Hemorrhagic Stroke

Scott D. Smith, MDa, Clifford J. Eskey, MD, PhDb,*

KEYWORDS

� Hemorrhagic stroke � Intracerebral hemorrhage� Subarachnoid hemorrhage� Susceptibility-weighted imaging � Vascular malformation� Aneurysm

When patients present to the emergency roomwith sudden onset of focal neurologic symptomsor altered consciousness, hemorrhagic stroke isa major focus of emergency diagnostic evalua-tion. The entities that compose hemorrhagicstroke are readily diagnosed with advancedimaging. Emergency surgical or endovasculartherapies may be life saving. Hemorrhagicstroke is defined as an acute neurologic injuryoccurring as a result of bleeding into the head.There are 2 distinct mechanisms: bleedingdirectly into the brain parenchyma (intracerebralhemorrhage [ICH]), or bleeding into the cerebro-spinal fluid (CSF) containing sulci, fissures, andcisterns (subarachnoid hemorrhage [SAH]).Although both entities are less common thanacute ischemia, they both convey greatermorbidity and mortality. Hemorrhagic strokehas well-studied and characteristic imagingfeatures. Treatment can be challenging andsubstantially different from ischemic forms ofstroke. Some of the imaging principles relevantto ICH and SAH can be applied to other formsof intracranial hemorrhage, but the entities ofsubdural and epidural hemorrhage lie outsidethe scope of this discussion. Current imagingoptions for the detection of acute hemorrhageand the expected imaging findings for eachmodality are reviewed. Common and unusualcauses for each entity with attention to their dis-tinguishing imaging features are discussed. In

a Department of Radiology, Dartmouth-Hitchcock Medi03756, USAb Division of Neuroradiology, Department of RadiologyCenter Drive, Lebanon, NH 03756, USA* Corresponding author.E-mail address: Clifford.J.Eskey@Hitchcock.ORG

Radiol Clin N Am 49 (2011) 27–45doi:10.1016/j.rcl.2010.07.0110033-8389/11/$ e see front matter � 2011 Elsevier Inc. Al

addition, imaging strategies and recent work inspecific imaging findings that may guide patientmanagement in the future are discussed.

CLINICAL PRESENTATION

Rapid and accurate identification of hemorrhage isessential in acute stroke care, as the fundamentaltherapies for the management of ischemic andhemorrhagic stroke differ markedly. Both ischemicand hemorrhagic strokes are characterized by therelatively sudden onset of symptoms and neuro-logic deficits, the type and severity of which willvary according to lesion type, location, and size.

Classically described presentations do exist.For example, nearly all patients with SAH able toconverse will describe “the worst headache ofmy life.” One in 5 may report a less severe sentinelheadache in the hours or days leading up to theevent. The event may be accompanied by focalneurologic signs or other symptoms such asnausea/vomiting, loss of consciousness, orseizure. ICH, on the other hand, is classicallydescribed as a gradual process, with worseningof symptoms over minutes to hours. Headacheand nausea/vomiting are more frequent in ICHthan ischemic stroke. Despite these differences,there remains enough overlap in the clinicalpresentations that history and physical examina-tion alone are unreliable in differentiating hemor-rhagic from ischemic stroke, and current

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Smith & Eskey28

guidelines for each entity include brain imaging asan essential early component of the work-up.1,2

SELECTION OF IMAGING MODALITY

Contemporary options for acute stroke imaginginclude computed tomography (CT) and magneticresonance (MR) imaging. As recently as 2003, un-enhanced head CT was considered the imagingmodality of choice for the detection of acute intra-cranial hemorrhage.3 Continuing advances in MRtechnology have addressed several perceivedshortcomings and as a result MR is gainingincreasing acceptance as a first-line modality.CT remains in widespread use for both logistic

and diagnostic reasons. It is widely available ona 24 hour basis. There are no absolute contraindi-cations to CT scanning, whereas approximately10% of patients may be ineligible for MR imagingbecause of the presence of a pacemaker or ferro-magnetic foreign bodies. CT examination can becompleted in minutes (rather than 10s of minutesfor MR imaging). The speed of image acquisitionand relative ease of patient monitoring maximizeboth patient safety and the chance of good qualityresults, whereas in 10% of patients undergoingMR imaging other medical factors such as hypo-tension, agitation, or otherwise altered level ofconsciousness preclude the acquisition of diag-nostic MR images.4 The conspicuity of bloodproducts is high on CT and their appearance isspecific. For all these reasons, CT is better studiedthan MR imaging in the setting of acute stroke andhas been the primary modality for the largest trialsin acute stroke intervention. The immediate CTscanning of all patients with acute stroke hasbeen shown to be a cost-effective policy thatresults in improved quality of life outcomes.5

Increasingly, however, MR imaging is gainingfavor in the acute setting. Addressing some ofthe primary perceived deficiencies of the modality,faster sequences have been developed with thebroader availability of higher field strengths,stronger and faster gradients, and the applicationof ever-improving computing power. Studieshave shown that specific MR sequences arecomparable with CT when used for the detectionof acute and subacute blood products. MR hasalso been found to be more accurate in the detec-tion of chronic hemorrhage, the presence of whichis believed to affect the risk of thrombolytictherapy. Other advantages of MR over CT in theacute stroke setting include the detection of smallischemic infarcts, the differentiation of acute fromchronic ischemia, and the identification of satelliteischemic lesions that might better characterize themechanism of stroke.2 Unlike CT, to our

knowledge no outcomes or cost-effectivenessstudies have yet been performed evaluating MRimaging as the initial imaging modality.At our institution, CT remains the initial imaging

modality of choice because of its proven sensitivityand specificity, availability, and speed. CT angiog-raphy (CTA) is performed soon thereafter inpatients who are found to have ICH or SAH forwhich the cause is not immediately apparentfrom the clinical history. Digital subtraction angiog-raphy (DSA) and MR imaging are performed toevaluate for specific underlying causes (ie, aneu-rysm, vascular malformation, primary orsecondary neoplasm, amyloid angiopathy, hemor-rhagic infarction, or venous sinus thrombosis).

