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RadioGraphics EDUCATION EXHIBIT 1517

Cerebral Amyloid
Angiopathy: CT and
MR Imaging Findings1
Christine P. Chao, MD ● Amy L. Kotsenas, MD ● Daniel F. Broderick, MD
TEACHING
POINTS
See last page Cerebral amyloid angiopathy (CAA) is an important but underrecog-
nized cause of cerebrovascular disorders that predominantly affect el-
derly patients. CAA results from deposition of ␤-amyloid protein in
cortical, subcortical, and leptomeningeal vessels. This deposition is
responsible for the wide spectrum of clinical symptoms and neuroim-
aging findings. Many cases of CAA are asymptomatic. However, when
cases are symptomatic, patients can present with transient neurologic
events, progressive cognitive decline, or potentially devastating intra-
cranial hemorrhage. Computed tomography is the imaging study of
choice for evaluation of suspected acute cortical hemorrhage, which
may be accompanied by subarachnoid, subdural, or intraventricular
hemorrhage. Magnetic resonance imaging is best suited for identifica-
tion of small or chronic cortical hemorrhages and ischemic sequelae of
this disease, exclusion of other causes of acute cortical-subcortical
hemorrhage, and assessment of disease progression. Accurate recogni-
tion of imaging findings is important in guiding clinical decision mak-
ing in patients with CAA.
©
RSNA, 2006

Abbreviations: CAA ⫽ cerebral amyloid angiopathy, FLAIR ⫽ fluid-attenuated inversion recovery, GRE ⫽ gradient echo, ICH ⫽ intracranial hem-
orrhage, TIA ⫽ transient ischemic attack

RadioGraphics 2006; 26:1517–1531 ● Published online 10.1148/rg.265055090 ● Content Codes:

