Sections

Treatment

Approach Considerations

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

Anticonvulsants - To prevent seizure recurrence
Antihypertensive agents - To reduce BP and other risk factors of heart disease
Osmotic diuretics - To decrease intracranial pressure in the subarachnoid space

Management begins with stabilization of vital signs. Perform endotracheal intubation for patients with a decreased level of consciousness and poor airway protection. Intubate and hyperventilate if intracranial pressure is elevated, and initiate administration of mannitol for further control. Rapidly stabilize vital signs, and simultaneously acquire an emergent computed tomography (CT) scan. Glucose levels should be monitored, with normoglycemia recommended.^[1]Antacids are used to prevent associated gastric ulcers.

No effective targeted therapy for hemorrhagic stroke exists yet. Studies of recombinant factor VIIa (rFVIIa) have yielded disappointing results. Evacuation of hematoma, either via open craniotomy or endoscopy, may be a promising ultra-early-stage treatment for intracerebral hemorrhage that may improve long-term prognosis.

A combined analysis of INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) 1 and 2 suggested that in patients with intracerebral hemorrhage, intensive BP reduction early in their treatment lessens the absolute growth of hematomas, with the effect being especially pronounced in patients who have undergone prior antithrombotic therapy.^[30]

The study involved 1310 patients who had undergone repeat 24-hour CT scans, including 665 who received intensive BP reduction therapy (target BP < 140 mm Hg systolic) and 645 controls (target BP < 180 mm Hg systolic).^[30]A total of 235 patients in the intensive reduction and control groups had received antithrombotic medication prior to intracerebral hemorrhage.

The investigators found that, in patients who had not had prior antithrombotic therapy, hematoma volume increased 1.1 mL on repeat CT scan in those who underwent intensive BP reduction, compared with 2.4 mL in controls.^[30]In patients who had previously taken antithrombotics, however, the difference between the intensive-reduction and control groups was much greater, with the increase in hematoma volume being 3.4 mL in the intensive-reduction patients and 8.1 mL in the controls.

Management of Seizures

Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage; these seizures are often nonconvulsive.^{[31, 32]}According to American Heart Association/American Stroke Association (AHA/ASA) 2010 guidelines for the management of spontaneous intracerebral hemorrhage, patients with clinical seizures or electroencephalographic (EEG) seizure activity accompanied by a change in mental status should be treated with antiepileptic drugs.^[1]

Patients for whom treatment is indicated should immediately receive a benzodiazepine, such as lorazepam or diazepam, for rapid seizure control. This should be accompanied by phenytoin or fosphenytoin loading for longer-term control.

Prophylaxis

The utility of prophylactic anticonvulsant medication remains uncertain. In prospective and population-based studies, clinical seizures have not been associated with worse neurologic outcome or mortality. Indeed, 2 studies have reported worse outcomes in patients who did not have a documented seizure but who received antiepileptic drugs (primarily phenytoin).^[1]

The 2010 AHA/ASA guidelines do not offer recommendations on prophylactic anticonvulsants, but suggest that continuous EEG monitoring is probably indicated in patients with intracranial hemorrhage whose mental status is depressed out of proportion to the degree of brain injury

Prophylactic anticonvulsant therapy has been recommended in patients with lobar hemorrhages to reduce the risk of early seizures. One large, single-center study showed that prophylactic antiepileptic drugs significantly reduced the number of clinical seizures in these patients.^[31]

In addition, AHA/ASA guidelines from 2012 suggest that prophylactic anticonvulsants may be considered for patients with aneurysmal subarachnoid hemorrhage. In such cases, however, anticonvulsant use should generally be limited to the immediate post-hemorrhagic period. Routine long-term use is not recommended, but it may be considered in patients with a prior seizure history, intracerebral hematoma, intractable hypertension, or infarction or aneurysm at the middle cerebral artery.^[33]

Blood Pressure Control

No controlled studies have defined optimum BP levels for patients with acute hemorrhagic stroke, but greatly elevated BP is thought to lead to rebleeding and hematoma expansion. Stroke may result in loss of cerebral autoregulation of cerebral perfusion pressure.

Intensive BP reduction (target BP < 140 mm Hg systolic) early in the treatment of patients with intracerebral hemorrhage appears to lessen the absolute growth of hematomas, particularly in patients who have received previous antithrombotic therapy, according to a combined analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (INTERACT).^[30]

Suggested agents for use in the acute setting are beta blockers (eg, labetalol) and angiotensin-converting enzyme inhibitors (ACEIs) (eg, enalapril). For more refractory hypertension, agents such as nicardipine and hydralazine are used. Avoid nitroprusside because it may raise intracranial pressure.

The 2010 AHA/ASA guidelines acknowledge that evidence for the efficacy of managing BP in hemorrhagic stroke is currently incomplete. With that caveat, the AHA/ASA recommendations for treating elevated BP are as follows^[1]:

If systolic BP is over 200 mm Hg or mean arterial pressure (MAP) is over 150 mm Hg, then consider aggressive reduction of BP with continuous IV infusion; check BP every 5 minutes
If systolic BP is over 180 mm Hg or MAP is over 130 mm Hg and intracranial pressure may be elevated, then consider monitoring intracranial pressure and reducing BP using intermittent or continuous intravenous medications, while maintaining a cerebral perfusion pressure of 60 mm Hg or higher
If systolic BP is over 180 or MAP is over 130 mm Hg and there is no evidence of elevated intracranial pressure, then consider modest reduction of BP (target MAP of 110 mm Hg or target BP of 160/90 mm Hg) using intermittent or continuous intravenous medications to control it, and perform clinical reexamination of the patient every 15 minutes
In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe

For patients with aneurysmal subarachnoid hemorrhage, the 2012 AHA/ASA guidelines recommend lowering BP below 160 mm Hg acutely to reduce rebleeding.^[33]

A 2017 joint practice guideline from the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) calls for physicians to start treatment for patients who have persistent systolic blood pressure at or above 150 mm Hg to achieve a target of less than 150 mm Hg to reduce risk for stroke, cardiac events, and death.^[34]

The ongoing Antihypertensive Treatment in Acute Cerebral Hemorrhage-II (ATACH-II) phase 3 randomized clinical trial is designed to determine whether the likelihood of death or disability at 3 months after spontaneous supratentorial intracerebral hemorrhage is lower when systolic BP has been reduced to 180 mm Hg or below or to 140 mm Hg or below. In ATACH-II, intravenous nicardipine is started within 3 hours of stroke onset and continued for the next 24 hours.

Intracranial Pressure Control

Elevated intracranial pressure may result from the hematoma itself, from surrounding edema, or from both. The frequency of increased intracranial pressure in patients with intracerebral hemorrhage is not known.