INTRACRANIAL BLOOD PRODUCTS

One of the primary objectives of early strokeimaging is the identification and characterizationof hemorrhage. In the ideal setting, imaging willhave been obtained within less than 3 to 6 hoursof symptom onset, so that blood products shouldbe relatively fresh. However, this may not be thecase in clinical practice. Hemorrhage evolution isa dynamic process with imaging findings thatcan change over time.The molecular composition of extravasated

blood changes as the blood products breakdown and are reabsorbed. Five stages are typi-cally referenced: blood consists primarily of intra-cellular oxyhemoglobin in the hyperacute stage;during the acute stage this gradually loses itsoxygen to become deoxyhemoglobin; this is con-verted to intracellular methemoglobin by oxidativedenaturation in the early subacute stage; in the latesubacute stage, cell lysis occurs resulting in extra-cellular methemoglobin; this is converted to hemo-siderin and ferritin by macrophages in the chronicstage. Although there is good agreement in thenaming of each stage and the molecular composi-tion of the associated blood products, discrep-ancies persist amongst investigators in delimitingthe exact time interval of each stage.6e8 This isa reflection of the dynamic nature of the breakdown of blood products, a process that can occurat different rates between patients or even withinseparate areas of a hematoma.Hemorrhages into the various intracranial

compartments demonstrate similar, although notalways identical, progression over time. Subduraland epidural hematomas evolve similarly to ICH,although they progress through each stage moreslowly because of the higher oxygen tensionconveyed by the adjacent vascularized dura.Subarachnoid and intraventricular bleeds maydiffer in initial CT density and MR characteristics

Hemorrhagic Stroke 29

depending on the degree to which they mix withCSF. Their progression is also slow, againbecause of the relatively high local PO2.

6

ICHEpidemiology

ICH is the second most common cause of stroke,accounting for 10% to 15% of all strokes.1,9

Although long term functional outcomes for strokesurvivors are similar amongst hemorrhagic andischemic cohorts,10 ICH carries significantly highermortality risks, with 30-day mortality estimatesranging from 35% to 52%, a rate approximately5 times greater than the mortality for ischemicevents.1,9 The survival difference is mostpronounced immediately after a stroke, with aninitially 4-fold higher risk of death. This decreasesto 2.5- and 1.5-fold at 1 and 3 weeks respectively,and the increased mortality risk of ICH continuesto gradually decline such that no differencesbetween the 2 groups of survivors are seen 3months afterwards.11

CT Findings

The typical CT appearance of an acute hyperten-sive hemorrhage is a round or oval hyperattenuat-ing mass (Fig. 1). In the hyperacute setting thesetypically measure 40 to 60 Hounsfield units (HU),and can appear heterogeneous. As the clot orga-nizes it appears more homogeneous and hyper-dense, increasing to 60 to 80 HU in hours todays and 80 to 100 HU over the course of a few

Fig. 1. A 73-year-old man on warfarin presented withbalance problems and headache. Noncontrast headCT showed a 2.5�3.0 cm right parietal ICH.

days at which point it may be surrounded bya halo of hypoattenuation representing perihema-tomal edema.6

The conspicuity of a clot depends on severalfactors, including size, location, CT imagingparameters, and the window and level settingsused for reading. Smaller bleeds may be moreapparent on thin-slice imaging, and those locatedadjacent to the calvarium may be easier to detectwith a wider (150e250 HU) window setting. Insome cases it may be difficult to distinguishbetween focal calcification and blood. Usuallythis can be resolved with appropriate windowingand use of thin-section reconstructions. Alterna-tively, a dual kilovolt technique, which exploitsthe greater attenuation of calcium at lower tubevoltage, can be used.12 Caution must be used inthe setting of extreme anemia, where blood mayappear isodense to brain parenchyma becauseof low hematocrit. In the case of active extravasa-tion, liquid blood products can appear hypodenserelative to surrounding clot, resulting in the so-called swirl sign.”7 Similarly, acute hemorrhage inthe setting of coagulopathy may appear isodenseor may demonstrate a fluid/fluid level.7

As the hemorrhage ages, the CT density gradu-ally decreases by an average of 0.7 to 1.5 HU perday. In a progression that begins at the peripheryand continues to the center of the hematoma, hy-perdense clot first becomes isodense, andprogressively becomes hypodense until it iscompletely reabsorbed.6 In the absence of re-bleeding, the late sequelae of hemorrhage caninclude hypodense foci (37%), slit-like lesions(25%), calcification (10%), or no detectable abnor-mality (27%).13

MR Findings

The appearance of ICH similarly changes overtime on MR imaging. Many variables influencethe signal characteristics. These include factorsintrinsic to the hematoma such as age, size, loca-tion, and episodes of recurrent hemorrhage; tech-nical MR factors such as pulse sequence selectionand parameters, magnetic field strength, andbandwidth; also biologic qualities such as PO2,pH, protein concentration, and integrity ofa blood-brain barrier.6 A detailed discussion ofthe technical factors determining signal propertiesat each stage is beyond the scope of this discus-sion, but the MR signal of blood products reliablycorrelates with each of the previously identifiedstages. The resultant MR appearance is summa-rized in Table 1.

Spin-echo T1- and T2-weighted imaging tech-niques are known to be adequate for the

Table 1Evolution of intracranial blood products, CT and MR imaging appearance

Stage Main Product Time Frame6 CT T1/T2

Hyperacute Oxyhemoglobin First few hours Hyperdense Isointense/hyperintense

Acute Deoxyhemoglobin 1e3 d Hyperdense Isointense/hypointense

Early subacute Intracellularmethemoglobin

3e7 d Hyperdense Hyperintense/hypointense

Late subacute Extracellularmethemoglobin

4e7 d to 1 mo Isodense Hyperintense/hyperintense

Chronic Hemosiderin, ferritin >1 mo Hypodense Hypointense/hypointense

Smith & Eskey30

identification of subacute and chronic blood prod-ucts, however their sensitivity is poor comparedwith CT for hyperacute hemorrhage. Gradientrecalled-echo (GRE) imaging techniques with T2*weighting are substantially more sensitive tohyperacute hemorrhage.14e16 Unlike spin-echosequences, spin refocusing with gradient reversaldoes not refocus static magnetic field inhomoge-neity. The paramagnetic properties of blood prod-ucts induce local field inhomogeneity resulting insignal loss on T2*-weighted sequences. Severalstudies have evaluated the accuracy ofT2*-weighted GRE imaging compared with CT inthe detection of hyperacute ICH in all patients pre-senting with acute stroke (both excluded the eval-uation of SAH.) MR was found to provide equaldetection of acute ICH and to provide betterdetection of chronic hemorrhage.17,18 Newerthree-dimensional (3D) susceptibility-weightedimaging (SWI) sequences have also been devel-oped which use a 3D fast low-angle shot (FLASH)technique with flow compensation. Although thesewere initially used as a tool for MR venography,19

