Clinical Neurology and Neurosurgery 128 (2015) 17–24

Contents lists available at ScienceDirect

Clinical Neurology and Neurosurgery
journal homepage: www.elsevier.com/locate/clineuro

Review

Subarachnoid hemorrhage in systemic lupus erythematosus:
Systematic review and report of three cases
Ramon Torné a,b,∗ , Ana Rodríguez-Hernández a , Teuddis Bernard a , Fuat Arikan Abelló a,b ,
Jordi Vilalta Castan a,b , Juan Sahuquillo a,b
a
b

Department of Neurosurgery, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain

a r t i c l e

i n f o

Article history:
Received 30 June 2014
Received in revised form
29 September 2014
Accepted 26 October 2014
Available online 4 November 2014
Keywords:
Fusiform aneurysm
Multiple aneurysms
Subarachnoid hemorrhage
Systemic lupus erythematous
Fusiform aneurysm

a b s t r a c t
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disorder of multifactorial etiology with a
broad range of clinical manifestations. Cerebral disorders such as psychosis, seizures and cerebrovascular
accidents are commonly described in SLE patients. Subarachnoid hemorrhage (SAH) presents a higher
incidence than in the general population. Saccular aneurysms are the most frequent cause, but uncommon
forms of SAH had been repeatedly reported in SLE patients. Through three case examples we outline these
uncommon patterns, which we hypothesized, might be responsible for the higher incidence of SAH in
SLE patients.
Methods: We present three patients previously diagnosed with SLE, who suffered a SAH and we perform
a systematic literature review.
Results: All three cases presented with a Fisher grade IV bleeding. One harbored a distal middle cerebral
artery aneurysm, another had multiple aneurysms, and the youngest patient had no findings on the
cerebral angiography. A focal vasculitic process seemed most likely responsible for the two aneurismal
cases. The angiography negative case was attributed to severe SLE systemic complications and had an
unexpected bad outcome. Literature review yielded 39 previously reported cases.
Conclusions: The uncommon SAH patterns make etiological diagnosis challenging. Management can also
be daunting due to both local and systemic consequences of SLE. Awareness of these uncommon patterns,
management challenges, and higher likelihood of bad outcomes may help physicians dealing with this
disease. Further research to unveil the mechanisms behind it is granted to fully understand SAH in SLE
patients.
© 2014 Elsevier B.V. All rights reserved.

Contents
1.
2.

3.
4.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Literature review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
Cases report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Ilustrative cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Case 1: Distal fusiform aneurysm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
History and examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abbreviations: ACA, anterior cerebral artery; AICA, anterior inferior cerebellar artery; CNS, central nervous system; CT, computed tomography; EVD, external ventricular
drain; GCS, Glasgow Coma Scale; ICG, indocyanine green; MRSA, methicillin-resistant staphilococcus; MCA, middle cerebral artery; mRS, modified rankin score; PCoA,
posterior communicating artery; SAH, subarachnoid hemorrhage; SLE, systemic lupus erythematous.
∗ Corresponding author at: Department of Neurological Surgery, Vall d’Hebron Hospital, Universitat Autònoma de Barcelona, Paseo Vall d’Hebron, 119-129, Barcelona, CP
08035, Spain. Tel.: +34934894589
E-mail address: ramtorne@me.com (R. Torné).
http://dx.doi.org/10.1016/j.clineuro.2014.10.018
0303-8467/© 2014 Elsevier B.V. All rights reserved.

18

5.

6.
7.

8.

