Seminars in Arthritis and Rheumatism ] (2014) ]]]–]]]

Contents lists available at ScienceDirect

Seminars in Arthritis and Rheumatism
journal homepage: www.elsevier.com/locate/semarthrit

Amyloid Beta-Related Angiitis—A Case Report and Comprehensive
Review of Literature of 94 Cases
Abhijeet Danve, MDa,n, Marjorie Grafe, MDb, Atul Deodhar, MRCP, MDa
a
b

Division of Arthritis & Rheumatic Diseases (OP-09), Oregon Health & Science University, 3181, SW Sam Jackson Park Road, Portland, OR 97239
Department of Pathology, Oregon Health & Science University, Portland, OR

a r t i c l e in fo

Keywords:
Amyloid Beta-Related Angiitis
Inflammatory cerebral amyloid angiopathy
Cerebral amyloid angiopathy
Vasculitis
Primary CNS vasculitis

a b s t r a c t
Background: Amyloid Beta-Related Angiitis (ABRA) is a rare cause of central nervous system vasculitis
complicating cerebral amyloid angiopathy. Data regarding its prevalence, clinical features, management,
and outcomes are scant.
Objectives: To describe a patient with ABRA and discuss clinical features and management of ABRA.
Methods: A case report and review of literature were conducted of all reported cases of ABRA in the
English literature.
Results: The exact etiology of ABRA is not clear, though it is thought to be secondary to an inflammatory
response to beta amyloid (Aβ) in the walls of blood vessels. Role of ApoE e4/e4 genotype and its association
with autoimmune diseases have been reported. ABRA shares many clinical features with primary
CNS vasculitis. Patients with ABRA are relatively younger than those with non-inflammatory cerebral
amyloid angiopathy (CAA), but older than patients with primary central nervous system vasculitis (PCNSV).
Acute-onset cognitive behavioral abnormalities, focal neurological deficits, seizures, or unusual headaches
are the most common presentations of ABRA. Majority have elevated CSF proteins. Up to 70% of patients
have ApoE e4/e4 genotype. MRI is the most important diagnostic tool and is almost always abnormal.
Characteristically, MRI shows hyperintensities on T2-weighted (T2W) or fluid-attenuation inversion
recovery (FLAIR) images with minimal gadolinium enhancement. On susceptibility-weighted images
(SWI), a majority of the patients have the presence of microbleeds at cortico-subcortical junction. It may
be possible to diagnose typical patients based on clinical features and MRI findings alone, obviating the
need for brain biopsy. Brain biopsy is the gold standard and shows transmural granulomatous vasculitis
superimposed on CAA. ABRA responds well to steroids in majority. Patients usually need additional
immunosuppressants, especially to prevent relapse. MRI abnormalities resolve with treatment and recur
with the relapse.
Conclusions: ABRA is a rare but treatable cause of progressive dementia and should be considered in the
differential diagnosis of rapid-onset CNS dysfunction in patients older than 60 years. It has characteristic
MRI findings and responds well to steroids and other immunosuppressant therapy.
& 2014 Elsevier Inc. All rights reserved.

Introduction
Amyloidosis is a disorder of protein folding in which normally
soluble proteins are deposited in the extracellular space as
insoluble fibrils that progressively disrupt the tissue structure
and function [1]. Cerebral amyloid angiopathy (CAA) is localized
amyloidosis affecting cerebral blood vessels, commonly resulting
from imbalance between production and clearance of normally
produced beta amyloid (Aβ) from the brain [2]. CAA is responsible
for 12–15% of cases of lobar intracranial hemorrhages in elderly
and can also cause cognitive decline [3], transient ischemic attacks,

n

Corresponding author.
E-mail addresses: drdanve@hotmail.com, danve@ohsu.edu (A. Danve).

http://dx.doi.org/10.1016/j.semarthrit.2014.02.001
0049-0172/& 2014 Elsevier Inc. All rights reserved.

and focal seizures [4]. Very rarely, patients with CAA develop
secondary central nervous system (CNS) vasculitis triggered by
immune response to Aβ, which is called “inflammatory CAA” or
Amyloid Beta-Related Angiitis (ABRA).
We present our experience with this condition and the largest
comprehensive case review about ABRA. We discuss several new
insights into the etiopathogenesis, diagnosis as well as management of ABRA.