they are also useful in the evaluation of ICH

Fig. 2. A 44-year-old man with 2-week history of right fronwith a crescent-shaped hemorrhage within an area of hypright transverse sinus contains high attenuation material (tbosis). (B) T2*-GRE MR with signal dropout at known crescenot visible on CT. (C) SWI MR demonstrates further signT2*-GRE.

(Fig. 2). Studies have shown that such 3D SWIsequences are more sensitive than CT or evenother T2*-GRE MR imaging in the detection ofboth chronic microhemorrhage and small volumehemorrhage within an acute infarct.20,21

Causes and Patterns of ICH

The presence of ICH alone is enough to alter theongoing work-up and treatment plan of a patientwith acute stroke. In most clinical scenarios,further characterization of the hemorrhage itselfand adjacent structures helps to further shapediagnostic and therapeutic goals. There arenumerous causes of ICH, and although severalclassic patterns of presentation have beendescribed, there remains overlap among entities.The typical imaging appearance and potential dis-tinguishing characteristics that can be of use infurther directing care are reviewed.

Primary causes of ICHHypertension is the most common cause of spon-taneous ICH in adults.22 The underlying mecha-nism seems to be related to the effects of

totemporal headaches. (A) Noncontrast head CT (NCT)oattenuation in the posterior left temporal lobe. Thehis hemorrhage was secondary to venous sinus throm-nt-shaped blood and smaller focus of blood anteriorlyal dropout representing blood products not seen on

Hemorrhagic Stroke 31

systemic blood pressure on small penetratingarteries that arise from major intracranial vessels.Specifically, these vessels are the lenticulostriatearteries arising from the middle cerebral arteries,thalamoperforating and thalamogeniculatearteries from the posterior cerebral arteries, andthe pontine and brainstem perforators arisingfrom the basilar artery. In response to hyperten-sion, these small vessels can develop intimalhyperplasia, intimal hyalinization, and medialdegeneration, which predispose them tofocal necrosis and rupture.23 Some investigatorssuggest that vessel injury can lead to microaneur-ysms, termed Charcot-Bouchard aneurysms,which are prone to subsequent rupture, resultingin micro- or macrohemorrhages.24 The classiclocation of macroscopic hypertensive ICH alsoreflects the territories supplied by these smallperforators, with 60% to 65% of bleeds in the pu-tamen and internal capsule, 15% to 25% in thethalamus, and 5% to 10% in the pons.7 Althoughthe deep locations are most characteristic, hyper-tension remains a significant risk factor for lobarhemorrhage in the absence of other underlyingcauses.25,26

Hypertensive hemorrhages originating in thebasal ganglia and brainstem have a propensity toextend into the nearby ventricular system(Fig. 3). Intraventricular blood characteristicallyappears hyperdense on CT, and can range involume from a thin dependent layering tocomplete filling of one or all of the ventricles. TheMR appearance of intraventricular hemorrhage

Fig. 3. A 48-year-old woman with hypertension pre-sented with sudden onset of left hemiparesis andaphasia. There was ICH centered in the right lentiformnuclei with intraventricular extension.

(IVH) at the various stages is similar to that ofICH, although the progression from stage to stageis typically slower.6 Like ICH, IVH appears hypoin-tense on SWI. Unlike ICH, IVH is readily identifiedon fluid-attenuated inversion recovery (FLAIR)sequences, because of its marked T2 hyperinten-sity relative to the adjacent dark CSF signal.

Another secondary finding that may be seenmore often in the setting of hypertensive hemor-rhage than other causes is the presence of micro-bleeds in the distribution of the small perforatingvessels. These are the sequelae of hypertensivearteriopathy resulting in very small volumebleeding that is generally chronic and often multi-focal. These microbleeds are not typically de-tected by CT. The characteristic MR appearanceof a microbleed is that of a focal area of signalloss (<10 mm) on a susceptibility-weightedsequence. This finding has been pathologicallycorrelated with the presence of hemosiderin-laden macrophages adjacent to small bloodvessels.27

Cerebral amyloid angiopathy Cerebral amyloidangiopathy (CAA) is another common cause ofspontaneous ICH. This is a disease with a strongpredilection for advanced age, rarely seen inpatients younger than 60 years and with progres-sively increasing incidence after the age of 65years. CAA is characterized by the deposition ofamyloid beta-peptide in the small- and medium-sized vessels of the leptomeninges and cortex,with relative sparing of vessels in the basal ganglia,white matter, and posterior fossa.28 The exactmechanisms resulting in deposition are not wellunderstood, although there seem to be associa-tions with specific mutations in an amyloidprecursor protein as well as specific alleles of theapolipoprotein E gene. Affected vessels undergofibrinoid degeneration, necrosis, and microaneur-ysm formation. These weakened segments cansubsequently rupture, resulting in either micro-bleeds or larger hematomas. In contrast to hyper-tensive ICH, CAA-related hemorrhages tend tooccur in the cortex and subcortical white matter.Early descriptions suggested an equal distributionthroughout the supratentorial brain,28 althoughlater series have suggested that bleeding occursmore often in the temporal and occipital lobes.29

As in hypertensive ICH, the microbleeds associ-ated with CAA are not visible on CT, and arebest detected as focal areas of signal dropout onT2*-GRE or 3D SWI MR sequences (Fig. 4). Thewidely used Boston criteria for the diagnosis ofCAA rely heavily on the imaging features of bothmacro- and microhemorrhages when pathologicevidence is not available (Table 2).

