INTRACEREBRAL HEMORRHAGE

INTRACEREBRAL HEMORRHAGE

Current Diagnosis

• Obtain a thorough history, including time of symptom onset

• Imaging of the cerebral vessels should be performed in all patients younger than 55 years and should be strongly considered in all patients in whom underlying aneurysm or arteriovenous malformation is suspected.

• Obtain contrast-enhanced neuroimaging if underlying cerebral mass or tumor is suspected.

Current Therapy

• Maintain airway, breathing, and circulation; stabilize the neck if fracture is considered.

•   Detect and emergently correct coagulopathy.

• Arrange an emergent neurosurgical consultation for cerebellar hemorrhage.

Epidemiology

Intracerebral hemorrhage (ICH) is most often the acute manifestation of a chronic, progressive disorder of the blood vessels of the brain.

With an estimated incidence rate of between 35 and 45 cases per 100,000 population in Europe and North America, ICH generally accounts for between 10% and 15% of acute strokes on those continents. The incidence is higher in East Asia, with estimates that ICH accounts for as many as 30% to 40% of acute stroke cases in those countries. Hospital-based series consistently reveal an acute mortality from ICH ranging between 35% and 65% and substantial permanent disability in at least 50% of survivors. Because mortality figures are all confounded by the fact that withdrawal of aggressive care by clinicians and families is a very common precipitant of death in these patients and often occurs in patients whose ICH is survivable, it is more useful to focus on rates of disability among survivors when discussing prognosis (see later).

Risk Factors

Risk factors for primary ICH include chronic conditions, chronic exposures, and acute physiologic derangements. Secondary ICH refers to hemorrhage that develops in the setting of vascular malformations, including saccular aneurysms, brain tumor, cerebral venous thrombosis, or hemorrhagic conversion of an ischemic infarct. Among patients older than 55 years, who account for the majority of cases, chronic hypertension, cerebral amyloid angiopathy, and chronic use of antithrombotic medication are the leading risk factors for primary ICH. History of a prior stroke, chronic alcohol use, and family history of ICH also contribute, and patients with severe coagulopathy, cocaine abuse, and liver disease are also at higher risk for ICH.

Accumulating data suggest that aggressive lowering of serum cholesterol or chronic use of statin therapy can increase risk for ICH in the elderly. Although chronic hypertension has long been identified as contributing to the largest proportion of ICH cases, recent population- based studies demonstrate a substantial fall in hypertension- associated ICH. In parallel, however, the aging of the population has led to the broader use of antithrombotic medications as well as increases in the prevalence of amyloid angiopathy. The result is that ICH incidence rates have not fallen.

Pathophysiology

ICH arises when a blood vessel within the brain ruptures and blood leaks out to form a hematoma. Because the skull is fixed in volume and is completely filled by brain, blood, and CSF, any accumulation of blood within the brain must necessarily compress, distort, and disrupt surrounding brain structures. The result is that the damage caused by ICH is due the mass effect of the hematoma as well as the toxic effects of the blood itself. The volume of blood that leaks out is thus the most potent predictor of outcome from ICH. In addition, extravasated blood can enter the CSF drainage system, leading to hydrocephalus, another predictor of poor outcome.

Bleeding in ICH often occurs over hours, a phenomenon that can be documented with serial head computed tomography (CT) scans. The volume of ICH can be compared between a CT scan obtained at the time of presentation to the emergency department and one obtained several hours later. The shorter the time interval between symptom onset and presentation to the emergency department, the more likely the patient is to have ongoing bleeding and hematoma expansion after the initial CT scan.

Location of the ICH within the brain can be a clue to the underlying vessel abnormality responsible for the rupture. Among patients 55 years and older, hemorrhage in lobar locations, the junction of the cortical gray matter and underlying white matter, are most commonly a manifestation of underlying cerebral amyloid angiopathy, although other underlying conditions such as chronic hypertension and an underlying vascular malformation may instead be responsible. By contrast, hemorrhages centered in the deep gray structures of the basal ganglia, thalamus, and the brain stem arise most often as a complication of chronic hypertension, with amyloid angiopathy playing no role. Hemorrhages in the cerebellum can arise from any of these conditions.

ICH in the setting of chronic antithrombotic therapy is increasing in incidence as use of anticoagulants becomes increasingly widespread.

