Hypertensive intracerebral hemorrhage …

Adrian Marchidann MD

Stroke & Vascular Disorders

Updated 06.05.2024
Released 07.16.1996
Expires For CME 06.05.2027

Hypertensive intracerebral hemorrhage

Author: Adrian Marchidann MD

See Contributor Disclosures

Editor: Steven R Levine MD

Hypertensive intracerebral hemorrhage

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Introduction

Overview

The author provides an update on the progress in imaging modalities utilized in patients with intracerebral hemorrhage. New prognosis scores are introduced, and the impact of an early do-not-resuscitate order is discussed. In addition, the latest clinical trials on blood pressure and intracranial pressure management are reviewed.

Key points

	• An increase in hematoma size that is associated with poor outcomes may be predicted by head CT.
	• Smooth and sustained control of blood pressure may improve functional outcomes.
	• Coagulopathy associated with intracerebral hemorrhage increases the mortality rate and should be urgently corrected.
	• Continuous hyperosmolar therapy, platelet transfusion without a clear indication, or antiepileptic medications in the absence of seizures are not beneficial.
	• Minimally invasive surgery for supratentorial hemorrhage may reduce mortality but not functional outcomes.
	• Surgical cerebellar hematoma evacuation is indicated if the volume is greater than 15 ml, in neurologic deterioration, brainstem compression, and hydrocephalus.
	• Patient mobilization should be considered after 24 hours from onset, but not before, as it is associated with increased 14-day mortality.
	• Graduated knee-to-thigh compression stockings are not beneficial for deep vein thrombosis prevention.
	• Caregiver education improves coping with the challenges posed by intracerebral hemorrhage.
	• The transfer of the patients to a center with specialized neurosurgical services may improve their outcome, whether they undergo surgery or not. Telemedicine may facilitate patient selection.
	• Although patients presenting in coma rarely survive after surgical treatment, there is not enough information to recommend selection criteria for surgery.

Historical note and terminology

Intracerebral hemorrhage is bleeding into the brain parenchyma resulting from the rupture of a cerebral artery. It accounts for approximately 10% of strokes (106; 115). Hypertension is the leading risk factor for intracerebral hemorrhage, although its role has decreased over the past decades (115; 46).

Intracerebral hemorrhage was first demonstrated at autopsy by Wepfer in 1658, long before blood pressure could be measured (41). The term spontaneous or primary intracerebral hemorrhage implies the absence of a structural vulnerability. However, the most common causes of primary intracerebral hemorrhage are hypertension and amyloid angiopathy.

The introduction of CT in 1973 has markedly improved the diagnosis of intracerebral hemorrhage. CT reliably diagnoses bleeding and differentiates it from ischemic stroke. Brain MRI provides additional information about its evolution and etiology. CT angiography improves the diagnosis of secondary intracerebral hemorrhage and is as effective as digital subtraction angiography at detecting most vascular malformations.

Surgical treatment of hypertensive intracerebral hemorrhage was first reported by Cushing (29). Despite advances in surgical techniques, such as CT-guided stereotactic aspiration and clot dissolution, with few exceptions, surgical treatment is still in the experimental phase.

Clinical manifestations

Presentation and course

	• Focal neurologic symptoms evolve over minutes to hours.
	• Large hematomas are associated with symptoms of increased intracranial pressure: headache, vomiting, and decreased alertness.
	• Small hematomas may mimic lacunar strokes.

In hypertensive intracerebral hemorrhage, focal neurologic deficits depend on the location, size, and effects (mass effect and edema) of the hemorrhage. The classic signs of intracerebral hemorrhage are summarized in Table 1 (20).

As the hematoma grows, the neurologic deficits reach a maximum severity, usually within 10 to 30 minutes, but it may take up to 3 hours to fully develop (20). A large hematoma characteristically causes progressive focal neurologic deficits accompanied by vomiting, headache, and decreased alertness. Conversely, small hematomas can mimic ischemic lacunar syndromes. Early improvement and a fluctuating course are not consistent with hemorrhage. Most intracerebral hemorrhages occur during activity hours.

Alertness is impaired in approximately 60% of cases due to the involvement of the reticular activating system. Coma commonly occurs in patients with hemorrhages into the thalamus or pons. When stupor and coma develop in patients with putaminal or lobar hemorrhage, the prognosis is poor.

Headache results from pressure on the pain-sensitive meninges or surface arteries and occurs in at least 60% of patients (115). Vomiting, caused by pressure on the floor of the fourth ventricle, is experienced by half of the patients (20).

Table 1. Signs of Intracerebral Hemorrhage at Various Sites

Motor and sensory signs
	Putaminal	• Contralateral hemiparesis, hemisensory loss, hemianopsia
	Thalamic	• Contralateral sensory loss, less weakness
	Pontine	• Quadriparesis decerebrate
	Cerebellar	• Ataxia
Oculomotor signs
	Putaminal	• Conjugate deviation to the same site
	Thalamic	• Conjugate deviation to the same site or opposite site, eyes down or down and in, hyperconvergence, skew, vertical gaze palsy
	Pontine	• Bilateral horizontal gaze paresis, preserved vertical reflex movements, ocular bobbing
	Cerebellar	• Ipsilateral sixth or conjugate gaze paresis; nystagmus
Pupils
	Putaminal	• Normal
	Thalamic	• Small and poorly reactive, ipsilateral smaller
	Pontine	• Small, reactive pupils
	Cerebellar	• Small reactive pupils, at times ipsilateral smaller pupils
Alertness
	Putaminal	• Normal if small lesion
	Thalamic	• Reduced
	Pontine	• Coma
	Cerebellar	• Stupor (larger lesion)
Behavioral signs
	Putaminal	• Aphasia (lt), Lt. neglect (rt)
	Thalamic	• Confusion, poor memory, aphasia (left thalamus), left-side neglect (right thalamus)

Ocular bobbing

A 68-year-old woman presented with deep coma (E1, V1, and M2) of 2 days duration. On examination the patient had pinpoint sluggishly reacting pupils, absence of extraocular movements on oculocephalic maneuvers, ocular bobbing, ...

Prognosis and complications

Cerebral edema. Approximately 60% of patients with stroke present with elevated blood pressure (140). High blood pressure within the first 24 hours after onset is associated with an increased risk of perihematomal edema (182), severe morbidity, and mortality (30).

Edema formation starts within 3 hours (172); it increases gradually and peaks at 10 to 20 days (74). There is a positive association between perihematomal edema and hyperthermia, likely mediated by the inflammatory response (73).

Early neurologic deterioration. Early neurologic deterioration was caused by hematoma expansion in approximately half of the patients. This is radiologically defined by an increase in size of 12.5 cm³ or greater than 1.4 times. Expansion occurs in up to 36% of patients within 24 hours but rarely afterward (82). Hematoma expansion was more frequent in patients with ionized calcium lower than 1.12 mmol/L (201).

Seizures. Seizures occur in approximately 25% of patients with primary intracerebral hemorrhage, especially in the lobar type (54%), when blood extends into the cerebral cortex. In half of these, the seizure begins within 24 hours of the onset of hematoma. Seizures may occur in patients with basal ganglia (19%) but not with thalamic, pontine, or cerebellar hematomas (38).

Seizures, initially focal, occur more often with cortical lesions, not hypertensive, in younger patients, and with severe neurologic deficits (126).

Continuous EEG detected seizures in up to 31% of patients with intracerebral hemorrhage despite anticonvulsant therapy (184; 27).

Temperature dysregulation. Hyperthermia, present in 39% of patients, is associated with increased mortality. Only 29% of cases are infectious. The hemorrhage volume, intraventricular extension, external ventricular drainage or surgical evacuation, and positive blood cultures are associated with hyperthermia (49). Fever caused by pontine hemorrhage is difficult to treat (161).

Hypothermia occurs more often in intracerebral hemorrhage than in traumatic brain injury, acute ischemic stroke, or subarachnoid hemorrhage. Hypothermia increases mortality more than fever (146).

Coma. Coma at presentation correlates with 64% mortality (168). Mortality within the first week is 32 times higher in patients with a Glasgow Coma Scale score lower than 8 and 14.5 times higher in those with signs of brainstem compression (196). Among these are absent corneal and occulocephalic responses and lack of localization of the painful stimulus (171).

Death. The overall mortality of primary intracerebral hemorrhage ranges between 25% and 50% (163; 20). Fatal outcome correlates with the size of the hematoma and Glasgow Coma Scale score (93). Other risk factors include age and systolic blood pressure on admission, fever, hyperglycemia, elevated neutrophil count, serum fibrinogen levels of greater than 523 mg/dL, and hypodensities on CT head (95; 72; 175; 08).

Mortality within 30 days of onset increases when the hematoma volume exceeds 32 ml or 21 ml in the supratentorial and infratentorial compartments, respectively (158). An even more dramatic increase in mortality occurs if the hematoma diameter is larger than 3 cm in the thalamus and cerebellum and larger than 1 cm in the pons. Mortality in cerebellar hematomas is significantly worse in unresponsive compared to responsive patients (135). The lesions smaller than 1.5 cm have an excellent outcome, except in elderly patients or associated intraventricular bleeding (84).

Radiological predictors of death are acute hydrocephalus and intraventricular hemorrhage (171). Intraventricular hemorrhage is associated with 66% death and disability as compared to 49% in intracerebral hemorrhage alone (77). Horizontal displacement (midline shift) of the pineal body of 3 to 4 mm from the midline is associated with drowsiness, 6 to 8.5 mm with stupor, and 8 to 13 mm with coma (152).

Mortality within 30 days of an event can be predicted by the ICH score. The elements of this score are the Glasgow Coma Scale score, the hematoma volume, the presence of intraventricular blood, the infratentorial origin of blood, and age (60). The functional outcome of intracerebral hemorrhage can be predicted by the FUNC score (153).

Recurrence of intracerebral hemorrhage. The recurrence rate of intracerebral hemorrhage is approximately 2.4% per year, with a 3.8-fold increase for lobar hemorrhage (67). Most recurrent hemorrhages occur at a different site (26). Up to 20% of recurrent intracerebral hemorrhages has a different cause, suggesting the need to investigate thoroughly every instance of recurrence (199; 193).

The risk factors for intracerebral hemorrhage recurrence include poor functional status, history of ischemia, lobar location, old age, ongoing anticoagulation, multiple microbleeds on MRI, surgical treatment, and renal insufficiency. SSRIs or NSAIDs were not associated with an increased risk of recurrence, and antihypertensive medication reduces this risk (85; 61; 165).

Recurrent hemorrhage was also associated with variant genotype combinations of ACE and αADDUCIN (112) and the presence of apolipoprotein E ε2 and ε4 alleles (111). The HAS-BLED score was developed to assess the risk of recurrent intracerebral hemorrhage (23).