Fig. 4. A 69-year-old woman who had an episode of acute vision loss a few weeks previously. (A) Axial T2-weighted MR image shows subtle gyriform hypointense signal along the cortex of the right occipital lobe. (B)Coronal T2*-GRE reveals marked signal dropout at site of right occipital hemorrhage and many small foci ofsignal dropout compatible with amyloid microhemorrhage.

Smith & Eskey32

Secondary causes of ICHIn the setting of acute ICH, imaging becomes theprimary tool for the detection or exclusion ofmany of the known secondary causes. Althoughsome entities may have characteristic findings onunenhanced CT or MR according to a strokeprotocol, multimodal evaluation including vascularevaluation and contrast enhancement canimprove sensitivity for underlying lesions. Themost common of the structural lesions that canresult in ICH include vascular malformations,neoplasms, and hemorrhagic infarction.

Table 2Boston criteria for the diagnosis of CAA with ICH

Definite CAA Postmortem e1. Lobar, c2. Severe C3. Absence

Probable CAA with supportingpathologic evidence

Clinical data a1. Lobar, c2. Some de3. Absence

Probable CAA Clinical data a1. Age �602. Multiple

corticos3. Absence

Possible CAA Clinical data aAge �60 year

1. Single lowithout

2. Multiplecause or

From Greenberg SM, Edgar MA. Case 22-1996- Cerebral hemorMed 1996;335(3):189e96; with permission.

Cerebral vascular malformations Four types ofintracranial vascular malformations are classicallydescribed. In order from most to least common,these include developmental venous anomalies(DVA), arteriovenous malformations (AVM), capil-lary telangiectasias, and cavernous malformations(CM). Of these, AVMs and CMs have potential forhemorrhage, whereas DVA and capillary telangi-ectasia are generally considered benign.

AVM The prevalence of AVM in adults is about0.2%, although they account for 4% of all primary

xamination finding all 3 ofortical, or corticosubcortical hemorrhage,AAof another causative lesion

nd pathologic specimen finding all 3 ofortical, or corticosubcortical hemorrhagegree of vascular amyloid deposition in specimenof another causative lesion

nd MR imaging finding all 3 ofyearshemorrhages restricted to lobar, cortical,

ubcortical regionsof another causative lesion

nd MR imaging findings:s ANDbar, cortical, or corticosubcortical hemorrhageanother cause ORhemorrhages with possible but not definitewith some hemorrhages in atypical location

rhage in a 69-year-old woman receiving warfarin. N Engl J

Hemorrhagic Stroke 33

ICH and up to one-third of all ICH in young adults.The risk of hemorrhage is about 2% per year in anunruptured AVM, and the risk for recurrent hemor-rhage is as high as 18% in the first year.30 AVMsare characterized by a connection between arterialand venous systems through a nidus of abnormalvascular channels without an intervening capillarybed. They typically consist of enlarged feedingarteries, a tightly packed vascular nidus consistingof shunt vessels with gliotic intervening brainparenchyma, and enlarged draining veins. Aneu-rysms may be present on feeding arteries or withinthe nidus. Pial arteriovenous fistulas are similarin many respects but lack the nidus present inAVM, and are much less common. Independentpredictors for AVM hemorrhage include hemor-rhagic presentation, advanced age, deep AVMlocation, and exclusively deep venous drainage.31

Additional important features are those used bySpetzler and Martin in creating a 5-point gradingsystem for the estimation of surgical resectionrisk (Table 3).

When hemorrhage is absent, CT reveals a masslesion with the attenuation of the normal cerebralvessels, often accompanied by calcifications.However, after intracranial hemorrhage, the hema-toma may obscure most or all of the AVM.Enlarged vessels nearby or calcifications withinthe hematoma are a clue to the presence of under-lying AVM (Fig. 5). CTA typically reveals thevascular nidus and associated enlarged vessels.MR typically shows flow voids along the high-flow feeding and draining vessels as well as withinthe nidus itself. Recent advanced techniquesusing 3-T time-resolved MR angiography have

Table 3Spetzler-Martin grading scale for AVMa

Graded Feature Points Assigned

Size of AVM

Small (<3 cm) 1

Medium (3e6 cm) 2

Large (>6 cm) 3

Eloquence of adjacent brain

Noneloquent 0

Eloquent 1

Pattern of venous drainage

Superficial only 0

Deep 1

a Grade 5 [size] 1 [eloquence] 1 [venous drainage]From Spetzler RF, Martin NA. A proposed grading

system for arteriovenous malformations. J Neurosurg1986;65(4):476e83; with permission.

shown 100% agreement with DSA in determiningSpetzler-Martin grade.32 Small AVMs or arteriove-nous fistulae may not be visible on cross-sectionalstudies (Fig. 6) and DSA remains the gold standardfor evaluation of underlying vascular anomaly inthe setting of spontaneous ICH. Occasionally, de-layed angiography can reveal vascular abnormali-ties that were not appreciable on initial imaging.33

In the setting of a negative initial work-up ina young patient, a second evaluation should beundertaken once the mass effect from the hema-toma has resolved.

CM The prevalence of CM is estimated to bebetween 0.3% and 0.6%.34 The lesion is charac-terized by a cluster of thin-walled vessels withoutelastic fibers or smooth muscle, typically witha rim of hemosiderin-laden gliotic tissue. The latteris caused by chronic microhemorrhage, which isuniversal, although the risk of clinically significantde novo hemorrhage is relatively low, around0.4% to 0.6% per year.35,36 Most patients presentwith seizures or neurologic deficit.34 In patientswho have already presented with hemorrhage,the risk of rebleeding is increased, at 4.5% to26% per year.35,36 The hemorrhage of a CM hasbeen found to be typically smaller in volume thanAVM or dural arteriovenous fistula, and as a resultthese patients often present with less severe clin-ical symptoms37 when the hemorrhage is not in thebrainstem or spinal cord. The lesion itself typicallyappears isodense to slightly hyperdense on unen-hanced CT and may contain calcifications. Faint orperipheral contrast enhancement is sometimespresent, although not a reliable sign. MR imagingis the modality of choice for the detection of CM.Their classic appearance on T2-weighted imagingis that of a reticulated, or popcorn-like mass ofvariable signal intensity, caused by blood productsin varying stages of evolution, with a hypointensehemosiderin rim (Fig. 7). Sequences with greatersusceptibility weighting are more sensitive in de-tecting smaller lesions. In a population of patientswith multiple CMs, 3D SWI detected 1.7 times asmany lesions as T2*-GRE and 8 times as manyas spin-echo T2 sequences.38 Unlike the othervascular malformations, CMs are classically an-giographically occult. If a CM is to be resected,contrast-enhanced CT or MR imaging should beperformed to look for an associated DVA, whichcan be found in 8% to 33% of cases.39 The inad-vertent resection of all or part of a DVA alongwith a CM could result in venous infarction. Thetypical appearance of DVA on contrast-enhancedimaging is that of a stellate arrangement of tubularveins meeting in a collector vein that drains toa sinus or ependymal surface.40