1From the Department of Radiology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224. Recipient of a Certificate of Merit award for an educa-
tion exhibit at the 2004 RSNA Annual Meeting. Received April 17, 2005; revision requested July 12 and received September 8; accepted September
14. All authors have no financial relationships to disclose. Address correspondence to A.L.K. (e-mail: kotsenas.amy@mayo.edu).
©
RSNA, 2006
 1518 September-October 2006
Introduction
Teaching Cerebral amyloid angiopathy (CAA) is an impor-
Point tant cause of spontaneous cortical-subcortical
intracranial hemorrhage (ICH) in the normoten-
sive elderly. CAA is a cerebrovascular disorder
characterized by the deposition of ␤-amyloid pro-
tein in the media and adventitia of small and me-
dium-sized vessels of the cerebral cortex, subcor-
tex, and leptomeninges. Both sporadic and he-
reditary forms may occur. Hereditary syndromes
of CAA are rare and generally demonstrate auto-
somal dominant transmission. Hereditary forms
of CAA display a broader range of clinical mani-
festations than the sporadic form and have been
seen at a younger age, as early as the third decade
in some variants (1). In contrast, the sporadic
form is more common in the elderly and increases
in both prevalence and severity with increasing
age. The focus of this article is the more common
sporadic, age-related form of CAA.
Although found at autopsy in only 33% of
60 –70 year olds, the prevalence of age-related
CAA increases to 75% of those older than 90
years (2). Despite its high prevalence, CAA re-
mains an underrecognized cause of cerebrovascu-
lar disease, clinically as well as at imaging, in part
because many patients are asymptomatic. When
symptomatic, typical presentations include acute
ICH, symptoms resembling a transient ischemic
attack (TIA), or dementia. However, these symp-
toms are not specific for CAA and are often not
readily associated with CAA.
Teaching CAA manifests radiologically as part or all of
Point a constellation of findings including acute or
chronic ICHs in a distinctive cortical-subcortical
distribution, leukoencephalopathy, and atrophy.
Early recognition of such imaging findings is im-
portant; not only is the radiologist sometimes the
first to raise the possibility of CAA, but the diag-
nosis of CAA most often requires a combination
of clinical assessment and radiologic evaluation
(3). With continued aging of the population,
CAA will become even more prevalent, making
correct characterization of imaging findings im-
portant.
In this article, we describe the histopathologic
and clinical features of sporadic CAA, discuss
diagnostic considerations, present the imaging
RG f Volume 26 ● Number 5
RadioGraphics
features, and review management and prognosis
and the differential diagnosis.
Histopathologic Features
CAA is characterized by the deposition of ␤-amy-
loid protein in the media and adventitia of small
and medium-sized vessels of the cerebral cortex,
subcortex, and leptomeninges, with sparing of
similarly sized vessels in the deep white matter
(1). CAA is not associated with the presence of
systemic amyloidosis (4). The structural changes
in the vascular wall related to ␤-amyloid deposi-
tion are associated with fibrinoid necrosis, focal
vessel wall fragmentation, and microaneurysms,
which all predispose the patient to repeated epi-
sodes of blood vessel leakage or frank hemor-
rhage. Furthermore, at sites of fibrinoid necrosis,
there may be luminal narrowing, which can lead
to ischemic change (4). Histologically, ␤-amyloid
deposits stained with Congo red show classic yel-
low-green birefringence under polarized light
(Fig 1).
Clinical Features
When CAA is symptomatic, there are several
clinical presentations, which include sudden neu-
rologic deficit (stroke) related to acute ICH,
symptoms resembling a TIA, or dementia.
The most common presentation of CAA is the
development of a sudden neurologic deficit sec-
ondary to an acute ICH (5). Specific clinical
symptoms and signs depend on both the size and
location of the ICH. ICH related to CAA can
have a similar presentation as acute ICH related
to other causes: headache, nausea and vomiting,
loss of consciousness, focal neurologic deficits,
and seizures.
CAA patients may also present with symptoms
resembling a TIA. Greenberg et al (6,7) noted
that the TIA-like symptoms associated with CAA
may be distinguished from a true TIA by the
smooth spread of symptoms from one body part
to another and may in fact be secondary to sei-
zures. Distinction between these TIA-like symp-
toms and true TIAs may be difficult but is impor-
tant, as the treatment may be different.
Dementia in CAA may be seen prior to symp-
tomatic ICH in 25%– 40% of patients. CAA-re-
lated dementia may be slowly progressive, similar
to that seen in patients with Alzheimer disease
 RG f Volume 26 ● Number 5 Chao et al 1519
RadioGraphics

Figure 1. Histologic appearance of ␤-amyloid deposition in cerebral cortical vessels. (a) Photomicrograph
(original magnification, ⫻100; Congo red stain) shows highlighted ␤-amyloid deposits along the vessel walls.
(b) Photomicrograph (original magnification, ⫻100; Congo red stain) obtained with polarized light shows the
classic yellow-green birefringence of the ␤-amyloid deposits.

dementia, with which CAA is frequently associ-
ated. Forty percent of CAA patients with demen-
tia show changes of Alzheimer disease at autopsy.
Conversely, up to 90% of patients with Alzheimer
disease have changes of CAA at autopsy (1). How-
ever, dementia may be present in patients with
CAA in the absence of pathologic changes of Alz-
heimer disease and may in those cases be related
to small vessel ischemic changes (1,5). Alterna-
tively, CAA has been seen in patients with sub-
acute cognitive decline that progresses rapidly
over the course of a few weeks. These patients
may present with confusion and disorientation,
without the focal neurologic deficits that may be
seen in patients with a cerebral infarct or CAA-
related acute ICH (8 –11).
Diagnostic Consider-
ations: The Boston Criteria
The clinical differentiation of CAA-related versus
non–CAA-related symptomatology may be very
difficult and unreliable, as there is significant
overlap in diseases that result in acute neurologic
deficits, TIA-like symptoms, and dementia.
The Boston criteria were developed in the mid-
Teaching
1990s as a tool to both improve and standardize
Point
the diagnosis of CAA (7,12). The criteria specify
four diagnostic categories: definite CAA, prob-
able CAA with supporting pathologic evidence,
probable CAA, and possible CAA, depending on
a combination of clinical, imaging, and histologic
data. A “definite” diagnosis of CAA is made with
a full postmortem examination providing confir-
mation of lobar, cortical, or corticosubcortical
ICH and severe CAA. Rarely, a biopsy may be
performed at the time of hematoma evacuation or
to exclude other causes of ICH. This pathologic
tissue may reveal CAA, which with the appropri-
ate clinical data, leads to a diagnosis of CAA as
“probable with supporting pathologic evidence.”
CAA is considered “probable” if there is an
 1520 September-October 2006 RG f Volume 26 ● Number 5
RadioGraphics
The Boston Criteria for Diagnosis of CAA