Case report
A 63-year-old right-handed Caucasian woman was admitted for
evaluation of an episode of seizure. She was in her usual state of
health until the day of admission when she had witnessed an

A. Danve et al. / Seminars in Arthritis and Rheumatism ] (2014) ]]]–]]]

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episode of generalized tonic–clonic seizure preceded by aura
consisting of seeing wavy dancing lines in front of her eyes.
She was admitted to a local hospital where computed tomography
(CT) scan of the brain was performed. The CT showed two
subcortical hypodense lesions in the right and the left frontoparietal lobes surrounded by edema. The lesions were suspected to
be metastases given her history of breast cancer. She was referred
to our hospital for neurosurgical evaluation. On arrival at
our hospital, the patient was asymptomatic. There was no
history of fever, night sweats, loss of appetite or weight, headaches, visual disturbances, loss of memory, abnormal behavior, and
focal weakness. She did not have any symptoms suggestive
of well-defined rheumatic disease including systemic vasculitides.
Her medical history was significant for breast cancer diagnosed 1
year prior to the presentation, treated with lumpectomy
followed by radiation therapy. The patient also had a history of
pernicious anemia and Grave's disease treated with radioiodine
therapy. Her home medications included anastrozole, levothyroxine, aspirin, calcium, monthly cyanocobalamin injections, ferrous
sulfate, and subcutaneous injections of denosumab every 6
months for osteoporosis prophylaxis. Her sister and brother had
rheumatoid arthritis. She lived with her husband and ran a candy
business. She denied current or past smoking, alcohol, or illicit
drug use.
On physical examination, pulse was 84 beats per min, blood
pressure was 137/64 mmHg, and respiratory rate was 14 breaths
per min. General examination included skin which was normal.
Neurological examination was completely normal including higher
cognitive functions, cranial nerves, motor, sensory as well as
cerebellar examination results. Results of her routine laboratory
tests were unremarkable and those of serological tests as well as
CSF are shown in Table 1.
She underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain (Fig. 1), which showed abnormal cortical and
subcortical hyperintensities in both temporal and frontal lobes
on T2W and FLAIR images with vague contrast enhancement of
bi-temporal lesions and left frontal perisylvian lesion. Gradientecho imaging (GEI) demonstrated innumerable punctate hypointense foci, probably due to micro-hemorrhages within or around
each lesion. Cerebrospinal fluid studies were unremarkable except
for elevated proteins.
As per the neurosurgery team, MRI features were atypical
for metastases and biopsy was recommended to guide
further management. Stereotactic right temporal lobe brain
biopsy was done. It did not show any evidence of malignancy or
infection.

Table 1
Lab test
Cerebrospinal fluid
Proteins
Glucose
Cells
WBC
RBC
Culture
Flow cytometry

ANA
Rheumatoid factor
ANCA
HBsAg
HCV Ab
Quantiferon
SPEP
Cryoglobulins

Patient’s result
Clear colorless
57
59
4
263
Negative
No malignant cells
Small lymphocytes
CD4:CD8 ratio 2.8:1.0
Negative
o 10
Negative
Negative
Negative
Negative
Normal
Negative

Normal value

15–45
40–70
0–5 per hpf
o1 per hpf

o15

Fig. 1. (A–C) T2W sequences showing abnormal cortically and subcortically based
hyperintensities throughout both temporal lobes, and in the frontal lobes.
(D) Gradient-echo imaging study showing punctate hypointense foci due to
microbleeds corresponding areas. (E) No significant enhancement with gadolinium
contrast.