R. Torné et al. / Clinical Neurology and Neurosurgery 128 (2015) 17–24

4.2.
Diagnostic studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Case 2: Angiographically negative SAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.
History and examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Case 3: Multiple aneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.1.
Etiology of SAH in SLE patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.2.
Management strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.3.
Clinical outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Author contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease
characterized by complex-mediated lesions of blood vessels in
multiple body organs, leading to different types of vascular complications. Incidence rate of SLE is quoted between 1 and 10/100,000
per year depending on the population studied (sex, ethnicity, geographical location and age). The incidence is markedly higher in
non-Caucasian population [1]. Immune complexes that cause vasculitis in Lupus may contain DNA and Anti-DNA antigens, or Ro
and Anti-Ro antigens and usually affect small vessels; medium and
large vessels are only exceptionally affected [2]. The central nervous system (CNS) can be affected in 25–50% of SLE patients mostly
due to seizures, psychosis, and cerebrovascular accidents [3]. Incidence of subarachnoid hemorrhage (SAH) is considered higher in
SLE patients than in the general population, with a rate of 49.4 vs.
10.2 per 100,000 person-years [4]. However, the underlying cerebral vasculitis described in SLE does not justify the pathophysiology
of all the SAH cases, and the causes leading to this increased incidence remain unclear [5,6].
In this manuscript, we review case reports of SAH in SLE patients
found in the medical literature. While we do not have enough
information to assess the causes of SAH in SLE patients, we hypothesized that there would be a few clinical identifiable patterns
whose detailed description may help improving diagnostic and
management strategies of these complex cases. Bad prognostic
spontaneous SAH, multiple aneurysms and fusiform or uncommon
aneurysm might reflect the characteristic behavior of SAH in SLE.
We also review our own experience with SAH in SLE patients and
report three additional cases that we managed in our department.
2. Methods
2.1. Literature review
We have conducted a systematic literature search in PubMed
and MedLine using “systemic lupus erythematosus” and “subarachnoid hemorrhage” as key words and free text searches. We limited
language to English, French and Spanish and publication period
from January 1980 to December 2013. Abstracts of identified references were initially screened and full publications of potentially
relevant articles were obtained for further examination. The references of each included report were also screened for additional
manuscripts. The initial search strategy identified 25 manuscripts.
We eliminated 9 of them that were not written in English, French
or Spanish. Full text of the remaining 16 articles were obtained
and 4 of them were excluded for reporting other causes of SAH
(such as traumatic vertebral dissection) not corresponding with
aneurysmatic or angio-negative SAH. References of the remaining

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12 articles yielded 6 extra manuscripts meeting our search criteria. Out of them, one article by a Japanese author reported two
new cases in English and reviewed 55 more from the Japanese literature. Detailed data for the two cases reported in English was
extracted but original data for the remaining 55 cases was either
incomplete or written in Japanese and therefore, was excluded.
Overall, we found 18 unique articles reporting SAH in 39 SLE
patients.

2.2. Cases report
Between January 1996 and December 2013, we identified 3
patients previously diagnosed with SLE out of the 641 who were
admitted with non-traumatic SAH and prospectively collected in
our service database. Their demographic features, clinical presentation, management strategy and outcomes were thoroughly
reviewed.
Clinical outcomes were assessed using the modified Rankin
Score (mRS). Good outcomes were defined as a final mRS score of
0–2, and poor outcomes were defined as a final mRS greater than
2. Improvement was defined as a decrease in mRS score (change
in the mRS of less than or equal to zero), and deterioration was
defined as an increase in mRS score (change in the mRS of greater
than zero).

3. Results
To the best of our knowledge, 39 patients with SLE and SAH
have been described in English, Spanish or French articles. Table 1
summarizes the main features, treatment strategy and outcomes of
all these reported cases. Eleven cases presented an angiographically
negative SAH and 5 out of those 11 had a bad outcome (4 deaths, 1
severe disability). Out of the remaining 27 reported cases, all with
a confirmed aneurysmatic SAH, 6 patients presented with multiple
aneurysms and 6 had a either a fusiform aneurysm, an aneurysm
in an atypical location or both.
The analysis of this search revealed that three main patterns
have been consistently reported as leading to SAH in SLE patients.
First, distal fusiform aneurysms with aberrant morphology in
uncommon locations [7,8]; second, multiple saccular aneurysms
[9]; and third, angiographically negative SAH with an unexpected
bad prognosis [10].

3.1. Ilustrative cases
Each of these cases illustrate one of the aforementioned 3 main
patterns usually responsible for SAH in SLE patients.

R. Torné et al. / Clinical Neurology and Neurosurgery 128 (2015) 17–24

19

Table 1
Summary of main SAH features, SLE activity, management strategy and outcomes of previously reported cases.
Case reports

Asian
patients

No. of
patients

Type of aneurysm

Location

Systemic disease

Treatment

Outcome

Asai et al. (1989)

Yes

1

Multiple, saccular

PCoA, BA, ACA
aneurysm

All clipped except
the BA aneurysm

Dead

Atanes et al. (1989)

No

1

Multiple, saccular

Baizabal Carvallo
et al. (2007)

No

10

5 aneurysms, 5
negative SAH

Left ACA, Left PCoA
aneurysms
4 MCA, 1 PCoA

Trasnmural
angeitis by
pathology
Active SLE

No neurological
deficits
1 DSA negative SAH
and 3 patients with
aneurysm died, the
other survived

Brah et al. (2012)

No

1

Multiple, fusiform

Steroids and
ciclophosphamide
2 aneurysms were
not treated, 2
clipped, 1
endovascular
embolization
Embolization

Gillard et al. (2002)

No

1

Multiple, fusiform

NA

Hashimoto
et al. (1986)
Kelley et al. (1980)