Clinical Postmortem Pathologic Cortical

Diagnostic Category History Examination Specimen ICH*
Definite CAA Yes Yes Yes ...
Probable CAA with Yes No Yes ...
pathologic evidence
Probable CAA Yes No No ⬎1
Possible CAA Yes No No 1 only
*ICH ⫽ intracranial hematoma.

appropriate clinical history as well as imaging

findings of multiple cortical-subcortical hemato-
mas, which may be of varying ages and sizes, in a
patient 55 years old or older, with no other clini-
cal or radiologic cause of hemorrhage. Finally,
clinical data suggesting CAA and the imaging
finding of a single cortical-subcortical hematoma
in a patient older than 55 years, without other
cause of hemorrhage, leads to a “possible” diag-
nosis of CAA (13) (Table).
As histologic analysis is often not practical,
recognition of the imaging findings of CAA is im-
portant for correct diagnosis and proper treat-
ment of patients. Knudsen et al (3) studied 39
cases of cortical-subcortical ICH to validate the
Boston Criteria. Clinical and magnetic resonance
(MR) imaging evidence of CAA was compared
with results from autopsy, biopsy, or surgical
evacuation of hematomas. In those patients diag-
nosed with “probable” CAA by means of the Bos-
ton Criteria, 13 of 13 patients (100%) had a
pathologic diagnosis of CAA. A diagnosis of “pos-
Figure 2. Determination of ICH location in a 74-
sible” CAA was confirmed in 16 of 26 patients year-old man with acute onset of expressive aphasia,
(62%) with pathologic specimens. confusion, and a right-sided facial droop. Axial nonen-
hanced CT scan shows a left-sided frontal cortical
Imaging of CAA ICH, a finding most consistent with CAA-related ICH.
Pathologic tissue obtained at hematoma evacuation
Imaging Evaluation was positive for CAA. The location of an ICH is help-
ful in determining the cause of the ICH in a patient
The clinical presentation of a patient dictates the
with a sudden neurologic deficit.
imaging work-up. A patient presenting with an
acute neurologic deficit or TIA-like symptoms
should undergo nonenhanced computed tomog- lishment of the presence or absence of an ICH
raphy (CT) of the head. CT allows rapid estab- and exclusion of the main clinical differential di-
agnostic consideration of an acute cerebral infarc-
 RG f Volume 26 ● Number 5 Chao et al 1521
RadioGraphics

Figure 3. Sensitivity of GRE imaging for hemosiderin in an 80-year-old man with dementia that has pro-
gressed over the past 4 years. (a) Axial GRE MR image shows multiple foci of signal loss in cortical-subcortical
locations. In a patient with a diagnosis of probable CAA, these foci are consistent with chronic microhemor-
rhages. (b) Axial T2-weighted fast spin-echo MR image does not show the foci of chronic microhemorrhage.