Elevate the head of the bed to 30°. This improves jugular venous outflow and lowers intracranial pressure. The head should be midline and not turned to the side. Provide analgesia and sedation as needed. Antacids are used to prevent gastric ulcers associated with intracerebral hemorrhage.

More aggressive therapies, such as osmotic therapy (ie, mannitol, hypertonic saline), barbiturate anesthesia, and neuromuscular blockage, generally require concomitant monitoring of intracranial pressure and BP with an intracranial pressure monitor to maintain adequate cerebral perfusion pressure of greater than 70 mm Hg. A randomized, controlled study of mannitol in intracerebral hemorrhage failed to demonstrate any difference in disability or death at 3 months.^[35]

Hyperventilation (partial pressure of carbon dioxide [PaCO₂] of 25 to 30-35 mm Hg) is not recommended, because its effect is transient, it decreases cerebral blood flow, and it may result in rebound elevated intracranial pressure.^[3]Glucocorticoids are not effective and result in higher rates of complications with poorer outcomes.

Hemostatic Therapy

The use of hemostatic therapy with rFVIIa to stop ongoing hemorrhage or prevent hematoma expansion has generated much interest. However, research to date has failed to support this off-label use of rFVIIa.^{[36, 37, 38]}

A preliminary study of treatment rFVIIa demonstrated reduced mortality and improved functional outcomes. Unfortunately, the results of a subsequent randomized trial that was larger than the preliminary study revealed no overall benefit from treatment; hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome.^[39]

Diringer et al found that a higher dose of rFVIIa was associated with a small increase in the risk of arterial thromboembolic events in patients who presented less than 3 hours after spontaneous intracerebral hemorrhage. Arterial events were also associated with the presence of cardiac or cerebral ischemia at presentation, with advanced age, and with antiplatelet use.^[40]

The investigators also found that with the use of 20 or 80 mcg/kg rFVIIa, the rates of venous events were similar to those with placebo.

Treatment of Anticoagulation-associated Intracranial Hemorrhage

Patients on warfarin have an increased incidence of hemorrhagic stroke. Morbidity and mortality for warfarin-associated bleeding is high, with over one half of patients dying within 30 days. Most episodes occur with a therapeutic international normalized ratio (INR), but overanticoagulation is associated with an even greater risk of bleeding.

The need to reverse warfarin anticoagulation is a true medical emergency, and reversal must be accomplished as quickly as possible to prevent further hematoma expansion. Options for reversal therapy include the following:

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

FFP versus PCC

Because vitamin K requires more than 6 hours to normalize the INR, it should be administered with either FFP or PCC. FFP is the standard of care in the United States^[41]; however, FFP needs to be given in a dose of 15-20 mL/kg and therefore requires a large-volume infusion. PCC contains high levels of vitamin K-dependent cofactors and thus involves a smaller-volume infusion than FFP and more rapid administration.^{[42, 43]}However, PCC is associated with high rates of thrombotic complications.

No randomized, controlled trial has studied the safety and efficacy of FFP versus PCC for reversing the effects of warfarin in patients with intracranial hemorrhage. The International Normalised ratio normalisation in patients with Coumarin-related intracranial Haemorrhages (INCH) trial, a prospective, randomized, controlled, multicenter trial comparing the 2 agents, began recruiting subjects in 2009.^[44]

FVIIa

Based upon the available medical evidence, the use of FVIIa is currently not recommended over other agents. The PCC available in the United States contains only low levels of FVII, however, and Sarode et al have described successful, rapid reversal of vitamin K antagonist–related coagulopathy using a combination of low-dose FVIIa with PCC, although they note the need for caution in patients at high risk for thrombosis.^[41]

Patients on heparin (either unfractionated or low molecular weight heparin [LMWH]) who develop a hemorrhagic stroke should immediately have anticoagulation reversed with protamine.^[3]The dose of protamine is dependent upon the dose of heparin that was given and the time elapsed since that dose.

Patients with severe deficiency of a specific coagulation factor who develop spontaneous intracerebral hemorrhage should receive factor replacement therapy.^[1]

Reversal of antiplatelet therapy and platelet dysfunction

There is controversy about whether patients on antiplatelet medications (eg, aspirin, aspirin/dipyridamole [Aggrenox], clopidogrel) should be given desmopressin (DDAVP) and/or platelet transfusions. Patients with renal failure and platelet dysfunction may also benefit from the administration of desmopressin (DDAVP). The 2010 AHA/ASA guideline for management of spontaneous intracerebral hemorrhage recommends platelet transfusions only when such hemorrhaging complicates severe thrombocytopenia.^[1]

Statins

Inpatient statin use and maintenance may improve outcomes post intracerebral hemorrhage.

In a retrospective multicenter cohort study of 3481 patients with intracerebral hemorrhage over a 10-year period, Flint et al found that inpatients who received a statin (lovastatin, simvastatin, atorvastatin, pravastatin sodium) had better 30-day survival rates following the bleeding event and were more likely to be discharged home or to a rehabilitation center than those who didn’t receive a statin while hospitalized—despite the fact that the statin users had significantly more severe illness and more comorbidities than non statin users.^{[45, 46]}Moreover, those whose statins were discontinued during their hospitalization had worse outcomes than those who remained on statins.

Inpatients treated with a statin had an 18.4% unadjusted 30-day mortality rate compared to 38.7% for those not treated with a statin during their admission.^{[45, 46]}After adjustment for various factors (age, sex, race/ethnicity, comorbidities, number of intracerebral hemorrhage cases by hospital, dysphagia), statin users were also more likely to be alive at 30 days (odds ratio [OR], 4.25; 95% confidence interval [CI], 3.46-5.23; P< .001). Inpatients treated with statins had a 51.1% rate of discharge to home or to a rehabilitation facility compared to 35.0% for patients not treated with statins while hospitalized. Furthermore, patients who discontinued statin therapy after hospital admission had an unadjusted mortality rate of 57.8% compared to 18.9% for patients using a statin before and during hospitalization; they were also significantly less likely to be alive at 30 days (OR, 0.16; 95% CI, 0.12-0.21; P< .001).^{[45, 46]}

Invasive Therapy

A potential treatment for hemorrhagic stroke is surgical evacuation of the hematoma. However, the role of surgical treatment for supratentorial intracranial hemorrhage remains controversial. Outcomes in published studies are conflicting. The international multicenter Trial in Intracerebral Haemorrhage (STICH), which compared early surgery with initial conservative treatment, failed to demonstrate a surgery-related benefit.^[47]

In contrast, a meta-analysis of trials for surgical treatment of spontaneous supratentorial intracerebral hemorrhage found evidence for improved outcome with surgery if any of the following applied^[48]:

Surgery undertaken within 8 hours of ictus
Volume of the hematoma 20-50 mL
Glasgow coma score 9-12
Patient age 50-69 years

In addition, evidence suggests that a subset of patients with lobar hematoma but no intraventricular hemorrhage may benefit from intervention.^[49]A study in this group of patients (STICH II) has been completed, but results are still pending.^[50]

In patients with cerebellar hemorrhage, surgical intervention has been shown to improve outcome if the hematoma is greater than 3 cm in diameter. It can be lifesaving in the prevention of brainstem compression.