However, the brain biopsy showed typical findings of ABRA
(Fig. 2), mainly transmural infiltration of vessel walls by lymphocytes and macrophages with the formation of granulomas and
multinucleated giant cells in the background of cerebral amyloid
angiopathy. Focal hemorrhage, fibrinoid necrosis, thrombosis, and
recanalization were also present. No organism was identified on
GMS, PAS, Gram, AFB, and Steiner stains. Immunohistochemical
stains revealed Aβ in blood vessels walls and abundant CD68 þ
macrophages, some of which contained Aβ. CD3 þ T cells with few
CD20 þ B cells were also seen.
The patient was treated with high-dose prednisone (1 mg/kg/
day) and six monthly infusions of cyclophosphamide. She was
also given Levetiracetam for seizure prophylaxis. Repeat MRI
3 months after the admission showed almost complete resolution

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Fig. 2. (A) Hematoxylin and eosin stain demonstrates inflammation in the vessel wall, including multinucleated giant cells (arrows). There is thrombus (T) in the vascular
lumen. The adjacent brain parenchyma has many reactive astrocytes (asterisks). (B) Congo red stain is positive in the wall of a small arteriole and a capillary (arrows). (C) The
same Congo red-stained section viewed with polarized light shows green birefringence (arrows), confirming that the red staining is amyloid. (D) Multinucleated giant cells in
a blood vessel wall are positive for CD68 (brown stain, arrows), as are scattered microglia in the brain parenchyma. (E) Immunohistochemical stain demonstrates A beta in
the wall of a small arteriole and multiple capillaries (arrows on representative vessels). There is an inflammatory infiltrate in the wall of the arteriole (asterisk). Magnification
bar in (A) ¼ 100 μm. All photographs are at the same magnification. (For interpretation of the references to color in this figure legend, the reader is referred to the web
version of this article.)

of T2 and FLAIR hyperintense lesions in both the cerebral hemispheres with mild persistent hyperintensity in the right posterior
temporal lobe. The patient had stable cortical and subcortical
microbleeds on gradient-echo imaging in both the cerebral hemispheres suggestive of amyloid angiopathy. Prednisone was being
tapered gradually and she was started on azathioprine. She
developed acute liver injury in the form of elevated liver enzymes
(up to 800 U/L) from azathioprine which resolved after discontinuation. Mycophenolate was then started as a steroid-sparing agent.
At the follow-up visits after 3, 6, 8, and 11 months, she has been
asymptomatic and has had no recurrent seizures. Repeat MRI
again 11 months after admission shows almost complete resolution of T2W hyperintensities.

Methods
OVID MEDLINE was searched for relevant articles between 1946
and 2012 using the following key words: “cerebral amyloid
angiopathy,” “vasculitis,” “inflammatory CAA,” and “A BetaRelated Angiitis.” All relevant articles were retrieved, and additional references quoted in these articles were checked. There have
been case series and reviews in the literature, which include those
by Schwab et al. [10], Scolding et al. [9], Kinnecom et al. [12],
Salvarani et al. [5], and Chung et al. [7]. Information was extracted
from these published reviews for 72 patients. We found 23 additional cases after 2009, excluding our case. Clinical data for two
patients from Kinnecom et al. were not available, and two more
patients' case reports were in a language other than English, hence

they were not included. Information about demographic data,
clinical features, lab and imaging findings, treatment, and followup was extracted and is summarized in Table 2. We also discuss
the possible etiology and differential diagnosis of ABRA.

Results
Clinical features
Of 94 patients, 50 were men (53%), and the mean age was 65.2
years (range 42–87). Patients had either acute (54%) or subacute
(46%) presentation. The most common presenting symptom (71%)
was cognitive or behavioral changes, which ranged from mild
cognitive impairment to frank dementia, hallucinations, personality changes, confusion, and coma. The second commonest
presentation was focal neurological deficits (FND) which affected
51% (47/92) of patients. FND included hemiparesis, hemisensory
loss, aphasia, hemianopia, hemineglect, and cerebellar ataxia. Focal
deficits caused by lesions in the posterior cerebral circulation
predominated, probably because of preferential deposition of Aβ
amyloid in occipital lobes. Moreover, 30% of patients presented
with seizures and 35% with headaches. As opposed to previous
studies where seizures occurred variably from 0% to 31% in
patients, our review suggested the incidence of seizures to be
36%. Four patients had transient ischemic attack-like onset [5–8],
and 77% had two or more of the four most commonly described
clinical features.

