(2022) 22:449
Xia and Lv BMC Neurology
https://doi.org/10.1186/s12883-022-02979-6

Open Access

CASE REPORT

Cerebral amyloid angiopathy‑related
inflammation with posterior reversible
encephalopathy syndrome‑like presentation:
a case report
Cheng Xia and Yan Lv*

Abstract
Background: Cerebral amyloid angiopathy-related inflammation (CAA-RI), which presents with acute or subacute
cognitive or functional decline, focal or multifocal neurologic deficits, new onset of seizures, or a combination of
seizures and neurologic deficits, shares clinical and radiologic similarities with posterior reversible encephalopathy
syndrome (PRES). Differential diagnosis is critical because the treatment principle for these 2 conditions differs greatly.
Here, we present a case of PRES-like CAA-RI and the strategy used to discriminate between the 2 conditions.
Case presentation: A patient with probable CAA-RI was first thought to suffer from PRES. Initial high-dose methylprednisolone therapy caused rapid improvement of the neurologic symptoms but abrupt discontinuation of corticosteroids resulted in clinical relapse and deterioration. Subsequent reinitiation of high-dose methylprednisolone
followed by tapering off of oral prednisone led to clinical and radiologic recovery at the 3-month follow-up.
Conclusions: We suggest that in cases where it is difficult to distinguish between CAA-RI and PRES solely based on
magnetic resonance imaging, a good response to corticosteroids and an apolipoprotein E (ApoE) ε4/ε4 genotype are
critical for establishing a diagnosis of CAA-RI. If there is clinical deterioration, sudden withdrawal of high-dose corticosteroid during the active phase of CAA-RI should be avoided.
Keywords: Cerebral amyloid angiopathy-related inflammation, Posterior reversible encephalopathy syndrome,
Differential diagnosis, Vasogenic edema, Corticosteroid
Background
Cerebral amyloid angiopathy-related inflammation
(CAA-RI) was previously classified as a rare autoimmune
encephalopathy subtype of cerebral amyloid angiopathy
(CAA) that presents with acute or subacute cognitive or
functional decline, focal or multifocal neurologic deficits, new onset of seizures, or a combination of seizures
and neurologic deficits. These neurologic symptoms are
*Correspondence: lana323@foxmail.com
Department of Neurology, General Hospital of Northern Theater Command,
Shenyang, China

correlated with white matter vasogenic edema, cerebral
microbleeds (CMBs), and cortical superficial siderosis
[1]. However, current evidence indicates that CAA-RI is
an autoimmune encephalopathy linked to increased antiamyloid beta (Aβ) antibodies in the cerebrospinal fluid
(CSF) of patients with cerebral amyloid deposition, which
is not strictly and solely related to a subtype CAA but
also to Alzheimer disease, with and without confirmed
CAA co-pathology [2]. A diagnosis of definite CAA-RI
requires histopathologic confirmation; however, recent
clinico-radiologic criteria [3] and detection of anti-Aβ
autoantibodies in CSF [4] have improved the diagnostic

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capacity and obviated the need for an invasive brain
biopsy.
Posterior reversible encephalopathy syndrome (PRES)
is a rare clinico-radiologic syndrome typically presenting
with acute or subacute altered mental status, headaches,
seizures, and visual disturbances [5, 6]. White matter
vasogenic edema is the main radiologic manifestation.
At present, there are no universally accepted criteria
for diagnosis, which is made based on clinical context
and the clinician’s judgment [7]. The disorder is usually
reversible when the precipitating cause (eg, hypertension) is treated with specific medication. Although corticosteroid therapy is not a standard treatment for PRES,
it is helpful for relieving vasogenic edema caused by
inflammation or trauma.
Here we describe the process of diagnosing and treating a case of PRES-like CAA-RI.

Case presentation
A 58-year-old man with a medical history of hypertension for about 30 years and ultrasonic lithotripsy
9 days prior presented to the emergency department
with drowsiness, loss of appetite, emesis, and left limb
weakness that had lasted 1 week. Physical examination revealed a blood pressure of 169/94 mmHg (range,
124–185 to 58–112 mmHg in the days prior to admission), lethargy, impaired memory and attention, and left
hemiparesis. Head noncontrast computed tomography
(CT) showed multiple subcortical hypodense changes.
The next morning, the neurologic deficit was worsening, and there was also right limb weakness with bilateral extensor plantar response. At noon on the same day,
the patient experienced a seizure. Emergency magnetic
resonance imaging (MRI) showed diffuse hyperintensities on T2-weighted images localized subcortically in the
white matter of both hemispheres, predominantly in the
temporal and occipital lobes, and several small cortical
and subcortical hypointense signal changes in bilateral
temporal lobes consistent with CMBs on susceptibilityweighted imaging (SWI). The apparent diffusion coefficient map suggested vasogenic edema (Fig. 1. A–D).
The angiogram was negative for cerebral venous sinus
thrombosis.
Laboratory tests showed normal total and differential leukocyte counts, normal prothrombin and partial
thromboplastin time, normal thyroid peroxidase antibody, Na 139 mmol/l, blood urea nitrogen 5.06 mmol/l,
ammonia 28 μmol/l, and elevated serum C-reactive
protein level (8.5 mg/dl; normal < 0.20 mg/dl). The
CSF analysis showed 13 cells/mm3 (mononuclear cells,
10 cells/mm3; polynuclear cells, 3 cells/mm3) and elevated total protein concentration (207 mg/dl) with an

