LETTER TO THE EDITORS

Cerebral amyloid angiopathy revealed by rapidly progressingleptomeningeal lesions

Armelle Chouraki • Adeline Rollin-Sillaire • Vincent Deramecourt •

Fahed Zairi • Emilie Le Rhun • Charlotte Cordonnier •

Christine Delmaire • Claude-Alain Maurage • Florence Pasquier

Received: 10 February 2014 / Revised: 13 May 2014 / Accepted: 14 May 2014

� Springer-Verlag Berlin Heidelberg 2014

Dear Sirs,

Cerebral amyloid angiopathy (CAA) causes intracere-

bral haemorrhages and is associated with cognitive

impairment and Alzheimer’s disease. In autopsy series, the

estimated prevalence of CAA is high (20–40 % in non-

demented subjects; 50–60 % in dementia) [1]. Brain

magnetic resonance imaging (MRI) usually reveals cere-

bral microbleeds (CMB), white matter (WM) changes,

lobar haemorrhages and silent acute cortical ischemic

lesions. Convexity subarachnoid haemorrhage (cSAH) and

cortical superficial siderosis (cSS) have been recently

described [2]. Rarer, inflammatory forms (CAAi) are

characterized by the presence of extensive WM and men-

ingeal lesions [3].

Here, we report the case of a 64-year-old woman suf-

fering from a non-inflammatory CAA presenting with an

MRI suggestive of leptomeningitis in the clinical context of

partial seizure.

The patient was referred to our hospital because of

repeated and stereotyped episodes of numbness in the

tongue with dysarthria followed by progressive paresthesia

and hypoesthesia of the left arm and lower facial area in

the last 3 days. Examination revealed epicritic hypoaes-

thesia and slight hypopallesthesia of the left hemibody.

Partial ictal manifestations were confirmed by a right

temporal epileptic focus on electroencephalography. Initial

brain MRI showed an aspect of leptomeningitis in the right

frontal (Fig. 1a, b) and cSS in the right central sulcus

(Fig. 1c). Angio-MRI was normal. Three cerebrospinal

fluid (CSF) tests showed only a slight hyperproteinorachia

(0.7 g/L). All tests in search of an inflammatory, infectious,

neoplastic or a paraneoplastic cause were negative except

for a positron emission tomography showing uptake of two

small axillary lymph nodes (benign). Twelve days after

admission, MRI showed a bilateral extension of the pial

lesions (Fig. 1d, e, f) still progressing one month after

A. Chouraki � A. Rollin-Sillaire (&) � V. Deramecourt �F. Zairi � E. Le Rhun � C. Cordonnier � C. Delmaire �C.-A. Maurage � F. Pasquier

Univ Lille Nord de France, UDSL, 59000, Lille, France

e-mail: adeline.rollin@CHRU-lille.fr

A. Chouraki � A. Rollin-Sillaire � V. Deramecourt � F. Pasquier

Laboratory of Excellence DISTALZ, Memory Clinic, EA 1046,

Lille University Hospital, 59000 Lille, France

V. Deramecourt � C.-A. Maurage

Department of Pathology, Lille University Hospital, 59000 Lille,

France

F. Zairi

Department of Neurosurgery, Lille University Hospital,

59000 Lille, France

E. Le Rhun

Neurooncology, Lille University Hospital, 59037 Lille, France

E. Le Rhun

Department of Medical Oncology, Oscar Lambret Center,

59020 Lille, France

C. Cordonnier

Stroke Unit, Neurology Department, Lille University Hospital,

59000 Lille, France

C. Delmaire

Department of Neuroradiology, Lille University Hospital,

59000 Lille, France

123

J Neurol

DOI 10.1007/s00415-014-7378-8

admission (Fig. 1g, h, e). The left occipital region was

biopsied. Histological examination revealed Ab-positive

CAA with intense leptomeningeal and cortical perivascular

microglial activation without lymphocytic or granuloma-

tous angiitis (Fig. 2).

This case illustrates an unusual presentation of CAA with

partial seizures, corresponding to Transient Focal Neuro-

logical Symptoms and Signs (TFNSSs), and rapidly pro-

gressive leptomeningeal MRI abnormalities. When CAA is

revealed by leptomeningeal abnormalities, it is usually

Fig. 1 Successive MRI done by the patient. First row: MRI on

admission, a Right frontal leptomeningeal hyperintensities on FLAIR

sequence. No corresponding hypointensities in T2* or hyperintensi-

ties on T1 were observed making the possibility of a large cSAH

unlikely. b Gadolinium contrast enhancement of the right frontal

meninges; c Cortical superficial siderosis of the right central sulcus

evoking cSS. Second row Second MRI. d, e Progression of the FLAIR

hyperintensities to the right frontal, temporal, parietal and occipital

areas and appearance of hyperintensities in the left parietal and

occipital regions. f Progression of the Gadolinium-enhanced menin-

geal lesions. We considered this aspect and its progression as linked

to a possible inflammatory process caused by the microglial activation

detected at the biopsy possibly provoked by the amyloid deposits in

the vessels walls. Third Row MRI one month after admission. g, h, iProgression of the leptomeningeal lesions

J Neurol

123

associated with angiitis, clinically characterized by a con-

fusional state or an impaired level of consciousness, a rapidly

progressive cognitive impairment, sometimes seizures,

headaches and/or hallucinations [3–5]. Brain MRI shows

WM hyperintensities, sometimes with multiple CMB, usu-

ally without leptomeningeal enhancement [3, 4, 6, 7]. A

cerebro-meningeal biopsy shows angiodestructive, some-

times granulomatous inflammation, infiltrated by lympho-

cytes and multinucleated giant cells [3], absent here.