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Table 2
Otherse

Total

16
69 (46–83)b
7/9

22
67.6 (52–87)a
11/11

94
65.2 (42–87)a
50/44

6/8
0/8
7/8
4/8

9/16
7/16
9/16
7/16

13/22
12/22
15/22
4/22

66/92 (71%)
34/92 (36%)
47/92 (51%)
33/92 (35%)

10/13

NA

NA

2/4

12/17 (70%)

11/18
8/18
12/21

4/5
1/5
NA

7/8
5/8
NA

8/11
5/11
1/1

12/17
7/17
3/3

42/59 (71%)
26/59 (44%)
16/16 (100%)

MRI
White matter changesc
Micro-bleed on SWI/GEI
Enhancement
Improvement with Rx

13/20
4
7/10
4/5

12/12
6/7
d

10/12

6/8
NA
5/8
4/6

14/14
4/4
5/9
6/9

21/21
11/13
6/11
13/15

66/75 (88%)
21/24 (87%)
23/38 (60%)
37/47 (79%)

Pathology
Vasculitis or perivasculitis

34/34

14/14

8/8

16/16

19/20f

91/92 (99%)

Response to therapy
Relapse

12/20
NA

10/12
3/12

6/8
2/8

10/12
NA

19/20
3/14g

57/72 (79%)
8/34 (23%)

Study

Scolding et al. [9]

Kinnecom et al. [12]

Salvarani et al. [5]

Chung et al. [7]

No of patients
Age
Sex (M/F)

34
67.3 (43–82)a
17/17

14
63.2 (45–79)a
9/5

8
63 (42–84)a
6/2

Clinical features
CB change
Seizures
Focal deficits
Headache

29/34
8/34
15/34
12/34

9/12
7/12
1/12
6/12

ApoE e4/e4

NA

CSF
Elevated proteins
Pleocytosis
Oligoclonal bands
Repeat CSF

NA ¼ not available; CB ¼ cognitive behavioral.
a

Mean (range) age.
Median (range) age.
Hyperintensities on T2W or FLAIR images.
d
Little or no enhancement.
e
22 Includes our case in Refs. [8,13–15,16,21,22,25,40–49].
f
2 Patients were treated presumptively.
g
As per the reported information.
b
c

A total of 10 patients had a history of prior malignancy,
including our patient [9]. The types of malignancies included were
melanoma; cancers of pancreas (n ¼ 1), prostate (n ¼ 2), bowel
(n ¼ 2), breast (n ¼ 2), and bladder (n ¼ 1); multiple myeloma
(n ¼ 1); and basal cell carcinoma (n ¼ 1). There were 11 patients
with autoimmune diseases—hypothyroidism (n ¼ 4), Grave’s
disease (n ¼ 2), rheumatoid arthritis (RA) (n ¼ 2), autoimmune
hepatitis (n ¼ 1), and pernicious anemia (n ¼ 2) [6,10,11].
Investigations
Inflammatory markers including ESR and CRP were elevated in
14 of 47 (29.7%) patients where the information was available. ApoE
was checked in 17 cases [12–16]. Genotype e4/e4 was present in 12,
e2/e3 in four, and e2/e4 in one patient. CSF showed elevated protein
ranging from 0.5 to 5.73 g/L in 42 of 59 patients (71%). Lymphocytic
pleocytosis was present in 26 of 59 patients (44%). Oligoclonal
bands were absent in all 16 patients where it was checked
[9,13,15,17,18–21]. One patient had antibodies to Aβ 40 and Aβ 42
(Aβ amyloid can be 40 (Aβ 40) or 42 (Aβ 42) amino acid-long
peptide chain) in the CSF [13]. There was a high CD4-to-CD8 ratio
and an increased number of activated CD69 þ T lymphocytes in CSF
in one patient [15]. Repeat CSF was performed in two cases after the
treatment and in both cases abnormalities resolved [13,15]. EEG was
available for 28 patients: 22 had nonspecific findings, five had
epileptogenic focus, and one had normal EEG.
MRI results were reported for 77 of 92 patients (83%). A total of
75 (97.4%) patients had abnormal MRI findings. The most common
findings were asymmetrical bilateral white matter hyperintensity
on T2W and FLAIR images, which was reported in 66 of 75 (88%)
patients; 26% patients had mass like lesions, which were either
non-enhancing or minimally enhancing. Where it was reported,