Biological basis

	• Uncontrolled hypertension is the most common cause of spontaneous intracerebral hemorrhage.
	• Chronic hypertension may be distinguished from stress hypertension by physical examination and ancillary tests.

Etiology and pathogenesis

Elevated blood pressure occurs in 60% of patients with intracerebral hemorrhage presenting to the hospital (140). Systolic blood pressure above 200 mmHg and the proportion of blood pressure measurements above 180 mmHg were associated with hematoma expansion (82; 148). However, another study did not confirm this relationship (78).

Chronic hypertension is the major cause of nontraumatic or spontaneous intracerebral hemorrhage. Thirty-nine single nucleotide polymorphisms (SNP) were found to be related to blood pressure. Although no single SNP was associated with intracerebral hemorrhage or pre-hemorrhage hypertension, the blood pressure-based unweighted genetic risk score was associated with the risk of intracerebral hemorrhage and deep but not lobar intracerebral hemorrhage (36).

The diagnosis of hypertensive intracerebral hemorrhage is based on (1) a history of hypertension; (2) a location typical for penetrating arteries, such as putamen, thalamus, pons, and cerebellum; and (3) no other cause of intracerebral hemorrhage.

Chronic hypertension may be distinguished from the stress response by the presence of cardiomegaly on chest x-ray, left ventricular hypertrophy by electrocardiogram or echocardiogram, renal dysfunction, or hypertensive retinopathy on funduscopic examination.

In a large population study, the relative risk of hypertension for intracerebral hemorrhage was 3.9 (14). For the combination of hypertension by history, left ventricular hypertrophy, and cardiomegaly, the relative risk was 5.4. For black persons with a history of hypertension, the relative risk was 8.2; for hypertension, left ventricular hypertrophy, and cardiomegaly, the relative risk was 13.3.

Extreme work overload, defined as overtime above 100 hours/month, increases the risk of hypertensive intracerebral hemorrhage compared to overtime below 60 hours/month (121).

Pathology. The association between miliary aneurysms of intracerebral arteries and parenchymal hemorrhage described by Charcot (24) was later supported by other investigators (156; 28).

Most hypertensive intracerebral hemorrhages are caused by the rupture of arterioles with diameters between 50 and 200 µm. Both aneurysmal and nonaneurysmal hemorrhages, due to rupture of lipohyalinotic or arteriosclerotic arteries, occur in the deep regions of the brain (43).

Postmortem angiography revealed an association between hypertension and miliary aneurysms in the small vessels (100 to 300 µm in diameter) of the basal ganglia, internal capsule, thalamus, and, less commonly, centrum semiovale and cortical gray matter (156; 28). This explains the location of most hypertensive hemorrhages in the deep structures: putamen (40% to 50% of cases), subcortical white matter–lobar (20%), thalamus (15%), cerebellum (8%), pons (8%), and caudate nucleus (8%) (20).

Another study found ruptured miliary aneurysms in a minority of histological specimens. The predominant finding was degeneration of the arterial media near bifurcations, the most likely site for rupture (174). The Charcot-Bouchard aneurysm is not a significant cause of intracerebral hemorrhage but a marker of cerebrovascular disease severity (102).

Hemorrhage occurs not only in the arteries damaged by chronic hypertension but also in the normal small arteries during spikes of blood pressure as during emotional stress, cold weather, severe dental pain, sympathomimetic drug abuse, and trigeminal stimulation (19; 92).

Cerebral amyloid angiopathy is caused by the deposition of the beta-amyloid peptide in the walls of arterioles and capillaries of the leptomeninges, cerebral cortex, and cerebellar hemispheres (lobar territories). Cerebral amyloid angiopathy occurs in elderly patients with apolipoprotein E genotypes containing the ε2 or ε4 alleles.

A pathogenetic classification of intracerebral hemorrhage was proposed—SMASH-U: structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). Structural lesions, like cavernomas and arteriovenous malformations, caused 5% of the hemorrhages. Approximately 14% of cases were caused by anticoagulation and 5% by systemic disease. Amyloid angiopathy and hypertensive angiopathy were the most common causes at 20% and 35% respectively. Etiology remained undetermined in 21% of cases (109).

Hematoma expansion predicts poor outcome. After the baseline CT, hematoma expansion is seen on repeat CT in 26% of patients after 1 hour and in another 12% after 20 hours of the initial scan (13). The predictors of hematoma expansion were early repeat CT, irregular shape of hematoma, and increasing plasma level of matrix metalloproteinase-9 (198).

The pressure exerted by the blood accumulation injures the local brain parenchyma and dissects it for some distance. If large, the hematoma causes midline shift, and compression of the brainstem’s vital centers may lead to coma and death. Within 1 hour from onset, accumulation of serum proteins resulting from blood clot retraction leads to formation of the perihematoma edema (189).

Hypertensive intracerebral hematoma (autopsy specimen)

Axial section showing a large hematoma, originating in the left thalamus. The hemorrhage has dissected into the lateral ventricles. (Contributed by Dr. Sherman Stein.)

After 2 to 4 days, inflammatory cells arrive at the margins of the hemorrhage. Hemosiderin-laden macrophages and extracellular deposits of hematoidin are present after 3 weeks. The level of CD163, a scavenger receptor for hemoglobin, was significantly lower in patients with larger perihematoma edema and may be a useful prognostic biomarker (154).

Astrocytic proliferation occurs in the neighboring parenchyma. Apoptosis plays a major role in cell death after intracerebral hemorrhage and is associated with activation of nuclear factor-kB (NF-kB), ICAM-1 IL-1B (192). In the chronic stage, the hematoma shrinks to a cavity lined by hemosiderin-laden macrophages.

Extension of the hemorrhage into the subarachnoid space has been associated with fever and worse outcome (55).

In 2% to 3% of hemorrhagic strokes, there are multiple foci of bleeding. The presumed mechanism is bleeding from the penetrating arteries caused by sustained hypertension during acute cerebral hemorrhage. The differential diagnosis includes hematologic disorders, vasculitis, anticoagulant therapy, illicit drug use, cerebral amyloid angiopathy, or hemorrhage due to multiple infarctions with hemorrhagic transformation (107).

Epidemiology

	• Intracerebral hemorrhage accounts for 10% of strokes.
	• Hypertension is the leading cause of intracerebral hemorrhage.
	• Over the past few decades, the proportion of patients with intracerebral hemorrhage due to hypertension has decreased.

Intracerebral hemorrhage accounts for approximately 10% of strokes (106; 115). The annual incidence is estimated to be between 10 and 22.9 per 100,000 with a male predominance (60%) (54; 89; 12).

Hypertension is the leading cause of intracerebral hemorrhage. The significantly higher incidence in the black population as compared to the white population (32 vs. 12 per 100,000) may reflect the higher prevalence of hypertension (54). Additionally, untreated hypertension raises the risk of intracerebral hemorrhage in all anatomic locations, more so in Blacks and Hispanics compared to Caucasians (190). Over the past several decades, the proportion of intracerebral hemorrhage caused by hypertension declined from 84% to 50% (46). This may reflect both improvements in hypertension treatment and diagnostic imaging of alternative causes of intracerebral hemorrhage.

In young adults 16 to 49 years of age, the incidence is lower, 4.9 out of 100,000. The most common risk factors are hypertension (29.8%) and smoking (22.3%). Structural lesions are more common in young compared to elderly patients (25% vs. 4.9%). In patients younger than 40 years of age, intracerebral hemorrhage tends to be less severe and has a better prognosis (155). In 22.5% of cases, no etiology was found after MRI and angiography were performed (88).

Although no seasonal variation has been identified, the risk of intracerebral hemorrhage increases significantly between 8:00 am and 4:00 pm (132). In a small study, a drop in atmospheric pressure 2 days before ictus was associated with deep but not lobar intracerebral hemorrhage, suggesting a link to hypertensive etiology (70).

Differential diagnosis

Confusing conditions

As the clinical features of ischemic and hemorrhagic stroke often overlap, CT is used to quickly and reliably differentiate between these types of strokes. Determining the cause of intracerebral hemorrhage is based on demographic and risk factors and the location and appearance of the lesion on CT and MRI.

Amyloid angiopathy. Amyloid angiopathy occurs in the elderly and results in microinfarcts, subarachnoid hemorrhage, intracerebral hemorrhage, and dementia. Multiple hemorrhages occur over time at several sites within the cerebral hemispheres, especially in the parietal and occipital lobes. Bleeding in the basal ganglia, thalamus, pons, and cerebellum is rare. Beta-amyloid may be detected by temporal artery biopsy (179).

Drug-related intracerebral hemorrhage. Sympathomimetic drugs and stimulants associated with intracerebral hemorrhage include amphetamine, methamphetamine, cocaine, phencyclidine, phenylpropanolamine, ephedrine, and methylphenidate (131; 18; 64). Headache, drowsiness, confusion, and psychosis suggest the etiology. The location of the drug-induced intracerebral hemorrhage closely mimics hypertensive intracerebral hemorrhage except that more of the drug-related hematomas are lobar. The diagnosis is confirmed by a history of recent drug use and a positive drug screen.

Anticoagulant and antiplatelet-related intracerebral hemorrhage. Intracerebral hemorrhage caused by anticoagulation occurs at a rate of 1% per year; 70% are intracerebral hematomas, of which 60% are fatal. Risk factors include older age, hypertension, prior ischemic stroke, and intensity of anticoagulation. Heparin, especially if given as a bolus, warfarin if INR is greater than 3.0, and aspirin use are associated with intracerebral hemorrhage (59; 16; 44). In a population-based study, prior use of either warfarin or aspirin are independent predictors of death after intracerebral hemorrhage (160).

Thrombolytic therapy–related intracerebral hemorrhage. Thrombolysis-related hemorrhage occurs in 0.36% of patients with acute myocardial infarction and 6.4% of patients with ischemic stroke (129). The location can be deep, lobar, or in the infarcted area. In a pooled analysis, 7 of 10 patients who died of thrombolysis-related hemorrhage and underwent autopsy had cerebral amyloid angiopathy (108).

Hematological disorders. A few examples are hemophilia, thrombocytopenia, and leukemia.

Vascular malformation and aneurysm. Any young patient with lobar or subependymal intracerebral hemorrhage who is not hypertensive should be evaluated for vascular malformation with a contrast-enhanced CT or MRI. Delayed scans may detect lesions missed in the acute stage due to compression by the adjacent hematoma.

Brain tumor. Glioblastoma multiforme is the most frequent cause of intracerebral hemorrhage from a primary tumor (99). Although choriocarcinoma and malignant melanoma have a high frequency of intracerebral hemorrhage (50% and 29%, respectively), the most common metastatic cause of intracerebral hemorrhage is bronchogenic carcinoma (159). Tumor diagnosis is suggested by a contrast-enhanced lesion surrounded by vasogenic edema on CT or MRI.

