Imagen Cerebral Nejm

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Review Article

Medical Progress

812 March 19 , 1998

The New England Journal of Medicine

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First of Two Parts

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ILMAN

, M.D.

From the Department of Neurology, University of Michigan, Ann Arbor. Address reprint requests to Dr. Gilman at the Department of Neurology,University of Michigan Medical Center, 1500 E. Medical Center Dr., TC1914, Ann Arbor, MI 48109-0316.

1998, Massachusetts Medical Society.

XCITING advances in anatomical imaginghave greatly improved our capacity to detectpathologic processes in the nervous system,

localize these processes precisely, and predict thetype of disease more accurately than ever before(Table 1). These advances, coupled with new andemerging therapies for previously untreatable diseas-es, have expedited the evaluation of patients withneurologic disorders and permitted the rapid initia-tion of therapy. In acute ischemic stroke, for exam-ple, brain imaging is required before the administra-tion of recombinant tissue plasminogen activator,and treatment within three hours of onset greatly improves the outcome.

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The rapid evolution of techniques of anatomicalimaging has occurred in parallel with developments

in physiologic imaging. Physiologic imaging permitsevaluation of changes in metabolic processes, either within focal regions or diffusely in the brain, includ-ing cerebral blood flow, blood volume, tissue oxy-genation, metabolic rate for glucose, and biochemi-cal changes within brain cells, including changes instructures such as neurotransmitter receptors.

During the early phases of development and re-finement of current imaging methods, the view arose that imaging would obviate the need for neu-rologists and neurosurgeons. Subsequent events dem-onstrated that imaging does not replace, but rathersupplements, their work. Imaging is costly and t ime-consuming, and physicians do their patients a disserv-

ice if they order these tests before taking a history,conducting a thorough physical and neurologic ex-

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amination, and determining the location and type of pathologic process responsible for the symptoms.

This article provides a succinct guide to the cur-rently available techniques for imaging the brain, abrief description of their methods, a list of the prin-cipal neurologic disorders requiring imaging, andrecommendations concerning the most useful imag-ing technique for each disorder. Several textbooksprovide additional information.

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IMAGING TECHNIQUES

The central nervous system can be imaged withanatomical and physiologic techniques. Anatomicalimaging provides information about the structure of the skull, the brain, the vascular supply of the nerv-ous system, and the cerebrospinal fluid spaces. Phys-iologic imaging provides information about the func-tional state of brain tissues, including water content,blood flow, blood volume, metabolism, and bio-chemistry.

X-Ray Techniques

Passage of x-radiation through tissue attenuatesthe radiation, and the intensity of the exiting radia-tion can be measured with sensitive film or detec-tors. X-ray computed tomography (CT) permits theexamination of tissue by the same principle as con-

ventional x-ray imaging, except that radiation passessuccessively through tissue from multiple differentdirections, detectors measure the degree of attenua-tion of the exiting radiation relative to the incidentradiation, and computers integrate the informationand construct the images in cross section. Adminis-tration of contrast material increases x-ray attenua-tion owing to the high atomic number and electrondensity of the iodinated compounds used. The useof intravenous contrast medium with CT allows ex-amination of the integrity of the bloodbrain barri-er, which consists of the tight junctions between theendothelial cells of blood vessels and astrocytes. Dis-ruption of the bloodbrain barrier occurs in many neurologic disorders, including acute stroke, braintumors, inflammatory and some infectious cerebraldiseases, and some stages of multiple sclerosis.

CT has the advantages of widespread availability,short study time, sensitivity for detection of calcifi-cations and acute hemorrhage, and excellent visual-ization of the anatomy of bone, such as the skullbase and vertebrae. It is useful when magnetic reso-nance imaging (MRI) cannot be used, as in people

with ferromagnetic aneurysm clips,

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foreign ob- jects in the eye, pacemakers, and other metal pros-theses.

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CT images are less degraded by motion ar-

Downloaded from www.nejm.org on August 29, 2007 . Copyright 1998 Massachusetts Medical Society. All rights reserved.


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tifacts than MRI scans. CT is preferred in rapidly evolving neurologic disorders, when direct observa-tion of the patient and life-support equipment arerequired during scanning. Indeed, many hospitalsmaintain CT scanners in their emergency rooms tofacilitate rapid imaging with constant observation of patients in unstable condition. Although CT is thepreferred imaging technique for patients who re-quire monitoring, MRI can be performed when vir-tually any monitoring device is in use. Both MRIand CT with iohexol for myelography have replacedmyelography with oil-based contrast agents, greatly improving patients comfort and reducing the chanceof subsequent arachnoiditis.