patchy enhancement was noticed in 23 of 38 patients (60%). SWI
or GEI images were available for 24 patients, and 21 of them (87%)
had evidence of micro-hemorrhages mainly in the cortical area
near the sulci affecting parietal, occipital, and frontal lobes. Repeat
MRI after the treatment showed improvement in white matter
lesions in 38 of 47 (80%) patients.
Cerebral angiography was performed in 21 patients, and only
two had mild abnormalities reported. One patient had subtle
bilateral vascular narrowing affecting small branch vessels of the
middle and anterior cerebral arteries, and the other patient had
alternating areas of vasoconstriction and normal caliber involving
large and medium-sized cerebral arteries. When performed, MRA
was normal in all 11 patients.
Biopsy was performed in all 94 but two patients. These two
patients were diagnosed to have probable ABRA based on typical
clinical features and MRI and were treated empirically with
steroids [16,22].
Of 92 patients, 74 had brain biopsy and 18 underwent autopsy.
Biopsy showed vasculitis in 80 (78%) patients and perivasculitis in
20% of patients. One patient had an inconclusive biopsy. Among
the patients with vasculitis, transmural inflammation with
CD68 þ macrophages and CD3 þ T cells was the main findings.
Frequently multinucleated giant cells were described and a few
macrophages had Aβ engulfed in the cytoplasm, these macrophages were present in close vicinity to CD4 cells. There were
fewer CD20 þ cells as compared to CD4 cells. Vasculitis was
present only in the vessels affected by the amyloid deposition
but not in deeper white matter vessels. There was striking colocalization of vasculitis in amyloid-laden blood vessels, and
vessels which do not have CAA were spared. Immunohistochemical stains show predominantly beta amyloid deposition with
increased ratio of Aβ 40 to Aβ 42.

A. Danve et al. / Seminars in Arthritis and Rheumatism ] (2014) ]]]–]]]

Treatment
Treatment details were reported for 90 patients; 73 patients
received corticosteroids. Cyclophosphamide (CYC) was administered in 31 patients, azathioprine in six, methotrexate in two, and
mycophenolate mofetil in two patients [20,23]. One patient
received only CYC without corticosteroids [24]. Of 73 patients
treated with steroids, 57 (78%) patients showed clinical improvement which was either complete or partial. Patients who were
started on immunosuppressive therapy early had better prognosis.
Of 57 patients, who showed improvement, 15 had a relapse (26%),
either after reduction or cessation of immunosuppression, but
responded well after reinstitution of therapy. One patient had
relapse of disease twice and both times he responded to the
azathioprine monotherapy [25]. Follow-up was reported in 84
patients, which ranged from 3 to 13 years. In review of 22 patients
reported after 2009, only one patient died acutely from massive
intracranial hemorrhage, but overall majority of the patients
responded well to immunosuppressive therapy.

Discussion
Cerebral amyloid angiopathy (CAA) is a form of localized
amyloidosis affecting mainly the cortical and leptomeningeal
vessels of cerebral lobes, preferentially occipital lobes and cerebellum [26]. As per the autopsy studies, the prevalence of CAA
could be as high as 21% in people aged 61–70 years and increases
further with age [27]. Sporadic CAA with Aβ deposition is the most
common of various forms of CAA. It results from chronic imbalance
between production and clearance from the brain of the normally
present but inherently amyloidogenic protein called Aβ amyloid
[2]. Neurons and other parenchymal cells of the brain are the

Fig. 3. Elimination of Aβ from the brain. Aβ is (i) produced by neurons and other
cells in the brain and then (ii) diffuses with interstitial fluid and other solutes
through the narrow extracellular spaces (ECS) of the brain to (iii) the bulk flow
lymphatic drainage pathways in the basement membranes of capillaries and in the
tunica media of artery walls, and (iv) out of the brain to cervical lymph nodes.
Smooth muscle cells and perivascular macrophages take up Aβ and are part of the
elimination pathway. Degradation of Aβ occurs in the brain parenchyma, by
neprilysin and other enzymes, and Aβ is absorbed into the blood by LRP-1
(lipoprotein receptor-related protein-1)-mediated mechanisms in capillary
endothelia. These mechanisms for the elimination of Aβ from the brain tend to
fail with age and in Alzheimer disease.

