrhages larger than 3 cm
may extend into the fourth ventricle and lead to the develop-
ment of acute hydrocephalus and require ventriculostomy place-
ment. The threshold for surgical evacuation of the hematoma
should be low and considered at the earliest sign of deteriora-
tion. The major goal is decompression of the posterior fossa to
prevent blockage of the fourth ventricle and compression of
542  SECTION XII  •  Cerebrovascular Diseases

the adjacent brainstem. Fortunately, if impending brainstem Box 58-1  Common Causes of
compression is recognized early, there are often only minimal Intracerebral Hemorrhage
residual deficits after surgery, even with extensive cerebellar
evacuation and decompression. The potentially positive recov- 1. Primary intracerebral hemorrhage
ery from cerebellar hemorrhages and decompressive surgery Hypertension
Idiopathic
reflects that the deep cerebellar nuclei, crucial for gait coordina-
2. Vascular malformations
tion and balance, are often spared from direct damage. Aneurysm
Arteriovenous malformation
Cavernous angioma
PONTINE/MIDBRAIN HEMORRHAGE
3. Embolic infarct
Pontine and midbrain hemorrhages are relatively uncommon 4. Anticoagulant therapy
but have the most devastating outcome compared with other
sites of primary intracranial hemorrhages. Three distinct vascu-
lar territories dictate the clinical presentation. The paramedian Box 58-2  Uncommon Causes of
penetrators, arising directly from the basilar trunk, are the Intracerebral Hemorrhage*
primary arteries supplying the midline pons or midbrain. ICH
in this location causes bilateral damage and is often fatal. Sudden 1. Endocarditis
onset of deep coma, quadriparesis, ophthalmoplegia, and bilat- 2. Venous sinus thrombosis
3. Malignancy: primary, metastatic
eral papillary abnormalities are the presenting signs.
4. Blood diathesis
Another group of small arteries, the short circumferential DIC, ITP, TTP
penetrators, courses laterally, supplying the lateral basis pontis, Leukemia
where a hemorrhage may predominantly cause unilateral bulbar Multiple myeloma
symptoms with profound dysphagia. The third important Sickle cell disease
group of vessels, the long circumferential arteries, arises from 5. Other hematologic disorders, particularly coagulopathies
Hemophilia
the anterior–inferior cerebellar artery and primarily supplies the
von Willebrand factor deficiency
lateral tegmentum. ICH within this segment leads to relatively Afibrinogenemia
minor symptoms, including facial numbness and ataxia second- 6. Vasculitis
ary to involvement of the spinal trigeminal and vestibular nuclei. Polyarteritis nodosa
However, involvement of the intrinsic pontine nuclei, such as Systemic lupus erythematosus
the cochlear and facial nuclei, are also affected, which leads to Wegener granulomatosis
a more serious outcome. Takayasu arteritis
Temporal arteritis
Pontine hemorrhages often have a relatively gradual clinical
Chemical vasculitis
presentation evolving over hours. Neurologic deficits, including Primary CNS vasculitis
horizontal gaze palsies, miotic sluggishly reactive pupils, quadri- Sympathomimetics (amphetamine, cocaine,
paresis, and coma, are the expected clinical signs. Certain unique phenylpropanolamine)
eye findings, including ocular bobbing and the one-and-a-half 7. Systemic disorders
syndrome, provide excellent diagnostic clues to pontine hemor- Sarcoidosis
rhages. Some patients also exhibit twitching of the limbs and Behçet syndrome
CNS infections, particularly herpes zoster
face and rippling of torso muscles. Dysautonomia with irregular
8. Trauma
pulse, erratic breathing patterns, and an increase in body tem-
perature have also been observed. Vivid, sometimes frightening, *DIC, disseminated intravascular coagulation; ITP, idiopathic
formed hallucinations, called peduncular hallucinosis, occur thrombocytopenic purpura; TTP, thrombotic thrombocytopenic
purpura.
relatively often in patients with involvement of the midbrain
tegmentum.