Endovascular treatment of aneurysms

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

A cerebral angiogram was performed in a 57-year-old man with a family history of subarachnoid hemorrhage and who was found on previous imaging to have a left distal internal carotid artery (ICA) aneurysm. The lateral projection from this angiogram demonstrates a narrow-necked aneurysm arising off the posterior aspect of the distal supraclinoid left ICA, with an additional nipplelike projection off the inferior aspect of the dome of the aneurysm. There is also a mild, lobulated dilatation of the cavernous left ICA.

View Media Gallery

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

View Media Gallery

The International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling reported that independent survival was higher at 1 year with endovascular coiling and that the survival benefit continued for at least 7 years.^[51]This randomized, multicenter, international trial included 2143 patients. The investigators also noted that the risk of late rebleeding was small in both groups but higher in the endovascular coiling group, reconfirming the higher long-term anatomic cure rate of surgery.^{[51, 52]}

More recently, the Barrow Ruptured Aneurysm Trial (BRAT), which included 358 patients, demonstrated superior functional outcome at 1 year with endovascular coil embolization than with microsurgical clipping for acutely ruptured intracerebral aneurysm. Further, in contrast to the ISAT results, no patient in the endovascular embolization group suffered a recurrent hemorrhage.^[53]Outcomes at 3-year follow-up of the BRAT patients continued to favor coil embolization, though the difference no longer reached statistical significance.^[54]

Endovascular treatment of aneurysms may be favored over surgical clipping under the following circumstances^[55]:

The aneurysm is in a location that is difficult to access surgically, such as the cavernous internal carotid artery (ICA) or the basilar terminus
The aneurysm is small-necked and located in the posterior fossa
The patient is elderly
The patient has a poor clinical grade

The following factors militate against endovascular treatment:

Wide-based aneurysms or those without an identifiable neck
Aneurysms with a vessel extending off the aneurysm dome
Severely atherosclerotic or tortuous vessels that limit the endovascular approach

Although vasospasm may be treated with intra-arterial pharmaceutical agents, such as verapamil or nicardipine, balloon angioplasty can be used for opening larger vessels (see the images below). The combination of the 2 treatments appears to provide safe and long-lasting therapy for severe, clinically significant vasospasm.^[56]

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

View Media Gallery

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

View Media Gallery

Ventriculostomy

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

Antihypertensives

The 2010 AHA/ASA guidelines for spontaneous ICH recommend that after acute intracerebral hemorrhage, patients without medical contraindications should have BP well controlled, especially for hemorrhage in typical hypertensive vasculopathy locations.^[1]In addition, the guidelines strongly recommend maintenance of BP below 140/90 mm Hg to prevent a first stroke. In patients with hypertension plus either diabetes or renal disease, the treatment goal is BP below 130/80 mm Hg.^[57]

BP-lowering medications include thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). For patients with diabetes, the use of ACEIs and ARBs to treat hypertension is a class I-A recommendation (strongest and best-documented), according to the 2011 AHA/ASA primary prevention guidelines.^[1]Beta blockers are considered second-line agents given their inferiority in preventing vascular events, despite producing similar reductions in BP. (Adverse effects of ACEIs include cough [10%], which is less common with ARBs.)

Although statin therapy is recommended for primary prevention of ischemic stroke (class I-A recommendation),^[57]especially if other risk factors are present, some studies have found an increased risk of intracerebral hemorrhage with statin use. However, a meta-analysis of 31 randomized, controlled trials of statin therapy found that active statin therapy was not associated with a significant increase in intracerebral hemorrhage.^[58]

In the Heart Outcomes Prevention Evaluation (HOPE) study, the addition of the ACEI ramipril to all other medical therapy, including antiplatelet agents, reduced the relative risk of stroke, death, and myocardial infarction by 32% compared with placebo.^[59]Only 40% of the efficacy of ramipril could be attributed to its BP-lowering effects. Other postulated mechanisms included endothelial protection.

Whether the beneficial effect of ramipril represents a class effect of ACEIs or whether it is a property unique to ramipril is unclear.

In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a regimen based on perindopril, an ACEI, was superior to placebo.^[60]Although this drug alone was not superior to placebo, the combination of perindopril with indapamide (a thiazide diuretic) substantially reduced the recurrence of stroke.^[60]Much of the effect in reducing stroke recurrence was attributable to the lowering of BP, in contrast to findings for ramipril from the HOPE study.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed slight superiority of chlorthalidone (a thiazide diuretic) over lisinopril (an ACEI) in terms of stroke occurrence.^[61]

The Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE) demonstrated that an ARB (losartan) was superior to a beta blocker (atenolol) in reducing the occurrence of stroke.^[62]

The Morbidity and Mortality after Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study found that the ARB eprosartan was superior to the calcium channel blocker nitrendipine in the secondary prevention of stroke and transient ischemic attack (TIA).^[63]This was true despite comparable BP reductions. The absolute annual difference in stroke and TIA risk was approximately 4%. The study was relatively small, and most events were TIAs.

Lifestyle interventions

Smoking cessation, a low-fat diet (eg, Dietary Approaches to Stop Hypertension [DASH] or Mediterranean diets), weight loss, and regular exercise should be encouraged as strongly as pharmacologic treatment. Written prescriptions for exercise and medications for smoking cessation (ie, nicotine patch, bupropion, varenicline) increase the likelihood of success with these interventions.

Reducing sodium intake and increasing consumption of foods high in potassium to reduce BP may also help in primary prevention.^[57]High alcohol intake should be reduced, as drinking more than 30 drinks per month has been tied to increased risk of intracerebral hemorrhage.

Exercise

A Finnish study showed that the likelihood of stroke in men with the lowest degree of physical fitness (maximal oxygen uptake [VO_2max] < 25.2 mL/kg/min) was more than 3 times greater than in men with the highest degree of physical fitness (VO_2max >35.3 mL/kg/min).^[64]level of physical fitness was a more powerful risk factor than low-density lipoprotein cholesterol level, body mass index, and smoking, and it was nearly comparable to hypertension as a risk factor.