5

major source of Aβ which is usually cleared by enzymatic degradation, absorption by transcytosis, or perivascular drainage
[28,29,30] (Fig. 3). Deposition of amyloid in the blood vessels
leads to vasculopathy, which is responsible for clinical features of
CAA, like intracranial bleed, cognitive decline, and dementia.
Very rarely CAA is associated with the development of CNS
vasculitis, which shares many clinical features with primary CNS
vasculitis. It has been reported in the literature by various names—
Amyloid β-Related angiitis (ABRA), primary angiitis of the CNS
associated with CAA; amyloid angiopathy and granulomatous
angiitis of the CNS; cerebral amyloid inflammatory vasculopathy;
and cerebral amyloid angiitis and cerebral amyloid angiopathy
associated with giant cell arteritis [9,17,18,31–34]. It was first
reported by Reid and Maloney in 1974.
Why only a few patients with CAA develop secondary CNS
vasculitis is unclear. Clinically ABRA behaves more like PCNSV
than typical CAA, which may raise suspicion that ABRA is a chance
association between CAA and PCNSV. Several observations have
ruled out this possibility. Firstly, it has distinct radiological
features, which are not commonly seen in case of PCNSV.
Secondly, there is striking co-localization of areas of vasculitis
and vessels affected by CAA. Thirdly, Aβ is found to be engulfed by
macrophages expressing MHC class II antigens which are in close
vicinity of CD4 helper cells, implying causative role of amyloid in
inducing the inflammation [15]. Vasculitis appears to be an autoimmune response to Aβ [35]. It was observed that immunization
with Aβ reduced plaque burden in patients with AD and hence a
trial of Aβ 42 immunization of patients with moderate AD was
initiated in 2001 [36]. Later the trial was halted because of
development of subacute meningoencephalitis in 18 of 372 (6%)
patients who had clinical features, imaging findings, and pathological features very similar to ABRA [37]. Similarly, vasogenic
edema and microbleeds were reported in a subgroup of subjects
in phase 1 and phase 2a studies of a humanized antiamyloid
antibody [38].
Whether the inflammation is triggered by Aβ or its associated
components like ApoE, Serum amyloid P component, or cystatin C
is not clear. Genotypes e4/e4 and e2/e4 of ApoE have been found to
be associated with development of ABRA. As we know, e4
genotype is associated with increased burden of amyloid in the
vessels. Also the mean age of patients with ABRA is lesser than that
of those with CAA without inflammation [5,7,9,12]. Why these
patients develop CAA at an earlier age is not clear. Many of these
patients were reported to have autoimmune diseases like hypothyroidism, Grave's disease, pernicious anemia, rheumatoid arthritis, and autoimmune hepatitis. It is possible that autoimmunity
plays a role in the causation of this vasculitis. Also upon review of
literature, we found 10 patients who had various malignancies
reported which were treated prior to the development of vasculitis. Two of these patients had received radiation therapy. In an
autopsy study of 123 brains from patient who died of malignant
neoplasms, radiation therapy to brain was more likely to be
associated with the development of CAA [39].
Patients with ABRA are younger (mean age 67 years) than those
with non-inflammatory CAA (77 years) but older than patients
with primary CNS vasculitis (45 years) [5]. They usually do not
have features of systemic vasculitis.
There are no specific diagnostic lab tests or serologies. Inflammatory markers do not help in diagnosis or monitoring of treatment. CSF examination helps to exclude infections or
malignancies. About 71% of patients have variably elevated CSF
protein levels, and 40% have CSF pleocytosis with predominant
lymphocytes. ApoE genotyping may help in diagnosis and may
have a role in causation of CAA and possibly ABRA.
MRI is probably the most important diagnostic test next to the
cerebral biopsy. MRI findings are quite characteristic and may