In most cases of ICH, especially when hypertension is absent,
follow-up imaging studies are essential to investigate the
SECONDARY INTRACEREBRAL
possibilities of underlying predisposing pathology. Contrast-
HEMORRHAGE enhanced brain MRI scanning performed about 3 months later,
ICH not directly caused by hypertension is encountered with after extravasated blood has been allowed to reabsorb, may
vascular malformations, hemorrhagic transformation of isch- uncover an underlying lesion initially obscured by the acute
emic stroke, anticoagulants, as well as fibrinolytic agents or hematoma.
irreversible antiplatelet therapy (Box 58-1). Primary amyloid Occult vascular malformations were possibly the most
angiopathy is often the underlying cause of nonhypertensive underdiagnosed causes of lobar hemorrhages prior to CT and
lobar hemorrhage. Less common causes include primary MRI scanning and were frequently missed by early angiography
and metastatic malignancies, sinus thrombosis with venous due to the presence of clot and mass effect on the brain. They
infarctions and bleeds, acquired or inherited coagulopathies, were diagnosed only during surgical or pathologic specimen
induced or autoimmune vasculitides and systemic granulo­ inspection after hematoma removal. The most common occult
matous disorders, central infectious processes, and trauma vascular lesions include small AVMs and cavernous angiomas
(Box 58-2). (Fig. 58-3A–D).
 CHAPTER 58  •  Intracerebral Hemorrhage  543

Thalamic Hemorrhage Secondary to AVM Box 58-3  Tumors Causing Intracerebral Hemorrhage*
A Primary CNS
Mixed glioma
B Epidermoid cyst
Pituitary adenoma
Oligodendroglioma
Ependymoma
Choroid plexus papilloma
Meningioma
Craniopharyngioma
Glioblastoma
Astrocytoma
CT with left thalamic Lateral view; vertebral angio- Metastatic
hemorrhage and blood in gram with thalamic AVM
ventricles. Melanoma
Kidney
Cavernous Hemangioma Lung
Breast
C D Osteogenic sarcoma
Ovary
Colon

*In order of frequency.

petechial bleeding develops in more than 50% of patients with

embolic infarcts. Although it is often implied that cardioembolic
strokes are more likely to be associated with development of
CT with small acute hemor- T2-weighted MR with variable
rhage in the left medial temporal intensity pattern and black halo
HBI, some investigators suggest that any large infarct, regard-
lobe close to the lateral ventricular (paramagnetic effect of iron, less of mechanism, is predisposed to such bleeding. The use of
horn (arrow). Fe3+) (arrow). IV heparin or heparinoid for secondary stroke prevention also
Hemorrhagic Transformation With Intravenous tPA Therapy. promotes the development of HBI. However, the presence of
petechial hemorrhage without frank hematoma formation does
E F not seem to worsen neurologic outcome.
Along with typical subarachnoid hemorrhage, aneurysmal
rupture can, at times, cause intraparenchymal hematoma with
focal neurologic signs (Fig. 58-4A&B). The location of the
blood often hints to the site of the aneurysm. Lateral temporal
lobe hematomas suggest MCA aneurysmal rupture while
medially located bleeds are associated with carotid artery
aneurysms. Frontal hematomas indicate anterior communicat-
ing artery aneurysm. Posterior communicating artery aneu-
rysms cause thalamic hemorrhages, often with intraventricular
extension.
Primary or metastatic brain tumors can lead to ICH (Box
Axial CT showing large right Comparable axial CT 11 days 58-3; Fig. 58-4C&D). A single small hemorrhage from a meta-
MCA territory infarction (hypo- post stroke and intravenous tPA
density) with moderate mass therapy showing multiple small
static lesion, as can be seen with melanomas or hypernephro-
effect. petechial hemorrhages (arrows). mas, may be difficult to distinguish from primary ICH unless
evidence of other lesions is identified. Other clues, such as an
Figure 58-3  Common Causes of Intracerebral Hemorrhage. atypical cortical or subcortical location of the bleed, irregular
margins, and unexpected contrast enhancement of the lesion
must prompt further investigations to exclude systemic disor-
Hemorrhagic brain infarct (HBI), in contrast to primary ders. A detailed dermatologic examination may reveal irregu-
intracranial hemorrhage, is a secondary phenomenon that larly pigmented lesions, suggesting melanoma, and ultrasound
occurs as a result of ischemic damage to both the brain paren- or body CT scan may uncover a renal tumor.
chyma and the vessel wall distal to the site of occlusion. The
vascular wall endothelium and the blood–brain barrier are sub-
sequently damaged and leak with reperfusion as they no longer Antithrombotic- and Anticoagulant-
tolerate normal arterial pressure. Petechial bleeding and, at Induced ICH
times, gross hemorrhage through the damaged vessel into the The question of whether aspirin promotes ICH remains unclear,
infracted area may be seen (Fig. 58-3E&F). It is estimated that but the Physicians’ Health Study, a randomized, double-blinded,
544  SECTION XII  •  Cerebrovascular Diseases
A. CT with blood in left sylvian fissure.
C. CT showing dense right frontal subcortical mass
with edema representing a hemorrhagic colon
cancer metastasis.