Hemorrhagic infarction. Hemorrhagic transformation usually occurs after an embolic cerebral infarction. Typically, the neurologic deficits are maximal at onset. Mild bleeding may be asymptomatic. Hemorrhagic transformation appears on CT scan as spotted and mottled high attenuation inside the infarction.

Unusual causes of intracerebral hemorrhage. The following conditions all have in common an acute rise in blood pressure or blood flow: exposure to cold weather, dental pain or manipulation, manipulation of the trigeminal nerve, carotid endarterectomy, and correction of congenital heart defects and cardiac transplantation in the young (20). The location of the hematomas in these conditions is identical to that of intracerebral hemorrhage in chronically hypertensive patients.

Associated or underlying disorders

Left ventricular hypertrophy. Left ventricular hypertrophy is associated with chronic hypertension and intracerebral hemorrhage (136).

Hypothyroidism. Hypothyroidism leads to endothelial disorders and atherosclerosis and is found more often in patients with intracranial hemorrhage (71).

Diagnostic workup

Any patient with intracerebral hemorrhage should have the coagulation parameters (prothrombin time and international normalized ratio) tested in addition to a hemogram, blood chemistry panel, and troponin.

Non-contrast CT. Head CT may detect and localize the hematoma, distinguish it from ischemic stroke, and evaluate for hematoma expansion and its complications: cerebral edema, hydrocephalus, and brain herniation (203). The resolution of CT is a few millimeters. Intracerebral hemorrhage appears as an area of high density, with an absorption value between 40 and 90 Hounsfield units (166). This high-density lesion is due to hemoglobin protein (globin) within the extravasated blood (127).

Vasogenic edema is plasma derived and surrounds the acute hematoma (17). After 7 to 10 days, the high-attenuation values of the hematoma begin to decrease, always from the periphery towards the center. The entire hematoma becomes isodense in 2 to 3 weeks if small or in 2 months if large (127). The reduction in size and attenuation values of intracerebral hematoma occurs at rates of 0.65 mm and 1.4 Hounsfield units per day, respectively (34). The final stage in the CT evolution is the complete absorption of the necrotic and hemorrhagic tissue, leaving a residual cavity after 2 to 4 months. At times, this cavity can be indistinguishable from an old cerebral infarct.

Hypertensive intracerebral hematoma (CT)

This unenhanced image shows a large, deep, right-sided hematoma with mass effect and dissection into the lateral ventricles. (Contributed by Dr. Sherman Stein.)

Heterogenous intensities within the hematoma and irregular margins (hypodensities, fluid level, swirl, black hole, island, or satellite sign) are markers for increased risk of hematoma expansion and poor prognosis (123; 122). A repeat CT scan is useful within 24 hours of onset or in patients with a low Glasgow Coma Score (GCS) or neurologic deterioration (01; 100).

Contrast-enhanced CT. Contrast-enhanced CT facilitates the diagnosis of an arteriovenous malformation or a neoplasm. "Ring enhancement" occurs between 1 to 6 weeks from the onset of intracerebral hemorrhage and may last up to 2 to 6 months. It is due to hypervascularity at the periphery of the hematoma or disruption of the blood-brain barrier (34; 203).

CT angiogram. In patients younger than 70 years with lobar spontaneous intracerebral hemorrhage, younger than 45 years with deep or posterior fossa intracerebral hemorrhage, or between 45 to 70 years without hypertension, CT angiogram in combination with venography may diagnose the cause of intracerebral hemorrhage.

Contrast extravasation on early CT angiography (“spot sign”) may predict hematoma expansion (51; 186). The Spot Sign Score (SSSc), which includes the number of spot signs, their maximum axial dimension, and attenuation, predicts significant expansion of hematoma, severe disability, and mortality (150). The “blush sign” seems to be a better predictor than the spot sign for hematoma expansion (181).

MRI and MR angiogram. In addition to distinguishing hemorrhage from infarction, MRI provides insight into the evolution of hemorrhage by detecting the chemical changes in hemoglobin. Five stages of an evolving hematoma have been described: (1) hyperacute (first 24 hours), (2) acute (1 to 3 days), (3) early subacute (longer than 3 days), (4) late subacute (longer than 7 days), and (5) chronic (longer than 2 weeks). Four zones have also been described: (1) inner core, (2) outer core, (3) rim, and (4) reactive brain (09). However, the MRI findings do not correlate with those of autopsy. The different stages of hemorrhage, the changes of hemoglobin, and the intensity on MRI are described in Table 2 (09).

Table 2. Stages of Hemorrhage

Stage	Hemoglobin	T1-Weighted	T2-Weighted
Hyperacute	Oxyhemoglobin	Dark	Bright
Acute	Deoxyhemoglobin	Dark	Very dark
Subacute
• Early • Late	Methemoglobin Methemoglobin	Bright Bright	Dark Bright
Chronic
• Center • Rim	Hemachrome Hemosiderin	Bright Dark	Bright Very dark

Using diffusion-, T2-, and T2* -weighted images, MRI has been shown to detect intracerebral hemorrhage within 6 hours of onset. Typically, the hemorrhage appears target-like (39). The hyperacute hemorrhage is composed of three distinct areas: (1) center: isointense to hyperintense signal on T2* - and T2-weighted images; (2) peripheral: hypointense (deoxyhemoglobin) mostly on T2* -weighted images; (3) rim: hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, representing vasogenic edema surrounding the hematoma (98).

In patients with spontaneous intracerebral hemorrhage with negative CT angiogram/venogram, brain MRI and MRA may reveal non-macrovascular causes of bleeding. Among these are cerebral amyloid angiopathy, vasculopathy, cavernoma, and malignancy.

Gradient-echo T2-weighted MRI detects chronic microbleeds in more than half of the patients (54%) with primary intracerebral hemorrhage. Microbleeds appear as round, hypointense foci smaller than 5 mm due to the perivascular hemosiderin. They result either from hypertensive vasculopathy or from cerebral amyloid angiopathy (185). The microbleeds located in the basal ganglia, thalamus, and infratentorial region are more likely to be associated with primary intracerebral hemorrhage (151).

Enlarged perivascular spaces (EPVS) seen on brain MRI are a promising marker of small vessel disease and are common in patients with intracerebral hemorrhage. Based on their anatomical distribution, the mechanism of formation may be inferred. Severe centrum semiovale EPVS may indicate cerebral amyloid angiopathy, whereas basal ganglia EPVS suggests hypertensive arteriopathy (25).

Catheter intra-arterial digital subtraction angiography. Cerebral arteriography is used in selected cases for further confirmation or plan of treatment of arteriovenous malformation, aneurysm, tumor, and vasculitis if detected by CT angiogram. Patients younger than 70 years with lobar intracerebral hemorrhage, younger than 45 years with deep/posterior fossa intracerebral hemorrhage, and 45 to 70 years without hypertension and a negative CT or MR angiogram may benefit from digital subtraction angiography (202). In patients without a clear cause and a negative angiogram, a repeat angiogram 3 to 6 months later may uncover small vascular malformations initially obscured by the hemorrhage (69).

Extension of the hemorrhage into the ventricular system is not usually associated with vascular malformations and the yield of catheter angiography is low (80).

However, digital subtraction angiography is recommended in patients with isolated intraventricular hemorrhage or abnormal CTA or MRA suggestive of a macrovascular cause.

Although CT angiography is as accurate as digital subtraction angiography for diagnosing vascular lesions, it cannot characterize the angioarchitecture (195). A simple, practical score to detect secondary intracerebral hemorrhage (SICH) based on noncontrast CT characteristics, age, and presence of hypertension or coagulopathy may guide further cerebrovascular imaging (31). CT angiography must be carefully reviewed, even in elderly patients, if the hemorrhage location is atypical for hypertensive arteriopathy. For example, an aneurysm of the lateral posterior choroidal artery was found on the CT angiogram of a 60-year-old man (45).

Management

The most important measures to control hypertensive intracerebral hemorrhage include the following:

• Airway and breathing maintenance
• Blood pressure control
• Intracranial pressure control
• Drainage of intraventricular blood
• Seizure control
• Management of neurologic and medical complications

The American Heart Association/American Stroke Association has published a comprehensive guideline for the treatment of spontaneous intracerebral hemorrhage in adults (52).

Ventilation. Airway patency and maintenance oxygen saturation above 95% are the first concerns. Endotracheal intubation is needed in case of impaired consciousness, hypoxia (PO2 < 60 mmHg, PCO2 > 50 mmHg), or aspiration of secretions (134). Prolonged coma or pulmonary complications beyond 2 weeks may require elective tracheostomy.

Blood pressure control. Aggressive blood pressure control does not cause ischemia within the tissue surrounding the hematoma. Here, the cerebrovascular reactivity is preserved, and the metabolism is reduced (138; 83). Diffusion- and perfusion-weighted MRI showed no evidence of an ischemic penumbra around the hematoma (164).

At the same time, the clinical trials of intensive blood pressure control failed to demonstrate improved clinical outcomes or mortality (04; 75; 76; 141). Moreover, a meta-analysis of four studies including 3315 patients found that although intensive blood pressure reduction was safe, it did not reduce the unfavorable outcome (178). However, controlling hypertension within 2 hours of onset, reaching the target within 1 hour, and avoiding large variability in systolic blood pressure may improve the functional outcome (125).

The lack of improved outcomes despite the aggressive lowering of blood pressure may be explained by a case report of global cerebral ischemia following the rapid decrease in blood pressure to a normal level (48). Moreover, in the ATACH-2 trial, patients whose systolic blood pressure was decreased below 140 mmHg within 2 hours and was maintained for at least 2 hours had higher rates of neurologic and cardiac adverse events (142). Another study of 286 patients found an association between systolic blood pressure below 120 mmHg and ischemic lesions. No ischemic lesions were seen if the lowest systolic blood pressure was above 130 mmHg (15).

Although the optimal blood pressure target and urgency of achieving it are unknown, the current guidelines recommend treatment based on mean arterial pressure and intracranial pressure, with a goal of cerebral perfusion pressure greater than 60 mmHg.

If the systolic blood pressure is 150 to 220 mmHg, rapid lowering to 140 mmHg (range 130 to 150 mmHg) with minimal fluctuations is safe and may improve the functional outcome. However, decreasing the systolic blood pressure to less than 130 mmHg in the same patients is potentially harmful (52). Moreover, analysis of the MSTIE III trial data found that a large hematoma volume on admission, a drop in systolic blood pressure by more than 80 mmHg within 24 hours, and moderate to severe white matter disease were associated with diffusion weighted imaging lesions on follow-up MRI (147).

In a small study, decreased mortality, SISRS, and pneumonia, compared to amlodipine (81). Insufficient data exist about treating severe, sustained systolic blood pressure higher than 220 mmHg.

Intracranial pressure monitoring and control. Intracranial pressure above 20 mmHg for more than 5 minutes is considered elevated. This may result from the mass effect of hematoma and secondary hydrocephalus. The compartmentalized structure of the brain favors an increase in intracranial pressure only around the hematoma (22).