The principal disadvantages of CT are the adverseeffects of ionizing radiation and the insensitivity of the test, as compared with MRI, for many commonneurologic diseases. CT is also less sensitive thanMRI in patients with disorders in the posterior fossa(brain stem and cerebellum) and the floor of themiddle fossa (temporal lobes) because of beam-hardening artifacts, which result from computer er-rors generated by the sudden change in tissue den-sity in these locations from a relatively low level in

brain to a high level in bone. The costs of imaging vary with the type and complexity of the study required. However, CT on average costs about 50percent less than MRI; MRI, on average, costs about50 percent less than positron-emission tomography (PET).

Ultrasonography

Ultrasound devices use a piezoelectric element ina transducer that converts electrical energy intosound energy. These devices operate on the princi-ple that movement of the source of a reflected soundrelative to the receiver alters the sound frequency.Ultrasound devices are widely used to measureblood-flow velocity, permitting assessment of thecarotid and vertebral arteries in the neck and, withtranscranial Doppler ultrasonography, the intracra-nial vessels. Performing ultrasound studies requiresskill and experience. Currently a major use of ultra-sonography is for ischemic cerebrovascular disease.This use has assumed great importance, becausetreatment of high-grade carotid stenosis with endar-terectomy and medical therapy, as compared withmedical therapy alone, improves the outcome.

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*CT denotes x-ray computed tomography, MRI magnetic resonance imaging, PET positron-emission tomography,SPECT single-photon-emission computed tomography, and TCD transcranial Doppler ultrasonography.

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Cerebral or cerebellar ischemic infarction CT in the first 1224 hr; MRI after 1224 hr (diffusion-weighted and per-fusion-weighted MRI augments the findings, especially in the first 24 hr,and even before 8 hr)

Cerebral or cerebellar hemorrhage CT in the first 24 hr; MRI after 24 hr; MRI and endovascular angiographyfor suspected arteriovenous malformation

Transient ischemic attack MRI to identify lacunar or other small lesions; ultrasound studies of the ca-rotid arteries; magnetic resonance angiography

Arteriovenous malformation CT for acute hemorrhage; MRI and endovascular angiography as early aspossible

Cerebral aneur ysm CT for acute subarachnoid hemorrhage; CT angiography or endovascularangiography to identify the aneurysm; TCD to detect vasospasm

Brain tumor MRI without and with injection of contrast materialCraniocerebral trauma CT initially; MRI after initial assessment and treatmentMultiple sclerosis MRI without and with injection of contrast materialMeningitis or encephalitis CT without and with injection of contrast material initially; MRI after initial

assessment and treatmentCerebral or cerebellar abscess CT without and with injection of contrast material for initial diagnosis or,

if stable, MRI instead of CT; MRI without and with injection of contrastmaterial subsequently

Granuloma MRI without and with injection of contrast materialDementia MRI; PET; SPECTMovement disorders MRI; PETNeonatal and development disorders Ultrasound in unstable premature neonates; otherwise MRIEpilepsy MRI; PET; SPECTHeadache CT in patients suspected of having structural disorders



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trasonography is an important tool for real-timemonitoring of brain structure during surgical proce-dures on the brain, for detecting vasospasm aftersubarachnoid hemorrhage, and for detecting hydro-cephalus, germinal-matrix hemorrhage, and periven-tricular leukomalacia in neonates.

MRI

Placement of tissue in a strong magnetic fieldcauses certain naturally occurring isotopes (atoms)

within the tissue to line up within the field, orient-ing the net tissue magnetization in the longitudinaldirection. Many isotopes are affected, but currentMRI uses signals derived from 1

H, the most plentifulendogenous isotope. When in a magnetic field, theseatoms do not orient precisely with the axis of thefield, but wobble a few degrees off center. Transientapplication of a radio-frequency pulse perpendicularto the applied magnetic field reorients the net t issuemagnetization from the longitudinal to the trans-

verse plane, thereby increasing the tissue energy lev-el. When the radio-frequency pulse is turned off, thenet tissue magnetization returns to its previous ori-entation, resulting in a magnetic resonance signalthat receiver coils can detect. Application of differ-ential-gradient magnetic fields to the tissue understudy permits reconstruction of the signal from indi-

vidual volume units in space. The result is a clear im-age of the tissue studied. Particular sequences suchas T

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-, T

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-, proton-density-, and spinecho-weightedimages enhance the utility of MRI. Use of the intra-

vascular contrast material gadoliniumdiethylenetri-amine pentaacetic acid (gadoliniumDTPA) withMRI alters the magnetic susceptibility of adjacenttissue, thereby providing information about the in-tegrity of the bloodbrain barrier.