Figure 58-4  Uncommon Causes of Intracerebral Hemorrhage.
placebo-controlled trial looking at aspirin in cardiovascular
disease, suggested a trend toward increased risk. There were
2.1% hemorrhagic strokes in the treatment group and 1.1% in
the placebo group. This increase was not seen in many other
clinical trials testing the benefits of aspirin for the prevention of
stroke. Several trials using warfarin for stroke prevention in
patients with atrial fibrillation have demonstrated intracerebral
bleeding rates of 0.5–1.8 per year. The highest risk for bleeding
was seen in patients older than age 75 years. The combination
of warfarin and aspirin suggested similar rates of systemic bleed-
ing, approximately 2.4 per year, and no difference in rates of
ICH. The use of intravenous heparin in the setting of acute
stroke has not been systematically studied as to benefit or com-
plications. A few studies have suggested no risk of ICH whereas
others indicated a risk of approximately 2%, especially when
heparin is used in the setting of an acute stroke. The Interna-
tional Stroke Trial used subcutaneous heparin at 12,500 U twice
daily versus 5000 U twice daily or a combination of subcutane-
ous heparin and aspirin. At 14 days, the risk of ICH was 1.8%
for the high heparin dose and 0.7% for the low heparin dose.
Rates were similar when heparin was combined with aspirin.
Heparinoid formulations as well have shown a risk of ICH of
2.4% versus 0.8% for controls.
Amyloid Angiopathy
Amyloid angiopathy is an uncommon arteriolar and venular
vasculopathy with hyaline eosinophilic depositions and
B. Lateral left internal carotid angiogram with small
distal MCA aneurysm (arrowheads).
D. CT showing small left frontal hemorrhage in a
patient with leukemia and bleeding diathesis.
subsequent weakness of the vessel wall and microaneurysm for-
mation. It is the cause of ICH in 10% of patients age 60 years
or older and 20% in patients older than age 70 years. The usual
areas of ICH are lobar, both in the subcortical area and the
cortex, routinely sparing the basal ganglia, the thalamus, and the
brainstem. In the Dutch and Icelandic familial forms of amyloid
angiopathy, the mean age for ICH occurrence is as young as 30
years of age. In contrast to the nonfamilial form, ICH in the
familial forms of amyloid angiopathy may also affect the brain-
stem and the cerebellum along with the more typical cortical
and subcortical loci.
MRI evidence of previous asymptomatic small hemorrhages
is encountered in many patients (Fig. 58-5). However, cases of
rapidly successive, small intracranial hemorrhages within a short
time period with progressive disability and death have been
described. The presence of subcortical white matter disease seen
on CT or MRI scans may be a reflection of chronic ischemia
from amyloid-laden arterioles. These changes may suggest a
higher risk for future hemorrhages and therefore a more
cautionary approach to anticoagulation or the potential use of
thrombolytic agents is advised.
Endocarditis
The true incidence of endocarditis is unknown. Rheumatic
heart disease was formerly the primary cause of bacterial endo-
carditis, with the most common agent being Streptococcus viri-
dans. More virulent forms of endocarditis have emerged as the
use of intravenous drugs has increased. Furthermore, the use of

A. CT with moderate-sized left frontal hema- B. GRE MRI shows high-intensity lesion with a C. GRE MRI showing multiple small paramag-
toma with edema. hypointense rim representing blood products.
Figure 58-5  Amyloid Angiopathy.
implanted long-term catheters or other similar devices, particu-
larly in hemodialysis or immunocompromised patients, has
increased the risk of infection. Native valve acute endocarditis
usually has an aggressive course, with Staphylococcus aureus and
group B streptococci the typical organisms. Underlying struc-
tural valve disease need not be present.