The 2011 AHA/ASA guidelines for the primary prevention of stroke, which address hemorrhagic and ischemic stroke, emphasize exercise and other lifestyle modifications. The guidelines endorse the 2008 Physical Activity Guidelines for Americans, which include a recommendation of at least 150 minutes per week of moderate-intensity aerobic physical activity.^[57]

Consultations

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

Medication

[Guideline] Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010 Sep. 41(9):2108-29. [QxMD MEDLINE Link].
Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003 Jan. 2(1):43-53. [QxMD MEDLINE Link].
[Guideline] Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation. 2007 Oct 16. 116(16):e391-413. [QxMD MEDLINE Link].
Kim EY, Na DG, Kim SS, Lee KH, Ryoo JW, Kim HK. Prediction of hemorrhagic transformation in acute ischemic stroke: role of diffusion-weighted imaging and early parenchymal enhancement. AJNR Am J Neuroradiol. 2005 May. 26(5):1050-5. [QxMD MEDLINE Link].
Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012 Jan 3. 125(1):e2-e220. [QxMD MEDLINE Link].
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan. 24(1):35-41. [QxMD MEDLINE Link].
Thrift AG, Dewey HM, Macdonell RA, McNeil JJ, Donnan GA. Incidence of the major stroke subtypes: initial findings from the North East Melbourne stroke incidence study (NEMESIS). Stroke. 2001 Aug. 32(8):1732-8. [QxMD MEDLINE Link].
Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008 May 10. 371(9624):1612-23. [QxMD MEDLINE Link].
Mullins ME, Lev MH, Schellingerhout D, Gonzalez RG, Schaefer PW. Intracranial hemorrhage complicating acute stroke: how common is hemorrhagic stroke on initial head CT scan and how often is initial clinical diagnosis of acute stroke eventually confirmed?. AJNR Am J Neuroradiol. 2005 Oct. 26(9):2207-12. [QxMD MEDLINE Link].
Nighoghossian N, Hermier M, Adeleine P, Blanc-Lasserre K, Derex L, Honnorat J, et al. Old microbleeds are a potential risk factor for cerebral bleeding after ischemic stroke: a gradient-echo T2*-weighted brain MRI study. Stroke. 2002 Mar. 33(3):735-42. [QxMD MEDLINE Link].
Auer RN, Sutherland GR. Primary intracerebral hemorrhage: pathophysiology. Can J Neurol Sci. 2005 Dec. 32 Suppl 2:S3-12. [QxMD MEDLINE Link].
Thrift AG, Donnan GA, McNeil JJ. Epidemiology of intracerebral hemorrhage. Epidemiol Rev. 1995. 17(2):361-81. [QxMD MEDLINE Link].
Gokaslan ZL, Narayan RK. Intracranial hemorrhage in the hypertensive patient. Neuroimaging Clin N Am. 1992. Vol. 2:171-86.
International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19. 360(8):753-64. [QxMD MEDLINE Link]. [Full Text].
Rist PM, Buring JE, Ridker PM, Kase CS, Kurth T, Rexrode KM. Lipid levels and the risk of hemorrhagic stroke among women. Neurology. 2019 Apr 10. [QxMD MEDLINE Link].
Chapman AB, Rubinstein D, Hughes R, Stears JC, Earnest MP, Johnson AM, et al. Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med. 1992 Sep 24. 327(13):916-20. [QxMD MEDLINE Link].
Regalado E, Medrek S, Tran-Fadulu V, et al. Autosomal dominant inheritance of a predisposition to thoracic aortic aneurysms and dissections and intracranial saccular aneurysms. Am J Med Genet A. 2011 Sep. 155A(9):2125-30. [QxMD MEDLINE Link].
Dubey N, Bakshi R, Wasay M, Dmochowski J. Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke. J Neuroimaging. 2001 Apr. 11(2):184-8. [QxMD MEDLINE Link].
Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995 Dec 14. 333(24):1581-7. [QxMD MEDLINE Link].
González RG. Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain". AJNR Am J Neuroradiol. 2006 Apr. 27(4):728-35. [QxMD MEDLINE Link].
Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 Suppl):483S-512S. [QxMD MEDLINE Link].
Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997 May 3. 349(9061):1269-76. [QxMD MEDLINE Link].
Shiber JR, Fontane E, Adewale A. Stroke registry: hemorrhagic vs ischemic strokes. Am J Emerg Med. 2010 Mar. 28(3):331-3. [QxMD MEDLINE Link].
Flaherty ML, Woo D, Haverbusch M, Sekar P, Khoury J, Sauerbeck L, et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005 May. 36(5):934-7. [QxMD MEDLINE Link].
Global Burden of Stroke. The Atlas of Heart Disease and Stroke. MacKay J, Mensah GA. World Health Organization. [Full Text].
Sacco S, Marini C, Toni D, Olivieri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009. 40:394–399.
Centers for Disease Control and Prevention (CDC. Prevalence of stroke--United States, 2005. MMWR Morb Mortal Wkly Rep. 2007 May 18. 56(19):469-74. [QxMD MEDLINE Link].
Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001 Apr. 32(4):891-7. [QxMD MEDLINE Link]. [Full Text].
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 Jul. 28(7):1406-9. [QxMD MEDLINE Link].
Hughes S. BP Control More Important in ICH Patients on Antithrombotics. Medscape Medical News. May 15 2014. Available at http://www.medscape.com/viewarticle/825206. Accessed: May 20 2014.
Passero S, Rocchi R, Rossi S, Ulivelli M, Vatti G. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002 Oct. 43(10):1175-80. [QxMD MEDLINE Link].
Vespa PM, O'Phelan K, Shah M, Mirabelli J, Starkman S, Kidwell C, et al. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology. 2003 May 13. 60(9):1441-6. [QxMD MEDLINE Link].
Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012 Jun. 43(6):1711-37. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, Forciea MA, et al. Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. January 17, 2017. [Full Text].
Misra UK, Kalita J, Ranjan P, Mandal SK. Mannitol in intracerebral hemorrhage: a randomized controlled study. J Neurol Sci. 2005 Jul 15. 234(1-2):41-5. [QxMD MEDLINE Link].
