edema cerebral

W258 AJR:199, September 2012

Cerebral Edema

Res idents ’ Sect ion • Pat tern of the Month

WEB This is a Web exclusive article.

AJR 2012; 199:W258–W273

0361–803X/12/1993–W258

© American Roentgen Ray Society

Mai-Lan Ho1

Rafael Rojas Ronald L. Eisenberg

Ho ML, Rojas R, Eisenberg RL

1All authors: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215. Address correspondence to R. L. Eisenberg ([email protected]).

Keywords: cerebral edema

DOI:10.2214/AJR.11.8081

Received October 3, 2011; accepted after revision March 7, 2012.

Residents

inRadiology

This article reviews the pathophysiology and imaging appearances of cerebral edema or increased water content. Edema is a common response to various forms of brain injury, and the causes can be categorized as cytotoxic, vasogenic, inter-stitial, or combined. Identification of the dominant imaging pattern, in conjunc-

tion with additional radiologic findings and clinical history, often yields clues to the diagno-sis. Table 1 lists the types of cerebral edema and their associated causes.

CT is the initial screening examination for patients presenting with new-onset neurologic symptoms. On CT, edema manifests as decreased attenuation relative to surrounding normal parenchyma. Standard CT brain viewing settings (window width, 100 HU; window level, 40 HU) highlight the contrast between gray and white matter, whereas narrower stroke window settings (window width, 30 HU; window level, 30 HU) accentuate focal areas of hypodensity. Abnormalities can be characterized in terms of location; pattern of gray-white matter involve-ment and associated mass effect as evidenced by midline shift; sulcal, ventricular, cisternal effacement; and cerebral herniation. Coronal and sagittal multiplanar reformation images are frequently useful for further localization and quantification.

MRI provides excellent soft-tissue contrast resolution and thus is often requested for evaluation of underlying lesions. On MRI, edema produces high signal on T2-weighted imaging and low signal on T1-weighted imaging. Diffusion-weighted imaging (DWI) and apparent diffusion coef-ficient (ADC) sequences distinguish between cytotoxic edema (restricted diffusion) and vaso-genic or interstitial edema (normal or increased diffusion). Diffusion-tensor imaging (DTI) uses tensor analysis to calculate the degree of anisotropy on the basis of the magnitude and direction of water diffusion in each voxel in the brain. A commonly used parameter is fractional anisot-ropy, which reflects the principal directional eigenvector of molecular motion and is used in white matter tractography. FLAIR se-quences, which suppress CSF signal, are use-ful for visualizing periventricular signal ab-normalities due to interstitial edema. T2* gra-dient-recalled echo (GRE) and susceptibility-weighted imaging sequences are useful for identifying associated hemorrhage or calcifi-cation. Time-of-flight images and abnormal flow voids can suggest the presence of a vas-cular malformation. Contrast enhancement may be seen in neoplasms, active infection or inflammation, and vascular lesions.

Symptoms of cerebral edema are nonspe-cific and related to secondary mass effect, vascular compromise, and herniation. Clinical and radiologic changes are usually reversible in the early stages as long as the underlying cause is corrected. With mild edema, increased brain volume is compensated for by decreases

Ho et al.Cerebral Edema

Residents’ SectionPattern of the Month

TABLE 1: Distribution of Cerebral Edema

Cytotoxic

Arterial infarction

Small vessel disease

Vasogenic

Neoplasm

Hemorrhage

Venous thrombosis

Arteriovenous shunts

Interstitial

Hydrocephalus

Combined

Trauma

Hypoxic-ischemic encephalopathy

Osmotic

Hydrostatic

Infection or inflammation

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in CSF and blood volume. However, rapidly progressive edema overwhelms cerebral autoregu-latory mechanisms, resulting in structural compression; cerebral ischemia; and, ultimately, fatal cerebral herniation. To prevent this, a variety of empirical medical treatments are used, including hyperventilation, osmotherapy (mannitol and hypertonic saline), loop diuretics, hypothermia, sedation (propofol, barbiturates), and neuromuscular paralysis (succinylcholine). Corticoste-roids, which reduce the permeability of the blood-brain barrier, can also be used to control vaso-genic edema. For cases refractory to medical management, such as severe trauma and major strokes, emergency decompressive craniectomy may be performed as a last resort.

In this article, we will review the pathophysiology and imaging appearances of various causes of cerebral edema. Characterization of edema location and distribution, along with associated parenchymal abnormalities, is critical for early and accurate diagnosis, workup, and intervention.