The advantages of MRI are the absence of ioniz-ing radiation, exquisite sensitivity to blood flow, thecapacity to produce images in planes with any orien-tation, sensitivity to the accumulation of iron in tissue,high soft-tissue contrast resolution, high sensitivity to tissue edema, and absence of beam-hardening ar-tifacts. MRI is the imaging procedure of choice formost neurologic diseases and is more sensitive thanCT for demyelinating and other white-matter diseas-es, primary and metastatic intracerebral neoplasms,degenerative diseases, nonacute hemorrhage, and cer-ebral infarction. Conventional MRI is not as effec-tive as CT for detecting abnormal calcification, dis-orders of cranial and vertebral bones and joints, andacute subarachnoid hemorrhage. In the past, the rel-atively long time needed for scanning limited theuse of MRI in acute craniocerebral trauma and inunstable, rapidly evolving, or life-threatening disor-ders. Advances such as ultrafast and echoplanar im-aging have made MRI as fast as CT. However, the

value of echoplanar images for routine brain imag-ing is not equal to that of standard fast spinecho

images, because of the lack of versatility and exces-sive sensitivity to magnetic-gradient artifacts. MRIprovides excellent visualization of the spinal cord, al-though myelography with CT and iohexol remainsan important procedure.

MRI is superior to CT in demonstrating mostcentral nervous system lesions, except for acute sub-arachnoid hemorrhage, calcified lesions, skull frac-tures, and various craniofacial and sinus-related ab-normalities. Nevertheless, the choice between MRIand CT for the initial evaluation of patients withneurologic disorders is not clear-cut, for several rea-sons. First, the relative advantage of MRI over CTranges from minimal to substantial, depending onthe type of pathologic change. Second, the severity of symptoms, urgency of the problem, and priorprobability of underlying structural disease vary andare part of the challenge of clinical medicine. Third,as already noted, the average difference in cost be-tween CT and MRI is substantial. CT has remainedan effective technique for the initial neuroimagingexamination for these reasons, and also because CTexaminations of the head that are of reasonablequality can be performed quickly, even in uncooper-ative patients.

Many developments have improved the usefulnessof MRI. They include fluid-attenuated inversion re-covery, which gives a high signal for parenchymal le-sions and a low signal for cerebrospinal fluid

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; dif-fusion-weighted imaging, which can detect cytotoxicedema and is sensitive to early ischemic changes

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;echoplanar imaging, which uses improved gradientdesign to acquire ultrafast images, a requirement forfunctional MRI

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; and combinations of these tech-niques.

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Magnetic resonance angiography allowsnoninvasive visualization of the cerebral and extra-cerebral vasculature. Magnetic resonance spectrosco-py provides a noninvasive means of studying cerebralmetabolites, brain pH, and some neurotransmitters

without the use of ionizing radiation.

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FunctionalMRI is a method of imaging the oxygenation statusof hemoglobin in order to visualize local changes incerebral blood flow that reflect changing neuronalactivity in response to a specific sensory stimulus ormotor task.

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Although the technique gives bettertemporal resolution than current radionuclide tech-niques and is used widely, interpretation of the re-sults is complex and actively debated.

Radionuclide Scanning

Highly versatile methods of studying cerebralfunction have emerged from the development of PET and single-photon-emission computed tomog-raphy (SPECT). These techniques use a radiolabeledbiologically active compound (radioligand tracer)and a kinetic model describing the fate of the traceras it participates in a biologic process. PET imagingrequires the intravenous injection or inhalation of a



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radioligand labeled with a positron-emitting isotope,accumulation of the ligand in the brain, and subse-quent emission of positrons from the ligand into theadjacent tissue during radioactive decay. Positronsare the antimatter equivalent of electrons. The colli-sion of an electron and a positron annihilates bothparticles, converting their masses to energy in theform of two photons (gamma rays) that leave thebrain at an angle of 180 degrees to each other andcan be detected.

The radioligands most frequently used are [

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F]flu-orodeoxyglucose for measuring cerebral metabolicrates for glucose

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and [

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O]water for determiningcerebral blood flow.

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Carbon-11 is used to labelmany biologic compounds that can quantify bio-chemical changes in the brain, such as striatal mono-amine deficiency in Parkinsons disease

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and multiple-system atrophy,

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and changes in benzodiazepine

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and opiate

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receptors. The use of PET is limited by its high cost, the need for a cyclotron nearby to pro-duce radioisotopes with short half-lives, and its re-stricted spatial and temporal resolution.