Yes

2

Left SCA was
clipped, ACA and
MCA aneurysms
were not treated.
Both clipped

No

Mimori et al. (2000)

4 with active SLE

SCA and
lenticulostriated
arteries
Left SCA, fusiform
ACA, saccular MCA

Active SLE

Saccular

BA, ACA aneurysms

Active SLE

1

Fusiform aneurysm

PCoA aneurysm

Yes

10

4 saccular, 4
Spontaneous SAH,
an 2 with not
angiography done

MCA, 2 PCoA, 1
ACA aneurysm

Transmural
angeitiis by
pathology
5 with active SLE

Nagayama et al.
(1989)
Nakai et al. (2000)
Lim et al. (2013)
Owada et al. (2009)

Yes

1

Saccular

Basilar artery

No SLE activity

Yes
Yes
Yes

1
1
2

Saccular
Blister Aneurysm
1 Multiple
aneurysms, 1
saccular aneurysm

Refai et al. (2008)

No

1

Spontaneous SAH

Left SCA
ICA
Bilateral MCA and
Carotid aneurysm.
One PCoA
aneurysm
No

Rozet et al. (2004)
Sakaki et al. (1990)

Yes
Yes

1
2

Saccular
Saccular

PICA
MCA, ACA

Sánchez-Ojanguren
et al. (1999)
Segura et al. (1998)

No

1

Saccular

ACA aneurysm

No

1

Spontaneous SAH

Tang et al. (2011)

Yes

1

Multiple fusiform
dilatations

Active SLE

Medical treatment
with steroids

Dead

1 Hemiplegic, 1
without deficits
Dead

3 clipped, and 1
patient died before
a surgical
treatment could be
done
Clipped

7 Deaths, 3
survived

No SLE activity
NA
Active SLE (both)

Embolization
Stents with coiling
Both patients were
clipped

Good recovery
Dead
Both good recovery

Active SLE

Steroids

Active SLE
Transmural
angeiitis by
pathology in both
cases
Active SLE

Clipped
1 Clipped, 1
conservative
treatment

No neurological
deficits
Dead
1 good recovery,
the other was dead

Clipped

Dead

No aneurysm in
two angiographies

Active SLE

No neurological
deficits

Multifocal (ICA,
MCA, . . .)

Active SLE

Steroids, gamma
globulins and
plasmapheresis
Conservative
treatment

Left hemiplegia

Gait disturbance

Abbreviations: PCoA: posterior communicating artery; BA: basilar artery; ACA: anterior cerebral artery; SLE: Systemic Lupus Erythematosus; MCA: middle cerebral artery;
DSA: digital substraction angiography SCA: superior cerebellar artery; EC-IC: extracranial-to-intracranial, ICA: internal carotid artery; PICA: posterior inferior cerebellar
artery; NA: not available.

4. Case 1: Distal fusiform aneurysm

normal caliber and course. No other vascular abnormalities were
observed.

4.1. History and examination
A 34-year-old man complained of sudden severe headache and
left-sided hemihypoesthesia. He had been diagnosed with SLE six
months prior, and was being treated with prednisone, azathioprine
and hydrochloroquine for his disease. On the neurological exam, he
was alert and oriented. He had left hemibody hypoesthesia but no
motor deficit was observed.
4.2. Diagnostic studies
Head CT scan revealed a right-sided 25 cm3 parietal hemorrhage with cortical SAH (Fig. 1a). CT angiography showed a 5 mm
fusiform aneurysm of a right middle cerebral artery (MCA) M4 segment (Fig. 1b). The rest of the distal MCA and its branches had

4.3. Management
A right fronto-parietal craniotomy was performed and a wide
dural opening exposed a tortuous, thickened angular artery with a
5 mm fusiform aneurysm (Fig. 1c and d). The aneurysm morphology prevented it from being occluded with regular neck clipping
and therefore it was trapped. The inflow and outflow ends of the
parent artery were too small and friable to suture, therefore, endto-end re-anastomosis or any other direct revascularization options
were discarded. The intraparenchymal hematoma was evacuated
through a corticotomy in the parietal lobe to relieve the mass effect.
A postoperative angiogram demonstrated complete exclusion
of the aneurysm and adequate filling of the entire right MCA territory despite the M4 occlusion (Fig. 1e). Histological examination

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R. Torné et al. / Clinical Neurology and Neurosurgery 128 (2015) 17–24

Figure 1. Imaging studies and intraoperative pictures of case 1. A: Preoperative brain CT-scan (axial view) showing the right parietal hematoma. B: Preoperative brain CT
angiography (3D reconstruction) revealing a distal MCA M4 segment fusiform aneurysm (arrow). C: Postoperative imaging. Right internal carotid injection angiogram (lateral
view) demonstrating complete occlusion of the aneurysm (arrow). D: Intraoperative picture showing the subarachnoid blood around the aneurysm prior to beginning of the
dissection. E: Intraoperative picture showing the excluded and resected aneurysm that was sent to pathology for further study.