Cytotoxic EdemaCytotoxic edema results from derangements in adenosine triphosphate (ATP)-dependent

transmembrane sodium-potassium and calcium pumps and is usually caused by cerebral is-chemia or excitotoxic (secondary to excessive neurotransmitter stimulation) brain injury. This leads to intracellular accumulation of fluid in neurons, glial cells, axons, and myelin sheaths. The gray matter is affected first because of its high metabolic activity and greater astrocyte density. Ultimately, both the gray and white matter become involved, with corresponding loss

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Fig. 1—Middle cerebral artery (MCA) infarct.A, Unenhanced CT image of early MCA infarct shows subtle edema in right lentiform nucleus, consisting of putamen (white arrow) and globus pallidus (black arrow).B, Unenhanced CT image of subacute MCA infarct shows cytotoxic edema that causes loss of left insular ribbon (arrow).C, Unenhanced CT image shows hyperdense MCA sign on right (arrow).

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of differentiation on CT. There is overall re-striction of diffusion of water molecules across the cell membrane and within the cy-toplasm resulting in regional high signal on DWI and low signal on ADC images. Initial-ly, the blood-brain barrier remains intact and extracellular water does not increase, yield-ing normal DTI maps and fractional anisot-ropy. Severe or repeated insults overwhelm transmembrane ion pumps, causing cell death with breakdown of the blood-brain barrier and resulting vasogenic edema. Late compli-cations include neuronal apoptosis, atrophy, and gliosis.

Arterial InfarctionAcute arterial infarction produces a hy-

poxic state with rapid ATP depletion second-ary to depolarization, inflammation, oxida-tive or nitrosative stress, and apoptosis. Cy-totoxic edema develops within 30 minutes of arterial occlusion, peaks between 24 and 72 hours after infarction, and persists for up to 24 hours after reperfusion. On CT, loss of gray-white matter differentiation corresponds to a major vascular distribution. Early signs of middle cerebral artery infarction include obscuration of the lentiform nucleus (Fig. 1A) and loss of the insular ribbon (Fig. 1B);

these areas of normally high gray-white contrast are supplied by small perforating branches. A large intravascular thrombus may also appear as increased attenuation on unenhanced scans (hyperdense artery sign) (Fig. 1C). Progressive edema results in an increase in overall volume, manifested by effacement of sulci, ventricles, and cisterns.

Emergent evaluation of acute stroke begins with unenhanced CT, which screens for focal edema, hemorrhage, and mass effect. If imaging or clinical findings suggest acute stroke, fur-ther assessment can be performed with contrast-enhanced CT angiography or time-of-flight MR angiography. These modalities generate multiplanar and volume-rendered reconstructions of the intracranial circulation, which are useful for characterizing vascular abnormalities, includ-ing occlusions, stenoses, dissections, aneurysms, and anatomic variants (Fig. 2).

MRI can also be used in the acute stroke setting, although technical and personnel require-ments restrict its application in many centers. DWI is the most sensitive sequence for detec-tion of hyperacute infarction (< 30 minutes after presentation), preceding the identification of changes on CT (6 hours) and T2-weighted imaging (6–12 hours). Restricted diffusion in acute infarcts corresponds to areas of increased and decreased signal on DWI and ADC maps, respectively. As infarcts evolve into the subacute and chronic stages, there is progres-sion to vasogenic edema and encephalomalacia. This is reflected by progressive increase in T2/FLAIR intensity, with concomitant normalization of diffusivity (Fig. 3). Unenhanced time-of-flight MR angiography or arterial spin labeling can also be performed. However, spatial resolution is inferior compared with CT, and the images are prone to motion, suscep-tibility, and flow artifacts.

Complementary modalities for quantifying cerebral blood flow include SPECT and xenon CT. In SPECT, 99mTc-labeled HMPAO (hexamethylpropylene amine oxime) is taken up by cerebral tissue in concentrations proportional to blood flow. Xenon CT uses xenon gas, which is radiodense and lipid-soluble. Once dissolved in the blood, it can pass through the blood-brain barrier into the parenchyma. Images are obtained before, during, and after inhalation.

