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Intracerebral Hemorrhage: Pathophysiology, Diagnosis and Management
Intracerebral Hemorrhage: Pathophysiology, Diagnosis and Management
Clinical Review 15
CLINICAL REVIEW
ABSTRACT
Stroke is one of the leading causes of death globally and in Canada. There are two major classifications of
stroke: ischemic and hemorrhagic. Intracerebral hemorrhage (ICH) – a subtype of hemorrhagic stroke – is as-
sociated with substantial morbidity and mortality. The varied clinical presentation of ICH, ranging from minor
neurological deficits to fatal herniation syndromes arises from parenchymal damage, elevated intracranial
pressure and cardiopulmonary instability. Diagnosis is based on clinical presentation, laboratory investiga-
tions and imaging, which include computed tomography (CT), magnetic resonance imaging (MRI) and angi-
ography. Validated clinical scoring systems for stroke, such as the ICH and FUNC scores, allow for improved
prognosis assessment. Management is comprised of surgical, endovascular and medical interventions. Surgi-
cal clipping and endovascular coiling are used as a preventative measure for cerebral aneurysms, while the
current medical therapies attempt to limit the neurological sequelae following stroke by limiting the extent of
parenchymal involvement. Currently there are no proven therapies for brain protection, although this is cur-
rently a major target for research. Thus, stratification of hemorrhagic stroke based on clinical, laboratory and
imaging findings enables appropriate treatment and assessment of patients at risk of hematoma expansion
in order to prevent clinical deterioration and adverse sequelae.
S
INTRODUCTION EPIDEMIOLOGY
troke is one of the leading causes of death in Canada, The World Health Organization (WHO) estimates that 15
accounting for approximately 14,000 deaths annually1 million patients worldwide suffer from stroke annually. Ap-
and is a significant source of morbidity. Stroke can be proximately one third of these cases die, one third are left
classified into ischemic and hemorrhagic, with the former disabled and one third have a good outcome.3 High blood
representing the vast majority of cases (87%).2 In hemorrhag- pressure is a contributing factor in more than 12.7 million
ic stroke, bleeding can occur within the cerebral parenchyma strokes annually worldwide. 3 Incidence is greater among the
or within the meninges. Intracerebral hemorrhage (ICH) is elderly and those of African and Asian decent.4,5 The over-
defined as bleeding into the brain parenchyma. The current all incidence of new or recurrent hemorrhagic strokes in the
review excluded epidural hematoma, subdural hematoma United States is 795,000 people pear year. The majority of
and subarachnoid haemorrhage but includes intraventricular these are new strokes (approximately 610,000).6 In 2000,
hemorrhage. Prognoses of hemorrhagic strokes depend on stroke accounted for 7% of all deaths in Canada.7 Generally,
the initial clinical presentation, rapidity of diagnosis and time ICH accounts for ~10% of all strokes and is associated with
to initiation of intervention. This paper is a non-systematic a 50% case fatality rate.8 Since 1980, the incidence of hyper-
review of the current literature on intracranial hemorrhage tensive ICH has declined, reflecting improved blood-pressure
(ICH). An overview of the epidemiology, common risk fac- control in the population.9
tors, pathogenesis, clinical manifestations, diagnosis and
treatment approach to ICH are presented.
16 Clinical Review Volume 10 No. 1, 2013
PATHOGENESIS
ICH consists of three distinct phases: (1) initial hemor-
rhage, (2) hematoma expansion, and (3) peri-hematoma ede-
ma.19 The initial hemorrhage is caused by rupture of cerebral
arteries influenced by the aforementioned risk factors. The dis-
ease outcome depends primarily on the latter two phases of
progression. Hematoma expansion, occurring hours after ini-
tial symptom onset, involves an increase in intracranial pres-
sure (ICP) that disrupts the integrity of the local tissue and the
blood-brain barrier. Additionally, obstructed venous outflow
induces the release of tissue thromboplastin, resulting in local
coagulopathy2. In over a third of patients, hematoma expan-
sion is associated with hyperglycemia,20, 21,22 hypertension,23
and anticoagulation.24-26 The initial size of the hemorrhage
and the rate of hematoma expansion are important prognos-
tic variables in predicting neurologic deterioration. Hematoma
size >30 ml is associated with greatly increased mortality.27
Following the expansion, cerebral edema forms around the
hematoma, secondary to inflammation and disruption of the
Figure 1. Common locations of cerebral aneurysms are near
blood-brain barrier. This peri-hematoma edema is the primary
the anterior communicating and anterior cerebral arteries, etiology for neurological deterioration and develops over days
at the junctions near the middle cerebral artery and at the following the initial insult.