of the aneurysm wall demonstrated an intimal layer thickening,
severe fragmentation and dissapearence of elastic fibers suggesting a likely previous injury that originated the pseudoaneurysm.
No fibrinoid necrosis was seen. Neither lymphocytes nor plasma

cells suggesting active vaculitis were identified. Postoperatively,
the patient’s hyposensitivity in the left side improved and he was
discharged on postoperative day 11 with a modified Rankin Score
(mRS) of 1.

R. Torné et al. / Clinical Neurology and Neurosurgery 128 (2015) 17–24

21

hospitalization floor where she slowly recovered from a myopatic
tetraparesis and bradypsychia secondary to the intraventricular
hemorrhage. After spending a total of six months at our institution,
she was transferred to a rehabilitation facility with a mRS of 4. Nineteen months after discharge she had improved to mRS 3. During a
reagudization of her SLE and a new severe drop of her platelet count
to 15,000, she presented with another intraventricular hemorrhage
and sepsis that finally led to her exitus.
6. Case 3: Multiple aneurysms

Figure 2. Imaging studies of case 2. A: Brain CT scan (axial view) showing the initial
Fisher IV subarachnoid hemorrhage.

5. Case 2: Angiographically negative SAH
5.1. History and examination
A 24-year-old woman was transferred to our hospital after a
sudden severe headache and a generalized seizure. At the time of
onset, she was admitted in another hospital were she was being
studied for fever, nephritis, hypertension, arthritis and pleuropericarditis that finally led to a SLE diagnosis. Once in our hospital,
the neurological exam revealed that she was disoriented both in
time and space. No other neurological deficits were present at
the time, but she developed severe agitation during the next few
hours finally prompting orotracheal intubation for management.
Head CT scan revealed a Fisher IV subarachnoid hemorrhage with
an incipient ventricular dilatation (Fig. 2a). A four-vessels cerebral
angiography revealed an infudibular origin of the right AICA as the
only finding. But no aneurysms, arteriovenous malformations or
dural arteriovenous-fistula were observed. Angiography revealed
no findings consistent with vasculitis.
5.2. Management
Subsequent CT imaging confirmed the onset of hydrocephalus,
which prompted placement of an external ventricular drain. The
patient also presented a severe autoinmune leucopenia and thrombopenia (as low as 10,000 platelets) that was medically treated
with steroids and danazol. Ten days after being admitted in the ICU,
she developed a Corynebacterium sp ventriculitis and a methicillinresistant Staphilococcus (MRSA) sepsis. These caused a severe
worsening of her neurological status. Despite proper placing verified by CT, the EVD stopped working and required revision. In the
setting of low platelet count, the revision provoked an intraventricular hemorrhage that slowly cleared over the course of two weeks.
However the patient did not tolerate the closure of the ventricular
drainage and a definitive ventriculo-peritoneal shunt was placed.
Three months after her admission, she was transferred to a regular