Neuroangiography is considered the reference standard for evaluation of the cerebral cir-culation. However, it is an invasive procedure with associated risks, most importantly, cere-bral embolism. Nevertheless, neuroangiography is the standard of care for patients requiring

Fig. 2—CT angiography of infarct. Volume-rendered reconstruction image of circle of Willis shows filling defects involving distal left internal carotid artery (arrowhead), A1 segment of anterior cerebral artery (thin arrow), and M1–M2 segments of middle cerebral artery (thick arrow).

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interventions, such as intraarterial thrombolysis and thrombectomy, angioplasty or stenting, and aneurysm or arteriovenous malformation (AVM) clipping or coiling (Fig. 4).

Stroke prognosis depends on patient age, duration of symptoms, cause and severity of oc-clusion, affected vascular territory, and presence of collateral circulatory pathways. In the first 3 hours after the onset of symptoms, nonhemorrhagic ischemic stroke is treated with systemic IV tissue plasminogen activator (tPA). After this time window, IV tPA is no longer effective. Within 6 hours, intraarterial tPA can be directly administered during angiography. Mechanical devices, such as the MERCI (Mechanical Embolus Removal in Cerebral Ischem-ia, Concentric Medical) retriever, can be used for additional thrombectomy. Antiplatelet agents, such as clopidogrel (Plavix, Sanofi-Aventis) and aspirin, minimize parenchymal dam-age and decrease the risk of future stroke.

Small Vessel DiseaseSmall perforating vessels branch from the circle of Willis and vertebrobasilar circulation to

supply the basal ganglia, deep white matter, cerebellum, and brainstem. Hypertension and ath-erosclerosis predispose to injury of these penetrating end arteries, resulting in lacunar infarcts or hemorrhage. Advanced age, radiation injury, meningoencephalitis, vasculitis, and autoim-mune disorders are additional risk factors. Amyloid angiopathy is a special form of microangi-opathy in which β-amyloid peptide accumulates within vessel walls, predisposing to multifocal

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Fig. 3—MR images of patient with infarct who has mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS).A, T2-weighted image reveals increased signal in both occipital lobes, right (thick arrow) greater than left (thin arrow).B, Diffusion-weighted image also shows bilateral hyperintensities, right (thick arrow) greater than left (thin arrow).C, Apparent diffusion coefficient image shows decreased signal on right (thick arrow) but normal signal on left (thin arrow). Therefore, right-sided lesion is acute infarct with true restricted diffusion. Left-sided lesion represents subacute or chronic infarct with T2 shine-through on diffusion-weighted images.

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and lobar hemorrhagic strokes. Depending on the region affected, the clinical presenta-tion may be silent or include some combina-tion of motor, sensory, and ataxia or move-ment symptoms. The time course may be acute, chronic, or fluctuating. If there is sig-nificant white matter involvement, subcortical dementia (Binswanger disease) may develop, with deterioration of executive functions. True cortical signs, including memory loss and aphasia, are not present.

On CT, small vessel ischemic disease manifests as multiple white matter hypoden-sities in the subcortical and periventricular white matter in the region of small penetrat-ing end arteries. Focal lacunes can also be seen in the basal ganglia and supratentorial regions (Fig. 5A). Spontaneous hemorrhage, which is common in patients with hyperten-sion, is generally located in the basal ganglia or thalami. In the presence of sepsis or con-genital heart disease, shower emboli can also produce watershed infarcts at the borders between vascular zones. MRI shows T2/FLAIR hyperintensity in ischemic areas (Fig. 5B). Diffusion restriction is present in the acute phase but normalizes in the sub-acute and chronic phases.

Other causes of microangiopathy show varying distributions of cerebral involvement. In amyloid angiopathy, multifocal and lobar hemorrhagic strokes are common. GRE/suscepti-bility-weighted imaging is useful for detecting foci of occult microhemorrhage (Fig. 6).

Vasogenic EdemaVasogenic edema is caused by breakdown of the tight endothelial junctions comprising the

blood-brain barrier, secondary to either physical disruption or release of vasoactive compounds.

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Fig. 4—Angiography of infarct in same patient as in Figure 3. Injection of left common carotid artery before treatment (left) reveals filling defect in distal left internal carotid artery (ICA) (arrowhead), with failure of opacification of anterior cerebral artery (ACA) and middle carotid artery (MCA). After chemical and mechanical thrombolysis (right), there is complete opacification of ICA, ACA (thin arrow), and MCA (thick arrow).