Fig. 5. A 59-year-old woman with known large AVM presented with dysarthria and ataxia. (A) NCT shows largeleft ICH with intraventricular extension. Irregular calcifications adjacent to blood suggest underlying vascularmalformation. (B) Prehemorrhage T2-weighted MR shows many flow voids of varying sizes in the nidus of a largeAVM. Large cortical and subependymal draining veins are present. (C) DSA with large left frontotemporal AVMand multiple large early draining veins.

Smith & Eskey34

Neoplasm Hemorrhage as a result of a primary ormetastatic neoplasm accounts for 1% to 14% ofICH.41 The propensity for bleeding varies by histo-logic tumor type; those most often presenting withmacroscopic hemorrhage are listed in Box 1. Thehemorrhage can be confined within the tumor or

Fig. 6. A 45-year-old man with sudden onset of expressivesurrounding edema. (B, C) Axial and coronal images from(D) DSA revealed a pial arteriovenous fistula fed by a tortuing vein. A small aneurysm (arrow) is present near the fis

may extend into the brain parenchyma and othercompartments. On unenhanced CT or MRimaging, the resultant hemorrhage appears similarto that from any other cause, although a few signsare believed to be suggestive of underlyingneoplasm. Hematomas caused by tumor are

aphasia. (A) NCTwith left frontal ICH and small halo ofCTA were unrevealing for underlying vascular lesion.ous middle cerebral artery branch with an early drain-tulous site.

Fig. 7. A 47-year-old man with hypertension presents with 24 hours of headache, right-sided weakness, slurredspeech and confusion. (A) NCTwith large left frontal ICH and local mass effect. (B) T1-weighted MR with slightlyhyperintense hematoma with relatively hypointense center. (C) T2-weighted MR with heterogeneous T2 prolon-gation and susceptibility-related signal loss. There is a central lobulated structure with peripheral rim and centralpopcorn hyperintensity, suspicious for cavernous malformation. (D) SWI MR with concentric areas of signal lossconsistent with blood in different stages of evolution.

Box 1Brain tumors likely to hemorrhage

Metastases (primary)

Melanoma

Lung

Kidney

Thyroid

Choriocarcinoma

Primary brain tumors

Pituitary adenoma

Glioblastoma/oligodendroglioma

Ependymoma/subependymoma

Peripheral neuroectodermal tumor

Epidermoid

Data From Osborn AG. Diagnostic neuroradiology. StLouis (MO): Mosby; 1994.

Hemorrhagic Stroke 35

associated with a greater degree of surroundingvasogenic edema than nonneoplastic hema-tomas.42 Neoplastic hematomas have been char-acterized as relatively more heterogeneous andhave shown slower than expected degradation ofblood products. An irregular or incomplete hemo-siderin rim on MR may also be an indicator ofunderlying mass.43 Complete evaluation shouldinclude contrast-enhanced imaging regardless ofthe imaging modality. Although minor enhance-ment may be present about subacute hematomas,it is rarely present acutely. The presence of anythick or nodular enhancement is suggestive ofthe presence of underlying neoplasm (Fig. 8). Asin the case of vascular malformation, an underlyingtumor can be obscured, particularly if it is small inrelation to the hematoma size. Delayed imagingshould be strongly considered in the case ofa negative acute work-up.

Hemorrhagic infarction Hemorrhagic infarction(HI), also referred to as hemorrhagic transforma-tion of an infarct, typically refers to bleeding into

Fig. 8. A 42-year-old man with sudden onset right hemiparesis and slurring of speech. (A, B) NCT and noncontrastT1-weighted MR imaging with irregular left thalamic hematoma. (C) Post-Gd T1-weighted MR with incompleteperipheral enhancement that is nodular in areas. (D) 6-week follow-up NCT with decreasing density of bloodproducts. (E, F) T1-weighted pre- and postcontrast MR revealed an irregular enhancing mass markedly increasedin size. Pathology confirmed glioblastoma multiforme.

Smith & Eskey36

an area of preexisting arterial ischemia. An earlyprospective study identified HI in 43% ofinfarcts,44 and depending on the investigativemodality, incidence has been reported to be ashigh as 85%.45 These hemorrhages tend to occurin 2 patterns: petechial hemorrhage and paren-chymal hematoma.46 Petechial hemorrhage is oflittle clinical significance by itself and whether itshould alter plans for anticoagulation is question-able, whereas in parenchymal hematomas morethan 30% of the ischemic area correlated with clin-ical deterioration and poor outcome.47 HI usuallyoccurs around the second week following infarctwhen presenting spontaneously; early hemor-rhagic transformation is more common in thesetting of thrombolysis and mechanical clotretrieval.The CT appearance of petechial hemorrhage is

that of subtle increased density with indistinctmargins, with the density sometimes appearingspeckled or punctate. Signal intensity may varyon spin-echo MR imaging, but characteristicsignal dropout is seen on T2*-weightedsequences. On both CT and MR imaging there isa strong predilection for petechial hemorrhage to

occur primarily in gray matter structures (Fig. 9).Parenchymal hematoma secondary to ischemiacan be difficult to distinguish from other causesof ICH on CT and MR imaging. The distinction ismost often made by history because the infarctionusually precedes hemorrhagic transformation byat least a few days. This reinforces the need fortimely initial imaging. In some cases it is possibleto distinguish a larger area of cytotoxic edemaaffecting white matter and cortex outside thearea of hematoma. As with other types of hemor-rhage, MR performance is markedly improvedwith the inclusion of diffusion-weighted imagingand susceptibility-weighted sequences, whichwhen used detect both infarction and hemorrhagewith greater frequency than CT.48 The clinicalvalue of this improved sensitivity in the setting ofischemia remains as yet uncertain. Most treatmentstudies to date have used CT findings. HI in thesetting of thrombolytic therapy for ischemiaremains an area of great clinical interest. Therehave been significant efforts to identify pretreat-ment imaging characteristics that may help topredict the incidence or severity of treatment-related hemorrhage.49e51