Avorn J, Kesselheim A. A hemorrhage of off-label use. Ann Intern Med. 2011 Apr 19. 154(8):566-7. [QxMD MEDLINE Link].
Yank V, Tuohy CV, Logan AC, et al. Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications. Ann Intern Med. 2011 Apr 19. 154(8):529-40. [QxMD MEDLINE Link].
Logan AC, Yank V, Stafford RS. Off-Label Use of Recombinant Factor VIIa in U.S. Hospitals: Analysis of Hospital Records. Ann Intern Med. 2011 Apr 19. 154(8):516-22. [QxMD MEDLINE Link].
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008 May 15. 358(20):2127-37. [QxMD MEDLINE Link].
Diringer MN, Skolnick BE, Mayer SA, Steiner T, Davis SM, Brun NC, et al. Thromboembolic events with recombinant activated factor VII in spontaneous intracerebral hemorrhage: results from the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial. Stroke. 2010 Jan. 41(1):48-53. [QxMD MEDLINE Link].
Sarode R, Matevosyan K, Bhagat R, Rutherford C, Madden C, Beshay JE. Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage. J Neurosurg. 2012 Mar. 116(3):491-7. [QxMD MEDLINE Link].
Lankiewicz MW, Hays J, Friedman KD, Tinkoff G, Blatt PM. Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost. 2006 May. 4(5):967-70. [QxMD MEDLINE Link].
Huttner HB, Schellinger PD, Hartmann M, Köhrmann M, Juettler E, Wikner J, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke. 2006 Jun. 37(6):1465-70. [QxMD MEDLINE Link].
Steiner T, Freiberger A, Griebe M, Hüsing J, Ivandic B, Kollmar R, et al. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages--the INCH trial: a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex--study design and protocol. Int J Stroke. 2011 Jun. 6(3):271-7. [QxMD MEDLINE Link].
Flint AC, Conell C, Rao VA, et al. Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition. JAMA Neurol. 2014 Sep 22. [QxMD MEDLINE Link]. [Full Text].
Anderson P. In-hospital statins linked to better outcome in ICH. Medscape Medical News. September 22, 2014. [Full Text].
Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005 Jan 29-Feb 4. 365(9457):387-97. [QxMD MEDLINE Link].
Gregson BA, Broderick JP, Auer LM, Batjer H, Chen XC, Juvela S, et al. Individual patient data subgroup meta-analysis of surgery for spontaneous supratentorial intracerebral hemorrhage. Stroke. 2012 Jun. 43(6):1496-504. [QxMD MEDLINE Link]. [Full Text].
Steiner T, Vincent C, Morris S, Davis S, Vallejo-Torres L, Christensen MC. Neurosurgical outcomes after intracerebral hemorrhage: results of the Factor Seven for Acute Hemorrhagic Stroke Trial (FAST). J Stroke Cerebrovasc Dis. 2011 Jul-Aug. 20(4):287-94. [QxMD MEDLINE Link].
Mendelow AD, Gregson BA, Mitchell PM, Murray GD, Rowan EN, Gholkar AR. Surgical trial in lobar intracerebral haemorrhage (STICH II) protocol. Trials. 2011 May 17. 12:124. [QxMD MEDLINE Link]. [Full Text].
Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005 Sep 3-9. 366(9488):809-17. [QxMD MEDLINE Link].
Byrne JV. The aneurysm "clip or coil" debate. Acta Neurochir (Wien). 2006 Feb. 148(2):115-20. [QxMD MEDLINE Link].
McDougall CG, Spetzler RF, Zabramski JM, Partovi S, Hills NK, Nakaji P, et al. The Barrow Ruptured Aneurysm Trial. J Neurosurg. 2012 Jan. 116(1):135-44. [QxMD MEDLINE Link].
Lanzino G. The Barrow Ruptured Aneurysm Trial. J Neurosurg. 2012 Jan. 116(1):133-4; discussion 134. [QxMD MEDLINE Link].
Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968 Jan. 28(1):14-20. [QxMD MEDLINE Link].
Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980 Jan. 6(1):1-9. [QxMD MEDLINE Link].
[Guideline] Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Feb. 42(2):517-84. [QxMD MEDLINE Link]. [Full Text].
McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012 Aug. 43(8):2149-56. [QxMD MEDLINE Link].
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000 Jan 20. 342(3):145-53. [QxMD MEDLINE Link].
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001 Sep 29. 358(9287):1033-41. [QxMD MEDLINE Link].
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002 Dec 18. 288(23):2981-97. [QxMD MEDLINE Link].
Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002 Mar 23. 359(9311):995-1003. [QxMD MEDLINE Link].
Schrader J, Lüders S, Kulschewski A, Hammersen F, Plate K, Berger J, et al. Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES). Stroke. 2005 Jun. 36(6):1218-26. [QxMD MEDLINE Link].
Kurl S, Laukkanen JA, Rauramaa R, Lakka TA, Sivenius J, Salonen JT. Cardiorespiratory fitness and the risk for stroke in men. Arch Intern Med. 2003 Jul 28. 163(14):1682-8. [QxMD MEDLINE Link].
Yock-Corrales A, Mackay MT, Mosley I, Maixner W, Babl FE. Acute childhood arterial ischemic and hemorrhagic stroke in the emergency department. Ann Emerg Med. 2011 Aug. 58(2):156-63. [QxMD MEDLINE Link].
Ahmed N, Näsman P, Wahlgren NG. Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke. 2000 Jun. 31(6):1250-5. [QxMD MEDLINE Link]. [Full Text].
Aso K, Ogasawara K, Sasaki M, Kobayashi M, Suga Y, Chida K, et al. Preoperative cerebrovascular reactivity to acetazolamide measured by brain perfusion SPECT predicts development of cerebral ischemic lesions caused by microemboli during carotid endarterectomy. Eur J Nucl Med Mol Imaging. 2009 Feb. 36(2):294-301. [QxMD MEDLINE Link].
Becker H, Desch H, Hacker H, Pencz A. CT fogging effect with ischemic cerebral infarcts. Neuroradiology. 1979 Oct 31. 18(4):185-92. [QxMD MEDLINE Link].
Borisch I, Horn M, Butz B, Zorger N, Draganski B, Hoelscher T, et al. Preoperative evaluation of carotid artery stenosis: comparison of contrast-enhanced MR angiography and duplex sonography with digital subtraction angiography. AJNR Am J Neuroradiol. 2003 Jun-Jul. 24(6):1117-22. [QxMD MEDLINE Link].