Fig. 5—Small vessel ischemic disease.A, Unenhanced CT image at level of centrum semiovale shows diffuse subcortical white matter hypodensity as well as more focal hypodensities (arrows) representing lacunes.B, FLAIR image shows multiple periventricular hyperintense foci.

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As a result, intravascular proteins and fluid exude into the extracellular space. Expanded extra-cellular fluid yields decreased T1 signal, increased T2 signal, and decreased fractional anisot-ropy. The white matter is preferentially affected because of its lower density with multiple un-connected parallel axonal tracts.

In the early stages, vasogenic edema may be reversible with reconstitution of the blood-brain barrier. Excess fluid can be resorbed via bulk flow of CSF and lymphovascular clear-ance, and extracellular protein is either digested by macrophages or transported back into cells via transmembrane carriers. However, chronic or recurrent injury often produces irre-versible myelin damage. In addition, mass effect from edema can reduce cerebral perfusion pressure, leading to ischemia and cytotoxic edema.

NeoplasmBoth benign and malignant neoplasms are associated with vasogenic edema, which results

from tumor angiogenesis with disruption of the blood-brain barrier. Neoplastic lesions may be primary or secondary, unifocal or multifocal, and their imaging appearances vary with the underlying histology. On CT, vasogenic edema appears as regional hypodensity confined to the white matter. Due to low soft-tissue contrast, the responsible lesions are often incom-pletely characterized but may show focal areas of hemorrhage, calcification, or necrosis. MRI is usually ordered for tumor characterization and should include unenhanced and contrast-

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Fig. 6—Amyloid angiopathy.A, Unenhanced CT image identifies hyperdense region of acute hemorrhage (asterisk) centered in right basal ganglia, suggestive of hypertensive cause. Hematoma is surrounded by thin rim of vasogenic edema and extends into right frontal horn. Foci of chronic encephalomalacia are noted in both frontal lobes (arrows).B, T2-weighted MR image shows susceptibility in area of hemorrhage (asterisk), with hyperintense surrounding edema. There is also hemorrhage layering in both occipital horns (arrows).C, T2*-weighted gradient-recalled echo MR image again shows acute hemorrhage in right frontal horn (asterisk). There are multiple foci of susceptibility throughout cerebral parenchyma and sulci (white arrows), signifying chronic microhemorrhage and superficial siderosis. There is focal encephalomalacia in right frontal lobe (black arrow), corresponding with findings on CT.

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enhanced T1-weighted imaging, T2-weighted imaging, FLAIR, GRE/susceptibility-weighted imaging, DWI, ADC, and DTI sequences.

Two distinct types of peritumoral vasogenic edema have been described. Type 1 is seen in the immediate vicinity of low-grade and nonglial tumors, such as meningiomas and metastases. This type is thought to be secondary to parenchymal compression, with secondary ischemia and ne-crosis that persist even after tumor removal (Fig. 7A). Type 2 occurs with high-grade glial tu-mors, which are highly infiltrative and cause additional derangements of the blood-brain barrier. This pattern of edema spreads throughout the ipsilateral cerebral hemisphere, with fingerlike projections reflecting tumor microinvasion (Fig. 7B). After resection, there may be partial or complete resolution of edema over several months. Compared with type 1 edema, there is in-creased diffusivity on DWI and decreased fractional anisotropy on DTI, likely reflecting greater

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Fig. 7—Neoplastic vasogenic edema.A, In patient with type 1 edema associated with intracranial melanoma metastases, contrast-enhanced T1-weighted image reveals enhancing masses (arrows) in right frontal and left parietal lobes.B, FLAIR sequence in same patient as in A shows surrounding edema that is well circumscribed and confined to immediate vicinity of masses (arrows).C, In patient with type 2 edema in multifocal glioblastoma multiforme, contrast-enhanced T1-weighted image reveals multiple enhancing foci (arrows) in left occipital lobe.D, FLAIR sequence in same patient as in C shows diffuse infiltrative edema (arrows), reflecting tumor microinvasion. There is extension across midline through splenium of corpus callosum (asterisk), characteristic of glioblastoma multiforme.

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parenchymal destruction by malignant cell infiltration. When seen in small or benign tumors, this atypical pattern of edema is highly suspicious for malignant degeneration.

Definitive surgical management consists of complete resection, possibly with adjuvant che-motherapy and radiation. Corticosteroids used to reduce vasogenic edema likely operate by suppressing tumor angiogenesis factors such as vascular endothelial growth factor. Other experimental molecular agents have been used to target tumor cell growth, invasion, migra-tion, and apoptosis.