Fig. 9. A 56-year-old man status post trauma with known right parietal contusion, developed left gaze prefer-ence and right-sided neglect. (A) NCT with well-demarcated left occipital infarction. (B) NCT 5 days later withnew hyperattenuation in cortical pattern, consistent with petechial hemorrhage. (C) NCT with known right pari-etal parenchymal contusion; note preservation of overlying cortical ribbon.

Hemorrhagic Stroke 37

Other secondary causes of ICHThere are a large number of other rarer causes ofacute ICH. These disorders include cerebral aneu-rysm, venous sinus thrombosis, septic embolism,bleeding dyscrasia, supratherapeutic anticoagula-tion, thrombolytic therapy, CNS infection, mycoticaneurysm, moyamoya, vasculitis, and vasoactivedrugs. Often these entities are only suspectedbecause of key features in the patients’ clinicalhistory. Sometimes they may be suspected fromimaging findings.

Cerebral aneurysm Although most aneurysmruptures result in SAH, up to 34% are associatedwith ICH,52 and 1 series found that 1.6% of aneu-rysm ruptures result in ICH without SAH.53 Suchcases likely result from rupture of aneurysms thatare pointed into or embedded in cerebral paren-chyma. Ruptured aneurysm is a treatable causeof intracranial hemorrhage, and studies haveshown that early treatment results in betteroutcomes. Furthermore, conservative manage-ment of ICH from a ruptured aneurysm has beenassociated with mortality of greater than 80%.54

Whenever the hematoma extends from the baseof the brain, and particularly when SAH is alsopresent, rupture of a berry aneurysm should beconsidered in the differential diagnosis for ICH. Inthis setting, additional imaging to evaluate foraneurysm should be considered; both CTA andMR angiography (MRA) are reasonable alterna-tives. The imaging features specific to cerebralaneurysms are discussed in the section onsubarachnoid hemorrhage.

Venous sinus thrombosis Thrombosis of the intra-cerebral veins or dural sinuses has an estimatedincidence of 3 to 4 cases per 1 million adults,with 75% of cases presenting in women.55 In thelargest series to date, 39% were found to have

associated hemorrhage.56 The imaging appear-ance of the hematoma itself can be nonspecific,thus the identification of secondary signs is essen-tial to making this diagnosis. A hyperattenuatingcortical or deep vein adjacent to the hematomahad greater than 97% specificity in 1 retrospectivestudy.57 Contrast-enhanced CT may show theempty delta sign representing nonenhancingthrombus in involved sinuses.58 Associatededema often precedes hemorrhage, followsvenous rather than arterial distributions, and isgenerally greater than that seen with primary ICH.

MR sequences such as T2 or FLAIR may bebetter able to demonstrate parenchymal edemaor ischemia. Venous thrombus has classicallybeen described as T1 hyperintense, although thesignal characteristics can vary considerably overtime and may be confusing.59 In the larger duralsinuses, the presence of uniform T1 isotense orT1 hyperintense signal is suggestive of thrombus,particularly when sinus expansion is present.Time-of-flight MR venography improves detectionof sinus thrombus, although pitfalls in interpreta-tion remain as a result of in-plane signal dropoutmimicking thrombosis and T1 bright thrombusmimicking flow. Contrast-enhanced and four-dimensional MR venography techniques60 as wellas CT venography further improve diagnosticaccuracy.

Dural arteriovenous fistula Dural arteriovenousfistulae (DAVFs) make up about 10% of all intracra-nial arteriovenous shunting malformations.61 Thislesion consists of a direct connection between du-ral arteries and dural veins without interveningvasculature. Unlike AVMs, they are believed to beacquired lesions secondary to trauma, surgery,infection, or venous sinus thrombosis. Theyproduce intracranial venous hypertension and,when this becomes sufficiently severe, ICH.62

Smith & Eskey38

Male sex, posterior fossa location and advancedage are risk factors for hemorrhage.63 Theselesions are typically difficult to see on noncontrastCT, although enlarged veins or transosseous chan-nels may be visible. Standard MR imaging also haspoor sensitivity for this entity although dilatedcortical veins and sinus thrombosis may be de-tected.64 Time-of-flight MRA improves depictionof arterial feeders and fistula site.65Onestudy usingtime-resolved contrast-enhanced MRA at 3 Tyielded 100% concordance with DSA in identifica-tion of fistula site and venous collaterals althoughonly 68% agreement for main arterial feeders.66

As with AVM, DSA remains the gold standard forboth detection and characterization of DAVF. Ina young patient with ICH of uncertain cause,DAVF should be specifically sought with selectiveinjection of vessels supplying thedural vasculature.