However, we noticed intense microglial activation in the

leptomeninges and perivascular spaces which has been

reported in patients with sporadic severe CAA and lobar

cerebral haemorrhage, multiple cortical infarction/CMB and

interpreted as a reaction towards the amyloid deposits in the

vessels walls [8]. Nonetheless, we cannot totally exclude

CAAi since only one biopsy was performed and has maybe

missed the characteristic inflammation.

TFNSSs constitute the second most commonly descri-

bed clinical presentation of CAA, characterized by ste-

reotypical episodes of progressive sensory symptoms,

partial motor seizures and visual symptoms mimicking

aura. They could be related to the haemorrhagic compo-

nents of CAA (CMB, cSS and cSAH) [1].

Lastly, the main CAA-related MRI findings were absent.

Our patient did not meet the Boston criteria for CAA.

However, cSS was observed and matched the recently

adopted MRI correlates of sporadic CAA [2]. A diagnosis

of CAA becomes possible when applying the revised

Boston criteria [9, 10].

The clinical and neuroradiological presentations of CAA

are heterogeneous and emphasize the need to update the

definition of this condition. It would be interesting to test

the diagnostic value of combining clinical features with

MRI markers and CSF biomarkers (such as Ab40) and

compare these improved criteria with the neuropathologi-

cal examination.

Conflicts of interest On behalf of all authors, the corresponding

author states that there is no conflict of interest.

Ethical standard The manuscript submitted for publication has

been performed in accordance with the ethical standards laid down in

the 1964 Declaration of Helsinki and its later amendments.

References

1. Charidimou A, Gang Q, Werring DJ (2012) Sporadic cerebral

amyloid angiopathy revisited: recent insights into pathophysiology

and clinical spectrum. J Neurol Neurosurg Psychiatry 83:124–137

2. Linn J, Herms J, Dichgans M, Bruckmann H, Fesl G, Freilinger T

et al (2008) Subarachnoid hemosiderosis and superficial cortical

hemosiderosis in cerebral amyloid angiopathy. AJNR Am J

Neuroradiol 29:184–186

3. Scolding NJ, Joseph F, Kirby P, Mazanti I, Gray F, Mikol J et al

(2005) Ab related angiitis: primary angiitis of the central nervous

system associated with cerebral amyloid angiopathy. Brain

128:500–515

4. Chung KK, Anderson NE, Hutchinson D, Synek B, Barber PA

(2011) Cerebral amyloid angiopathy related inflammation: three

case reports and a review. J Neurol Neurosurg Psychiatry

82:20–26

Fig. 2 Brain and meningeal

biopsy of the left occipital

region. a Brain and meningeal

biopsy stained with

hematoxylin-eosin reagent.

Note the thickened,

hypercellular aspect of the pial

mater (asterisk). The

leptomeningeal arteriolar walls

were eosinophilic and laminated

(arrows). b Immunostaining of

Ab pathological staining of the

leptomeningeal and cortical

arteriolar walls.

c Immunostaining of CD68,

revealing infiltration of the pial

matter by macrophages.

d Immunostaining of CD3,

revealing the presence of only a

few scattered T lymphocytes.

Scale bar 50 l

J Neurol

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5. Maia LF (2007) Mackenzie Ian R.A., Feldman HH. Clinical

phenotypes of Cerebral Amyloid Angiopathy. J Neurol Sci

257:23–30

6. Kinnecom C, Lev MH, Wendell L, Smith EE, Rosand J, Frosch

M et al (2007) Course of cerebral amyloid angiopathy-related

inflammation. Neurology 68:1411–1416

7. Eng JA, Frosch MP, Choi K, Rebeck W, Greenberg SM (2004)

Clinical manifestations of cerebral amyloid angiopathy-related

inflammation. Ann Neurol 55:250–256

8. Yamada M, Itoh Y, Shintaku M, Kawamura J, Jensson O,

Thorsteinsson L et al (1996) Immune reactions associated with

cerebral amyloid angiopathy. Stroke 27:1155–1162

9. Smith EE, Greenberg SM (2003) Clinical diagnosis of cerebral

amyloid angiopathy: validation of the boston criteria. Curr Ath-

eroscler Rep 5:260–266

10. Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M

et al (2010) Prevalence of superficial siderosis in patients with

cerebral amyloid angiopathy. Neurology 74:1346–1350

J Neurol

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