HemorrhageVasogenic edema is frequently seen adjacent to large areas of intracranial hemorrhage second-

ary to hypertension, trauma, coagulopathies, amyloid angiopathy, vascular abnormalities, stroke,

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Fig. 8—Cerebral venous thrombosis.A, Unenhanced CT image shows cord sign of hyperdense thrombus within left transverse and sigmoid sinuses (arrows). There is subtle adjacent vasogenic edema (asterisk).B, Rotational maximum-intensity-projection image of MR venogram shows marked attenuation of left transverse and sigmoid sinuses (arrows). Abnormal signal indicative of thrombus was confirmed on T1-weighted imaging.

Fig. 9—Arteriovenous malformation (AVM).A, Unenhanced CT image shows lobulated hyperdense lesion with calcified phleboliths (arrow). Note mild surrounding vasogenic edema (asterisks).B, CT angiography image shows AVM involving entire left cerebral hemisphere, with nidus in left frontal lobe.

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and metastases. The mechanism is presumed to involve exudation of serum proteins during clot formation, leading to perihematoma inflammation and blood-brain barrier breakdown. Edema manifests as surrounding hypoattenuation on CT scans and as T2/FLAIR hyperintensity on MR images. At times, it may produce mass effect up to twice the volume of the original lesion (Fig. 6). Medical management may be instituted to reduce elevated intracranial pressure. Impending herniation may require surgical evacuation and decompressive craniectomy.

Venous ThrombosisCerebral venous thrombosis is a rare form of infarction in which there is obstruction of

venous outflow, leading to parenchymal congestion and breakdown of the normal blood-brain barrier. Risk factors include trauma, thrombophilic conditions (dehydration, pregnancy, can-cer, medications, hypercoagulopathies), and chronic inflammation or infection. Patients may present with headache, vision changes, and seizures. Strokelike symptoms can also occur but are typically more indolent and poorly lateralized in comparison with arterial disease.

On unenhanced CT, hyperdense clot within the affected vein may produce a cord sign. Surrounding vasogenic edema is not confined to a typical arterial distribution (Fig 8A). Hem-orrhagic transformation is common and appears heterogeneous and gyriform. CT venography confirms the presence of filling defects, with the classic empty delta sign produced by throm-bus in the superior sagittal sinus. MR venography can also be used for assessment for cerebral venous thrombosis. However, because T2 flow-related artifacts are common, T1-weighted

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Fig. 10—Dural arteriovenous fistula.A, Unenhanced CT image shows marked vasogenic edema in left temporal lobe, with linear areas of sparing (arrows).B, T2-weighted MR image shows increased signal corresponding to edema. Multiple serpiginous internal flow voids are noted, with dilated perimedullary (thin white arrow), transcortical (black arrow), and cortical (thick white arrow) veins.C, Contrast-enhanced T1-weighted MR image shows avid enhancement of dural arteriovenous complex.

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sequences should be examined to verify sig-nal changes in the region of suspected throm-bus (Fig. 8B).

Treatment of cerebral venous thrombosis involves anticoagulants; on rare occasions, systemic or angiographic thrombolysis may be required. Even in cases of hemorrhagic transformation, the potential benefits of anti-coagulation almost always outweigh the risks. Without treatment, increasing perfusion pres-sures are transmitted back into the arterial sys-tem, leading to arterial infarction with associ-ated cytotoxic edema. Severe cases may re-quire ventriculostomy or decompressive cra-niectomy to prevent fatal herniation.

Arteriovenous ShuntsCerebral arteriovenous shunts can be classi-

fied as AVMs or arteriovenous fistulas (AVFs). These lesions are characterized by abnormal communication between the cerebral arterial and venous systems. AVMs are congenital mal-formations characterized by an intervening capillary bed or central nidus. In contrast, AVFs have direct arteriovenous communications and are more often acquired than congenital. These may oc-cur secondary to venous thrombosis or obstruction from trauma, infection, hypercoagulable states, neoplasms, or vascular disease.

Mechanisms of cerebral edema in arteriovenous shunts are incompletely understood. Po-tential causes include impaired venous drainage, arterial steal phenomena, and rupture with hemorrhage. Venous hypertension can be caused by hemodynamic shunting, thrombosis, mass effect, or hydrocephalus. Elevated venous pressures lead to outflow obstruction, edema, and ultimately ischemia.