The intracranial pressure is monitored by a sensor inserted into the brain parenchyma. An external ventricular device allows measuring the intracranial pressure and drainage of the cerebrospinal fluid to maintain a set pressure. The drainage is considered when hydrocephalus caused by the bleeding leads to decreased consciousness. Because the external ventricular device is likely to fail and need replacement, a new IRRAflow self-irrigating catheter, which combines automatic irrigation, monitoring, and drainage of the CSF, has been tested successfully. This catheter decreased the duration of drainage, rate of external ventricular device exchange, and length of stay in the ICU (40).

It is reasonable to monitor intracranial pressure in patients with a Glasgow Coma Scale (GCS) score lower than 8 due to the hematoma, clinical evidence for transtentorial herniation, significant intraventricular hemorrhage, or hydrocephalus. The cerebral perfusion pressure goal is 50 to 70 mmHg, depending on the status of cerebral autoregulation (61).

Noninvasive measuring of the intracranial pressures is done by transcranial Doppler or optic nerve sheath diameter (103; 21). However, in the only multicenter-controlled trial in traumatic brain injury patients, conducted in Ecuador and Bolivia, invasive monitoring of increased intracranial pressure failed to improve outcome compared to using clinical status and CT imaging (50). A systematic review and meta-analysis of 14 studies including 24,792 patients found no reduction in mortality by invasive monitoring. However, a newer study showed some benefits of invasive monitoring (200).

General measures. General measures for intracranial pressure reduction include elevation of the head of the bed to 30°, mild sedation, and avoidance of endotracheal tube ties that might impair the cerebral venous return (194). Stool softeners may also help.

Hypertonic solutions. Hyperosmolar therapy can transiently reduce intracranial pressure. However, neither mannitol nor hypertonic saline of 3% reduce mortality (06; 188). A meta-analysis did not find a significant difference between these agents (145). The rebound phenomenon of increasing edema volume after hypertonic solutions infusion limits the efficacy of this measure (143). Hyperosmolar therapy is only a temporizing measure (52).

Controlled hyperventilation. Hypocarbia (pCO2 25 to 33 mmHg) resulting from controlled hyperventilation induces cerebral vasoconstriction (94). Cerebral blood flow decreases almost immediately, though it may take up to 30 minutes for maximum effect to occur. Refractory intracranial hypertension may benefit from induced barbiturate coma.

Ventriculostomy. Ventriculostomy for CSF drainage can reduce intracranial pressure and may improve the outcomes in patients with hydrocephalus if this contributes to decreased consciousness. However, this procedure may be complicated by hemorrhage and infections (33).

If intracranial pressure is refractory to all medical management, decompressive craniectomy has been used; however, even if performed early (less than 48 hours), it does not improve mortality compared to medical treatment (130).

Cerebral microdialysis is used for measuring the lactate/pyruvate ratio as a marker of brain tissue hypoxia (87) and invasive brain oxygen monitoring (62) are still in the experimental stages. A small prospective randomized study showed that brain oxygen monitoring seems to be superior to intracranial pressure monitoring alone (97).

Intraventricular hemorrhage management. Intraventricular hemorrhage occurs in 45% of patients with spontaneous intracerebral hemorrhage (56). A retrospective review demonstrated that external ventricular drain reduced mortality and improved short-term outcomes in these patients (65). The CLEAR-IVH trial showed that in patients with small intracerebral hemorrhage and large intraventricular hemorrhage, administration of low-dose tPA in the ventricular system to facilitate blood clot removal is safe; however, the impact on functional recovery is unknown (117). The CLEAR III trial showed that although ventricular irrigation with alteplase was safe, it did not improve functional outcomes at the mRS=3 cutoff compared to saline (58).

Seizures. Depressed levels of consciousness out of proportion to the size or location of the hemorrhage should prompt continuous EEG monitoring. Clinical or electrographic seizures should be treated, but the use of anticonvulsants prophylactically in patients without documented seizures is not recommended (110).

Hemostatic treatments. Recombinant activated factor VII (rFVIIa) failed to show a significant difference in clinical outcome, despite its ability to prevent hematoma enlargement (11; 37). Similarly, the effectiveness of tranexamic acid has not been established (177).

Prevention and treatment of medical complications. Fluid and electrolyte balance should be monitored, particularly if hyperosmolar agents and diuretics are used. Inappropriate antidiuretic hormone secretion can occur in patients with intracerebral hemorrhage.

Dysphagia. Dysphagia is diagnosed in 68% of patients with intracerebral hemorrhage (173). All patients should undergo formal dysphagia screening to prevent aspiration pneumonia (68). Patients should receive nothing by mouth for the first 24 to 48 hours, and normocaloric parenteral or enteral nutrition should be instituted within 48 hours.

Percutaneous endoscopic gastrostomy was needed in 25% of intracerebral hemorrhage cases (86).

Myocardial infarction. Approximately 0.3% of patients with intracerebral hemorrhage develop acute myocardial infarction during the first 3 days of treatment and increased mortality from 2% to 14.5% (47). In one study, elevated troponin was associated with increased in-hospital mortality but not at 30 days if not associated with ECG changes in another study (105; 162). Continuous cardiac monitoring for 24 to 72 hours and serial cardiac enzymes should be obtained to detect cardiac arrhythmia or ischemia (52).

Neurogenic pulmonary edema. Pulmonary edema develops in 35% of patients with intracerebral hemorrhage and is responsible for 37% mortality in 1 year (79). Acute respiratory distress syndrome occurs in 27% of patients with intracerebral hemorrhage; it is associated with a high tidal volume and with inpatient mortality (35). Low tidal volume ventilation with attention to avoid increased intracranial pressure or hypoxia is reasonable (104).

Renal dysfunction. Renal failure occurred in 8% of patients with intracerebral hemorrhage and is not increased by CT angiography (133). Renal dysfunction is also associated with cerebral microbleeds in patients with intracerebral hemorrhage (91). Acute renal failure is associated with higher rates of in-hospital mortality and moderate to severe disability at discharge (157)

Pulmonary embolism. Pulmonary embolism may occur in bedridden individuals with hemiplegia. Deep vein thrombosis can be prevented by heparin (5000 IU subcutaneous injections every 12 hours) or low molecular weight heparin in patients with lack of mobility after 24 to 48 hours of intracerebral hemorrhage onset. Intermittent pneumatic compression devices decrease the risk of pulmonary embolism and should be instituted on the day of diagnosis (61). If anticoagulation is contraindicated, using a retrievable filter may serve as a bridge until coagulation is safely initiated. In patients with proximal deep vein thrombosis or pulmonary embolism, anticoagulation may be started after 1 to 2 weeks of hemorrhage onset (52).

Fever. Fever occurs frequently and is associated with increased mortality. Infections or inflammatory causes should be investigated and treated. A Cochrane analysis failed to prove any benefit of targeted temperature management (32).

Hyperglycemia. Monitoring glycemia helps avoid both hypoglycemia (< 40 to 60 mg/dL) and hyperglycemia (> 180 to 200 mg/dL) (NICE-SUGAR Investigators 2009).

Do not resuscitate. A do-not-resuscitate order instituted early is an independent predictor for poor outcomes as it may lead to a lower intensity of care (63). Avoidance of do-not-resuscitate orders within the first 5 days, along with management according to the guidelines, reduces mortality more than expected based on the intracerebral hemorrhage score (120).

Statin use. Statin use after intracerebral hemorrhage may be associated with early neurologic improvement and reduces mortality at 6 months (175). Moreover, stopping statins may increase mortality (176).

Surgical treatment. The preoperative state of alertness and hematoma volume are the main determinants of outcome. A Glasgow Coma Scale score less than 8 and a volume greater than 60 ml were associated with a mortality rate of 91% (10). Intraventricular extension of hemorrhage is associated with worse outcomes (169).

Craniotomy for supratentorial hemorrhage. A large clinical trial, the International Surgical Trial for Intracerebral Hemorrhage (STICH), demonstrated that surgical evacuation within 24 hours of randomization is not superior to conservative management. Patients with lobar clots larger than 30 mL and within 1 cm of the surface appeared to benefit from surgery (169). However, the STICH II trial that enrolled conscious patients with superficial lesions between 10 and 100 mL did not show a benefit of early surgery (170).

A meta-analysis of 10 trials including 2059 patients suggests that surgery for supratentorial hematomas is associated with a reduction in death and disability, but the result is not very robust (139). In comatose patients with a large hematoma, large midline shift, or elevated intracranial pressure refractory to medical management, craniectomy with or without hematoma evacuation may be considered. However, its lifesaving effectiveness is unknown (52).

The optimal timing of surgery for supratentorial hemorrhage is unknown. In a randomized feasibility study, surgery within 24 hours of onset did not improve morbidity at 3 months (204). Surgery performed within 12 hours of randomization was as effective as conservative management. However, subgroup analysis showed a small benefit from surgery earlier than 21 hours, especially in those with poor prognosis (170). A meta-analysis of eight surgical trials (2816 cases) shows that surgery improves outcomes if randomization occurred within 8 hours of ictus; the Glasgow Coma Scale was 9 to 12, and the hematoma volume was 20 to 50 ml (53). However, ultra-early (within 4 hours from onset) surgery was associated with an increased risk of rebleeding and mortality (119).

Less is known about surgical intervention in patients with a Glasgow Coma Scale score lower than 8. In a small retrospective series, all comatose patients who lost upper brainstem reflexes and had extensor posturing died despite emergency craniotomy (144). For patients with a Glasgow Coma Scale score less than 8, surgical intervention was associated with an increased risk of poor outcomes and is probably harmful (169). Decompressive hemicraniectomy without clot evacuation in dominant-sided hemorrhage with intracranial pressure crisis was also attempted in five patients with a Glasgow Coma Scale score between 5 and 9. At 6 months, one patient died, two were dependent (mRS 4 and 5), and two were independent (mRS 2 and 3) (66).

Craniotomy for infratentorial hemorrhage. In patients with a cerebellar hematoma volume greater than 15 mL, neurologic worsening, hydrocephalus, or brainstem compression, urgent surgical decompression may be lifesaving. However, the impact of craniotomy on the functional status is unclear (90; 52).

Initial loss of consciousness strongly predicts poor survival (42). Obliterated cisterns predict a poor outcome irrespective of treatment, and ventricular drainage alone is not indicated (180).

Minimally invasive surgery. Minimally invasive surgery with endoscopic or stereotactic aspiration aims at reducing the morbidity associated with conventional craniectomy. In a randomized trial, minimally invasive surgery of the basal ganglia hemorrhage did not reduce mortality but improved the functional outcome at 3 months in the surviving patients (191). A systematic review and meta-analysis of five randomized controlled trials and nine prospective controlled studies involving 2466 patients showed that patients with supratentorial intracerebral hemorrhage benefit more from minimally invasive surgery than from craniectomy (197).

