□ CASE REPORT □
11

C-PiB PET Imaging of Encephalopathy Associated with
Cerebral Amyloid Angiopathy
Renpei Sengoku 1,2, Satoshi Matsushima 3, Yoshitake Murakami 4, Takahiro Fukuda 5,
Aya M. Tokumaru 6, Masaya Hashimoto 1, Masahiko Suzuki 1, Kiichi Ishiwata 7,
Kenji Ishii 7 and Soichiro Mochio 8

Abstract
We herein report that the clinical, laboratory, and radiographic features and positron emission tomography
(PET) imaging may provide valuable clues to the pathogenesis of cerebral amyloid angiopathy (CAA)associated encephalopathy, which currently remains unclear. We herein describe two cases of encephalopathy
with CAA, with an emphasis on PET imaging with 11C-Pittsburgh compound B (11C-PiB) and 18Ffluorodeoxyglucose (18F-FDG). One case of Alzheimer’s disease for which a brain biopsy was performed
showed CAA-related inflammation. Another case that had developed sudden sensory aphasia presented with
posterior reversible encephalopathy syndrome-like vasogenic edema in the left temporal region with 11C-PiB
uptake and microhemorrhages. 11C-PiB and 18F-FDG PET are useful for detecting CAA-associated encephalopathy, including atypical CAA cases.
Key words: cerebral amyloid angiopathy, vasogenic edema, PET, sensory aphasia, hemodialysis
(Intern Med 53: 1997-2000, 2014)
(DOI: 10.2169/internalmedicine.53.1731)

Introduction
Cerebral amyloid angiopathy (CAA) characteristically
shows localized amyloid deposition in cerebral blood vessels, including the small- and medium-sized arteries of the
leptomeninges and superficial cortex. The clinical manifestations of CAA include leukoencephalopathy or encephalopathy (1, 2). T2* weighted images (WI) or susceptibilityweighted images (SWI) can detect microbleeding to provide
support for a diagnosis of CAA (3, 4). SWI can identify
many more microhemorrhages than conventional T2*WI
magnitude techniques (5). A recent study described the correlation of SWI focal intensities to tissue pathology in post
mortem human CAA-affected brain (6). We herein present
two cases of encephalopathy with CAA, one with a clinical

course of Alzheimer’s disease (AD) modified by CAArelated inflammation, and another with atypical initial manifestations of CAA. We describe the findings with an emphasis on positron emission tomography (PET) imaging with
11
C-Pittsburgh compound B ( 11 C-PiB ) and 18 Ffluorodeoxyglucose (18F-FDG).

Case Reports
Case 1
A 72-year-old man presented with hypertension and a history of cognitive decline that manifested at the age of 65
and gradually progressed until he was 71 years old, when it
accelerated. His caregiver described that he suffered from
memory disturbances; for example, he was unable to find

１

Department of Neurology, The Jikei University School of Medicine, Japan, ２Department of Neurology, Tokyo Metropolitan Geriatric Hospital,
Japan, ３Department of Radiology, The Jikei University School of Medicine, Japan, ４Department of Neurology, Saiseikai Kurihashi Hospital,
Japan, ５Department of Neuropathology, The Jikei University School of Medicine, Japan, ６Department of Diagnostic Radiology, Tokyo Metropolitan Medical Center of Gerontology, Japan, ７Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan and ８The Jikei
University School of Nursing, Japan
Received for publication September 8, 2013; Accepted for publication March 4, 2014
Correspondence to Dr. Renpei Sengoku, renpei_sengoku@tmghig.jp

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Intern Med 53: 1997-2000, 2014

DOI: 10.2169/internalmedicine.53.1731

Figure 1. MRI and PET scans of Case 1. A: Brain MRI showed cortical and subcortical microbleeds on T2*WI, predominantly in the dorsal portion of the bilateral temporo-parieto-occipital
lobes. B: Axial brain MRI T2*WI exhibited a high-intensity area (HIA) in the right temporo-parietooccipital white matter with edema. C: 11C-PiB-PET showed accumulation in the fronto-parieto-temporal lobe and precuneus in an AD-like pattern. D: 18F-FDG-PET revealed hypometabolism in the
right temporo-parieto-occipital lesion.