On unenhanced CT, arteriovenous malformations may be visible as lobulated hyperdense masses with internal calcified phleboliths. CT, MRI, or conventional angiography reveals a serpiginous tangle of vessels with a central nidus connecting the feeding arteries and draining veins (Fig. 9). AVFs are characterized by direct connections between the cerebral, dural, or

Fig. 11—Ependymitis granularis. FLAIR MR image shows small triangular areas of hyperintensity (arrows) around anterolateral frontal horns. This represents normal anatomic variant.

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Fig. 12—Normal pressure hydrocephalus.A, Unenhanced CT image shows marked lateral ventricular enlargement out of proportion to sulci. Hypodensities surrounding frontal and occipital horns (arrows) reflect transependymal migration of CSF.B, FLAIR MR image again shows central ventricular dilation and grade 1 periventricular hyperintensities (arrows). Scattered foci of microvascular disease are also present.

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pial arteries and veins. On MRI, slow-flow malformations show increased T2 (fluid) signal, whereas high-flow malformations and fistulas produce T2 signal voids (flow artifact) (Fig. 10). Although the primary pattern of edema is vasogenic, hemodynamically significant le-sions may produce ischemia with associated cytotoxic edema.

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Fig. 13—Traumatic brain injury.A, Unenhanced CT image shows hemorrhagic contusions with internal blood products and surrounding edema in inferior frontal lobes, left (asterisk) greater than right.B, Unenhanced CT image in same patient as in A shows hemorrhagic contusion in left anterior temporal lobe (asterisk).C, Unenhanced CT image of different patient with diffuse axonal injury shows multiple punctate hemorrhages (arrows) centered at gray-white junction.D, FLAIR image in same patient as in C shows multiple regions of signal abnormality indicating edema (arrows).E, Gradient-recalled echo image in same patient as in C shows additional foci of microhemorrhage (arrows).

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Most AVMs can be managed expectantly. However, AVFs and large AVMs require interven-tion because of significant hemodynamic effects. Transcatheter embolization or surgical exci-sion may be performed, depending on lesion size, location, and pattern of venous drainage.

Interstitial EdemaInterstitial (hydrocephalic) edema occurs in the setting of increased intraventricular pres-

sures, which cause rupture of the ventricular ependymal lining. This allows transependymal migration of CSF into the extracellular space, most commonly the periventricular white mat-ter. Fluid composition is identical to CSF, with similar ionic concentrations and negligible protein levels (as opposed to vasogenic edema). Various causes of interstitial edema include obstructing masses, meningitis, subarachnoid hemorrhage, and normal pressure hydrocepha-lus. In contrast, ependymitis granularis refers to small triangular areas of abnormal signal around the anterolateral frontal horns (Fig. 11). This normal anatomic variant results from regionally decreased myelin, increased extracellular fluid, or focal breakdown of the epen-dymal lining with gliosis. On CT, the combination of ventriculomegaly and increased peri-ventricular hypodensity is suggestive of the diagnosis of interstitial edema (Fig. 12A). MRI is a more sensitive imaging modality, showing hypointensity on T1-weighted imaging and peri-ventricular hyperintensity on T2-weighted imaging/FLAIR (Fig. 12B). Periventricular hy-perintensity can be graded according to its severity. Grade 1 (discontinuous) appears as focal signal abnormalities adjacent to the frontal and occipital horns and the atria of the lateral ventricles. Grades 2 and 3 (continuous and periventricular halo) completely surround the ventricles and are of varying thickness. Grade 4 (diffuse white matter abnormality) extends to the gray-white matter junction. Because of the extracellular location of edema, DTI maps may show regionally decreased fractional anisotropy. However, the average overall diffusiv-ity is normal on DWI and ADC maps.

In symptomatic patients, decompression with resection of the obstructing lesion (noncom-municating hydrocephalus) or ventriculostomy catheter placement (communicating hydro-cephalus) allows normalization of ventricular pressures. In turn, this enables normal ante-grade resorption of interstitial fluid across the ependymal lining and back into the ventricular system. Without intervention, the findings ultimately progress to cerebral atrophy and gliosis.