The addition of thrombolysis with alteplase to the minimally invasive surgery for intracerebral hemorrhage evacuation (MISTIE) trial reduced the clot size and perihematomal edema compared to patients who received placebo, but it did not improve clinical outcome (118; 124; 113). However, at 365 days, mortality was lower in the minimally invasive surgery group compared to the medical management group without an increase in the proportion of patients with severe disability (114).

For patients with a supratentorial intracerebral hemorrhage volume of greater than 20 to 30 mL and a GCS of 5 to 12, minimally invasive surgery reduced mortality compared to medical management alone and functional disability compared to conventional craniotomy (52).

A meta-analysis comparing endoscopic surgery, minimally invasive surgery and urokinase, minimally invasive surgery and alteplase, craniotomy, and standard medical management found that endoscopic surgery was the most effective in improving survival and minimizing disability (96).

An alternative to tPA thrombolysis, still in the experimental stage, is transcranial MR-guided focused ultrasound (116).

Frameless, image-driven robotic stereotactic assistance (ROSA) of catheter insertion is a new development (03). A pilot study of CT-guided endoscopic surgery (Intraoperative CT–guided Endoscopic Surgery for Brain Hemorrhage, ICES) showed similar results to the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation, MSTIE, but lacked the power to detect a benefit (183). A meta-analysis of 28 studies shows that adding mild hypothermia to minimally invasive surgery improved neurologic outcomes and decreased mortality compared to surgery alone (57).

Transfer to another facility. Not all hospitals have neurosurgical services. Considering the uncertainty regarding the efficacy of the surgical intervention, the decision to transfer a patient with intracerebral hemorrhage to a neurosurgical center is often made. In a study of 1175 cases, the transferred patients had a lower risk of death relative to those remaining at the referral center, even if they did undergo surgery (02). Where remote consultation is considered, decision-making should rely not only on head CT imaging but also on the video assessment of the patient (187).

Outcomes

Deciding too early not to resuscitate is an independent risk for poor outcomes. Data from a nationwide inpatient sample show that in the United States, the in-hospital mortality of patients who underwent surgical treatment was 27.2%, and the complication rate was 41%. Male gender, preoperative comorbidities, complications, and low surgery volume were associated with increased in-hospital mortality (137).