Subacute endocarditis due to alpha-hemolytic streptococci or
enterococci usually occurs in the setting of structural valve
disease and has a more indolent course. Staph. aureus and fungal
infections are surpassing streptococcal bacteria as causes for
valvular infection. Mitral and aortic valves are especially vulner-
able. The mitral valve is more consistently associated with neu-
rologic complications than is the aortic valve. In one study, more
than 28% of those with bacterial endocarditis had neurologic
complications. Mortality was 77% with staphylococcal infec-
tions and 36% with streptococcal infections. Cerebral infarc­
tions occurred in up to 50% of patients, ICH occurred in 2.1%,
and subarachnoid hemorrhage in 0.8%.
Bacterial mycotic aneurysms are often small and located
peripherally, unlike berry and fungal mycotic aneurysms found
at the bifurcations in the circle of Willis. Corresponding ICH
is therefore typically located superficially in the more distal part
of the vessels. However, the more peripheral locations are not
necessarily less devastating than the more typical deeper hemor-
rhages. The presumed hemorrhage mechanism is pyogenic arte-
ritis resulting in blood vessel wall erosion and rupture or rupture
of mycotic aneurysm (present in only 12% of patients). Patients
receiving anticoagulation as treatment of a presumed ischemic
stroke were more likely to suffer hemorrhages. ICH occurred
in 24% of patients receiving anticoagulation in the setting of
ischemic infarcts or TIAs caused by endocarditis. Repeated
blood culture and transesophageal echocardiography are the
cornerstones of diagnosis in endocarditis and, if both are posi-
tive, have a sensitivity higher than 90%.
Varied clinical profiles of TIA, stroke, and subarachnoid
hemorrhage typify the presentation of an atrial myxoma. There-
fore, a cardiac embolic evaluation, including transesophageal
echocardiography and electrocardiography, are needed.
CHAPTER 58  •  Intracerebral Hemorrhage  545
netic lesions consistent with multiple small
previous hemorrhages (arrows).
Vasculitis
Although systemic necrotizing vasculitides, usually associated
with peripheral complication such as mononeuritis multiplex,
are rarely the cause of cerebral infarction or hemorrhage,
primary CNS angiitis is commonly associated with both. The
disease course is subacute and presents with mental status
changes, headaches, focal deficits, and seizures. Systemic lupus
erythematosus is another disorder with a variable degree of
CNS involvement. Autopsy series, however, suggest a high fre-
quency of subarachnoid hemorrhage and, to a lesser extent,
intracerebral and subdural hemorrhages.
Moyamoya
Moyamoya is a rare primary angiopathy of unknown etiology
associated with cerebral vascular occlusive disease due to fibro-
cellular thickening of the intima and thinning of the media. The
carotid siphons and the proximal middle cerebral arteries are
typically involved with numerous small vessels developing
around the site of occlusion, usually at the base of the circle of
Willis. Two forms of Moyamoya exist, the familial and athero-
sclerotic form. The familial form is most commonly seen in
Japan and affects children aged around 10 years. These children
often experience recurring bouts of hemiplegia or aphasia. Some
symptoms may stutter or progress over a few weeks. The ath-
erosclerotic form occurs in older patients, who may present with
recurring TIAs or ICHs. Early in the disease, symptoms may
be difficult to interpret, and MRI findings are often unspecific.
Careful observation for flow voids within the major vessels may
demonstrate abnormalities that can prompt further investiga-
tion with angiography. ICH occurs mostly in the older-patient
form because of small friable vessels sprouting within the basal
ganglia.
Arteriovenous Malformation
Prevalence of arteriovenous malformation (AVM) is unknown,
but estimates range from 1 to 2 per 100,000 individuals. Luckily
546  SECTION XII  •  Cerebrovascular Diseases
only 10% become symptomatic from bleeding. Patients often
present with headaches, TIA-like spells and seizures. The risk
of bleeding from an AVM is estimated at 3% per year. However,
the risk of rebleeding in the first year is as high as 30%. AVM
with associated aneurysmal lesions, poorly developed venous
drainage, and location near the ventricles hold a higher risk for
bleeding. Management of symptomatic AVMs includes surgical
decompression and removal of the AVM, if it is accessible.
Other interventions include a combination of catheter-based
intervention plus surgery. Small vascular malformations may be
treated with focused radiation, although the latter approach may
take years to obliterate the malformation. Brain swelling and
hemorrhage may complicate treatment because of altered flow
dynamics. Some experts advocated treatment of the malforma-
tion in stages to allow the brain and the malformation to adjust
gradually to changes in blood flow.