tion. Nonenhanced head CT is the preferred im-
aging modality for initial work-up as it provides
crucial information regarding the characteristics
of the ICH, including size, location, shape, and
extension to the extraaxial spaces (Fig 2).
If an ICH is present in a cortical-subcortical
location suspicious for CAA, the patient should
undergo additional evaluation with MR imaging
including a gradient-echo (GRE) sequence. GRE
is currently the most sensitive MR imaging se-
quence for detection of the chronic cortical-sub-
cortical microhemorrhage. Local magnetic field
inhomogeneity related to the presence of hemo-
siderin causes a marked loss of signal at T2*-
weighted GRE imaging (Fig 3). These chronic
microhemorrhages can be associated with acute
CAA-related ICH, and detection of these chronic
microhemorrhages with GRE imaging increases
the probability for CAA.
A patient presenting with dementia is usually
evaluated initially with brain MR imaging, as the
clinical presentation is often nonspecific and the
causes of dementia are numerous. It is critical to
maintain a high index of suspicion for CAA, espe-
cially in the elderly, and to ensure a thorough
evaluation by including a GRE sequence in all
patients who are 70 years old or older (14).
In general, angiography does not play a role in
the evaluation of CAA.
Intracranial Hemorrhage
Often the acute presenting finding in CAA-re-
lated cerebrovascular disease, CAA-related ICH
represents only 2% of all ICH but is an important
cause of hemorrhage in normotensive elderly pa-
tients without trauma (1), representing 38%–74%
 1522 September-October 2006 RG f Volume 26 ● Number 5
RadioGraphics
Figure 4. Recurrent CAA-related ICH in a 65-year-old woman with progressive aphasia, right
visual field deficits, and headache. (a) Axial nonenhanced scan from the initial CT study shows a
discrete, ovoid, left-sided occipital ICH. (b) Axial GRE MR image obtained the same day shows
numerous cortical-subcortical microhemorrhages, a finding most compatible with a diagnosis of
probable CAA. One month later, the patient returned to the emergency department with an in-
creasing level of confusion. (c) Axial nonenhanced CT scan obtained at that time shows a larger,
more devastating, left-sided parieto-occipital hemorrhage. Owing to the presence of multiple corti-
cal-subcortical microhemorrhages, which are highly suggestive of CAA, the larger ICH was thought
to represent recurrent hemorrhage rather than a hemorrhagic infarction. The patient was not a sur-
gical candidate and was discharged to a hospice 1 week later, where she died after a few days.
 RG f Volume 26 ● Number 5
RadioGraphics
Figure 5. CAA-related macrohemorrhage with asso-
ciated subarachnoid hemorrhage in an 81-year-old man
with acute dysphasia and agitation. Axial nonenhanced
CT scan shows an irregular, 4 ⫻ 5-cm, left-sided fron-
toparietal cortical ICH. The high attenuation in adja-
cent sulci (arrowheads) is consistent with subarachnoid
hemorrhage. The patient had a diagnosis of probable
CAA on the basis of a history of two spontaneous right-
sided frontal ICHs.
of ICH cases in the elderly (3). Symptomatic ICH
is commonly large (⬎5 mm), in contrast to mi-
crohemorrhages (ⱕ5 mm), which are often clini-
cally silent. Regardless of the size, CAA-related
ICH exhibits a distinctive cortical-subcortical dis-
tribution that generally spares the deep white
matter, basal ganglia, and brainstem (Fig 4a).
This cortical-subcortical distribution of ICH in
CAA correlates with the anatomic distribution of
␤-amyloid– containing vessels (15–17). Rarely,
the cerebellum is involved (18). CAA-related
ICH can involve any lobe of the cerebral hemi-
spheres (1,16,19). Other neuroimaging findings
suspicious for CAA-related ICH include multi-
plicity (Fig 4b) and recurrence of ICH (Fig 4c).
Chao et al 1523
Figure 6. CAA-related macrohemorrhage with asso-
ciated subdural hemorrhage in a 77-year-old man with
severe headache and difficulty walking. Axial nonen-
hanced CT scan shows a large right-sided posterior
parietal ICH with irregular borders in a cortical loca-
tion. There is a small right-sided posterior parafalcine
subdural hemorrhage (arrow). The large hematoma
causes marked effacement of right cerebral sulci and
approximately 9 mm of subfalcine herniation. The pa-
tient underwent emergency hematoma evacuation;
CAA was demonstrated at histologic analysis.
Macrohemorrhages.—Large intracerebral
hemorrhage (⬎5 mm in size) is most often acutely
symptomatic and may manifest as headaches as-
sociated with emesis, focal neurologic deficits,
seizures, coma, or death. Nonenhanced CT is the
imaging study of choice in the initial evaluation of
patients with suspected acute ICH, allowing rapid
yet precise demonstration of location, size, and
any other associated hemorrhage.
CAA-related macrohemorrhages typically ex-
hibit irregular borders (15) and may be associated
with subarachnoid hemorrhage (Fig 5), subdural
hemorrhage (Fig 6), or, less commonly, intraven-
 1524 September-October 2006 RG f Volume 26 ● Number 5
RadioGraphics