Although it is likely that excessive doses of antithrombotic medication (e.g., supratherapeutic prothrombin times in patients receiving warfarin [Coumadin]) can cause ICH in the absence of an underlying chronic disorder of the blood vessels of the brain, the majority of ICH cases in patients receiving antithrombotic medication occur in the absence of an overdose. This suggests that the majority of cases of antithrombotic-associated ICH arise in patients with an underlying disorder of the cerebral vessels such as cerebral amyloid angiopathy or hypertensive vasculopathy.

Recurrent ICH is common among survivors of ICH. In particular, patients 55 years and older who survive a lobar hemorrhage have a risk of recurrent lobar ICH in the range of 10% per year. The explanation for this is likely the inexorable progression of the underlying blood vessel disease, amyloid angiopathy. On the other hand, whereas survivors of ICH in the nonlobar regions are also at high risk for recurrent ICH, adequate control of hypertension following the initial ICH appears to substantially reduce that risk, suggesting that hypertension-related disease of the cerebral blood vessels can be arrested.

Prevention

Adequate control of chronic hypertension reduces the incidence of ICH in addition to reducing the incidence of a broad range of cardiovascular and other conditions. Although no specific therapies are shown to be effective in preventing ICH in patients with cerebral amyloid angiopathy, recognition of this condition might become useful in selecting patients for long-term antithrombotic use. Chronic statin therapy can increase risk of ICH, but more studies are required to inform the decision to withhold statins from patients at high risk for ICH.

Clinical Manifestations

Symptomatic ICH manifests with an acute stroke syndrome such as the sudden development of impaired consciousness, language difficulty, disorientation, or weakness. Nausea and vomiting can be prominent, particularly in patients with cerebellar hemorrhages as well as those who rapidly develop substantial mass effect or hydrocephalus. Headache and seizure at the onset of symptoms are more common in ICH than in ischemic stroke.

Small asymptomatic ICH occurs in the setting of diseases like chronic hypertension and cerebral amyloid angiopathy. These hemorrhages, usually only detectable on magnetic resonance imaging (MRI) of the brain that includes susceptibility-weighted sequences sensitive to the permanent hemosiderin deposits left by all hemorrhages, are increasingly recognized as contributing to age- related deterioration in cognition and memory, as well as gait.

Diagnosis

ICH is a medical emergency. Rapid diagnosis and urgent critical care management (airway, breathing, circulation) are essential, particularly because ICH patients can deteriorate rapidly within hours of presentation. Noncontrast CT scan of the brain is the gold standard for confirming acute ICH, and all patients with suspected acute stroke or ICH should undergo an emergent noncontrast CT scan. In centers where emergent MRI is available, it can be substituted for noncontrast CT only if susceptibility-weighted sequences are performed.

Angiographic imaging in the form of traditional catheter-based angiography or CT angiography should be performed in any patient younger than 55 years or in patients in whom underlying vascular malformation or ruptured saccular aneurysm is suspected. The history and laboratory evaluation, summarized in Box 1, should be focused on identifying possible contributing causes as well as targets for treatment.

Box 1
Focused Evaluation of Intracerebral Hemorrhage
Assess airway, breathing, circulation

History

Time of symptom onset (or when last seen well)

Recent trauma or surgery

Headache

Seizures

Alcohol or drug abuse

History of hypertension

Prior stroke

Liverdisease

Cancer

Coagulopathy

Medications, including antithrombotics

Physical Examination

General physical examination

Glasgow Coma Scale

NIH stroke scale

Neuroimaging

Computed tomography, magnetic resonance imaging

CT angiography for patients younger than 55 years or in whom an underlying vascular lesion is suspected

Venography if venous sinus thrombosis is suspected Cervical spine imaging if trauma is suspected

Laboratory

Electrolytes

Complete blood count

Coagulation panel

Toxicology screen

Electrocardiogram

Abbreviation: NIH = National Institutes of Health.

Differential Diagnosis

Emergent neuroimaging can confirm the presence of ICH (Box 2). For patients in whom the history is not obtainable, or who have associated trauma, it is sometimes difficult to distinguish traumatic from nontraumatic ICH. It is therefore essential to examine head imaging for skull fractures and the presence of subdural or subarachnoid hemorrhage, which might be traumatic in origin.

Box 2
Differential Diagnosis of Intracerebral Hemorrhage
Primary Intracerebral Hemorrhage

Cerebral small-vessel disease

Cerebral amyloid angiopathy

Hypertensive vasculopathy

Secondary Intracerebral Hemorrhage

Vascular malformations

Cerebral venous thrombosis

Hemorrhagic conversion of an ischemic infarct

Moya moya disease

Cerebral vasculitis

Bacterial endocarditis

Brain tumor

Trauma

Treatment

After the focused evaluation (see Box 1) is completed, emergency care is devoted to preventing neurologic deterioration (Box 3). Blood pressure elevation is common in ICH; clinical trials suggest that reducing systolic blood pressure below 140 is safe, but does not clearly improve outcomes. Most clinicians lower systolic blood pressure below 160.