The family of a 55-year-old man with a history of SLE, hypertension, smoking and alcohol abuse called the emergency services
because he had suffered a sudden severe headache followed by a
generalized seizure and a loss of consciousness. The emergency services found him in a Glasgow Coma Scale (GCS) 7 (eyes 1, verbal
1, motor 5); proceeded to orotracheal intubation and transfer to
our center. Head CT scan revealed a Fisher IV subarachnoid hemorrhage with a 50 mm right frontal hematoma related to the genu of
the corpus callosum with no midline shift or mass effect (Fig. 3a).
A cerebral angiography showed a right 13 mm Anterior Cerebral
Artery (ACA) pericallosal segment aneurysm and a 5 mm right Posterior Communicating Artery (PCoA) aneurysm (Fig. 3b).
The SAH distribution and the hematoma pointed toward the pericallosal aneurysm as responsible for the acute bleed. Considering
the distal location and the wide neck of the aneurysm, surgical management was preferred as the first therapeutic option. A bifrontal
craniotomy with a subarachnoid interhemispheric approach was
performed. The course of the distal ACA branches were followed
down the interhemispheric fissure and around the corpus callosum
until the aneurysm was exposed at the pericallosal bifurcation and
proximal control was gained. A straight 10 mm clip stacked up
with another 5 mm straight clip was placed through the aneurysm
neck. The surrounding hematoma was then evacuated. The PCoA
aneurysm was considered unruptured and occluded endovascularly in a delayed fashion. A postoperative angiogram confirmed
complete occlusion of the aneurysm and patency of the parent vessel (Fig. 3c). Initially the patient needed a ventricular drainage for
acute hydrocephalus management, but no permanent shunt was
necessary in the long term. He improved postoperatively and was
discharged home 4 weeks after admission with a mRS of 3. At the
last available follow-up, two years after the SAH, the patient had a
mRS of 1.
7. Discussion
Central nervous system (CNS) involvement in systemic lupus
erythematous (SLE) is relatively common. Almost half of the
patients suffer some kind of symptoms from CNS manifestations.
Stroke, mostly ischemic but also hemorrhagic, accounts for 15%
of CNS disease [11]. However, proof of vasculitis affecting the
intracranial vessels and justifying the incidence of stroke is rare.
Therefore, the real causes behind the CNS involvement remain
unclear. Among the hemorrhagic strokes, the higher incidence of
SAH in SLE patients is an even more intriguing matter. There are
SLE patients with a SAH due to a saccular aneurysm as it occurs in
the general population [12]. But most case reports of SLE patients
presenting a SAH do not describe this as the source of the subarachnoid bleed. Uncommon lesions like distal fusiform aneurysms
[7,9,13–16] or clinical entities like angio-negative SAH with an
unusual torpid clinical course [10,17] are frequently described
when SAH occurs in SLE. Multiple aneurysms outside the typical
branching sites, are also frequently reported as the pathological
finding in SLE patients with SAH [9,13,18–20]. Here we aim to
summarize all this literature by describing what we found to be

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the three most typical clinical scenarios reported in patients with
SAH and SLE. This tendency warrants further research that could
establish a new clinical classification for SAH in SLE patients.
7.1. Etiology of SAH in SLE patients

Figure 3. Preoperative and postoperative imaging studies of case 3. A: Preoperative
brain CT-scan (axial view) showing the right frontal hematoma abutting the genu
of the corpus callosum and subarachnoid blood in the interhemispheric cistern. B:
Right internal carotid artery angiogram, (lateral view). A 13 mm bilobulated pericallosal aneurysm and 5 mm PCoA aneurysm can be seen. C: Postoperative imaging.
Right internal carotid injection angiogram (lateral view) demonstrating complete
occlusion of both the pericallosal aneurysm and the PCoA aneurysms.

These three unusual forms of SAH affecting SLE patients point
toward an uncommon underlying physiopathology most likely
related to the systemic disease. However, the real terms of this
relationship and the reasons for the aforementioned increased SAH
incidence in SLE patients remain unclear.
Classical risk factors for SAH such as atherosclerosis and hypertension happen to be relevant complications also seen in SLE. The
treatment of SLE in the acute phases consists mostly of medical
therapy with steroids and/or cytotoxic immunosuppressants. It is
well known that these drugs can cause hypertension as a side effect
[7,8,21], which could result in aneurysm formation and rupture,
and therefore, could be one of the explanations for the higher rate
of SAH in SLE patients. This hypothesis is also supported by the
fact that higher daily steroid use (>10 mg) has been reported as an
independent risk factor for increased incidence of SAH [4,9].
Vasculitis, when present, could also influence the incidence
of SAH. Inflammation of arteries narrows the arterial lumen,
compromises cerebral blood flow, and causes a variety of
atherosclerotic-like symptoms leading to ischemia and hemodynamic stress, which have also been previously identified as
aneurysms inducers. Furthermore, focal vascultitis could be the
cause of the uncommon aneurysms in unusual locations that are
frequently described in patients with SLE [10,22–24]. However,
only three authors have been able to prove anatomopathological
findings supporting focal transmural angiitis in fusiform aneurysms
[14,19,24]. Our case #1—distal fusiform aneurysm—, represents one
of these uncommon lesions. Anatomopathological findings in our
patient revealed a pseudoaneurysm with a wall defect but without
lymphocytic infiltration, and thus an active focal vasculitic process
was ruled out. Therefore, although focal vasculitis might be a plausible explanation for the higher incidence of fusiform aneurysms
in SLE patients, the inconsistent pathology reports should make us
think of other primary and/or concomitant causes that we have
missed so far [7,8,13,16].
Multiple aneurysms seem to occur more frequently in SLE
patients. From our knowledge, only Owada et al. reviewed an
incidence of single and multiple aneurysms of 69.5% and 31.6%,
respectively, among Japanese SLE reports [10,20,25]. Saccular or
berry aneurysms would be explained by an increased incidence of
hypertension; fusiform distal aneurysms could be somehow related
to focal vasculitis; but the higher incidence of multiple aneurysms
in SLE patients lacks a plausible explanation. Unexpectedly, Akio
Asai et al. [19] found a transmural angiitis in one of the saccular aneurysms of a SLE patient harboring multiple aneuryms. We
presented a patient with multiple aneurysms (case #3) but no specimen was delivered to pathology in the surgical aneurysm and the
other one was treated with endovascular procedures. Despite the
lack of a solid evidence, the higher incidence of multiple aneurysms
in SLE patients and the eventual presence of vasculitic pathological
findings point toward a vasculitic component behind these SAH in
SLE patients.
Several cases of SLE patients and SAH without pathological findings in the angiography have been reported [26,27]. Furthermore,
most of these “angio-negative” cases rarely have a perimesencephalic blood distribution and some of them even had autopsy
confirming the absence of cerebral aneurysms [10,28]. In the general population, angio-negative SAH is thought to be of venous
origin, usually happens in older patients, has a typical perimesencefalic blood distribution, a benign clinical course and patients usually
do not rebleed [29]. Case #2 of our report is an angio-negative