Figure 7. CAA-related macrohemorrhage with associ-

ated intraventricular hemorrhage in an obtunded 81-year-
old man. (a) Sagittal nonenhanced T1-weighted MR im-
age shows a large frontal cortical ICH. (b) Axial GRE MR
image shows that the right-sided frontal cortical ICH ex-
tends to the right lateral ventricle. GRE images also re-
vealed multiple cortical-subcortical microhemorrhages, a
finding most consistent with a diagnosis of probable CAA.
(c) Axial fluid-attenuated inversion-recovery (FLAIR)
MR image shows the more rarely associated intraventricu-
lar hemorrhage (arrows) as well as subarachnoid hemor-
rhage (arrowhead).

tricular hemorrhage (Fig 7) (15–17). Subarach-

noid and subdural hemorrhage may be due to
direct extension of the cortical-subcortical hemor-
rhage into the subarachnoid or subdural space
(1,20) or to primary subarachnoid or subdural
hemorrhage resulting from disruption of the lep-
tomeningeal vessels by ␤-amyloid (21). Intraven-
tricular extension of cortical-subcortical CAA-
related macrohemorrhage may also be seen, de-
pending on its size and location (1). Microhemorrhages.—Petechial hemorrhages
(ⱕ5 mm in size) are generally asymptomatic.
Walker et al (14) found evidence of microhemor-
 RG f Volume 26 ● Number 5
RadioGraphics
Figure 8. CAA-related microhemorrhage in a 76-
year-old woman with memory loss, seizures, and head-
aches. CAA was diagnosed with biopsy at another insti-
tution. Axial GRE MR image shows multiple cortical-
subcortical microhemorrhages, a finding consistent
with CAA.
rhage in a characteristic cortical-subcortical distri-
bution in 15.5% of elderly patients more than 70
years of age. CT and conventional or fast spin-
echo T1- and T2-weighted MR imaging se-
quences are relatively insensitive for such small
microhemorrhages. Local magnetic field inhomo-
Teaching geneity related to the presence of hemosiderin in
Point foci of petechial hemorrhage causes a marked loss
of signal at T2*-weighted GRE imaging, which is
currently the most sensitive sequence for detec-
tion of the cortical-subcortical microhemorrhage
associated with CAA (14,22) (Fig 8). The pres-
Chao et al 1525
ence of these cortical microhemorrhages lends
specificity in patients presenting with acute ICH.
Leukoencephalopathy
Leukoencephalopathy—low attenuation of white
matter at CT or high signal intensity of white
matter at T2-weighted MR imaging—is a nonspe-
cific finding that can be due to demyelination,
ischemia, infarction, or edema. CAA should be
considered in the broad differential diagnosis of
leukoencephalopathy, especially if associated with
cortical-subcortical hemorrhage(s) or progressive
dementia (11). Two imaging patterns of leukoen-
cephalopathy in patients with CAA have been
reported.
Leukoencephalopathy with Sparing of U Fi-
bers.—A symmetric periventricular distribution
of white matter high signal intensity, sparing the
U fibers and associated with atrophy, is seen in
patients with a clinically protracted dementia,
similar to that seen in patients with Alzheimer
disease. These white matter lesions are similar to
those seen in Binswanger subcortical encepha-
lopathy and may have a similar etiology. How-
ever, in CAA, this ischemic white matter damage
is presumed to be caused by diffuse narrowing of
penetrating cortical vessels resulting from ␤-amy-
loid deposition in the adventitia (10,11). Low
attenuation at CT and/or high signal intensity at
T2-weighted MR imaging are most prevalent in
the centrum semiovale and deep white matter
with sparing of the U fibers, corpus callosum, and
internal capsules (Fig 9). These lesions can be
both diffuse and focal and may be severe in pa-
tients with long-standing dementia. In patients
with ICH, white matter lesions can be observed in
regions remote from the ICH.
 1526 September-October 2006 RG f Volume 26 ● Number 5
RadioGraphics