junction between the basilar and posterior cerebral artery.18 In up to 40% of ICH cases, the hemorrhage extends into
the cerebral ventricles causing intraventricular hemorrhage
(IVH).28 This is associated with acute obstructive hydro-
cephalus and substantially worsened prognosis.2,28 ICH and
accompanying edema may also disrupt or compress adjacent
MUMJ Clinical Review 17
Figure 2. Patient with spot sign demonstrating extravasation and hematoma expansion. A. Unenhanced CT demonstrates
left posterior putaminal and internal capsule hematoma with mild surrounding edema. B. A small focus of enhancement is
seen peripherally, consistent with the spot sign (black arrow). C. Post-contrast CT demonstrates enlargement of the spot sign,
consistent with extravasation (white arrow). D. Unenhanced CT image 1 day after presentation reveals hematoma enlargement
and intraventricular hemorrhage.39
MUMJ Clinical Review 19
with an ICH Score of 5 died within the 30 days.48 The limi- Table 4. The FUNC (Functional outcome risk stratification)
tation of the ICH score is that it is solely used to prognos- score assesses the patient for risk of functional impairment
ticate survival at 30 days without accounting for functional at 90 days post-stroke. The scores range from 0 to 11 based
on ICH volume, age, ICH location, GCS score, and pre-ICH
outcome. The ICH score should thus be used in combination
cognitive impairment. A greater score is associated with a
with the FUNC score to assess functional outcome. greater chance of functional independence, defined as GCS
>4, at 90 days. Limitations include lack of predictive value
for scores in the mid-range
Table 3. The ICH Score predicts 30-day mortality using
factors including GCS score, ICH volume, presence of Component Points
intraventricular hemorrhage (IVH), and age. The scale ranges ICH volume (cm3)
from 0 to 6 points. In the original study all patients with a <30 4
score of 0 survived and all patients with a score of 5 died 30-60 2
within 30 days. The limitation of the ICH score that is does >60 0
not account for functional outcome
Age (y)
Component Points <70 2
GCS score 70-79 1
3-4 2 >80 0
5-12 1 ICH location
13-15 0 Lobar 2
ICH volume (cm3) Deep 1
>30 1 Infratentorial 0
<30 0 GCS score
IVH ≥9 2
Yes 1 ≤8 0
No 0 Pre-ICH cognitive impairment
Infratentorial origin of ICH Absent 1
Yes 1 Present 0
No 0
Age (y)
>80 1 TREATMENT
<80 0 Surgical
Two surgical interventions are available for treating aneu-
rysms. The surgical approach entails placement of permanent
Another prognostic tool is the FUNC (Functional outcome alloy clips across the neck of the aneurysm through cranioto-
risk stratification) score. The patient is assessed for risk of my access. The patient is typically under general anesthesia.
functional impairment at 90 days post-stroke. The FUNC This prevents blood flow from reaching the aneurysm and
scores range from zero to eleven based on ICH volume, age, lowers the risk of rupture.14
site of ICH, GCS score and pre-ICH cognitive impairment49 The aneurysm can also be coiled through endovascular
(Table 4). A greater score is associated with a greater chance access while the patient is under general anesthesia or se-
of functional independence, defined as GCS ≥4 at 90 days.49 dation.14 Intra-procedural neurologic function is observed
According to Rost et al. (2008), no patient with a FUNC through neurophysiological monitoring. Using fluoroscopy
score ≤4 achieved functional independence and over 80% of and digital subtraction angiography, a catheter is advanced
those with a maximal FUNC score of 11 reached functional through the femoral artery, aorta, carotid artery and into the
independence at 90 days.49 The limitation, however, is that aneurysm. A sufficient number of detachable coils are then
only scores at the extreme ends seem to be clinically useful as positioned into the aneurysm to minimize the amount of
scores in the mid-range have little predictive value.49 blood filling the aneurysm.14,52-54 Systematic reviews have as-
Although these prognostic tool scores are important in the sociated the use of coils with lower rates of inpatient mortal-
hospital setting, the AHA recommends prompt and aggressive ity, shorter hospital stay and decreased treatment costs.14
full care upon ICH onset with postponement of new AND
(“Allow Natural Death”) orders until at least the second full Medical
day of hospitalization.50 This is because there is evidence that The patient’s vital signs must be immediately stabilized
a stated poor prognosis can lead to self-fulfilling prophecies according to ATLS guidelines.34 Patients with ICH are often
of early death.50 Withdrawal of care is the strongest predictor unable to protect their airway and may need endotracheal in-
of death after ICH44 and, thus, in the emergency setting new tubation (criteria for intubation, GCS <8). Rapid sequence