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6

obviate the need for brain biopsy in typical cases. In 2007,
Kinnecom et al. [12] and in 2010, Greenberg et al. [35] suggested
that typical clinical and MRI features may be sufficient for the
treatment of ABRA without requiring biopsy. As per literature,
three patients have been treated successfully for ABRA [16,22,35]
based on clinical and imaging findings without biopsy. MRI may be
dramatically abnormal with paucity of clinical findings. One-fourth
of patients can present with variably enhancing mass like T2W and
FLAIR lesions on T2W and FLAIR which can be misdiagnosed as
primary or metastatic brain malignancy especially if they have a
history of solid tumor in the past. GEI or SWI shows microhemorrhages which are typically located at cortico-subcortical
junction predominantly in temporal and occipital lobes. MRI
shows resolution of white matter abnormalities after treatment
and recurrence with relapse, thus making it an important test for
monitoring disease. MRA is usually normal and does not help in
diagnosis or monitoring. Gadolinium leptomeningeal enhancement is far less frequent in patients with CAA as compared to
those in ABRA, whereas lobar hemorrhage and microbleeds without enhancing lesions are more frequent.
It is important to stress that cerebral angiography, a common
investigation in CNS vasculitis, is usually normal probably because
of the small caliber of affected vessels, which are not captured
with angiography. Cerebral biopsy is the gold standard for diagnosis of ABRA. It should preferably be obtained from a radiologically abnormal area.
Age of presentation, MRI findings, and biopsy features help to
differentiate ABRA from PCNSV. Other diseases which present with
white matter changes and micro-hemorrhages like PRES should be
differentiated from ABRA. Other differentials include primary and
secondary CNS malignancies, infections like tuberculosis and
fungal diseases, rare diseases like Hashimoto's encephalitis, neurosarcoidosis, and acute disseminated encephalomyelitis.
Diagnostic criteria
In 2011 Chung et al. [7] proposed diagnostic criteria for definite
and probable ABRA, based on review of clinical, imaging, and
biopsy findings of 72 patients reported in the literature (Table 3).
In the past, treatment of ABRA consisted of surgery, shortcourse steroids, and even no treatment in a few cases. This led to
apparent poor prognosis as described in previous case series.

Table 3
Proposed diagnostic criteria by Chung et al.
Probable CAA-I
All of the following:
1. Acute or subacute onset of symptoms
2. 40 years of age or older
3. At least one of the following clinical features: headache, mental status or
behavioral change, focal neurological signs, and seizures
4. MRI shows patchy or confluent T2 or fluid-attenuation inversion recovery
hyperintensity which is:
a.
usually asymmetric
b.
with or without mass effect
c.
with or without leptomeningeal or parenchymal enhancement
5. Evidence of pre-existing CAA on susceptibility-weighted MRI sequences:
a.
multiple cortical and subcortical hemorrhages or
microhemorrhages and/or
b.
recent or past lobar hemorrhage
6. Absence of neoplastic, infectious, or other cause
Definite CAA-I
All of the above plus histopathological confirmation with
1. Perivascular, transmural, and/or intramural inflammation
2. Amyloid deposition within vessels of affected area in the cortex and
leptomeninges

Lately earlier diagnosis of ABRA with MRI and biopsy has
changed the natural history of ABRA. As per review by Chung
et al. [7] 10 of 12 patients responded to steroids, and in our review
(2009–2012), 19 of 20 patients have responded to the corticosteroids. Thus, the majority responds well to immunosuppressive
therapy with complete remission even up to 5 years. But few
patients could have relentless disease progression despite aggressive treatment leading to disability and even death.
Treatment needs to be individualized based on patient characteristics and comorbidities, but it may be reasonable to start with
high-dose corticosteroids. The initial response is usually seen
within the first few weeks [7]. There have been reports of relapse
of ABRA in about 26% of patients on reduction or cessation of
immunosuppressive therapy. Hence, further immunosuppression
is advisable. CYC, methotrexate, azathioprine, and mycophenolate
have been successfully used in various cases. Almost all the
relapsed patients respond to reinstitution of the treatment.

Conclusion
ABRA is a rare but treatable cause of progressive dementia and
neurological dysfunction in patients older than 60 year years and
should be considered in the appropriate clinical settings.

Acknowledgment
We would like to thank Ms. Lisa Perry (PharmD) for her
assistance in proofreading.
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