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23

SAH in a very young patient. Her clinical course was extremely
complicated due to low platelet count and various systemic complications. The patient spent six months admitted in the hospital
dealing with all the consequences of what we initially thought
would be a benign angio-negative SAH. Moreover, a year and a
half later she was admitted again with another angio-negative SAH
and ended up dying from systemic complications. Previous reports
also describe an extremely high mortality rate in SLE patients with
angio-negative SAH unless the patient has a venous-like perimesencefalic bleed [10,17].

nephritis. The poor prognosis in these patients, independently of
their younger age, should be made part of the discussion in the
decision making with the family and internal medicine colleagues.
Obviously, we should achieve the best possible hematological status prior to invasive treatment.
Vasculitis when present and treatments like immunosuppressants or glucocorticoids could also influence the incidence of SAH.
It seems that in some populations, older age, high dose (>10 mg
daily) steroid intake, and previous transfusions of red blood cells
or platelets are independent risk factors for SAH [4,34].

7.2. Management strategy

8. Conclusion

Therapeutic management of SAH in these patients is not well
established and depends highly on the underlying lesion causing the bleed and on the patient’s clinical condition. The frequent
hematologic and renal complications are important comorbidities
for any kind of invasive procedure. The intraventricular hemorrhage described in patient #2 is a clear example what should have
been a low risk procedure such as an EVD revision, turned into a
serious complication due to an extremely low platelet count.
When an aneurysm is present and requires occlusion, both surgical and endovascular options are challenging [30]. Unexpectedly
fragile intracranial arterial walls due to multifocal spread disease
make them difficult to handle and could prompt a rupture during
both surgical and endovascular procedures. Due to a non-saccular
morphology, the aforementioned fragility and uncommon locations [7] these aneurysms are rarely amenable to direct clipping
and instead require occlusion techniques like trapping and excision
with or without revascularization. On top of that, in case a bypass is
needed, selecting the appropriate donor and recipient vessels can
be challenging due to the general distribution of the disease [31]. In
Case #1, the aneurysm was distal enough to allow trapping of the
MCA M4 segment without needing a revascularization bypass. In
truth, the inflow and outflow ends of the vessel seemed too fragile
and friable to even attempt re-anastomosis. Collateral circulation
took over and the patient did not experience any new deficits from
his arterial occlusion. However, neurosurgeons should be aware
of these difficulties and plan several alternative bypasses in case
a revascularization therapy is needed either as a primary or as a
rescue therapy.
The development of saccular aneurysms in SLE patients may be
unrelated to their systemic disease and account instead for a defect
in the arterial wall just as it occurs in the general population [32,33].
The rupture, on the other hand, might be closely related to the SLE
activity mainly due to complications like arterial hypertension secondary to active vasculitis. Therefore, in order to prevent SAH in
SLE patients, not only the treatment of active SLE and its systemic
complications is important but also a strict control of cardiovascular risks factors (smoking, hypertension, hypercholesterolemia)
must be a core part of management strategy.