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Fig. 14—Hypoxic-ischemic encephalopathy.A, MR image of patient with carbon monoxide inhalation injury shows T2 signal abnormalities in both globus pallidi (arrows). Slow diffusion was identified on diffusion-weighted imaging and apparent diffusion coefficient sequences, indicating cytotoxic component.B, Unenhanced CT image in patient with global cerebral edema after cardiac arrest shows diffuse loss of gray-white differentiation from combined cytotoxic and vasogenic edema. Brain is markedly swollen, with effacement of sulci and ventricles and crowding of basal cisterns (arrows) producing “pseudo-subarachnoid hemorrhage” appearance.

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Combined EdemaSeveral disorders produce a mixed pattern of cytotoxic and vasogenic edema. This may be

due to multifocal or systemic disease or to pathophysiologic alterations associated with disease progression. Causes include trauma, hypoxic-ischemic encephalopathy, metabolic or toxic con-ditions, multisystem organ failure, hypertensive crises, and infection or inflammation. On CT and MRI, there is global loss of gray-white matter differentiation and effacement of the sulci, ventricles, and basal cisterns. If the underlying cause is not addressed, progression to transtento-rial and fatal brainstem herniation is inevitable. Aggressive intervention is indicated, including surgical decompression if the condition is refractory to medical management.

TraumaCerebral contusions are caused by direct head trauma, which classically affects the inferior

frontal and anterior temporal lobes. Coup injuries occur when a moving object impacts the stationary head, with injury immediately subjacent to the site of trauma. Contrecoup injuries occur when the moving head strikes a stationary object, causing inertial transmission of force to the side opposite the area impacted. Both cytotoxic and vasogenic edema are present, re-flecting reactive intracellular metabolite accumulation and traumatic opening of the blood-brain barrier. Vessel injury may cause hemorrhage (Fig. 13A).

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Fig. 15—Posterior reversible encephalopathy syndrome.A, Unenhanced head CT shows hypodensities in posterior occipital lobes (arrows) with primarily vasogenic pattern, although there are focal areas of cortical involvement.B, FLAIR MR image again shows symmetric hyperintensities (arrows) with both white and gray matter involvement.C, Contrast-enhanced T1-weighted MR image shows faint gyriform enhancement (arrows) in this region, thought to occur secondary to hypertension-induced transient vasodilation with breakdown of blood-brain barrier.

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Severe acceleration-deceleration forces, such as in high-speed motor vehicle accidents, may produce diffuse axonal injury. This occurs via differential shearing mechanisms and preferentially affects the gray-white matter junction, corpus callosum, and brainstem. When seen in children and the elderly, this constellation of findings should suggest nonaccidental trauma, particularly when the history is inconsistent with the degree of injury. Skeletal frac-tures, intracranial hemorrhages, and retinal hemorrhages are also characteristic and show both spatial and temporal heterogeneity.

On CT, areas of edema or hemorrhage may be fairly subtle. MRI is more sensitive, showing T2/FLAIR hyperintensity in regions of edema and GRE/susceptibility-weighted imaging susceptibility within foci of microhemorrhage (Fig. 13B). Restricted diffusion on DWI and ADC sequences indicates ischemia. DTI with tractography determines the degree of injury to white matter tracts. Over time, lesions evolve and become less conspicuous. In the late stages, residual hemosiderin and chronic atrophy may be identified.

Treatment of diffuse axonal injury is primarily supportive. Intracranial pressure should be continuously monitored in patients with initial Glasgow Coma Scale score below 9, abnormal CT findings, age greater than 40 years, motor posturing, or systolic blood pressure below 90 mm Hg. Emergent ventriculostomy or craniectomy may be required for decompression.

Hypoxic-Ischemic EncephalopathyHypoxic-ischemic encephalopathy is a pattern of brain injury resulting from partial oxygen

deprivation. The pathophysiology involves energy-dependent mitochondrial injury leading to eosinophilia, macrophage digestion, cortical atrophy, and gliosis. It is most frequently seen in preterm neonates secondary to birth asphyxia but can occur at any age. Causes include hypoxic (reduced environmental oxygen as may occur at high altitudes or secondary to diving or stran-gulation), hypoxemic (reduced blood oxygen, as with anemia, pulmonary or cardiac shunt, or carbon monoxide poisoning), ischemic (inadequate blood flow, as in infarction, shock, cardiac arrest, increased intracranial pressure), and histotoxic (impaired oxygen metabolism, as with Reye syndrome secondary to aspirin use in children, cyanide, triethyl tin, lead, hexachloro-phene, methionine sulfoxime, cuprizone, isoniazid, and dinitrophenol) conditions.