SPECT uses principles similar to those of PET,but the radioligands decay to emit only a single pho-ton. Many tracers have been used in SPECT studiesof the brain, notably xenon-133 and technetium-99mhexamethyl-propylamine-oxime for investiga-tion of blood flow in patients with ischemic stroke,subarachnoid hemorrhage, migraine, Alzheimers dis-ease and other neurodegenerative diseases, and com-plex partial epilepsy.

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SPECT has the shortcomingsof restricted resolution and quantitation and limited

versatility for studying cerebral biochemistry andmetabolism.

IMAGING IN NEUROLOGIC DISORDERS

Cerebrovascular Disease

Cerebral Infarction

The sudden onset of focal sensory loss, weakness,or speech disorder raises the possibility of cerebralischemia or infarction, particularly in older people

with hypertension, diabetes, hypercholesterolemia,heart disease, or a history of cigarette smoking. Rap-id and accurate assessment is crucial for treatment,since recombinant tissue plasminogen activator pro-

vides effective treatment for acute ischemic infarc-tion in the absence of cerebral hemorrhage if given

within three hours after onset.

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Accordingly, thecurrent management of suspected ischemic infarc-tion requires rapid transfer of the patient to the hos-pital, expeditious history taking and physical andneurologic examination, laboratory testing of hema-tologic and metabolic status, and an imaging study to detect an ischemic lesion and determine whetherhemorrhage has occurred. If the diagnosis of ische-mic stroke without hemorrhage can be made and allinclusion and exclusion criteria are met, treatment

with recombinant tissue plasminogen activator may be indicated. The value of this activator adminis-tered more than three hours after the onset of symp-toms is not known.

Currently, CT is the brain-imaging method of choice for the assessment of acute ischemic injury todetermine whether hemorrhage is present, becauseit is highly sensitive to hemorrhage, rapid, widely available, relatively low in cost, and noninvasive.

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CT will not detect an infarction in the first threehours after the onset of symptoms and may show anabnormality only many hours or days after the event(Fig. 1A). Hyperdensity of a major cerebral vessel isan important sign that can be detected by CT withinminutes of vessel thrombosis and hours before pa-renchymal changes occur.

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The finding of a hyper-dense vessel can be used in the appropriate clinicalsetting to consider a patient for aggressive endovas-cular lytic therapy. Mineralized vessels can be mis-taken for hyperdense vessels, however, giving a falsepositive result. CT has several disadvantages: it pro-

vides limited information about the nature and ageof an ischemic stroke during the crucial first threehours, and it has limited capacity to show vascularlesions in the brain stem and cerebellum and smallischemic infarctions deep within the cerebral hemi-spheres.

MRI, particularly diffusion-weighted and perfu-sion-weighted MRI, is more sensitive than CT to theearly pathologic changes of ischemic infarction be-cause it is superior in detecting brain edema.

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MRI is superior to CT in detecting small lacunarlesions, particularly those located deep within thecerebral hemispheres and in the brain stem and cere-bellum (Fig. 1B). In the future, as echoplanar imag-ing and diffusion-weighted imaging become widely available, these techniques may supplant CT becausethey can be performed in 6 seconds to 1.5 minutes.Nevertheless, at present CT is the procedure of choice in evaluating patients for tissue plasminogenactivator therapy because of the longer time current-ly needed to perform MRI in most institutions andbecause patients cannot be monitored easily duringscanning. After the initial CT scan, MRI is oftenused to determine the precise location and size of the infarction and to follow the lesion over time.

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However, CT can detect most infarctions within twoto four days after onset and can be used more costeffectively than MRI to follow the course of the in-farction over time.

Cerebral Hemorrhage

Cerebral hemorrhage can result from the transfor-mation of an ischemic infarction

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(Fig. 1C) or froma primary hemorrhage into the brain. The risk fac-tors include hypertension, a source of emboli in theheart or major arteries supplying the brain, antico-agulant therapy, coagulation defects, vascular mal-



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formations, infections, tumors, trauma, and, in eld-erly patients, amyloid angiopathy. The onset of cerebral hemorrhage is often sudden but it can beslow, and severe neurologic impairment is common.

After a hemorrhage into brain tissue, clot formationoccurs within one to two hours. The clot causesfocal attenuation of x-rays, and thus CT is highly sensitive in detecting cerebral hemorrhage. MRI isrelatively insensitive to acute subarachnoid hemor-rhage, but it is sensitive to acute intraparenchymalbleeding, particularly with gradient-echo MRI pulsesequences. As the oxyhemoglobin in a hematomabecomes deoxygenated with time, its magnetic sus-ceptibility changes, making the lesion more conspic-uous on MRI. CT is the procedure of choice in thefirst hours after cerebral hemorrhage, because of itsspeed and availability, but MRI is more sensitive af-ter the first hours.