Figure 9. Leukoencephalopathy in a 79-

year-old woman with slowly progressive
dementia similar to Alzheimer dementia.
(a, b) Axial nonenhanced CT scan (a) and
FLAIR MR image (b) show symmetric
periventricular leukoencephalopathy with
sparing of the U fibers, corpus callosum, and
internal capsules. The FLAIR image also
shows encephalomalacia and hemosiderin
from prior macrohemorrhage in the left fron-
tal lobe. (c) Axial GRE MR image shows
multiple bilateral cortical foci of hemosiderin,
thus increasing the specificity for a diagnosis
of probable CAA. The encephalomalacia and
hemosiderin in the left frontal lobe are also
seen.

Leukoencephalopathy with Involvement of U

Fibers.—Several case reports of patients with
pathologically proved CAA have described sub-
acute cognitive decline associated with leukoen-
cephalopathy that extends to involve U fibers and
is associated with mass effect likely related to
edema (9,11,23,24). At T2-weighted MR imag-
ing, white matter high signal intensity is most opsy. Harkness et al (23) proposed that these
prevalent in the centrum semiovale and deep changes may be secondary to ␤-amyloid–induced
periventricular regions, sparing the corpus callo- vasculopathy— cerebral amyloid inflammatory
sum and internal capsule (Fig 10). Most cases vasculopathy (CAIV). A few biopsy-proved cases
demonstrated perivascular inflammation at bi- of CAIV have responded to immunosuppressive
therapy, with at least partial resolution of leu-
koencephalopathy at imaging (8,10,24).
 RG f Volume 26 ● Number 5 Chao et al 1527
RadioGraphics

Figure 10. Leukoencephalopathy in a

61-year-old woman with rapidly progressive
cognitive decline. (a) Axial FLAIR MR
image shows asymmetric lobar leukoen-
cephalopathy extending to involve the U
fibers and exerting mass effect on the adja-
cent sulci, most prominently in the poste-
rior left parietal lobe. The absence of signal
abnormality at diffusion-weighted MR im-
aging made an ischemic process or acute
infarction unlikely. CAA was diagnosed
with biopsy. (b) Axial GRE MR image ob-
tained after biopsy shows a few cortical mi-
crohemorrhages (arrows). The patient was
treated with a short course of prednisone
taper therapy, which started at 40 mg and
produced clinical improvement. (c) Fol-
low-up axial FLAIR MR image obtained 1
year later shows near-complete resolution
of the leukoencephalopathy. CAA patients
with subacute cognitive decline and leu-
koencephalopathy may respond to immu-
nosuppressive therapy.