Media

References

01: AbdelFattah KR, Eastman AL, Aldy KN, et al. A prospective evaluation of the use of routine repeat cranial CT scans in patients with intracranial hemorrhage and GCS score of 13 to 15. J Trauma Acute Care Surg 2012;73(3):685-8. PMID 22929497
02: Abid KA, Vail A, Patel HC, King AT, Tyrrell PJ, Parry-Jones AR. Which factors influence decisions to transfer and treat patients with acute intracerebral haemorrhage and which are associated with prognosis. A retrospective cohort study. BMJ Open 2013;3(12):e003684. PMID 24345898
03: Alan N, Lee P, Ozpinar A, Gross BA, Jankowitz BT. Robotic stereotactic assistance (ROSA) utilization of minimally invasive placement of intraparenchymal hematoma and intraventricular catheters. World Neurosurg 2017;108:996.e7-e10. PMID 28919568
04: ATACH Investigators. Antihypertensive treatment of acute cerebral hemorrhage. Antihypertensive Treatment of Acute Cerebral Hemorrhage Investigators. Crit Care Med 2010;38(2):637-48. PMID 19770736
05: Bateman BT, Schumacher HC, Bushnell CD, et al. Intracerebral hemorrhage in pregnancy. Neurology 2006;67:424-9. PMID 16894102
06: Bereczki D, Fekete I, Prado GF, Liu M. Mannitol for acute stroke. Cochrane Database Syst Rev 2007;(3):CD001153. PMID 17636655
07: Biffi A, Teo KC, Castello JP, et al. Impact of uncontrolled hypertension at 3 months after intracerebral hemorrhage. J Am Heart Assoc 2021;10(11):e020392. PMID 33998241
08: Boulouis G, Morotti A, Brouwers HB, et al. Noncontrast computed tomography hypodensities predict poor outcome in intracerebral hemorrhage patients. Stroke 2016;47(10):2511-6. PMID 27601380
09: Bradley WG. Hemorrhage and hemorrhagic infection in the brain. In: Hasso AN, Truwit CL, editors. Neuroimaging clinics of North America. Philadelphia: WB Saunders, 1994:707-32.
10: Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy to use predictor of 30-day mortality. Stroke 1993;24(7):987-93. PMID 8322400
11: Broderick JP, Diringer MN, Hill MD, et al. Determinants of intracerebral hemorrhage growth: an exploratory analysis. Stroke 2007;38(3):1072-5. PMID 17290026
12: Broderick JP, Phillips SJ, Whisnant JP, et al. Incidence rate of stroke in the eighties: the end of the decline in stroke. Stroke 1989;20:577-82. PMID 2718196
13: Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28(1):1-5. PMID 8996478
14: Brott T, Thalinger K, Kertzberg V. Hypertension as a risk factor for spontaneous intracerebral hemorrhage. Stroke 1986;17:1078-83. PMID 3810704
15: Buletko AB, Thacker T, Cho SM, et al. Cerebral ischemia and deterioration with lower blood pressure target in intracerebral hemorrhage. Neurology 2018;91(11):e1058-66. PMID 30097480
16: Buring JE, Bogousslavsky J, Dyken M. Aspirin and stroke. Stroke 1998;29:885-6. PMID 9596229
17: Butcher KS, Baird T, MacGregor L, et al. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke 2004;35:1879-85. PMID 15178826
18: Cantu C, Arauz A, Murillo-Bonilla LM, Lopez M, Barinagarrementeria F. Stroke associated with sympathomimetics contained in over-the-counter cough and cold drugs. Stroke 2003;34(7):1667-72. PMID 12791938
19: Caplan LR. Intracerebral hemorrhage revisited. Neurology 1988;38:624-7. PMID 3352921
20: Caplan LR. Clinical features of spontaneous intracerebral hemorrhage. In: Kauffman HH, editor. Intracerebral hematomas. New York: Raven, 1992:31-47.
21: Cardim D, Robba C, Donnelly J, et al. Prospective study on non-invasive assessment of ICP in head injured patients: comparison of four methods. J Neurotrauma 2016;33(8):792-802. PMID 26414916
22: Chambers IR, Banister K, Mendelow AD. Intracranial pressure within a developing intracerebral haemorrhage. Br J Neurosurg 2001;15(2):140-1. PMID 11360378
23: Chan KH, Ka-Kit Leung G, Lau KK, et al. Predictive value of the HAS-BLED Score for the risk of recurrent intracranial hemorrhage after first spontaneous intracranial hemorrhage. World Neurosurg 2014;82(1-2):e219-23. PMID 23500346
24: Charcot JM, Bouchard C. Nouvelles recherches sur la pathogenie de I'hemorragie cerebrale. Arch Physiol Norm Pathol 1868;1:110-27.
25: Charidimou A, Meegahage R, Fox Z, et al. Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry. 2013;84(6):624-9. PMID 23412074
26: Chen ST, Chiang CY, Hsu CY, Lee TH, Tang LM. Recurrent hypertensive intracerebral hemorrhage. Acta Neurol Scand 1995;90:128-32. PMID 7785422
27: Claassen J, Jette N, Chum F, et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology 2007;69(13):1356-65. PMID 17893296
28: Cole FM, Yates PO. The occurrence and significance of intracerebral microaneurysms. J Pathol Bacteriol 1967;93:393-411. PMID 6054051
29: Cushing H. The blood pressure reaction of acute cerebral compression, illustrated by cases of intracerebral hemorrhage. Am J Med Sci 1903;125:1017-44.
30: Dandapani BK, Suzuki S, Kelley RE, Reyes-Iglesias Y, Duncan RC. Relation between blood pressure and outcome in intracerebral hemorrhage. Stroke 1995;26(1):21-4. PMID 7839391
31: Delgado Almandoz JE, Schaefer PW, Goldstein JN, et al. Practical scoring system for the identification of patients with intracerebral hemorrhage at highest risk of harboring an underlying vascular etiology: the Secondary Intracerebral Hemorrhage Score. AJNR Am J Neuroradiol 2010;31(9):1653-60. PMID 20581068
32: Den Hertog HM, van der Worp HB, Tseng MC, Dippel DW. Cooling therapy for acute stroke. Cochrane Database Syst Rev 2009;(1):CD001247. PMID 19160194
33: Diringer MN. Intracerebral hemorrhage: pathophysiology and management. Crit Care Med 1993;21:1591-603. PMID 8403973
34: Dolinskas CA, Bilaniuk LT, Zimmerman RA, et al. Computer tomography of intracerebral hematomas. I. Transmission CT observations on hematoma resolution. AJR Am J Roentgenol 1977;129:681-8. PMID 409244
35: Elmer J, Hou P, Wilcox SR, et al. Acute respiratory distress syndrome after spontaneous intracerebral hemorrhage. Crit Care Med 2013;41:1992-2001. PMID 23760151
36: Falcone GJ, Biffi A, Devan WJ, et al. Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage. Stroke 2012;43(11):2877-83. PMID 22933587
37: FAST Trial Investigators. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008;358(20):2127-37. PMID 18480205
38: Faught E, Peters D, Bartolucci A, et al. Seizures after primary intracerebral hemorrhage. Neurology 1989;39:1089-93. PMID 2761703
39: Fiebach JB, Schellinger PD, Grass A, et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage. A multicenter study on the validity of stroke imaging. Stroke 2004;35:502-7. PMID 14739410
40: Field NC, Custozzo AJ, Harland TA, et al. Drainage, irrigation, and fibrinolytic therapy (DRIFT) for adult intraventricular hemorrhage associated with primary hypertensive hemorrhages using IRRAflow self-irrigating catheter: a report of three cases and prior historical controls. World Neurosurg 2023;177:137-42. PMID 37356487
41: Fields WS, Lemak NA. A history of stroke: its recognition and treatment. New York: Oxford Univ Pr, 1989.
42: Firsching R, Huber M, Frowein RA. Cerebellar haemorrhage: management and prognosis. Neurosurg Rev 1991;14:191-4. PMID 1944934
43: Fisher CM. Pathological observation in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol 1971;30:536-50. PMID 4105427
44: Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008;71:1084-9. PMID 18824672
45: Fukuda H, Munoz D, Macdonald RL. Spontaneous thalamic hemorrhage from a lateral posterior choroidal artery aneurysm. World Neurosurg 2013;80(6):900.e1-6. PMID 23396071
46: Furlan AJ, Whisnant JP, Elveback LR. The decreasing incidence of primary intracerebral hemorrhage: a population study. Ann Neurol 1979;5:367-73. PMID 375807
47: Gattringer T, Niederkorn K, Seyfang L, et al. Myocardial infarction as a complication in acute stroke: results from the austrian stroke unit registry. Cerebrovasc Dis 2014;37(2):147-52. PMID 24481543
48: Gavito-Higuera J, Khatri R, Qureshi IA, Maud A, Rodriguez GJ. Aggressive blood pressure treatment of hypertensive intracerebral hemorrhage may lead to global cerebral hypoperfusion: case report and imaging perspective. World J Radiol 2017;9(12):448-53. PMID 29354210
49: Gillow SJ, Ouyang B, Lee VH, John S. Factors associated with fever in intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2017;26(6):1204-8. PMID 28187992
50: Global Neurotrauma Research Group. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012;367(26):2471-81. PMID 23234472
51: Goldstein JN, Fazen LE, Snider R, et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology 2007;68(12):889-94. PMID 17372123
52: Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke 2022;53(7):e282-361. PMID 35579034
53: Gregson BA, Broderick JP, Auer LM, et al. Individual patient data subgroup meta-analysis of surgery for spontaneous supratentorial intracerebral hemorrhage. Stroke 2012;43(6):1496-504. PMID 22511006
54: Gross CR, Kase CS, Mohr JP, et al. Stroke in South Alabama: incidence and diagnostic features—a population based study. Stroke 1984;15:249-55. PMID 6701932
55: Guth JC, Nemeth AJ, Rosenberg NF, et al. Subarachnoid extension of primary intracerebral hemorrhage is associated with fevers. Neurocrit Care 2014;20(2):187-92. PMID 24186539
56: Hallevi H, Albright KC, Aronowski J, et al. Intraventricular hemorrhage: Anatomic relationships and clinical implications. Neurology 2008;70(11):848-52. PMID 18332342
57: Han Y, Sheng K, Su M, Yang N, Wan D. Local mild hypothermia therapy as an augmentation strategy for minimally invasive surgery of hypertensive intracerebral hemorrhage: a meta-analysis of randomized clinical trials. Neuropsychiatr Dis Treat 2016;13:41-9. PMID 28096671
58: Hanley DF, Lane K, McBee N, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet 2017;389(10069):603-11. PMID 28081952
59: Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995;26:1471-7. PMID 7631356
60: Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32(4):891-7. PMID 11283388
61: Hemphill JC, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015;46(7):2032-60. PMID 26022637
62: Hemphill JC, Morabito D, Farrant M, Manley GT. Brain tissue oxygen monitoring in intracerebral hemorrhage. Neurocrit Care 2005;3:260-70. PMID 16377842
63: Hemphill JC, Newman J, Zhao S, Johnston SC. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke 2004;35(5):1130-4. PMID 15044768
64: Hemphill K, Tierney S, Tirschwell D, Davis AP. A review of methamphetamine use and stroke in the young. Front Neurol 2024;15:1397677. PMID 38721123
65: Herrick DB, Ullman N, Nekoovaght-Tak S, et al. Determinants of external ventricular drain placement and associated outcomes in patients with spontaneous intraventricular hemorrhage. Neurocrit Care 2014;21(3):426-34. PMID 24522761
66: Heuts SG, Bruce SS, Zacharia BE, et al. Decompressive hemicraniectomy without clot evacuation in dominant-sided intracerebral hemorrhage with ICP crisis. Neurosurg Focus 2013;34(5):E4. PMID 23634923
67: Hill MD, Silver FL, Austin PC, et al. Rate of stroke recurrence in patients with primary intracerebral hemorrhage. Stroke 2000;31:123-7. PMID 10625726
68: Hinchey JA, Shephard T, Furie K, et al. Formal dysphagia screening protocols prevent pneumonia. Stroke 2005;36(9):1972-6. PMID 16109909
69: Hino A, Fujimoto M, Yamaki T, Iwamoto Y, Katsumori T. Value of repeat angiography in patients with spontaneous subcortical hemorrhage. Stroke 1998;29(12):2517-21. PMID 9836762
70: Honig A, Eliahou R, Pikkel YY, Leker RR. Drops in barometric pressure are associated with deep intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2016;25(4):872-6. PMID 26803722
71: Hu S, Ma Q, Li B, Wu Q, Han R. Association of hypothyroidism with hypertensive intracerebral hemorrhage: a case-control study. World Neurosurg 2020;134:e8-e11. PMID 31421295
72: Hu X, Zhang JH, Qin X. Risk factors of early death in patients with hypertensive intracerebral hemorrhage during hospitalization. Acta Neurochir Suppl 2011;111:387-91. PMID 21725788
73: Iglesias-Rey R, Rodríguez-Yáñez M, Arias S, et al. Inflammation, edema and poor outcome are associated with hyperthermia in hypertensive intracerebral hemorrhages. Eur J Neurol 2018;25(9):1161-8. PMID 29751370
74: Inaji M, Tomita H, Tone O, et al. Chronological change of perihematomal edema of human intracerebral hematoma. Acta Neurochir Suppl 2003;86:445-8. PMID 14753483
75: INTERACT Investigators. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT). Stroke 2010;41(2):307-12. PMID 20044534
76: INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368(25):2355-65. PMID 23713578
77: INTERACT2 Investigators. Significance of intraventricular hemorrhage in acute intracerebral hemorrhage: intensive blood pressure reduction in acute cerebral hemorrhage trial results. Stroke 2015;46(3):653-8. PMID 25677598
78: Jauch EC, Lindsell CJ, Adeoye O, et al. Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage. Stroke 2006; 37(8):2061-5. PMID 16794216
79: Junttila E, Ala-Kokko T, Ohtonen P, et al. Neurogenic pulmonary edema in patients with nontraumatic intracerebral hemorrhage: predictors and association with outcome. Anesth Analg 2013;116:855-61. PMID 23429802
80: Kadkhodayan Y, Delgado Almandoz JE, Kelly JE, et al. Yield of catheter angiography in patients with intracerebral hemorrhage with and without intraventricular extension. J Neurointerv Surg 2012;4(5):358-63. PMID 21990524
81: Kalita J, Misra UK, Kumar B. Is β-blocker (atenolol) a preferred antihypertensive in acute intracerebral hemorrhage. Neurol Sci 2013;34(7):1099-104. PMID 23053838
82: Kazui S, Naritomi H, Yamamoto H, et al. Enlargement of spontaneous intracerebral hemorrhage: incidence and time course. Stroke 1996;27:1783-7. PMID 8841330
83: Kim-Han JS, Kopp SJ, Dugan LL, Diringer MN. Perihematomal mitochondrial dysfunction after intracerebral hemorrhage. Stroke 2006;37(10):2457-62. PMID 16960094
84: Kim JS, Lee JH, Lee M. Small primary intracerebral hemorrhage. Clinical presentation of 28 cases. Stroke 1994;25:1500-6. PMID 8023369
85: Kim YZ, Park YH, Song YG, Kim KH. Clinical analysis of factors predisposing the recurrence of primary intracerebral hemorrhage in patients taking anti-hypertensive drugs: a prospective cohort study. Clin Neurol Neurosurg 2013;115(5):578-86. PMID 22877684
86: Kiphuth IC, Kuramatsu JB, Lücking H, Kloska S, Schwab S, Huttner HB. Predictive factors for percutaneous endoscopic gastrostomy in patients with spontaneous intracranial hemorrhage. Eur Neurol 2011;65:32-8. PMID 21196737
87: Ko SB, Choi HA, Parikh G, Helbok R, Schmidt JM, Lee K, Badjatia N, Claassen J, Connolly ES, Mayer SA. Multimodality monitoring for cerebral perfusion pressure optimization in comatose patients with intracerebral hemorrhage. Stroke 2011;42:3087-92. PMID 21852615
88: Koivunen RJ, Satopää J, Meretoja A, et al. Incidence, risk factors, etiology, severity and short-term outcome of non-traumatic intracerebral hemorrhage in young adults. Eur J Neurol 2015;22(1):123-32. PMID 25142530
89: Kunitz SC, Gross CR, Heyman A, et al. The pilot stroke data bank: definition, design and data. Stroke 1984;15:740-6. PMID 6464070
90: Kuramatsu JB, Biffi A, Gerner ST, et al. Association of surgical hematoma evacuation vs conservative treatment with functional outcome in patients with cerebellar intracerebral hemorrhage. JAMA 2019;322(14):1392-403. PMID 31593272
91: Laible M, Horstmann S, Möhlenbruch M, et al. Renal dysfunction is associated with deep cerebral microbleeds but not white matter hyperintensities in patients with acute intracerebral hemorrhage. J Neurol 2015;262(10):2312-22. PMID 26174652
92: Lammie GA, Lindley R, Keir S, et al. Stroke-related primary intracerebral hemorrhage. Autopsy clues to underlying mechanism. Stroke 2000;31:1426-8. PMID 10835467
93: Lample Y, Gilad R, Eshely Y, et al. Neurological and functional outcome in patients with supratentorial hemorrhage. A prospective study. Stroke 1995;26:2249-53. PMID 7491645
94: Lassen NA. Control of cerebral circulation in health and death. Circ Res 1974;34:749. PMID 4598993
95: Leira R, Davalos A, Silva Y, et al. Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology 2004;63(3):461-7. PMID 15304576
96: Li M, Mu F, Su D, Han Q, Guo Z, Chen T. Different surgical interventions for patients with spontaneous supratentorial intracranial hemorrhage: a network meta-analysis. Clin Neurol Neurosurg 2020;188:105617. PMID 31775069
97: Lin CM, Lin MC, Huang SJ, et al. A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients. Biomed Res Int 2015;2015:529580. PMID 26413530
98: Linfante I. Can MRI reliably detect hyperacute intracerebral hemorrhage. Ask the medical student. Stroke 2004;35:506-7. PMID 14739405
99: Little JR, Dial B, Bellanger G, Carpenter S. Brain hemorrhage from intracranial tumor. Stroke 1979;10:283-8. PMID 462514
100: Maas MB, Rosenberg NF, Kosteva AR, et al. Surveillance neuroimaging and neurologic examinations affect care for intracerebral hemorrhage. Neurology 2013;81(2):107-12. PMID 23739227
101: MacMahon S, Peto R, Cutler JA, et al. Blood pressure, stroke and coronary heart disease. I. Effects of prolonged differences in blood pressure—evidence from nine prospective observational studies corrected for the regression dilution bias. Lancet 1990;335:765-74. PMID 1975346
102: Magaki S, Chen Z, Haeri M, et al. Charcot-Bouchard aneurysms revisited: clinicopathologic correlations. Mod Pathol 2021;34(12):2109-21. PMID 34326486
103: Maissan IM, Dirven PJ, Haitsma IK, Hoeks SE, Gommers D, Stolker RJ. Ultrasonographic measured optic nerve sheath diameter as an accurate and quick monitor for changes in intracranial pressure. J Neurosurg 2015;123(3):743-7. PMID 25955869
104: Malhotra A. Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med 2007;357:1113-20. PMID 17855672
105: Maramattom BV, Manno EM, Fulgham JR, Jaffe AS, Wijdicks EF. Clinical importance of cardiac troponin release and cardiac abnormalities in patients with supratentorial cerebral hemorrhages. Mayo Clin Proc 2006;81(2):192-6. PMID 16471073