Page 2 of 5

opening pressure of 400 m
­ mH2O. Both immunoglobulin G (IgG) and albumin were significantly increased in
the CSF (464 mg/l and 1.57 g/l, respectively), suggesting
severe disruption of the blood–brain barrier (BBB). The
IgG index was mildly elevated (0.89; normal ≤ 0.70);
however, no CSF oligoclonal IgG bands were detected.
The workup for rheumatic disease was negative. CSF
cultures showed no bacteria, mycobacteria, or fungi.
Polymerase chain reaction was negative for herpes simplex virus and Mycobacterium avium complex. Serum
and CSF antibodies suggestive of autoimmune encephalitis, central nervous system demyelinating disease, or
paraneoplastic encephalitis were not detected.
A diagnosis of PRES due to shock wave lithotripsy
and hypertension was initially suggested. Following
MRI, the patient was immediately given intravenous
(IV) methylprednisolone (1000 mg/day for 3 days and
then 500 mg/day for 3 days), mannitol, glycerol fructose, and torasemide, with nicardipine by infusion
for hypertension control; levetiracetam and valproic
acid were also administered out of concern for ongoing seizure activity. The neurologic symptoms rapidly
improved over the course of the following week, and
the therapy was adjusted according the principle of
PRES treatment with blood pressure control strictly
maintained and IV mannitol tapered off.
However, the patient’s mental status again deteriorated, with several vomiting episodes on day 10 after
withdrawal of methylprednisolone. The patient fell into
a stupor with obtunded pupils. An emergency head
CT scan showed patchy low-attenuation white matter
lesions predominantly in the right hemisphere with distinct mass effect. (see supplementary Fig. 1).
The diagnosis of PRES was questioned at that time
and CAA-RI was instead considered. Given that the
worsening of brain edema may have been caused by
methylprednisolone withdrawal, high-dose methylprednisolone (500 mg/day for 5 days) and dehydration therapy were immediately reinitiated followed by
oral prednisone (initially 60 mg/day, followed by 5 mg
tapering off every 10 days) (Fig. 1. I). Ten days after
methylprednisolone reinitiation, MRI showed that the
edema had subsided considerably although innumerable cortical CMBs appeared on SWI (Fig. 1. E, F). The
patient’s mental status gradually improved and he was
discharged 24 days later; the apolipoprotein E (ApoE)
gene report revealed a ε4/ε4 genotype.
At the 3-month follow-up, the patient had achieved
both clinical and radiologic recovery with oral prednisone 15 mg/day, although the multiple and scattered
subcortical CMBs showed no change (Fig. 1. G, H). A
final diagnosis of probable CAA-RI was made.

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Fig. 1 MRI findings and treatment timeline of the patient. A–D On day 2 after admission, the T2-weighted image showed diffused subcortical
white matter hyperintensities in both hemispheres, predominantly in the temporal and occipital lobes (A, B); the apparent diffusion coefficient map
showed increased diffusivity of the lesion consistent with vasogenic edema (C); and SWI showed several cortical and subcortical CMBs in bilateral
temporal lobes (D). Following initial MRI, high-dose methylprednisolone (1000 mg/day for 3 days and 500 mg/day for 3 days) and dehydration
therapy were administered, with rapid improvement of neurologic symptoms observed within 1 week. Head CT on day 10 after withdrawal of
methylprednisolone revealed significant aggravation of brain edema (see supplementary Fig. 1). E, F Ten days after high-dose methylprednisolone
reinitiation, MRI showed that the edema had largely resolved, but innumerable cortical CMBs appeared on SWI. G, H MRI at the 3-month follow-up
showed remarkable regression of white matter hyperintensities, with no change in CMBs. I Treatment timeline showing course of the disease with
different treatments. GF, glycerol fructose; MP, methylprednisolone; MT, mannitol; PS, prednisone; TM, torasemide

Discussion and conclusions
The case presented here highlights the challenge of
diagnosing a patient with a misleading initial presentation of CAA-RI. The medical history included hypertension and ultrasonic lithotripsy 2 days before the
onset of subacute encephalopathy. The largely symmetric subcortical vasogenic edema in the brain MRI and
acute occurrence of clinical symptoms rapidly resolved
after high-dose corticosteroid, dehydration, and

aggressive hypertension control. Such a course strongly
suggested PRES, which was supported by the blood
pressure on admission. PRES is seen in patients with a
hypertensive emergency but is also observed with other
conditions such as sepsis and eclampsia and exposure
to immunosuppressive drugs. Ultrasonic lithotripsy has
been reported as a cause of PRES [8]. The key pathophysiologic disturbance of PRES is endothelial dysfunction, which causes the breakdown of the BBB. Although