Cerebellar Hemorrhage

The risk factors for cerebellar hemorrhage are sim-ilar to those for cerebral hemorrhage. Cerebellarhemorrhage commonly begins with an occipital head-ache followed by nausea, vomiting, lightheadednessor vertigo, and ataxia of gait. A large hemorrhage of-ten causes progressive lethargy followed by comafrom compression of the brain stem. CT is the pro-cedure of choice (Fig. 1D) and should be performedimmediately, since patients are at risk for compres-sion of the brain stem and subsequent death.

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Sur-gical evacuation can be lifesaving after large hemor-rhages, but with small collections of blood, surgery may not be needed. CT or MRI can be used formonitoring over subsequent days. If a vascular mal-formation or an aneurysm is suspected as the causeof hemorrhage, endovascular angiography can beused to identify the bleeding site after the patientbecomes medically stable.

Transient Ischemic Attacks

Transient ischemic attacks are episodes of im-paired focal neurologic function resulting from vas-cular disease. The symptoms resolve completely

within 24 hours, and most episodes last less than1 hour. Transient ischemic attacks often result fromischemic cerebrovascular disease affecting either prox-imal or distal cerebral vessels, but cerebral embolioccasionally are responsible. Although transient is-chemic attacks may cause no pathologic changes, la-cunar infarction may occur. In a patient with anacute ischemic attack whose initial neurologic deficitshows no change during the first three hours, theCT scan commonly shows no abnormality, and thepatient should be evaluated for treatment with tissueplasminogen activator.

A patient with a history of transient ischemic at-tacks should be evaluated for risk factors that can betreated and have an evaluation of the cerebral arte-rial tree with ultrasound studies of the neck and, if indicated, an evaluation of the intracranial circu-lation with transcranial Doppler ultrasonography.Transesophageal echocardiography may be needed if the patient has an abnormal electrocardiogram orsymptoms or signs of heart disease, or if there areother reasons to suspect a cardiac source. MRIshould be performed to look for lacunar infarc-tions,

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and magnetic resonance angiography can beused to visualize the large and medium-sized extra-cranial and intracranial vessels noninvasively.

The possibility of a dissection in the carotid or ver-tebral artery should be considered if a patient with atransient (or permanent) ischemic disorder has painin the anterior (with carotid dissection) or posterior(with vertebral dissection) aspect of the neck, whichoccasionally may radiate into the head.

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Carotiddissection may cause atypical facial pain and a partialor complete ipsilateral Horners syndrome (ptosis,miosis, enophthalmos, and lack of sweating on theipsilateral side of the face) because of injury to sym-pathetic fibers in the carotid sheath. In these pa-tients, ultrasonography coupled with MRI of theneck provides excellent visualization of dissections,particularly with fat-suppressed, T

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-weighted axialMRI scans to visualize subintimal hematomas. How-ever, endovascular angiography should be performedif a dissection is not identified but is clinically sus-

pected.

Arteriovenous Malformations

Arteriovenous malformations are congenital dis-orders consisting of tangled collections of vessels,often with a feeder artery and tortuous assort-ments of veins

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(Fig. 2A and 2B). Arteriovenousmalformations are an important cause of intracere-bral hemorrhage and can also result in recurrentheadaches, seizures, ischemic or hemorrhagic infarc-tions, or subarachnoid hemorrhage. At times pro-

Figure 1.

Images of Ischemic and Hemorrhagic Cerebrovascu-lar Disorders.Panel A is a CT scan showing a large, subacute, nonhemor-rhagic infarction in the territory of the left middle cerebral ar-tery (arrowheads) in a 39-year-old woman with a two-day his-tory of weakness of the right upper and lower extremities.Panel B is an axial T

2

-weighted MRI showing a 1-cm lacunar in-

farction (arrow) in the region of the left internal capsule in a 30-year-old man with a one-month history of right hemiparesis.Panel C is a CT scan showing a large hemorrhagic infarction inthe territory of the left middle cerebral artery (arrowheads) ina 61-year-old man with sudden onset of right-sided weaknessthree hours earlier. Panel D is a contrast-enhanced CT scanshowing a 1.5-cm cerebellar hemorrhage (arrow) and an en-hancing vein (arrowheads), findings consistent with the pres-ence of a venous angioma, which was subsequently identifiedby catheter angiography, in a 22-year-old woman with suddenonset of headache several hours earlier. The hemorrhage, butnot the vein, was seen before the administration of contrastmaterial.



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