Atrophy CAA, atrophy is most likely the result of chronic

Prominence of the ventricular system and en- small vessel ischemia related to ␤-amyloid depo-
largement of the sulci representing generalized sition and is usually seen in association with
cerebral and cerebellar atrophy are nonspecific
imaging findings, especially in the elderly. In
 1528 September-October 2006 RG f Volume 26 ● Number 5
RadioGraphics

Figure 11. Probable CAA in a 72-year-old woman with speech difficulties and waxing and waning memory
loss. (a) Axial FLAIR MR image shows nonspecific atrophy as well as periventricular leukoencephalopathy and
prominent left-sided parieto-occipital leukoencephalopathy. (b) Axial GRE MR image shows cortical-subcorti-
cal microhemorrhages and a small left-sided parietal cortical-subcortical macrohemorrhage. These findings in-
crease suspicion for probable CAA.

leukoencephalopathy (Fig 11a). When atrophy
and leukoencephalopathy are seen in conjunction
with acute or chronic ICH in a cortical-subcorti-
cal location, the diagnostic specificity for CAA is
increased (Fig 11b).
Management and Prognosis
Although surgical intervention for an acute ICH
was previously thought to be contraindicated in
CAA patients because of fear of rebleeding (1),
more recent studies have not shown an increased
frequency of adverse outcome in most patients
with CAA-related ICH. Patients 75 years of age
or older, those with a hematoma in a parietal lobe
location, or those with associated intraventricular
hemorrhage are more likely to have an adverse
postoperative outcome and should be treated
nonsurgically (19,25).
Currently, there is no treatment to halt or re-
verse ␤-amyloid deposition. Thus, attention is Teaching
directed instead to the prevention of adverse out- Point
comes associated with the natural history of CAA,
such as recurrent hemorrhages or progressive de-
mentia. Furthermore, higher numbers of micro-
hemorrhages on the baseline GRE MR images are
predictive of a greater risk for recurrent bleeding,
future cognitive impairment, loss of functional
independence, or death (26).
Patients with a new diagnosis of CAA who re-
ceive anticoagulation for other disorders should
undergo evaluation of the risks and benefits of
continued anticoagulation and antiplatelet
therapy. Administration of anticoagulation
therapy for presumed TIA or warfarin for atrial
fibrillation and other disorders may potentiate the
risk of hemorrhage in a CAA patient. Rosand et al
(27) found that even therapeutic levels of antico-
agulation with warfarin (international normalized
 RG f Volume 26 ● Number 5 Chao et al 1529
RadioGraphics

Figures 12, 13. (12) Hypertension-related macrohemorrhage in an 80-year-old woman with right-sided
weakness and a blood pressure of 160/85 mm Hg. Axial nonenhanced CT scan shows an area of increased at-
tenuation in the left thalamus, a finding most consistent with an acute hypertensive ICH. (13) Hypertension-
related microhemorrhages in a 91-year-old woman with hypertension and unsteadiness. Axial GRE MR image
shows multiple small foci of hemosiderin in both basal ganglia and thalami, locations more consistent with a
hypertensive cause.

ratio ⱕ 3) are associated with an increased fre-
quency of warfarin-associated ICH in CAA pa-
tients. Furthermore, while warfarin has decreased
the annual risk of stroke in patients more than 75
years of age from 3.5%– 8.1% to less than 2%,
it carries an annual rate of ICH of 1.8%, even
higher in CAA patients, thus potentially offsetting
the benefit of warfarin in stroke prevention (27).
Other studies have shown fatal outcomes in CAA
patients undergoing thrombolytic or antiplatelet
therapy for various clinical indications (16). The
risk-benefit ratio of anticoagulation and thrombo-
lytic therapy in CAA patients should be carefully
considered on an individual basis.
Differential Diagnosis
A single large cortical-subcortical ICH in a pa-
tient presenting with an acute neurologic deficit is
not entirely specific for a diagnosis of CAA (16).
ICH is most commonly caused by hypertension,
trauma, bleeding diatheses, amyloid angiopathy,
illicit drug use (mostly amphetamines and co-
caine), and vascular malformations. Infrequent
causes include hemorrhagic tumors, ruptured
aneurysms, and vasculitis (28). The history,
physical examination findings, and laboratory
results often allow establishment of one of these
diagnoses. However, specific characteristics of the
ICH are just as important in the identification of
CAA-related ICH.
Hypertension is the most common cause of
nontraumatic hemorrhage in adults (29). In con-
trast to the typical cortical-subcortical location of
CAA-related hemorrhage, hypertensive hemor-
rhages, both large and small, most commonly oc-
cur in the deep gray matter, such as the basal gan-
glia or thalami, or the brainstem (Figs 12, 13).
 1530 September-October 2006 RG f Volume 26 ● Number 5
RadioGraphics