his way home after trips outside. He was admitted to our
hospital after exhibiting wandering behavior for one month.
An examination revealed acute progressive dementia and
spatial disorientation. He became disinhibited, urinated on
the ward, and removed his intravenous drip soon after insertion. His plantar responses were flexor bilaterally, and there
were no extra-pyramidal signs. The patient’s Mini-Mental
State Examination score was 16/30. He had been taking 50
mg atenolol and 5 mg amlodipine for hypertension and 5
mg pravastatin for several years. His cerebrospinal fluid
(CSF) cell counts and protein and glucose levels were
within normal ranges. The patient’s brain magnetic resonance imaging (MRI) scan taken on admission showed multiple cerebral microbleeds on T2*WI, predominantly in the
dorsal portion of bilateral temporo-parieto-occipital lobes
(Fig. 1A). T2*WI revealed a high-intensity area (HIA) in the
right temporo-parieto-occipital white matter with edema
(Fig. 1B). An excisional biopsy from the right parietooccipital lobe was performed. A neuropathological examination revealed severe amyloid deposits in the cortical and lep-

tomeningeal blood vessel walls (Fig. 2). This specimen revealed quite a few neurofibrillary tangles and neuropil
threads and numerous senile plaques (Fig. 2). An inflammatory perivascular infiltrate was also observed (Fig. 2). He
was given intravenous steroid pulse therapy and dexamethasone. HIAs improved on T2*WI and fluid-attenuated inversion recovery (FLAIR) imaging, although irreversible
changes remained. Static emission data were acquired for
45-51 min and 40-70 min after intravenous bolus injections
of 18F-FDG and 11C-PiB, respectively. 11C-PiB-PET accumulated in the fronto-parieto-temporal lobe and precuneus in an
AD-like pattern (Fig. 1C) (7, 8). 18F-FDG-PET revealed hypometabolism in the right temporo-parieto-occipital lesion
(Fig. 1D). The patient was homozygous for the ε4 allele of
the apolipoprotein E gene (APOE).
Case 2
A right-hand-dominant, 72-year-old man receiving hemodialysis for membranous nephropathy noticed an inability to
write his address correctly one day after hemodialysis. He

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Intern Med 53: 1997-2000, 2014

DOI: 10.2169/internalmedicine.53.1731

Figure 2. Neuropathological findings in Case 1. A: Brain biopsy specimen: immunocytochemistry for β-amyloid revealed
severe amyloid deposits in the cortical and leptomeningeal
blood vessel walls (scale bar=500 μm). B: Hematoxylin and Eosin staining showed thickening and hyalinization of the subarachnoid and intracortical blood vessels (scale bar=100 μm).

reported that he could not understand his own speech in
Japanese. Interestingly, he tried to speak in English, and he
could not understand what he said. A neurological examination revealed sensory aphasia. His systolic blood pressure
was 190 mmHg. The patient’s serum blood urea nitrogen,
creatinine, and uric acid levels were 72 mg/dL, 12.8 mg/dL,
and 8.5 mg/dL, respectively. His CSF laboratory values
were 2.6 white blood cells/mm3, 147 mg/dL protein, and 52
mg/dL glucose, and his CSF amyloid β1-42 protein level
was <25 pmol/L. The patient’s brain MRI showed HIA in
the left temporal cortex on FLAIR (Fig. 3A). There was no
HIAs on diffusion-weighted imaging. SWI revealed lowintensity areas in these regions and in the subarachnoid
space (Fig. 3B). He received antihypertensive treatment
without steroids or immunosuppressive drugs, and his symptoms completely resolved. A subsequent MRI revealed no
HIA, and posterior reversible encephalopathy syndrome
(PRES)-like changes were observed in the superior temporal
gyrus. PET was performed to detect amyloid deposits 10
months after onset. 11C-PiB-PET showed focal uptake in the
left temporal lobe (Fig. 3C). The regional uptake lesion observed on amyloid PET imaging corresponded to subarachnoid hemosiderosis and microbleeds, especially in the cortical and subcortical area of the left temporal lobes. We suggest that this focal uptake lesion was indicative of amyloid
angiopathy. The low 18F-FDG uptake was not in an AD-like
distribution; rather, it was only present in the left temporal
region (Fig. 3D).