SAH is an infrequent but important manifestation of cerebral
involvement in SLE and neurosurgeons should be aware of the special characteristics and technical difficulties associated with these
patients. The angiography should be carefully reviewed looking for
fusiform aneurysms in uncommon locations and searching all the
vascular territories to rule out multiple aneurysms.
SLE patients might present SAH with no evidence of an
aneurysm. Frequent systemic SLE complications like extremely low
platelet count, or treatment related complications due to corticotherapy could be held accountable for these “angio-negative”
forms of SAH. The scarce literature about it and the lack of definitive
evidence prevent us from inferring a causality relationship. However, bad outcome of this form of “angio-negative” SAH may be
expected and should be regarded by the physician.
Strict control of cardiovascular risk factors (smoking, hypertension, hypercholesterolemia), hematologic complications, and SLE
reactivations could improve the outcome in these patients and
should therefore be made a management priority.
This study of SAH in SLE patients is descriptive and does not
allow us to explain their unique morphology and etiology. However, we provide a simple way of classifying the uncommon clinical
patterns that are usually faced when dealing with SAH in a SLE
patient. The real causes underlying the higher incidence of SAH
in SLE patients remain yet unclear. Several physiopathological
hypotheses provide a partial explanation, but further research is
granted to fully understand the mechanisms behind this morbid
form of hemorrhagic stroke. Prospective studies focused on the
incidence of SAH, its clinical characteristics, aneurysm morphology and number, are warranted to fully understand the patterns of
subarachnoid hemorrhage in this rheumatologic disease.

7.3. Clinical outcomes
Despite their younger age and regardless of the type of aneurysm
they harbored, patient with SLE and SAH have a higher mortality
rate than other SAH patients. In the only available population study,
the in-hospital mortality rate for SLE patients was 60% vs. a 39% for
the general population suffering a SAH [19]. Not only in aneurysmatic SAH hemorrhage, but also and surprisingly, in those with
negative angiographies. This worst outcome could be explained due
to the severe medical problems such as infections and hematologic
issues related to the systemic disease. Case #2 was a young woman
who presented with SAH and a good GCS, yet was admitted for more
than 6 months in our hospital for multiple medical complications
such as severe thrombopenia with multiple systemic bleedings and

Conflict of interest
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this
paper.
Funding
No grant or industry funding was received to support the production of this work.
Author contributions
Torné was responsible for the conception and design of the
study as well as for the acquisition, analysis and interpretation of
data. He also drafted the article along with Rodríguez-Hernández
and Bernard who were also responsible for other study aspects;
Rodríguez-Hernández carried out the analysis and interpretation
of data while Bernard in association with Arikan, and Vilalta performed the Acquisition of data. Sahuquillo supervised the study. All
authors critically revised the article.

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References
[1] Goldblatt F, O’Neill SG. Clinical aspects of autoimmune rheumatic diseases.
Lancet 2013;382:797–808.
[2] Ramos-Casals M, Nardi N, Lagrutta M, Brito-Zerón P, Bové A, Delgado G, et al.
Vasculitis in systemic lupus erythematosus: prevalence and clinical characteristics in 670 patients. Medicine (Baltimore) 2006;85:95–104.
[3] Muscal E, Brey RL. Neurologic manifestations of systemic lupus erythematosus
in children and adults. Neurol Clin 2010;28:61–73.
[4] Chang Y-S, Liu C-J, Chen W-S, Lai C-C, Wang S-H, Chen T-J, et al. Increased
risk of subarachnoid hemorrhage in patients with systemic lupus erythematosus: a nationwide population-based study. Arthritis Care Res (Hoboken)
2013;65:601–6.
[5] Futrell N, Millikan C. Frequency, etiology, and prevention of stroke in patients
with systemic lupus erythematosus. Stroke 1989;20:583–91.
[6] Trentham DE. Letter: Berry aneurysms and lupus. N Engl J Med 1976;
295:114.
[7] Agarwalla PK, Walcott BP, Dunn IF, Thiex R, Frerichs K, Narang S, et al. Fusiform
aneurysms of the lenticulostriate artery. J Clin Neurosci 2013:1–5.
[8] Kelley RE, Stokes N, Reyes P, Harik SI. Cerebral transmural angiitis and ruptured aneurysm: a complication of systemic lupus erythematosus. Arch Neurol
1980;37:526–7.
[9] Gillard J, Loneragan R, Cross J. Atypical aneurysms, vasculitis and stroke in
systemic lupus erythematosus; 2002. p. 1–2.
[10] Mimori A, Suzuki T, Hashimoto M, Nara H, Yoshio T, Masuyama JI,
et al. Subarachnoid hemorrhage and systemic lupus erythematosus. Lupus
2000;9:521–6.
[11] Fortuna G, Brennan M. Systemic lupus erythematosus. Dent Clin NA
2013;57:631–55.
[12] Rozet I, Vavilala MS, Souter M, Lam AM. Global cerebral edema and subarachnoid hemorrhage in a patient with systemic lupus erythematosus. J Neurosurg
Anesthesiol 2004;16:164–6.
[13] Acioly MA, Farina EMG, Dalmônico AC, Aguiar LR. Severe cerebral vasculitis in
systemic lupus erythematosus: from stroke to multiple fusiform aneurysms.
Eur Neurol 2012;67:352–3.
[14] Kelly ME, Guzman R, Sinclair J, Bell-Stephens TE, Bower R, Hamilton S, et al.
Multimodality treatment of posterior fossa arteriovenous malformations. J
Neurosurg 2008;108:1152–61.
[15] Nakai Y, Hyodo A, Yanaka K, Akutsu H, Nose T. Distal superior cerebellar artery
aneurysm in a patient with systemic lupus erythematosus: case report. Surg
Neurol 2000;54:73–6.
[16] Brah S, Thomas G, Chapon F, Franques J, Jourde N, Harlé JR, et al. Subarachnoid hemorrhages form ruptured aneurysms as the presenting feature of lupus
cerebral vasculitis. Rev Med Interne 2012;33:10–3.
[17] Baizabal Carvallo JF, Cant uacute Brito C, Esta ntilde ol B, Garc iacute a Ramos GS.
Subarachnoid hemorrhage as a complication of systemic lupus erythematosus.
Cerebrovasc Dis 2007;24:301–4.