Figure 14. Large macrohemorrhage in a 66-year-old man with biopsy-proved brain metastases
from small cell lung cancer who presented with headache, light-headedness, and difficulty walking.
(a) Axial FLAIR MR image shows a large right-sided frontal cortical hematoma with surrounding
vasogenic edema. A fluid-fluid level is present, as is often seen in patients undergoing anticoagula-
tion therapy. This patient was taking clopidogrel for a coronary stent. (b) Axial contrast-enhanced
T1-weighted MR image shows a second, nonhemorrhagic metastatic lesion in the right temporal
lobe (arrow).

Although a hemorrhagic tumor may exhibit a
cortical-subcortical location similar to CAA-re-
lated hemorrhage, MR imaging may be helpful in
identifying additional enhancing lesions, leading
to a greater suspicion of metastatic disease (Fig
14).
Conclusions
CAA-related hemorrhage is an important cause of
morbidity and mortality in the normotensive el-
derly patient. Patients may present with a spec-
trum of clinical findings such as sudden neuro-
logic deficit (stroke), TIA-like symptoms, or de-
mentia that can be seen in disorders other than
CAA. However, neuroimaging demonstrates pat-
terns of involvement that are characteristic of
CAA, including cortical-subcortical location of
macro- and microhemorrhages, which may be
found concurrently with leukoencephalopathy
and atrophy. Early recognition of the constella-
tion of imaging findings associated with CAA fa-
cilitates a clinical diagnosis of CAA and proper
patient treatment.
Acknowledgment: We thank Murli Krishna, MD, for
contributing the pathologic slides.
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Cerebral Amyloid Angiopathy: CT and MR Imaging Findings

Christine P. Chao, MD et al
RadioGraphics 2006; 26:1517–1531 ● Published online 10.1148/rg.265055090 ● Content Codes:

Page 1518
Cerebral amyloid angiopathy (CAA) is an important cause of spontaneous cortical-subcortical
intracranial hemorrhage (ICH) in the normotensive elderly.

Page 1518
CAA manifests radiologically as part or all of a constellation of findings including acute or chronic
ICHs in a distinctive cortical-subcortical distribution, leukoencephalopathy, and atrophy.

Page 1519
The Boston criteria were developed in the mid-1990s as a tool to both improve and standardize the
diagnosis of CAA (7,12). The criteria specify four diagnostic categories: definite CAA, probable CAA
with supporting pathologic evidence, probable CAA, and possible CAA, depending on a combination
of clinical, imaging, and histologic data.

Page 1525
Local magnetic field inhomogeneity related to the presence of hemosiderin in foci of petechial
hemorrhage causes a marked loss of signal at T2*-weighted GRE imaging, which is currently the most
sensitive sequence for detection of the cortical-subcortical microhemorrhage associated with CAA
(14,22) (Fig 8).

Page 1528
Currently, there is no treatment to halt or reverse β-amyloid deposition. Thus, attention is directed
instead to the prevention of adverse outcomes associated with the natural history of CAA, such as
recurrent hemorrhages or progressive dementia.