106: Matsumoto N, Whisnant JP, Kurland LT, et al. Natural history of stroke in Rochester, Minnesota 1955 through 1969: an extension of previous study 1945 through 1954. Stroke 1973;4:20-9. PMID 4685804
107: Maurino J, Saposnik G, Lepera S, Rey RC, Sica RE. Multiple simultaneous intracerebral hemorrhages: clinical features and outcome. Arch Neurol 2001;58:629-32. PMID 11295994
108: McCarron MO, Nicoll JA. Cerebral amyloid angiopathy and thrombolysis-related intracerebral hemorrhage. Lancet Neurol 2004;3:484-90. PMID 15261609
109: Meretoja A, Strbian D, Putaala J, et al. SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage. Stroke 2012;43(10):2592-7. PMID 22858729
110: Messe SR, Sansing LH, Cucchiara BL, et al. Prophylactic antiepileptic drug use is associated with poor outcome following ICH. Neurocrit Care 2009;11(1):38-44. PMID 19319701
111: Misra UK, Kalita J, Somarajan BI. Recurrent intracerebral hemorrhage in patients with hypertension is associated with APOE gene polymorphism: a preliminary study. J Stroke Cerebrovasc Dis 2013;22(6):758-63. PMID 22410653
112: Misra UK, Kalita J, Somarajan BI, Kumar B, Das M, Mittal B. Do ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage. Neurol Sci 2012;33(5):1071-7. PMID 22198647
113: MISTIE Investigators. Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial. Lancet Neurol 2016;15(12):1228-37. PMID 27751554
114: MISTIE III Investigators. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019;393(10175):1021-32. PMID 30739747
115: Mohr JP, Caplan LR, Melski JW, et al. The Harvard Cooperative Stroke Registry: a prospective registry. Neurology (NY) 1978;28:754-62. PMID 567291
116: Monteith SJ, Kassell NF, Goren O, Harnof S. Transcranial MR-guided focused ultrasound sonothrombolysis in the treatment of intracerebral hemorrhage. Neurosurg Focus 2013;34(5):E14. PMID 23634918
117: Morgan T, Awad I, Keyl P, Lane K, Hanley D. Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl 2008a;105:217-20. PMID 19066112
118: Morgan T, Zuccarello M, Narayan R, Keyl P, Lane K, Hanley D. Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial. Acta Neurochir Suppl 2008b;105:147-51. PMID 19066101
119: Morgenstern LB, Demchuk AM, Kim DH, Frankowski RF, Grotta JC. Rebleeding leads to poor outcome in ultra-early craniotomy for intracerebral hemorrhage. Neurology 2001;56:1294-9. PMID 11376176
120: Morgenstern LB, Zahuranec DB, Sánchez BN, et al. Full medical support for intracerebral hemorrhage. Neurology 2015;84(17):1739-44. PMID 25817842
121: Morita Y, Yoshikawa T, Takahashi M. Long working hours and risk of hypertensive intracerebral haemorrhage among Japanese workers claiming compensation for overwork-related intracerebral haemorrhage: an unmatched case-control study. BMJ Open 2023;13(9):e074465. PMID 37739464
122: Morotti A, Arba F, Boulouis G, Charidimou A. Noncontrast CT markers of intracerebral hemorrhage expansion and poor outcome: a meta-analysis. Neurology 2020;95(14):632-43. PMID 32847959
123: Morotti A, Boulouis G, Dowlatshahi D, et al. Standards for detecting , interpreting, and reporting noncontrast computed tomographic markers of intracerebral hemorrhage expansion. Ann Neurol 2019;86(4):480-92. PMID 31364773
124: Mould WA, Carhuapoma JR, Muschelli J, et al. Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke 2013;44(3):627-34. PMID 23391763
125: Moullaali TJ, Wang X, Martin RH, et al. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage: a preplanned pooled analysis of individual participant data. Lancet Neurol 2019;18(9):857-64. PMID 31397290
126: Neshige S, Kuriyama M, Yoshimoto T, et al. Seizures after intracerebral hemorrhage; risk factor, recurrence, efficacy of antiepileptic drug. J Neurol Sci 2015;359(1-2):318-22. PMID 26671135
127: New PF. Computed tomography in the diagnosis of hemorrhagic stroke. In: Thompson RA, Green JR, editors. Advances in Neurology. New York: Raven, 1977:145-68.
128: NICE-SUGAR Study Investigators; Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360(13):1283-97. PMID 19318384
129: NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7. PMID 7477192
130: Nirula R, Millar D, Greene T, et al. Decompressive craniectomy or medical management for refractory intracranial hypertension: an AAST-MIT propensity score analysis. J Trauma Acute Care Surg 2014;76(4):944-52; discussion 952-5. PMID 24662856
131: Nolte KB, Brass LM, Fletterick CF. Intracerebral hemorrhage associated with cocaine abuse: a prospective autopsy study. Neurology 1996;46:1291-96. PMID 8628469
132: Nyquist PA, Brown RD Jr, Wiebers DO, Crowson CS, O'Fallon WM. Circadian and seasonal occurrence of subarachnoid and intracerebral hemorrhage. Neurology 2001;56:190-3. PMID 11160954
133: Oleinik A, Romero JM, Schwab K, et al. CT angiography for intracerebral hemorrhage does not increase risk of acute nephropathy. Stroke 2009;40:2393-7. PMID 19461032
134: Omae T, Ueda K, Ogata J, et al. Parenchymatous hemorrhage: etiology, pathology and clinical aspects. In: Toole JF, editor. Handbook of Clinical Neurology. Vascular Disease. Part II. New York: Elsevier, 1989:287-331.
135: Ott KH, Kase CS, Ojemann RG, Mohr JP. Cerebellar hemorrhage: diagnosis and treatment. A review of 56 cases. Arch Neurol 1974;31(3):160-7. PMID 4546748
136: Pallesen LP, Wagner J, Lambrou D, et al. Association of hypertensive intracerebral hemorrhage with left ventricular hypertrophy on transthoracic echocardiography. J Clin Med 2020;9(7):2148. PMID 32650380
137: Patil CG, Alexander AL, Hayden Gephart MG, Lad SP, Arrigo RT, Boakye M. A population-based study of inpatient outcomes after operative management of nontraumatic intracerebral hemorrhage in the United States. World Neurosurg 2012;78(6):640-5. PMID 22120557
138: Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage. Neurology 2001;57:18-24. PMID 11445622
139: Prasad K, Mendelow AD, Gregson B. Surgery for primary supratentorial intracerebral haemorrhage. Cochrane Database Syst Rev 2008;(4):CD000200. PMID 18843607
140: Qureshi AI, Ezzeddine MA, Nasar A, et al. Prevalence of elevated blood pressure in 563,704 adult patients with stroke presenting to the ED in the United States. Am J Emerg Med 2007;25(1):32-8. PMID 17157679
141: Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med 2016;375(11):1033-43. PMID 27276234
142: Qureshi AI, Palesch YY, Foster LD, et al. Blood pressure-attained analysis of ATACH 2 Trial. Stroke 2018;49(6):1412-8. PMID 29789395
143: Qureshi AI, Suarez JI, Bhardwaj A. Malignant cerebral edema in patients with hypertensive intracerebral hemorrhage associated with hypertonic saline infusion: a rebound phenomenon. J Neurosurg Anesthesiol 1998;10(3):188-92. PMID 9681408
144: Rabinstein AA, Atkinson JL, Wijdicks EF. Emergency craniotomy in patients worsening due to expanded cerebral hematoma. To what purpose. Neurology 2002;58:1367-72. PMID 12011282
145: Rickard AC, Smith JE, Newell P, Bailey A, Kehoe A, Mann C. Salt or sugar for your injured brain? A meta-analysis of randomised controlled trials of mannitol versus hypertonic sodium solutions to manage raised intracranial pressure in traumatic brain injury. Emerg Med J 2014;31(8):679-83. PMID 23811861
146: Rincon F, Hunter K, Schorr C, Dellinger RP, Zanotti-Cavazzoni S. The epidemiology of spontaneous fever and hypothermia on admission of brain injury patients to intensive care units: a multicenter cohort study. J Neurosurg 2014;121(4):950-60. PMID 25105701
147: Rivera-Lara L, Cho SM, Li Y, et al. Mechanistic evaluation of diffusion weighted hyperintense lesions after large spontaneous intracerebral hemorrhage: a subgroup analysis of MISTIE III. Neurocrit Care 2024;40(3):1140-50. PMID 38040993
148: Rodriguez-Luna D, Piñeiro S, Rubiera M, et al. Impact of blood pressure changes and course on hematoma growth in acute intracerebral hemorrhage. Eur J Neurol 2013;20(9):1277-83. PMID 23647568
149: Roerecke M, Kaczorowski J, Tobe SW, Gmel G, Hasan OSM, Rehm J. The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis. Lancet Public Health 2017;2(2):e108-20. PMID 29253389
150: Romero JM, Brouwers HB, Lu J, et al. Prospective validation of the computed tomographic angiography spot sign score for intracerebral hemorrhage. Stroke 2013;44(11):3097-102. PMID 24021687
151: Roob G, Lochner A, Schmidt R, et al. Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 2000;31:2665-9. PMID 11062292
152: Ropper AA. Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. N Engl J Med 1986;314:953-8. PMID 3960059
153: Rost NS, Smith EE, Chang Y, et al. Prediction of functional outcome in patients with primary intracerebral hemorrhage: the FUNC score. Stroke 2008;39(8):2304-9. PMID 18556582
154: Roy-O'Reilly M, Zhu L, Atadja L, et al. Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema. Ann Clin Transl Neurol 2017;4(11):793-800. PMID 29159191
155: Ruiz-Sandoval JL, Romero-Vargas S, Chiquete E, et al. Hypertensive intracerebral hemorrhage in young people: previously unnoticed age-related clinical differences. Stroke 2006;37(12):2946-50. PMID 17095739
156: Russell WR. Observation on intracerebral aneurysms. Brain 1963;86:425-42. PMID 14063893
157: Saeed F, Adil MM, Piracha BH, Qureshi AI. Acute renal failure worsens in-hospital outcomes in patients with intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2015;24(4):789-94. PMID 25680664
158: Safatli DA, Günther A, Schlattmann P, Schwarz F, Kalff R, Ewald C. Predictors of 30-day mortality in patients with spontaneous primary intracerebral hemorrhage. Surg Neurol Int 2016;7(Suppl 18):S510-7. PMID 27583176
159: Salcman M. Intracranial hemorrhage caused by brain tumor. In: Kaufman HH, editor. Intracerebral hematomas. New York: Raven, 1992:95-105.
160: Saloheimo P, Ahonen M, Juvela S, et al. Regular aspirin use preceeding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006;37:129-33. PMID 16322483
161: Samudra N, Figueroa S. Intractable central hyperthermia in the setting of brainstem hemorrhage. Ther Hypothermia Temp Manag 2016;6(2):98-101. PMID 26982342
162: Sandhu R, Aronow WS, Rajdev A, et al. Relation of cardiac troponin I levels with in-hospital mortality in patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Am J Cardiol 2008;102:632-4. PMID 18721527
163: Sawada T. Medical treatment of hypertensive intracerebral hemorrhage. In: Hashi K, Saito I, editors. Surgical Treatment of Hypertensive Intracerebral Hematoma. Tokyo: Mt. Fuji Workshop on CVD, 1986:23-7.
164: Schellinger PD, Fiebach JB, Hoffman K, et al. Stroke MRI in intracerebral hemorrhage. Is there a perihemorrhagic penumbra. Stroke 2003;34:1674-80. PMID 12805502
165: Schmidt LB, Goertz S, Wohlfahrt J, Melbye M, Munch TN. Recurrent intracerebral hemorrhage: associations with comorbidities and medicine with antithrombotic effects. PLoS One 2016;11(11):e0166223. PMID 27832176
166: Scott WR, New PF, Davis KR, et al. Computerized axial tomography of intracerebral and intraventricular hemorrhage. Radiology 1974;112:73-80. PMID 4598952
167: SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;256:3255-64. PMID 2046107
168: Steiner I, Gomori JM, Melamed E. The prognostic value of the CT scan in conservatively treated patients with intracerebral hematoma. Stroke 1984;15:279-82. PMID 6701936
169: STICH Investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral hematomas in the International Surgical Trial in Intracerebral Hemorrhage (STICH): a randomized trial. Lancet 2005;365:387-97. PMID 15680453
170: STICH II Investigators. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomized trial [published correction appears in Lancet. 2013;382:396]. Lancet 2013;382:397-408. PMID 23726393
171: St Louis EK, Wijdicks EF, Li H, Atkinson JD. Predictors of poor outcome in patients with a spontaneous cerebellar hematoma. Can J Neurol Sci. 2000 Feb;27(1):32–36. PMID 10676585
172: Suzuki R, Ohno K, Hiratsuka H, et al. Chronological change in brain edema in hypertensive intracerebral hemorrhage observed by CT and xenon-enhanced CT. In: Inaba Y, Klatzo I, Spatz M, editors. Brain Edema. Berlin: Springer, 1985: 613-20.
173: Takahata H, Tsutsumi K, Baba H, Nagata I, Yonekura M. Early intervention to promote oral feeding in patients with intracerebral hemorrhage: a retrospective cohort study. BMC Neurol 2011;11:6. PMID 21247473
174: Takebayashi S, Kaneko M. Electron microscopic studies of intracerebral hemorrhage. Stroke 1983;14:28-36. PMID 6823683
175: Tapia-Perez JH, Gehring S, Zilke R, Schneider T. Effect of increased glucose levels on short-term outcome in hypertensive spontaneous intracerebral hemorrhage. Clin Neurol Neurosurg 2014a;118:37-43. PMID 24529227
176: Tapia-Perez JH, Zilke R, Schneider T. Match-study of statin therapy in spontaneous intracerebral hemorrhage: is the discontinuation reasonable? J Neurosurg Sci 2016;60(3):301-12. PMID 25501007
177: TICH-2 Investigators. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet 2018;391(10135):2107-15. PMID 29778325
178: Tsivgoulis G, Katsanos AH, Butcher KS, et al. Intensive blood pressure reduction in acute intracerebral hemorrhage: a meta-analysis. Neurology 2014;83(17):1523-9. PMID 25239836
179: Tuttolomondo A, Maugeri R, Orlando E, et al. β-amyloid wall deposit of temporal artery in subjects with spontaneous intracerebral haemorrhage. Oncotarget 2018;9(78):34699-707. PMID 30410670
180: van Loon J, Van Calenbergh F, Goffin J, Plets C. Controversies in the management of spontaneous cerebellar haemorrhage: a consecutive series of 49 cases and review of the literature. Acta Neurochir (Wien) 1993;122:187-93. PMID 8372706
181: Vedicherla SV, Foo AS, Sharma VK, et al. The "Blush" sign on computed tomography angiography is an independent predictor of hematoma progression in primary hypertensive hemorrhage. J Stroke Cerebrovasc Dis 2018;27(7):1878-84. PMID 29571760
182: Vemmos KN, Tsivgoulis G, Spengos K, et al. Association between 24-h blood pressure monitoring variables and brain oedema in patients with hyperacute stroke. J Hypertens 2003;21(11):2167-73. PMID 14597861
183: Vespa P, Hanley D, Betz J, et al. ICES (Intraoperative Stereotactic Computed Tomography-Guided Endoscopic Surgery) for brain hemorrhage: a multicenter randomized controlled trial. Stroke 2016;47(11):2749-55. PMID 27758940
184: Vespa PM, O’Phelan K, Shah M, et al. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology 2003;60(9):1441-6. PMID 12743228
185: Viswanathan A, Chabriat H. Cerebral microhemorrhage. Stroke 2006;37:550-5. PMID 16397165
186: Wada R, Aviv RI, Fox AJ, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38(4):1257-62. PMID 17322083
187: Wagner A, Schebesch KM, Zeman F, et al. Primary cCT imaging based clinico-neurological assessment-calling for addition of telestroke video consultation in patients with intracerebral hemorrhage. Front Neurol 2018;9:607. PMID 30093878
188: Wagner I, Hauer EM, Staykov D, et al. Effects of continuous hypertonic saline infusion on perihemorrhagic edema evolution. Stroke 2011;42(6):1540-5. PMID 21512173
189: Wagner KR, Xi G, Hua Y, et al. Lobar intracerebral hemorrhage model in pigs. Rapid edema development in perihematomal white matter. Stroke 1996;27:490-7. PMID 8610319
190: Walsh KB, Woo D, Sekar P, et al. Untreated hypertension: a powerful risk factor for lobar and non-lobar intracerebral hemorrhage in whites, blacks, and hispanics. Circulation 2016;134(19):1444-1452. PMID 27737957
191: Wang WZ, Jiang B, Liu HM, et al. Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China. Int J Stroke 2009;4:11-6. PMID 19236490
192: Wang YX, Yan A, Ma ZH, et al. Nuclear factor-κB and apoptosis in patients with intracerebral hemorrhage. J Clin Neurosci 2011;18(10):1392-5. PMID 21782444
193: Wolf ME, Alonso A, Ebert AD, Szabo K, Chatzikonstantinou A. Etiologic and clinical characterization of patients with recurrent spontaneous intracerebral hemorrhage. Eur Neurol 2016;76(5-6):295-301. PMID 27806359
194: Wolfe TJ, Torbey MT. Management of intracranial pressure. Curr Neurol Neurosci Rep 2009;9:477-85. PMID 19818235
195: Wong GK, Siu DY, Abrigo JM, et al. Computed tomographic angiography and venography for young or nonhypertensive patients with acute spontaneous intracerebral hemorrhage. Stroke 2011;42(1):211-3. PMID 21088241
196: Wu YT, Li TY, Chiang SL, Chu HY, Chang ST, Chen LC. Predictors of first-week mortality in patients with acute spontaneous cerebellar hemorrhage. Cerebellum 2013;12(2):165-70. PMID 22907124
197: Xia Z, Wu X, Li J, et al. Minimally invasive surgery is superior to conventional craniotomy in patients with spontaneous supratentorial intracerebral hemorrhage: a systematic review and meta-analysis. World Neurosurg 2018;115:266-73. PMID 29730105
198: Yang Q, Zhuang X, Peng F, Zheng W. Relationship of plasma matrix metalloproteinase-9 and hematoma expansion in acute hypertensive cerebral hemorrhage. Int J Neurosci 2016;126(3):213-8. PMID 26708160
199: Yeh SJ, Tang SC, Tsai LK, Jeng JS. Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by SMASH-U classification system. Stroke 2014;45(9):2636-42. PMID 25052320
200: Yuan Q, Wu X, Sun Y, et al. Impact of intracranial pressure monitoring on mortality in patients with traumatic brain injury: a systematic review and meta-analysis. J Neurosurg 2015;122(3):574-87. PMID 25479125
201: Zhang YB, Zheng SF, Yao PS, et al. Lower ionized calcium predicts hematoma expansion and poor outcome in patients with hypertensive intracerebral hemorrhage. World Neurosurg 2018;118:e500-4. PMID 30257302
202: Zhu XL, Chan MS, Poon WS. Spontaneous intracranial hemorrhage: which patients need diagnostic cerebral angiography. A prospective study of 206 cases and review of the literature. Stroke 1997;28(7):1406-9. PMID 9227692
203: Zimmerman RD, Leads NE, Naidick TP. Ring blush associated with intracerebral hematoma. Radiology 1977;122:707-11. PMID 841056
204: Zuccarello M, Brott T, Derex L, et al. Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study. Stroke 1999;30(9):1833-9. PMID 10471432