AND orders or withdrawal of care are not recommended.45 intubation is the preferred approach with administration of
20 Clinical Review Volume 10 No. 1, 2013
short-acting IV thiopental (1-5 mg/kg) or lidocaine (1 mg/kg) scope of this paper but is covered by the 2010 AHA/ASA
to prevent the increase in ICP that may result from tracheal guidelines.50
stimulation.34,37 A chest X-ray and an EKG must be ordered to Intracranial pressure (ICP) management relies on eleva-
assess cardiopulmonary function. tion of the head of the bed to 40 degrees to improve jugular
A CT scan must then be obtained to determine further venous outflow. More aggressive therapies, such as osmotic
management and to make a final diagnosis.34 With ICH there therapy (mannitol, hypertonic saline) require intracranial
is often a need to transfer a patient to an intensive care unit pressure and BP monitoring to maintain an adequate cerebral
for ICP monitoring and potential neurosurgical intervention. perfusion pressure greater than 70 mmHg.2,50 These are rou-
Physicians should determine whether the level of care re- tinely used during transfer of patients from peripheral cen-
quired exceeds the capacity of their facility and if their patient tres. Special attention should be given to the risk of iatrogenic
needs to be transferred to the nearest tertiary stroke centre.2 hypotension caused by rapid and aggressive hypertensive
Bleeding, seizures, blood pressure, and intracranial pressure therapy, which can induce cerebral ischemia.57 For seizure
must be monitored and actively controlled. A new AHA/ASA control, the 2010 AHA/ASA guidelines recommended that
guideline states that glucose should be monitored and normo- patients with seizures accompanied by change in mental sta-
glycemia is recommended (Class I: Level of Evidence: C).50 tus should be treated with a benzodiazepine for rapid seizure
Special attention should be given to the risk of iatrogenic control and Phenytoin for long-term management.50 Figure 3
hypoglycemia associated with increased risk of mortality.50 represents a flowchart for the approach to ICH identifying the
Antacids are administered to prevent associated gastric ul- various steps involved from presentation through diagnosis
cers. Fever must be controlled and thromboembolic prophy- to treatment.
laxis undertaken with compression stockings. Normothermia
is recommended as even mild hyperthermia can accentuate
the cellular damage in the area of ischemic penumbra post- Step 1
Patient must be assessed and stabilized if necessary according to ATLS
stroke. Following 1-2 days of treatment, heparin therapy can guidelines.
• Patients with a GCS score under 9 require endotracheal intubation.33
be considered for further thromboembolic prophylaxis when
no increased risk of recurrent hemorrhage is suspected.27
Step 2
Reversal of warfarin anticoagulation is undertaken to con- Clinical History – Questions should be asked about any recent trauma,
trol bleeding and ICH. This must be accomplished as quickly hypertension, prior strokes, diabetes, smoking, alcohol, over-the-counter,
prescription or recreational drugs (specifically cocaine, warfarin, aspirin,
as possible to stop further hematoma expansion. Agents for other anticoagulants), hematologic disorders, liver disease, neoplasm,
reversal therapy include intravenous vitamin K (VAK), fresh infections, or AVM.33
54. Michael T. Froehler. Endovascular Treatment of Ruptured Intracranial Aneurysms. 56. Boulis NM, Bobek MP, Schmaier A, et al. Use of factor ix complex in warfarin-
Curr Neurol Neurosci Re. 2013; 13: 326. related intracranial hemorrhage. Neurosurgery. 1999; 45: 1113–18.
55. Huttner HB, Schellinger PD, Hartmann M, et al. Hematoma growth and outcome 57. Martins SCO, deFreitas GR, Pontes-Neto OM et al. Guidelines for acute ischemic
in treated neurocritical care patients with intracerebral hemorrhage related to oral stroke treatment – Part II: Stroke treatment. Arq Neuropsiquiatr. 2012; 70(11): 885-
anticoagulant therapy: comparison of acute treatment strategies using vitamin K, 93.
fresh frozen plasma, and prothrombin complex concentrates. Stroke. Jun 2006;
37(6): 1465-70.
Author Biographies
Fabio Magistris graduated from the University of Western Ontario with a degree in Medical Sciences before attending
McMaster University. He is currently in his first year of the MD program.
Stephanie Bazak graduated from Acadia University with a Bachelor of Science in Psychology. She is currently in her
second year of medicine at McMaster University
Jason Martin completed three years of the Medical Sciences program at the University of Western Ontario before attending
McMaster University. He is currently in his second year of the MD program. He has an active interest in neuroradiology.