Cerebral Cavernous Angioma
This vascular malformation is either inherited or sporadic.
Single lesions are seen in the sporadic form whereas the inher-
ited form often presents with multiple lesions. In the familial
form of the disease, three genes have been identified, CCM1/
KR1T1, CCM2/MGC4607, and CCM3/PDCD10. Large clusters
of family members with cavernous angioma have been identified
in Hispanic-American families. Often this condition presents
with TIA-like spells, seizures, or headaches. Lesions that are
diagnosed on MRI are frequently shown to have bled in the past.
When bleeding from cavernous angioma is significant, the
morphologic features of the lesion may be obscured, making
diagnosis acutely difficult. Repeat imaging studies, once there is
some resolution of the hematoma, may ultimately help reveal
the lesion.
MANAGEMENT AND PROGNOSIS
Many ICH patients initially presenting with a modest neuro-
logic deficit may rapidly worsen during the first 24 hours. Serial
CT scans demonstrate that ICH can recur or worsen even up
to 7 days after the ictus. As in the first vignette of this chapter,
recurrent or progressive ICH is often rapid and fatal, particu-
larly if the hemorrhage extends to the ventricular system and
produces acute hydrocephalus. Sudden volume increase, and
mass effect from enlarging ICH compromises the surrounding
microvasculature and leads to both mechanical and ischemic
tissue damage to the surrounding brain structures. Tissue shifts
compounded by evolving vasogenic cerebral edema over 24
hours may lead to transtentorial herniation. Excessive increases
in blood pressure, concomitant infection, fever, hyperglycemia
or hypoglycemia, and other medical conditions all worsen
outcome. The initial management of ICH, after ensuring
adequate ventilation and hemodynamic stability, involves
correcting coagulopathies, treating hypertension, and address-
ing the possibility of increased intracranial pressure. In patients
with intraventricular blood and early hydrocephalus, placement
of a temporary external drain should be considered. Beyond
these basics principles, the best treatment of ICH remains
unclear and quite variable from center to center and in different
countries. Although some advocate invasive techniques for
hematoma evacuation, others rely mostly on medical treatment
and supportive care.
At present, there are no strict recommendations for blood
pressure control in the setting of primary hypertensive ICH.
There is evidence to indicate that elevated BP greater than
210 mm Hg is associated with recurrent or expanding ICH but
lower BP measurement may not be. Indeed, far too aggressive
lowering of BP may lead to a potential drop in cerebral perfu-
sion pressure (CPP), especially in the presence of elevated ICP,
and cause secondary ischemia with worsening outcomes. The
present guidelines set by the American Heart Association/
American Stroke Association council suggest definite treatment
of SBP above 210 mm Hg or of MAP of 150 mm Hg with a
continuous infusion of a titratable IV medication such as nica-
rdipine, a beta-blocker, or nitroprusside if needed. For measure-
ments below this level but above 180 mm Hg systolic or MAP
of 130 mm Hg and in the presence of suspected ICP, a decrease
of BP to keep the CPP above 60 mm Hg is recommended. If
ICP is not present, careful monitoring with an attempt to avoid
hypertensive episodes is suggested. It is often useful to obtain
patients’ prior BP measurements from outpatient records or
from primary care providers if available. This may help guide
blood pressure control by providing a sense of where each
individual patient’s BP range of cerebral autoregulation was
before the ICH.
Surgical Trial in Intracerebral Hemorrhage (STICH, 2005)
was a multicenter international prospective randomized trial to
compare early surgery with initial conservative treatment for
patients with spontaneous supratentorial intracerebral hemor-
rhage. In this study, no overall benefit from early surgery when
compared to conservative treatment could be demonstrated.
Surgery demonstrated slightly better outcome (26.1% vs.