Bose A, Henkes H, Alfke K, Reith W, Mayer TE, Berlis A, et al. The Penumbra System: a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR Am J Neuroradiol. 2008 Aug. 29(7):1409-13. [QxMD MEDLINE Link].
Bozzao L, Bastianello S, Fantozzi LM, Angeloni U, Argentino C, Fieschi C. Correlation of angiographic and sequential CT findings in patients with evolving cerebral infarction. AJNR Am J Neuroradiol. 1989 Nov-Dec. 10(6):1215-22. [QxMD MEDLINE Link].
Bozzao L, Fantozzi LM, Bastianello S, Bozzao A, Argentino C, Lenzi GL, et al. Ischaemic supratentorial stroke: angiographic findings in patients examined in the very early phase. J Neurol. 1989 Sep. 236(6):340-2. [QxMD MEDLINE Link].
Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989 Jul. 20(7):864-70. [QxMD MEDLINE Link].
Brown PB, Zwiebel WJ, Call GK. Degree of cervical carotid artery stenosis and hemispheric stroke: duplex US findings. Radiology. 1989 Feb. 170(2):541-3. [QxMD MEDLINE Link].
Burdette JH, Ricci PE, Petitti N, Elster AD. Cerebral infarction: time course of signal intensity changes on diffusion-weighted MR images. AJR Am J Roentgenol. 1998 Sep. 171(3):791-5. [QxMD MEDLINE Link].
Carroll BA. Duplex sonography in patients with hemispheric symptoms. J Ultrasound Med. 1989 Oct. 8(10):535-40. [QxMD MEDLINE Link].
Chandra VR, Pandav R, Laxminarayan R, et al. Neurologic Disorders. Jamison DT, Measham AR, Breman JB, et al, eds. Disease Control Priorities in Developing Countries. 2nd ed. New York, NY: Oxford University Press and The World Bank; 2006. 627-43.
Chappell FM, Wardlaw JM, Young GR, Gillard JH, Roditi GH, Yip B, et al. Carotid artery stenosis: accuracy of noninvasive tests--individual patient data meta-analysis. Radiology. 2009 May. 251(2):493-502. [QxMD MEDLINE Link].
de Virgilio C, Toosie K, Arnell T, Lewis RJ, Donayre CE, Baker JD, et al. Asymptomatic carotid artery stenosis screening in patients with lower extremity atherosclerosis: a prospective study. Ann Vasc Surg. 1997 Jul. 11(4):374-7. [QxMD MEDLINE Link].
Delgado AL, Jahromi B, Muller N, Farhat H, Salame J, Zauner A. Endovascular therapy of cerebral vasospasm: two year experience with angioplasty and/or intraarterial administration of nicardipine and verapamil. Acta Neurochir Suppl. 2008. 104:347-51.
Eastwood JD, Lev MH, Azhari T, Lee TY, Barboriak DP, Delong DM, et al. CT perfusion scanning with deconvolution analysis: pilot study in patients with acute middle cerebral artery stroke. Radiology. 2002 Jan. 222(1):227-36. [QxMD MEDLINE Link].
Elster AD, Moody DM. Early cerebral infarction: gadopentetate dimeglumine enhancement. Radiology. 1990 Dec. 177(3):627-32. [QxMD MEDLINE Link].
Goldenberg G, Reisner T. Angiographic findings in relation to clinical course and results of computed tomography in cerebrovascular disease. Eur Neurol. 1983. 22(2):124-30. [QxMD MEDLINE Link].
González RG, Schaefer PW, Buonanno FS, Schwamm LH, Budzik RF, Rordorf G, et al. Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset. Radiology. 1999 Jan. 210(1):155-62. [QxMD MEDLINE Link].
Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis--Society of Radiologists in Ultrasound Consensus Conference. Radiology. 2003 Nov. 229(2):340-6. [QxMD MEDLINE Link].
Grant EG, Duerinckx AJ, El Saden SM, Melany ML, Hathout GM, Zimmerman PT, et al. Ability to use duplex US to quantify internal carotid arterial stenoses: fact or fiction?. Radiology. 2000 Jan. 214(1):247-52. [QxMD MEDLINE Link].
Karonen JO, Partanen PL, Vanninen RL, Vainio PA, Aronen HJ. Evolution of MR contrast enhancement patterns during the first week after acute ischemic stroke. AJNR Am J Neuroradiol. 2001 Jan. 22(1):103-11. [QxMD MEDLINE Link].
Kucinski T, Väterlein O, Glauche V, Fiehler J, Klotz E, Eckert B, et al. Correlation of apparent diffusion coefficient and computed tomography density in acute ischemic stroke. Stroke. 2002 Jul. 33(7):1786-91. [QxMD MEDLINE Link].
Lyden PD, Zivin JA. Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. Cerebrovasc Brain Metab Rev. 1993 Spring. 5(1):1-16. [QxMD MEDLINE Link].
Marks MP. CT in ischemic stroke. Neuroimaging Clin N Am. 1998 Aug. 8(3):515-23. [QxMD MEDLINE Link].
Martin PJ, Enevoldson TP, Humphrey PR. Causes of ischaemic stroke in the young. Postgrad Med J. 1997 Jan. 73(855):8-16. [QxMD MEDLINE Link]. [Full Text].
Meerwaldt R, Slart RH, van Dam GM, Luijckx GJ, Tio RA, Zeebregts CJ. PET/SPECT imaging: from carotid vulnerability to brain viability. Eur J Radiol. 2010 Apr. 74(1):104-9. [QxMD MEDLINE Link].
Minematsu K, Li L, Fisher M, Sotak CH, Davis MA, Fiandaca MS. Diffusion-weighted magnetic resonance imaging: rapid and quantitative detection of focal brain ischemia. Neurology. 1992 Jan. 42(1):235-40. [QxMD MEDLINE Link].
Nabavi DG, Cenic A, Craen RA, Gelb AW, Bennett JD, Kozak R, et al. CT assessment of cerebral perfusion: experimental validation and initial clinical experience. Radiology. 1999 Oct. 213(1):141-9. [QxMD MEDLINE Link].
Nishihara T, Nagata K, Tanaka S, Suzuki Y, Izumi M, Mochizuki Y, et al. Newly developed endoscopic instruments for the removal of intracerebral hematoma. Neurocrit Care. 2005. 2(1):67-74. [QxMD MEDLINE Link].
Noguchi K, Ogawa T, Inugami A, Fujita H, Hatazawa J, Shimosegawa E, et al. MRI of acute cerebral infarction: a comparison of FLAIR and T2-weighted fast spin-echo imaging. Neuroradiology. 1997 Jun. 39(6):406-10. [QxMD MEDLINE Link].