Specific Factors for ManagementConsiderations

Hematoma sizeThere are imaging features of acute ICH that arehelpful in managing patients and predicting neuro-logic outcomes. The location of hemorrhage andinvolvement of vital structures are strong predic-tors of outcome and influence the use of surgicaldecompression. For example, posterior fossahemorrhage carries a worse prognosis and moreoften requires surgical decompression. The totalvolume of ICH is a strong predictor of 30-daymortality, particularly when combined with thepresenting Glasgow Coma Scale score.67 Hema-toma volume can be quickly estimated on cross-sectional imaging by using the ABC/2 method,where A is the maximum hematoma diameter, Bis the diameter measured at 90� to A, and C isthe approximate number of slices containinghematoma multiplied by the slice thickness.68

Fig. 10. A 98-year-old man on warfarin presented withganglia hemorrhage extending to temporal lobe. (B) CThematoma (arrow) not contiguous with another vessel: th

Although outcomes generally worsen withincreasing clot size, those measuring more than60 cm3 in particular have been found to correlatewith poor outcomes.67 The proximity of the clotto the cerebral surface does seem to influencethe relative outcomes of nonsurgical managementversus decompression; clots within 1 cm of thecerebral surface had better outcomes withsurgical decompression.69

Hematoma expansionIn addition to size at presentation, the possibility ofongoing bleeding and hematoma expansionaffects outcomes and may guide therapeutic inter-vention. The incidence of substantial enlargementof an ICH is controversial with some studies sug-gesting that it is relatively common, occurring in38% of patients within the first 24 hours in 1prospective series,70 whereas other work has sug-gested that expansion after 24 hours is rare.71

Early expansion of a hematoma has been shownto increase the risk of mortality and poor functionaloutcome, with each 10% increase in hematomasize resulting in a 5% increased hazard of deathand 16% likelihood of worsening on the modifiedRankin scale of functional outcomes.72 Thesedata suggest that repeat imaging is warranted forthe detection of hematoma expansion. Imagingfindings that predict expansion may also identifythe patients most likely to benefit from such inter-ventions as Factor VII infusion.

CTA spot signThe presence of a 1- to 2-mm focus of intenseenhancement within a hematoma on the CTAsource images has been labeled the spot sign(Fig. 10). It is believed to represent the presenceof a small pseudoaneurysm or active extravasa-tion. This finding on CTA performed within 3 hours

confusion. (A) NCT with heterogeneous right basalA with punctuate focus of hyperattenuation withine spot sign.

Hemorrhagic Stroke 39

of symptom onset was independently predictive ofhematoma enlargement.73 A contrast-enhancedhead CT immediately after the CTA may demon-strate contrast leakage; that is, the delayed spotsign, and when this finding is added to the CTAspot sign, sensitivity and negative predictive valuefor predicting hematoma expansion areimproved.74

Another study included CTAs obtained any timewithin 24 hours of admission and included both thespot sign and the delayed spot sign if an imme-diate contrast-enhanced CT was obtained. Threefactors were found to be independent predictorsof hematoma expansion, including the number ofspot signs, the maximum axial dimension of thespot(s), and the maximum attenuation of thelargest spot.75 These were incorporated intoa spot sign score, and although this has not yetbeen independently validated, it has the potentialto serve as a predictor of hematoma expansionin ICH independent from other factors such astime of symptom onset and hematoma volume. Asecond review of the same cohort found that thespot sign score also served as an independentpredictor of in-hospital mortality and poor func-tional outcome among survivors at 3 months.76

Intraventricular hemorrhageA hematoma originating near a CSF space canspontaneously decompress into the adjacentintraventricular or subarachnoid space. Thepropensity for intraventricular spread is dependenton the size of the hematoma as well as its loca-tion.77 Intraventricular extension of ICH has beencorrelated with poor functional outcome andincreased mortality in several studies,77,78 andhas been incorporated into models for predictionof outcomes.79,80 The association seems to bemore robust when some measure of the volumeor degree of IVH is used, as several studies usinga binary variable for the presence or absence ofintraventricular blood have failed to show a strongassociation with worsened outcomes.79,81,82 Thepresence of hydrocephalus in the setting of intra-ventricular hematoma extension is a separatepredictor of poor outcome.83

SAHEpidemiology

Slightly less common than ICH, SAH accounts forbetween 3% and 5% of all strokes.9,84 Much likeICH, outcomes following SAH are poor, withobserved 30-day mortality in the range of 33% to45%.85,86 Most deaths caused by SAH occur earlyin the time course of the disease, with 61% ofdeaths occurring within 2 days of the initial event.86

Imaging Technique and Findings

Noncontrast CT is highly sensitive for SAH in theacute and subacute settings. The typical appear-ance of acute SAH is that of high attenuation mate-rial conforming to the subarachnoid space. It maybe localized or diffuse and is present within thesulci, fissures, or basal cisterns. Initial sensitivityis 98% within 12 hours of symptom onset.87 Thisdecreases over time, dropping to 93% 24 hoursafter onset88 and continuing to decline thereafteras a result of dilution and evolution of blood prod-ucts that combine to result in decreasing density.A negative CT should reliably exclude largervolume SAH such as that from an aneurysmrupture, but lumbar puncture with CSF analysisremains the standard with which CT is compared,and is strongly recommended to excludea CT-negative SAH such as might be seen froma sentinel bleed. Current guidelines recommendprompt CT scanning for the suspicion of SAHwith strong consideration for lumbar puncture tofollow if the CT is negative.84

MR has demonstrated added value in the diag-nosis of subacute SAH. Hyperacute blood prod-ucts in the subarachnoid space should appearhyperintense on T1- and proton densityeweightedimages as a result of the increased proteincontent. Similarly, the signal in blood-containingCSF fails to null on FLAIR sequences resulting inhyperintense signal in the affected CSF spaces(Fig. 11). When compared against CT, FLAIR andproton densityeweighted sequences have beenfound equally sensitive for the detection of SAHless than 12 hours from symptom onset.89 Thesensitivity of FLAIR imaging does not seem todrop off nearly as quickly as CT, and FLAIRremains more sensitive than CT in the first 2weeks.90,91 The use of FLAIR in the diagnosis ofSAH is limited by its low specificity (other CSFalterations from infection or increased proteincontent produce similar signal changes) and thepresence of flow-related artifacts about the brain-stem. Like CT, negative MR does not reliablyexclude low volume or dilute SAH, becausea review of patients with SAH who had negativeCT and positive lumbar puncture showed FLAIRsensitivity of less than 20%.92

Causes of SAH

Aneurysm ruptureThe most common cause of spontaneous SAH isthe rupture of a cerebral aneurysm, accountingfor about 85% of SAHs.93 Cerebral aneurysmsare present in about 2% of asymptomatic adults.94

Saccular aneurysms tend to occur at branchpoints along cerebral vessels, whether at

Fig. 11. A 69-year-old woman with intermittent severe headache of several days duration. (A) NCT was read asnormal with no evidence of increased density in the subarachnoid space. (B) FLAIR MR imaging with marked hy-perintensity of the CSF in the anterior interhemispheric fissure and sulci over the right cerebral convexity. (C) DSAwith lobulated right posterior communicating artery aneurysm.