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Adrian Marchidann MD

Dr. Marchidann of Kings County Hospital has no relevant financial relationships to disclose.
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Editor

Steven R Levine MD

Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.
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Former Authors

Te-Long Hwang MD

Patient Profile

Age range of presentation: 45 to 65+ years
Sex preponderance: male>female, >1:1
Heredity: none
Population groups selectively affected: African Americans
Occupation groups selectively affected: none selectively affected

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Hypertensive intracerebral hemorrhage

Associated Disorders

Chronic hypertension
Intracerebral hemorrhage

Differential Diagnosis

amyloid angiopathy
drug-related intracerebral hemorrhage
anticoagulant-related intracerebral hemorrhage
intracerebral hemorrhage due to thrombolytic therapy
hematological disorders
- vascular malformations
- aneurysm
- brain tumor
- hemorrhagic infarction
- exposure to very cold weather
- dental pain from manipulation of the trigeminal nerve
- carotid endarterectomy
- correction of congenital heart defects
- cardiac transplantation

	• Uncontrolled blood pressure after a hemorrhagic stroke is associated with recurrent stroke and mortality.
	• Treatment of hypertension is the most important preventive measure for intracerebral hemorrhage.
	• Treatment of isolated systolic pressure is also important.
	• Target blood pressure control is 130/80 mmHg.

Hypertensive intracerebral hemorrhage

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Signs of Intracerebral Hemorrhage at Various Sites

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Table 2. Stages of Hemorrhage

Management

Outcomes

Special considerations

Pregnancy

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Questions or Comment?

Also in This Category

Metal neurotoxicity

Vascular cognitive impairment

Ischemic stroke

Cerebral embolism

Hormonal contraception and stroke

Antiphospholipid antibody syndrome

Addictive disorders

Automatic-voluntary dissociation

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