Oliveira-Filho J, Silva SC, Trabuco CC, Pedreira BB, Sousa EU, Bacellar A. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology. 2003 Oct 28. 61(8):1047-51. [QxMD MEDLINE Link].
Oppenheim C, Logak M, Dormont D, Lehéricy S, Manaï R, Samson Y, et al. Diagnosis of acute ischaemic stroke with fluid-attenuated inversion recovery and diffusion-weighted sequences. Neuroradiology. 2000 Aug. 42(8):602-7. [QxMD MEDLINE Link].
Powers WJ, Grubb RL Jr, Darriet D, Raichle ME. Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans. J Cereb Blood Flow Metab. 1985 Dec. 5(4):600-8. [QxMD MEDLINE Link].
Pressman BD, Tourje EJ, Thompson JR. An early sign of ischemic infarction: increased density in a cerebral artery. AJR Am J Roentgenol. 1987. 149(3):583-6.
Saur D, Kucinski T, Grzyska U, Eckert B, Eggers C, Niesen W, et al. Sensitivity and interrater agreement of CT and diffusion-weighted MR imaging in hyperacute stroke. AJNR Am J Neuroradiol. 2003 May. 24(5):878-85. [QxMD MEDLINE Link].
Schaefer PW, Hassankhani A, Putman C, Sorensen AG, Schwamm L, Koroshetz W, et al. Characterization and evolution of diffusion MR imaging abnormalities in stroke patients undergoing intra-arterial thrombolysis. AJNR Am J Neuroradiol. 2004 Jun-Jul. 25(6):951-7. [QxMD MEDLINE Link].
Schaefer PW, Roccatagliata L, Ledezma C, Hoh B, Schwamm LH, Koroshetz W, et al. First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy. AJNR Am J Neuroradiol. 2006 Jan. 27(1):20-5. [QxMD MEDLINE Link].
Schramm P, Schellinger PD, Klotz E, Kallenberg K, Fiebach JB, Külkens S, et al. Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration. Stroke. 2004 Jul. 35(7):1652-8. [QxMD MEDLINE Link].
Schuierer G, Huk W. The unilateral hyperdense middle cerebral artery: an early CT-sign of embolism or thrombosis. Neuroradiology. 1988. 30(2):120-2. [QxMD MEDLINE Link].
Shetty SK, Lev MH. CT perfusion in acute stroke. Neuroimaging Clin N Am. 2005 Aug. 15(3):481-501, ix. [QxMD MEDLINE Link].
Skriver EB, Olsen TS. Transient disappearance of cerebral infarcts on CT scan, the so-called fogging effect. Neuroradiology. 1981. 22(2):61-5. [QxMD MEDLINE Link].
Smith TP, Enterline DS. Endovascular treatment of cerebral vasospasm. J Vasc Interv Radiol. 2000 May. 11(5):547-59. [QxMD MEDLINE Link].
Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008 Apr. 39(4):1205-12. [QxMD MEDLINE Link].
Sorensen A, Copen W, Ostergaard L, Vainio PA, Aronen HJ. Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow and mean tissue transit time. Radiology. 1999. 210 (2):519-27.
Sorensen AG, Buonanno FS, Gonzalez RG, Schwamm LH, Lev MH, Huang-Hellinger FR, et al. Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging. Radiology. 1996 May. 199(2):391-401. [QxMD MEDLINE Link].
Steiner T, Freiberger A, Griebe M, Hüsing J, Ivandic B, Kollmar R, et al. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages--the INCH trial: a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex--study design and protocol. Int J Stroke. 2011 Jun. 6(3):271-7. [QxMD MEDLINE Link].
Sunshine JL, Tarr RW, Lanzieri CF, Landis DM, Selman WR, Lewin JS. Hyperacute stroke: ultrafast MR imaging to triage patients prior to therapy. Radiology. 1999 Aug. 212(2):325-32. [QxMD MEDLINE Link].
Tomura N, Uemura K, Inugami A, Fujita H, Higano S, Shishido F. Early CT finding in cerebral infarction: obscuration of the lentiform nucleus. Radiology. 1988 Aug. 168(2):463-7. [QxMD MEDLINE Link].
Torres-Mozqueda F, He J, Yeh IB, Schwamm LH, Lev MH, Schaefer PW, et al. An acute ischemic stroke classification instrument that includes CT or MR angiography: the Boston Acute Stroke Imaging Scale. AJNR Am J Neuroradiol. 2008 Jun. 29(6):1111-7. [QxMD MEDLINE Link].
Toyoda K, Ida M, Fukuda K. Fluid-attenuated inversion recovery intraarterial signal: an early sign of hyperacute cerebral ischemia. AJNR Am J Neuroradiol. 2001 Jun-Jul. 22(6):1021-9. [QxMD MEDLINE Link].
Truwit CL, Barkovich AJ, Gean-Marton A, Hibri N, Norman D. Loss of the insular ribbon: another early CT sign of acute middle cerebral artery infarction. Radiology. 1990 Sep. 176(3):801-6. [QxMD MEDLINE Link].
von Kummer R, Meyding-Lamadé U, Forsting M, Rosin L, Rieke K, Hacke W, et al. Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol. 1994 Jan. 15(1):9-15; discussion 16-8. [QxMD MEDLINE Link].
Wetzel SG. Cerebral arteries and veins. Rubin GD, Rofsky NM, eds. CT and MR Angiography: Comprehensive Vascular Assessment. Philadelphia, Pa: Lippincott Williams & Wilkins; 2009. 381-441.
Williams LS, Yilmaz EY, Lopez-Yunez AM. Retrospective assessment of initial stroke severity with the NIH Stroke Scale. Stroke. 2000 Apr. 31(4):858-62. [QxMD MEDLINE Link].
Wintermark M, Maeder P, Thiran JP, Schnyder P, Meuli R. Quantitative assessment of regional cerebral blood flows by perfusion CT studies at low injection rates: a critical review of the underlying theoretical models. Eur Radiol. 2001. 11(7):1220-30. [QxMD MEDLINE Link].
Wong GK, Siu DY, Ahuja AT, King AD, Yu SC, Zhu XL, et al. Comparisons of DSA and MR angiography with digital subtraction angiography in 151 patients with subacute spontaneous intracerebral hemorrhage. J Clin Neurosci. 2010 May. 17(5):601-5. [QxMD MEDLINE Link].
Woodcock RJ Jr, Short J, Do HM, Jensen ME, Kallmes DF. Imaging of acute subarachnoid hemorrhage with a fluid-attenuated inversion recovery sequence in an animal model: comparison with non-contrast-enhanced CT. AJNR Am J Neuroradiol. 2001 Oct. 22(9):1698-703. [QxMD MEDLINE Link].
Zia E, Engström G, Svensson PJ, Norrving B, Pessah-Rasmussen H. Three-year survival and stroke recurrence rates in patients with primary intracerebral hemorrhage. Stroke. 2009 Nov. 40(11):3567-73. [QxMD MEDLINE Link].