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in PRES, vasogenic edema is often seen bilaterally in
parieto-occipital, holo-hemispheric watershed, or posterior frontal cortical and subcortical white matter on
MRI [7], atypical distribution of vasogenic edema and
CMBs have been reported [9, 10].
CAA-RI is increasingly considered as an autoimmune
encephalopathy linked to increased anti-Aβ antibodies in
the CSF of patients with cerebral amyloid deposition [4],
which has also been reported in clinical trials of amyloid
modification therapies [11]. Vasogenic edema possibly
caused by autoinflammation with anti-Aβ42 antibodies
was shown to be correlated with symptoms of acute or
subacute encephalopathy, and is the main MRI finding in
CAA-RI. It was suggested that clinical and radiologic criteria may help diagnose probable CAA-RI with good sensitivity and specificity, thereby avoiding cerebral biopsy
[3].
In our patient, the response to corticosteroids raised
our suspicion of CAA-RI. Initial high-dose methylprednisolone therapy caused rapid improvement of
the neurologic symptoms, whereas the sudden cessation of corticosteroid therapy resulted in clinical relapse
and deterioration. Subsequent reinitiation of high-dose
methylprednisolone followed by slow tapering off of
oral prednisone led to clinical and radiological recovery
at the 3-month follow-up. The patient’s ApoE genotype
confirmed our suspicion. According to Antolini et al., 5
IV boluses of high-dose corticosteroids and slow tapering off for several months until clear resolution of acute
fluid-attenuated inversion recovery white matter hyperintensities is a reasonable recommendation; there is a
higher risk of recurrence during CAA-RI treatment with
corticosteroids if IV high-dose IV corticosteroid pulse
therapy was suddenly stopped compared to slow tapering off of oral therapy [2]. It should be noted that the
patient’s clinical deterioration during the active phase
did not meet the definition of recurrence. Kimura et al.
also reported a female patient with CAA-RI who received
IV methylprednisolone (1000 mg/day for 3 days) without
subsequent oral corticosteroids [12]. Her symptoms transiently improved but there was progressive deterioration
of consciousness, and mechanical respiratory treatment
was required. Therefore, abrupt discontinuation of highdose corticosteroid without subsequent oral steroids during the active phase of CAA-RI should be avoided.
This report had several limitations. First, we did not test
for anti-Aβ autoantibodies in the CSF of our patient, which
could increase confidence in discriminating between PRES
and CAA-RI and would certainly increase diagnostic accuracy in challenging cases where MRI and clinical data alone
are insufficient. Second, biomarkers of neurodegeneration in the CSF including tau and Aβ fragments were not

Page 4 of 5

evaluated. Nonetheless, we recommended this analysis to
improve management of similar cases in the future.
In conclusion, we described a patient with probable
CAA-RI who showed clinical improvement after steroid
therapy and was initially thought to have PRES. We suggest that in cases where it is difficult to distinguish between
CAA-RI and PRES solely based on MRI, a good response
to corticosteroids and ApoE ε4/ε4 genotype are critical for
establishing a diagnosis of CAA-RI. If clinical deterioration
occurs, sudden withdrawal of high-dose corticosteroid during the active phase of CAA-RI should be avoided.
Abbreviations
CAA-RI: Cerebral amyloid angiopathy related inflammation; CAA​: Cerebral
amyloid angiopathy; CMBs: Cerebral microbleeds; PRES: Posterior reversible
encephalopathy syndrome; ADC: Apparent diffusion coefficient; CSF: Cerebrospinal fluid; BBB: Blood–brain barrier.

Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s12883-​022-​02979-6.
Additional file 1: Supplementary figure 1. Head CT on day 10 after
withdrawal of the initial methylprednisolone pulse therapy.
Acknowledgements
None.
Authors’ contributions
CX: Drafting/revision of the manuscript for content, including medical writing
for content; major role in the acquisition of data; analysis or interpretation of
data. YL: Study concept or design All authors have read and approved the final
manuscript to be published.
Funding
This study was funded by Doctoral Start-up Foundation of Liaoning Province
2019-BS-268. The funding body played no role in the design of the study and
collection, analysis, and interpretation of data and in writing the manuscript.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from
the corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate
This study has been approved by the Medical Ethical Research Committee of
General Hospital of Northern Theater Command. Informed consent to participate was obtained from the patient.
Consent for publication
Written informed consent to publish this information was obtained from
study participant. Proof of consent to publish from study participant can be
requested at any time.
Competing interests
The authors declare that they have no competing interests.
Received: 18 June 2022 Accepted: 10 November 2022

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