Fig. 12. A 72-year-old man with sudden onset severeheadache and confusion. NCT reveals diffusesubarachnoid hemorrhage filling the basal cisterns,interhemispheric fissure, and Sylvian fissures. A fillingdefect at the posterior aspect of the interhemisphericfissure was found to be an anterior communicatingartery aneurysm. Also note the small intraparenchy-mal hematoma in the inferior left frontal lobe.

Smith & Eskey40

a bifurcation or the origin of a side branch.95 Mostaneurysms (80%e85%) are located in the anteriorcirculation, commonly at the origins of the poste-rior or anterior communicating arteries or themiddle cerebral artery bifurcation; posterior circu-lation aneurysms are most often seen at the basilartip or posterior-inferior cerebellar artery origin.96

The annual risk of rupture for any given aneurysmis about 0.7%. Rupture risk is predicted by aneu-rysm size and location, with risk increasing signif-icantly for aneurysms greater than 7 mm indiameter, and an increased rupture risk for thosearising from the posterior communicating arteriesor posterior cerebral circulation.97

When spontaneous SAH is detected, the nextsteps of the imaging work-up are directed towarddetecting a ruptured aneurysm or other underlyingcause. The pattern of SAH at presentation can beof predictive value in localizing an aneurysm. Forexample, a ruptured anterior cerebral artery aneu-rysm is associated with a substantial amount ofblood in the interhemispheric fissure. Hemorrhagepatternmaybe less helpful for other aneurysm loca-tions.98 In some cases the aneurysm can be identi-fied directly on unenhanced imaging (Fig. 12). OnCT an aneurysmmay appear as a rounded or lobu-lated mass within the hematoma. The presence ofmural calcification can help to locate an underlyinganeurysm, and portions may be of high attenuationwhen there is intra-aneurysmal thrombus. Someaneurysms may be detected on MR as a flow voidor a mass with flow-related artifact in the phase-encoding direction.Aneurysm detection is markedly improved with

the use of dedicated vascular imaging in eithermodality. Review articles quote a sensitivity andspecificity of CTA in the range of 77% to100%.84,93 Sensitivity nears 100% for aneurysmgreater than 3 mm in size, although accuracy isreduced in the case of small aneurysms or

tortuous vessels. MRA has shown similar sensitiv-ities (85%e100%) for aneurysms greater than5 mm, although dropping to 56% less than thatsize.84 MRA at 3 T has shown promising resultswith 100% sensitivity and greater than 95% accu-racy compared with rotational DSA.99 DSA hasbeen the gold standard for vascular evaluationfor some time, although recent studies haveshown further improvements in aneurysm detec-tion with the addition of planar and 3D reconstruc-tions derived from a 3D rotational acquisition.100

In the patient presenting to the emergencyroom, the most common cause of SAH is

Hemorrhagic Stroke 41

craniospinal trauma. In most cases, the history isclear and the extent of SAH is small. In caseswhere SAH is prominent and the history of theinjury suggests the possibility that the SAH mayhave occurred first (and caused the trauma),a full evaluation for aneurysm is necessary.

Nonaneurysmal SAHThere are a variety of other conditions that canresult in nontraumatic SAH, all of which are rarecompared with aneurysmal SAH. There is someoverlap with lesions that can result in ICH, andentities include intracranial or spinal vascular mal-formations, neoplasm, primary vasculopathy, drugabuse, sickle cell anemia, coagulopathies, andpituitary apoplexy. Relevant clinical history canbe helpful in establishing the correct diagnosis inmany of these settings.

An important entity not included in this list is non-aneurysmal perimesencephalic SAH. Accountingfor between 21% and 68% of angiography-negative SAH,101 this is a specific entity firstdescribed in 1985, with a characteristic distributionof subarachnoid blood, negative angiographicwork-up, and a generally benign clinical course.The pattern of blood seen by CT or MR imaging isSAHcentered immediately anterior to themidbrain.This may or may not extend to the anterior part ofthe ambient cistern or the basal portions of the Syl-vian fissure.102 Furthermore, there can be no otheridentifiable source of hemorrhage on cross-sectional or angiographic imaging. The presenta-tion of this subgroup is typically indistinguishablefrom other types of SAH, but their prognosis isexcellent. Rates of recurrent hemorrhage, hydro-cephalus, and vasospasm are low and goodoutcomes were seen in 100%, compared with88% of other patients with SAH who were angiog-raphy negative and 64% of patients with aneu-rysmal SAH.101

Prognostic Indicators

There are several factors that can be evaluated atthe time of SAH presentation and used to directimmediate management or predict clinicaloutcomes. Acute hydrocephalus, usually in thesetting of IVH, is a surgical emergency requiringventriculostomy decompression. Aneurysm loca-tion and morphology are used to guide the treat-ment algorithm; each aneurysm requires carefulreview by an experienced cerebrovascular teamto determine optimum treatment. Features suchas branches arising from the aneurysm domeand difficult endovascular access favor surgicalclipping, whereas difficult surgical access, pres-ence of nearby perforating arteries, and neckcalcification favor endovascular treatment. The

Hunt and Hess grading scale is based on neuro-logic status at presentation and underlyingmedical comorbidities, and is used to estimatethe mortality of aneurysmal SAH.103 A gradingscale developed by Fisher and colleagues104

uses findings on the noncontrast CT at presenta-tion, such as thickness of SAH, the presence ofsubarachnoid blood clots, and intraventricular orintracerebral extension to predict the likelihoodof cerebral vasospasm.

SUMMARY

The timely and accurate identification of hemor-rhagic stroke is essential in the clinical manage-ment of patients presenting with acute strokesymptoms. Cross-sectional imaging should bereadily available and initial protocols shouldinclude unenhanced head CT or dedicated strokeprotocol MR imaging including blood-sensitive T2*or 3D SWI and FLAIR sequences. When detected,the appearance and location of hemorrhage canhelp to narrow the differential diagnosis, directadditional advanced imaging, guide immediatemanagement, and provide early prognostic infor-mation with regard to patient outcomes.

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