The injury may be focal, diffuse, or global, with the degree of severity ranging from tran-sient edema to irreversible infarction and necrosis. Acute lesions appear hypodense on CT and hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging because of associated edema or encephalomalacia. Contrast enhancement is variable and indicates a

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Fig. 16—Radiation necrosis.A, FLAIR MR image shows extensive bifrontal edema (thin arrows) with primarily vasogenic distribution and involvement of genu of corpus callosum (thick arrow). Frontal sinuses are also opacified.B, Contrast-enhanced T1-weighted image shows mild linear rim enhancement (arrows) and central areas of hypoenhancement.

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poorer prognosis as a reflection of ongoing injury. There is a cytotoxic pattern of edema, with restricted diffusion on DWI and ADC maps. The deep gray matter is typically most severely affected because of its high metabolic requirements (neuronal cell bodies and glia) and wa-tershed arterial distribution. Classic locations include the hippocampus; globus pallidus; and, to a lesser extent, the caudate nucleus, putamen, and thalamus (Fig. 14A). The cerebellum and brainstem are fairly resistant to hypoxia, and involvement of these regions indicates higher-grade injury. Advanced hypoxic-ischemic encephalopathy can produce a vasogenic edema pattern that involves white matter axons and myelin sheaths. This affects the periventricular and subcortical white matter, corpus callosum, and external and internal capsules (Fig. 14B). The severity of imaging findings in hypoxic-ischemic encephalopathy correlates with the clinical likelihood of developing delayed neuropsychiatric syndrome.

Osmotic EdemaOsmotic cerebral edema results when solute concentrations differ between the brain paren-

chyma and blood plasma. This produces an abnormal osmotic pressure gradient resulting in net flow of fluid from serum into the brain. Causes include conditions that dilute the plasma (including water intoxication, dialysis disequilibrium, hyponatremia, syndrome of inappro-priate antidiuretic hormone secretion, diabetic ketoacidosis, hepatorenal failure, and other metabolic conditions) and disorders that increase tissue osmolarity (hemorrhage, infarct, con-tusion). Both intracellular (cytotoxic edema) and extracellular (interstitial and vasogenic edema) components have been described.

Hydrostatic EdemaHydrostatic edema occurs in the setting of an acute increase in intracranial pressure and

may develop in neurosurgical patients, hypertensive crises, hypertensive nephropathy, eclampsia, pheochromocytoma, and Cushing syndrome. The increase in intravascular pres-sure causes reactive spasm of cerebral vessels, resulting in cerebral ischemia and cytotoxic edema. Eventually, cerebrovascular autoregulation is overwhelmed and there is flooding of the cerebral capillary bed, resulting in interstitial or vasogenic transudation of fluid into the extracellular space.

Infection or InflammationCerebral infection may be caused by bacteria; viruses; fungi; and other entities, such as prions.

Among the imaging manifestations are abscess, meningitis, ventriculitis, and encephalitis.

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Fig. 17—Cerebral abscess.A, T1-weighted contrast-enhanced image reveals lobulated fluid collection with irregular enhancing rim (arrow) in right parietal lobe.B, FLAIR image shows surrounding vasogenic edema (arrow).

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Inflammatory causes include demyelinating disorders (multiple sclerosis spectrum, posterior reversible encephalopathy syndrome (Fig. 15), progressive multifocal leukoencephalopathy), vasculitis, autoimmune syndromes, epilepsy, migraine, radiation (Fig. 16), and drug reactions. These entities produce vasogenic edema due to damage of the blood-brain barrier. Areas of internal restricted diffusion may also be present and may signify proteinaceous or hemor-rhagic contents (typically hyperintense on T1-weighted imaging) or ischemia with cytotoxic edema (hyperintense on T2-weighted imaging and hypointense on T1-weighted imaging). Contrast enhancement is most avid in the acute phase and declines over time. In cases of cere-bral infection, heterogeneous soft-tissue enhancement is suggestive of a phlegmon, whereas organized fluid with dense rim enhancement is concerning for abscess (Fig. 17).

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a scientific statement from the American Heart

Association. Stroke 2009; 40:3646–3378

4. Moritani T, Ekholm S, Westesson PL. Brain ede-

ma. In: Moritani T, Ekholm S, Westesson PL,

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5. Rabinstein AA. Treatment of cerebral edema.

Neurologist 2006; 12:59–73

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