[18] Atanes Sandoval A, Sánchez Bursón JM, Graña Gil J, Martínez Muñiz A, Galdo
Fernández F. Multiple aneurysms and cerebral vasculitis in systemic lupus
erythematosus. Med Clin (Barc) 1989;92:577–9.
[19] Asai A, Matsutani M, Fujimaki T, Takakaura K. Multiple saccular cerebral
aneurysms associated with systemic lupus erythematosus. Neurol Med Chir
(Tokyo) 1989:245–7.
[20] Owada T, Takahashi K, Kita Y. Subarachnoid hemorrhage in systemic lupus
erythematosus in Japan: two case reports and a review of the literature. Mod
Rheumatol 2009;19:573–80.
[21] Murphy G, Lisnevskaia L, Isenberg D. Systemic lupus erythematosus and
other autoimmune rheumatic diseases: challenges to treatment. Lancet
2013;382:809–18.
[22] Rodríguez-Hernández A, Lu DC, Miric S, Lawton MT. Aneurysms associated with
non-moyamoya collateral arterial networks: report of three cases and review
of literature. Neurosurg Rev 2011;34:517–22.
[23] Sakaki T, Morimoto T, Utsumi S. Cerebral transmural angiitis and ruptured cerebral aneurysms in patients with systemic lupus erythematosus. Neurochirurgia
(Stuttg) 1990;33:132–5.
[24] Lim YC, Kim BM, Suh SH, Jeon P, Kim SH, Ihn Y-K, et al. Reconstructive treatment
of ruptured blood blister-like aneurysms with stent and coil. Neurosurgery
2013;73:480–8.
[25] Kaminogo M, Yonekura M, Shibata S. Incidence and outcome of multiple
intracranial aneurysms in a defined population. Stroke 2003;34:16–21.
[26] Ellis SG, Verity MA. Central nervous system involvement in systemic lupus
erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977.
Semin Arthritis Rheum 1979;8:212–21.
[27] Tang SC, Lee CF, Lee CW, Jeng JS. Systemic lupus erythematosus flare
up manifestation as cerebral and spinal subarachnoid hemorrhage. Lupus
2011;20:1211–3.
[28] Refai D, Botros JA, Strom RG, Derdeyn CP, Sharma A, Zipfel GJ. Spontaneous isolated convexity subarachnoid hemorrhage: presentation, radiological findings,
differential diagnosis, and clinical course. J Neurosurg 2008;109:1034–41.
[29] van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid haemorrhage. Lancet
2007;369:306–18.
[30] Rodríguez-Hernández A, Zador Z, Rodríguez-Mena R, Lawton MT. Distal
aneurysms of intracranial arteries: application of numerical nomenclature,
predilection for cerebellar arteries, and results of surgical management. World
Neurosurg 2013;80:103–12.
[31] Takemoto K, Hatano T, Abekura Y, Takahashi JC, Miyamoto S. Successful flow
reduction treatment for a middle cerebral artery aneurysm in a patient with
systemic lupus erythematosus. Neurol Med Chir (Tokyo) 2013;53:192–5.
[32] Nagayama Y, Kusudo K, Imura H. A case of central nervous system lupus associated with ruptured cerebral berry aneurysm. Jpn J Med 1989;28:530–3.
[33] Sánchez-Ojanguren J, Matias J, Misis M, Olivé A. Systemic lupus erythemtosus,
berry aneurysms and subarachnoid haemorrhage. Clin Rheumatol 1999:165–6.
[34] Segura T, Figuerola A, León J, Vivancos J. Subarachnoid hemorrhage as a form
of onset of systemic lupus erythematosus. Rev Neurol 1998;160:984–5.