Discussion
We presented two cases of encephalopathy with CAA,

one with a clinical course of AD modified by CAA-related
inflammation, and another with atypical initial manifestations of CAA. The symptoms leading to admission were
acute encephalopathy associated with CAA as demonstrated
by 11C-PiB-PET and MRI. One case was neuropathologically
confirmed following a brain biopsy. These two cases suggest
that CAA encephalopathy might be mediated by underlying
inflammation and shares similar features with PRES.
In case 1, AD had been diagnosed two years previously.
An MRI revealed numerous microbleeds, and the patient’s
brain biopsy showed senile plaques (AD pathology) with
perivascular inflammatory changes. The specimen also exhibited fibrinoid necrosis of a parenchymal arteriole. PET
showed a remarkable AD-like pattern of 11C-PiB and 18FFDG uptake. Case 1 was homozygous for APOE ε4, and
steroids and immunosuppressive therapy were partially effective. Given the above findings, this case was considered
to involve CAA-related inflammation (2, 4). The pathogenesis of CAA in case 1 apparently involved vasogenic edema
and ischemic changes or gliosis associated with underlying
AD pathology.
Case 2 presented with acute onset sensory aphasia coexisting with unstable hypertension secondary to chronic renal failure. A MRI scan showed HIA in the left superior
temporal gyrus on T2*WI, and apparent diffusion coefficient
mapping revealed vasogenic edema. SWI detected many microbleeds in the area corresponding to the lesion observed
on FLAIR/T2WI. Although the investigations showed mild
11
C-PiB accumulation and focal hypometabolism atypical
AD, 11C-PiB uptake was observed in lesions with microbleeding, such as those in the left superior temporal
gyrus. We considered the following in differential diagnoses:
hypertensive vasculopathy, vascular malformation, PRES,
and CAA. Brain microbleeds associated with hypertensive
vasculopathy tend to be localized in the basal ganglia, internal capsule, brain stem, and cerebellum, whereas those associated with CAA are generally smaller with a posterior lobar
predilection (6). Because we did not perform conventional
digital subtraction angiography (9), we cannot completely
rule out a vascular malformation; however, we do not
strongly suspect this disorder. The patient’s sensory aphasia
fully resolved after antihypertensive therapy, and steroids
were unnecessary. Although the patient’s hypertensive state
influenced the clinical symptoms, the findings of 11C-PiB
PET and SWI were suggestive of CAA. Similarly, the presence of cortical or subcortical microbleeds and old subarachnoid hemorrhage on MRI supported a diagnosis of
CAA (8). The important point from this case is that the 11CPiB uptake lesions corresponded with the microbleeds observed on SWI scans. The patient’s sensory aphasia likely
occurred due to the lesion in the left superior temporal
gyrus. His symptoms might have been caused by PRES-like
focal vasogenic edema near vessels that were made vulnerable by amyloid deposition. Some authors suggest that amyloid angiopathy can alter vascular reactivity, leading to
dysautoregulation and altered blood-brain barrier integ-

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DOI: 10.2169/internalmedicine.53.1731

Figure 3. MRI and PET scans of Case 2. A: Brain MRI showed HIA in the left temporal cortex on
FLAIR. B: SWI revealed low-intensity areas representing old hemorrhages in these regions and the
subarachnoid space. C: 11C-PiB-PET showed focal uptake in the left temporal lobe. D: Low 18F-FDG
uptake was not in an AD-like distribution; rather, it was only observed in the left temporal region.

rity (10).
In conclusion, the 11C-PiB PET findings in these two
cases supported diagnoses of CAA encephalopathy. We suggest that amyloid imaging is a useful diagnostic tool for investigating atypical clinical courses of patients with CAA.
The authors state that they have no Conflict of Interest (COI).

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