23.8%), but survival rates appeared to be similar in surgically
and medically treated patients. Subgroup analysis suggested that
large hemorrhages, older age, and blood in the ventricles pre-
dicted poor outcome. Also the subgroup with superficial bleeds
and no intraventricular hemorrhage tended to fare better with
surgery than with medical treatment alone (49% vs. 37%). The
outcome from surgery likely depends on several factors, includ-
ing the fact that deep-seated basal ganglia or thalamic hemor-
rhages are difficult to evacuate without disrupting surrounding
normal structures and exacerbating brain damage, especially
with open craniotomy. A trial to evaluate the role of early
surgery in superficial supratentorial lobar hematomas without
intraventricular hemorrhage is ongoing. However, when a non-
dominant hemispheric or cerebellar ICH threatens impending
herniation and before the patient’s level of consciousness signi­
ficantly deteriorates, emergent surgery may be lifesaving and
may provide a reasonably good recovery, especially in younger
patients.
Patients who have small hematomas (smaller than 30 cm3)
seem to do generally well without surgical evacuation. However,
larger hematomas (larger than 60 cm3) do poorly, even when
evacuated surgically. Hematomas between 30 and 40 cm3 may
do best after surgical evacuation. There is no evidence that
minimally invasive surgery (microsurgery or endoscopy) hold
any advantage over open craniotomy, and the advantage of these
technique is yet to be determined. A few neurosurgical studies
have investigated the benefits of evacuating deep hematomas

using a continuous infusion of thrombolytic agents and suction
method. Thrombolytic agents such as tissue plasminogen acti-
vator have been infused into the hematoma. Although they
produce more rapid hematoma resolution, the long-term
clinical outcome seems unchanged. Generally, the therapeutic
approach must be individualized.
Rebleeding and hematoma expansion is a common cause of
acute deterioration and holds up to a 70% risk of death or
unfavorable outcome. Prevention of hemorrhage progression,
therefore, has become a central theme in the acute treatment of
primary ICH. To that end, pro-coagulants, such as activated
Factor VII, have been tested in patients with intracerebral hem-
orrhage (Factor Seven for Acute Hemorrhagic Stroke [FAST]).
Activated Factor VII initiates the clotting cascade by binding
to the surface of platelets and generating aX, which, in turn,
induces surface thrombin formation. This reaction is specific to
the site of bleeding as Factor VII works in the presence of tissue
factor released at the site of injured tissue. A safety study in 2005
demonstrated that patients treated within 3 hours of presenta-
tion with activated Factor VII had the hematoma increase only
by 11–16% compared to a 29% increase in the placebo group.
Mortality in this Phase II trial decreased from 29 to 18%. Clot-
ting events such as myocardial infarctions, deep venous throm-
bosis, pulmonary emboli, and ischemic strokes increased from
2% to 7%. A Phase III trial demonstrated that Factor VIIa did
indeed decrease ICH volume, but failed to show a clinical effect
with mortality and severe disability rates found comparable in
the treatment groups and the placebo group. It was postulated
that age might have played a role in diluting out the result and
that relatively healthy individuals below the age of 70 years may
be the ideal patients to respond to such treatments. At this time,
however, no pharmacological treatment is available to limit the
expansion of the spontaneous intracerebral hemorrhage in the
absence of a coagulopathy.
Expansion of the hematoma or rebleeding in patients
taking warfarin is another difficult management issue. Obvi-
ously, reversing the effects of warfarin is the first step in trying
to limit bleeding. The administration of vitamin K and fresh-
frozen plasma is often given acutely, but the benefits are not
realized for another 24 hours. Some have advocated the use of
prothrombin complex concentrate a (conglomerate of high
levels of vitamin K–dependent factors) or activated Factor VII
to help reverse the effects of warfarin. However, as mentioned
previously, there is a significantly increased risk of thromboem-
bolic events, and there are no studies at this time to help guide
such treatment.
SUMMARY
The overall mortality of patients with ICH is approximately
50% with lobar and basal ganglionic bleeds and up to 75% when
involving the brainstem. Of those who survive, only half will
achieve independent living. Initial presentation is predictive of
outcome. Individuals who present with coma and signs of
CHAPTER 58  •  Intracerebral Hemorrhage  547
herniation have poor prognoses. Rapid increase in intracranial
pressure with concurrent brainstem Duret hemorrhages leads
to irreversible reticular activating system damage and coma.
Patients in whom intraventricular blood leads to hydrocephalus
do not fare well either, with 90% suffering poor outcomes or
death.
The size of the initial hematoma, as defined by CT, is also
predictive. There is a mortality rate of approximately 50–75%
in patients with more than 40 mL of blood on CT at presenta-
tion. If the patient survives the bleed, the ultimate neurologic
recovery depends on the hemorrhage location and residual
deficits.
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