Box 3
Targeted Therapy to Prevent Deterioration in Acute Intracerebral Hemorrhage
Neck stabilization in any patient at risk for cervical spine injury Anticoagulant-associated ICH: Correct prothrombin time as rapidly as possible using intravenous vitamin K and prothrombin complex concentrate; dabigatran (Pradaxa) can be reversed with idarucizumab (Proxbind). Some clinicians use prothrombin complex concentrate to reverse Factor Xa inhibitors.

Severe thrombocytopenia or coagulation factor deficiency: Platelet and/or factor replacement. Platelet transfusion should not be given simply to treat those taking oral antiplatelet agents, as it worsens outcomes.

Blood pressure: Reduce systolic BP to 180 mm Hg for patients whose systolic BP is >220 mm Hg.

Avoid hypoglycemia.

Maintain euthermia.

Anticonvulsant medication: Only in patients who have had a seizure.

External ventricular drainage catheters: Consider for any patient with hydrocephalus or intraventricular hemorrhage.

Emergent surgical clot removal: Indicated for cerebellar hemorrhage with brain stem compression or neurologic deterioration.

Prevention of deep venous thrombosis: Intermittent pneumatic compression device and elastic stockings. Low-dose heparin should be started once serial CT scans confirm that bleeding has stopped and there is no longer any ICH expansion occurring.

Rehabilitation: Multidisciplinary rehabilitation should be offered to all ICH patients.

Abbreviations: BP = blood pressure; CT = computed tomography; ICH = intracerebral hemorrhage.

Because ICH is a devastating condition that most commonly affects the elderly, physicians and families are often confronted with the question of whether their patient or loved one would choose to survive the event. Accurate prediction of prognosis is essential to guide such decision-making. In this context, tools that predict mortality are of limited utility, as they do not give any guidance on the likelihood of functional recovery among survivors. The FUNC score (Table 1) enables prediction of the likelihood of recovering functional independence for patients with primary ICH. Tools such as the FUNC score calculator (http://www.massgeneral.org/stopstroke/funcCalculator.aspx) can be useful in guiding decisions about aggressiveness of care, but their precision remains to be proved. Clinicians are therefore advised to provide care according to the principles outlined in this chapter for all patients at the outset, and to proceed to limitation of aggressive care no sooner than 48 hours after admission to an intensive care unit.

Table 1

FUNC Score

Abbreviation: ICH = intracerebral  hemorrhage.

Monitoring

Initial monitoring of the ICH patient is best provided by an intensive care unit with neurointensive care specialists available. Because subclinical seizures are common in ICH patients, EEG monitoring should be considered in any patient who has had a seizure or whose level of consciousness is altered. Invasive monitoring of intracranial pressure should be considered in patients with evidence of shift of the intracranial contents on neuroimaging.

Complications

Prevention of ICH, particularly recurrent ICH, is increasingly recognized as a priority in making decisions about whether or not to offer chronic anticoagulation to elderly patients with atrial fibrillation, prosthetic heart valves, and other conditions accompanied by high risk of thromboembolic ischemic stroke. Given the established benefit of antithrombotic therapy for preventing ischemic stroke, decision- analysis models suggest that only patients at very high risk for ICH might benefit from antiplatelet therapy rather than anticoagulation, or even neither therapy. Factors that must be considered include the patient’s presumed risk for ICH, risk for thrombembolic stroke, expected outcomes from each should they occur, and the patient’s preferences.

References

1.     Becker K.J., Baxter A.B., Cohen W.A., et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology. 2001;56:766–772.

2.    Eckman M.H., Rosand J., Knudsen K.A., et al. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003;34:1710–1716.

3.     Eckman M.H., Wong L.K., Soo Y.O., et al. Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: How will screening with genetics and imaging help? Stroke. 2008;39:3308–3315.

4.    Kothari R.U., Brott T., Broderick J.P., et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke. 1996;27:1304–1305.

5.     Hemphill, et al. Guidelines for the management of spontaneous intracerebral hemorrhage. Stroke. 2015.

6.      Rost N.S., Smith E.E., Chang Y., et al. Prediction of functional outcome in patients with primary intracerebral hemorrhage: The FUNC score. Stroke. 2008;39:2304–2309.

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