Media Gallery

Axial noncontrast computed tomography scan of the brain of a 60-year-old man with a history of acute onset of left-sided weakness. Two areas of intracerebral hemorrhage are seen in the right lentiform nucleus, with surrounding edema and effacement of the adjacent cortical sulci and right sylvian fissure. Mass effect is present upon the frontal horn of the right lateral ventricle, with intraventricular extension of the hemorrhage.
Noncontrast computed tomography scan of the brain (left) demonstrates an acute hemorrhage in the left gangliocapsular region, with surrounding white matter hypodensity consistent with vasogenic edema. T2-weighted axial magnetic resonance imaging scan (middle image) again demonstrates the hemorrhage, with surrounding high-signal edema. The coronal gradient-echo image (right) demonstrates susceptibility related to the hematoma, with markedly low signal adjacent the left caudate head. Gradient-echo images are highly sensitive for blood products.
Noncontrast computed tomography scan (left) obtained in a 75-year-old man who was admitted for stroke demonstrates a large right middle cerebral artery distribution infarction with linear areas of developing hemorrhage. These become more confluent on day 2 of hospitalization (middle image), with increased mass effect and midline shift. There is massive hemorrhagic transformation by day 6 (right), with increased leftward midline shift and subfalcine herniation. Obstructive hydrocephalus is also noted, with dilatation of the lateral ventricles, likely due to compression of the foramen of Monroe. Intraventricular hemorrhage is also noted layering in the left occipital horn. Larger infarctions are more likely to undergo hemorrhagic transformation and are one contraindication to thrombolytic therapy.
Noncontrast computed tomography (CT) scanning was performed emergently in a 71-year-old man who presented with acute onset of severe headache and underwent rapid neurologic deterioration requiring intubation. The noncontrast CT scan (left image) demonstrates diffuse, high-density subarachnoid hemorrhage in the basilar cisterns and both Sylvian fissures. There is diffuse loss of gray-white differentiation. The fluid-attenuated inversion-recovery (FLAIR) image (right) demonstrates high signal throughout the cortical sulci and in the basilar cisterns, as well as in the dependent portions of the ventricles. FLAIR is highly sensitive to acute subarachnoid hemorrhage; the suppression of high cerebrospinal fluid signal aids in making subarachnoid hemorrhage more conspicuous than do conventional magnetic resonance imaging sequences.
Computed tomographic angiography examination and subsequent cerebral angiography were performed in 71-year-old man who presented with acute onset of severe headache and underwent rapid neurologic deterioration. Multiple aneurysms were identified, including a 9-mm aneurysm at the junction of the anterior cerebral and posterior communicating arteries seen on this lateral view of an internal carotid artery injection. Balloon-assisted coil embolization was performed.
Lateral view of a selective injection of the left internal carotid artery demonstrates a microcatheter passing distal to the aneurysm neck. This lateral view from an angiogram performed during balloon-assisted coil embolization demonstrates significantly diminished filling of the aneurysm.
Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral artery (ACA) and sylvian triangle. The pericallosal artery has been described as arising distal to the anterior communicating artery or distal to the origin of the callosomarginal branch of the ACA. The segmental anatomy of the ACA has been described as follows: (1) the A1 segment extends from the internal carotid artery (ICA) bifurcation to the anterior communicating artery, (2) A2 extends to the junction of the rostrum and genu of the corpus callosum, (3) A3 extends into the bend of the genu of the corpus callosum, and (4) A4 and A5 extend posteriorly above the callosal body and superior portion of the splenium. The sylvian triangle overlies the opercular branches of the middle cerebral artery, with the apex representing the sylvian point.
Frontal projection from a right vertebral artery angiogram illustrates the posterior circulation. The vertebral arteries join to form the basilar artery. The posterior inferior cerebellar arteries (PICA) arise from the distal vertebral arteries. The anterior inferior cerebellar arteries (AICA) arise from the proximal basilar artery. The superior cerebellar arteries (SCA) arise distally from the basilar artery before its bifurcation into the posterior cerebral arteries.
Frontal view of a cerebral angiogram with selective injection of the left internal carotid artery illustrates the anterior circulation. The anterior cerebral artery consists of the A1 segment proximal to the anterior communicating artery with the A2 segment distal to it. The middle cerebral artery can be divided into 4 segments: the M1 (horizontal segment) extends to the limen insulae and gives off lateral lenticulostriate branches, the M2 (insular segment), M3 (opercular branches), and M4 (distal cortical branches on the lateral hemispheric convexities).
Frontal view from a cerebral angiogram in a 41-year-man who presented 7 days earlier with subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA) aneurysm (which was treated with surgical clipping). There is significant narrowing of the proximal left ACA, left M1 segment, and left supraclinoid internal carotid artery, indicating vasospasm.
Angiographic view in a 41-year-man who presented 7 days earlier with subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA) aneurysm (which was treated with surgical clipping). Superimposed road map image demonstrates placement of a wire across the left M1 segment and balloon angioplasty. The left proximal ACA and supraclinoid internal carotid artery (ICA) were also angioplastied, and intra-arterial verapamil was administered. Follow-up image on the right after treatment demonstrates resolution of the left M1 segment and distal ICA, which are now widely patent. Residual narrowing is seen in the left proximal ACA.
A cerebral angiogram was performed in a 57-year-old man with a family history of subarachnoid hemorrhage and who was found on previous imaging to have a left distal internal carotid artery (ICA) aneurysm. The lateral projection from this angiogram demonstrates a narrow-necked aneurysm arising off the posterior aspect of the distal supraclinoid left ICA, with an additional nipplelike projection off the inferior aspect of the dome of the aneurysm. There is also a mild, lobulated dilatation of the cavernous left ICA.
Follow-up cerebral angiogram after coil embolization in a 57-year-old man with a left distal internal carotid artery aneurysm. Multiple coils were placed with sequential occlusion of the aneurysm, including the nipple at its inferior aspect. A small amount of residual filling is noted at the proximal neck of the aneurysm, which may thrombose over time.

of 13

Author

David S Liebeskind, MD, FAAN, FAHA, FANA Professor of Neurology and Director, Neurovascular Imaging Research Core, Director, Vascular Neurology Residency Program, Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine; Director, UCLA Outpatient Stroke and Neurovascular Programs; Director, UCLA Cerebral Blood Flow Laboratory; Associate Neurology Director, UCLA Stroke Center

David S Liebeskind, MD, FAAN, FAHA, FANA is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Society of Neuroimaging, American Society of Neuroradiology, National Stroke Association, Stroke Council of the American Heart Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Chief Editor

Andrew K Chang, MD, MS Vincent P Verdile, MD, Endowed Chair in Emergency Medicine, Professor of Emergency Medicine, Vice Chair of Research and Academic Affairs, Albany Medical College; Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Attending Physician, Department of Emergency Medicine, Montefiore Medical Center

Andrew K Chang, MD, MS is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American Academy of Pain Medicine, American College of Emergency Physicians, American Geriatrics Society, American Pain Society, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Acknowledgements

J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center

Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association

Disclosure: Nothing to disclose.

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Helmi L Lutsep, MD Professor, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, Oregon Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association

Disclosure: Co-Axia Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Concentric Medical Consulting fee Review panel membership

Denise Nassisi, MD Assistant Professor, Department of Emergency Medicine, Mount Sinai Medical Center

Denise Nassisi, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American Heart Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Jeffrey L Saver, MD, FAHA, FAAN Professor of Neurology, Director, UCLA Stroke Center, University of California, Los Angeles, David Geffen School of Medicine

Jeffrey L Saver, MD, FAHA, FAAN is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Neurological Association, and National Stroke Association

Disclosure: University of California The University of California Regents receive funds for consulting services on clinical trial design provided to Telecris, Ev3, and CoAxia. Consulting

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Hemorrhagic Stroke Treatment & Management

Approach Considerations