CASE REPORT

Global Cerebral Edema and Subarachnoid Hemorrhage in a
Patient With Systemic Lupus Erythematosus
Irene Rozet, MD, Monica S. Vavilala, MD, Michael Souter, MB, ChB, FRCA,
Arthur M. Lam, MD, FRCPC
Abstract: Systemic lupus erythematosus is a multifactorial autoimmune disease of complex etiology, which may be associated with cognitive dysfunction, seizures, and headache. The authors present an
unusual presentation of systemic lupus erythematosus complicated by
global cerebral edema and subarachnoid hemorrhage secondary to
rupture of a cerebral aneurysm. The complicated patient management
issues are discussed.
Key Words: cerebral aneurysm, cerebral edema, subarachnoid hemorrhage, lupus
(J Neurosurg Anesthesiol 2004;16:164–166)

A

16-year-old Filipino girl was admitted to an outside hospital with a 1-week history of progressive fatigue and
joint swelling. She had had intermittent arthralgia for 1 year, as
well as diarrhea for several weeks. Her medical history was
otherwise negative. On admission, the patient was alert and
oriented with normal vital signs. Physical examination was
significant for marked diffuse lower extremity edema. Laboratory evaluation revealed a hematocrit of 19.2% and gross
proteinuria. Nephrotic syndrome was diagnosed and the patient was treated with blood transfusion and 1 g intravenous
methylprednisolone. On hospital day 1, she developed a severe
headache with nausea and vomiting, followed by two brief seizures 3 hours apart. Computed tomography (CT) of the head
demonstrated a small left frontal subarachnoid hemorrhage
(SAH). On day 2, the patient was transferred to our institution,
where she was diagnosed with systemic lupus erythematosus
(SLE) (positive anti-ANA and anti-DNA titers). Renal biopsy
revealed diffuse membranoproliferative glomerulonephritis.
Transthoracic echocardiography revealed a moderate amount
Received for publication August 1, 2003; accepted September 4, 2003.
From the Departments of Anesthesiology (Drs Rozet, Vavilala, Souter, and
Lam), Pediatrics (Dr Vavilala), Neurological Surgery (Dr Lam), and Neurosurgical Intensive Care Unit (Drs Rozet, Souter, and Lam), University of
Washington, Seattle, Washington.
Reprints: Irene Rozet, MD, Acting Assistant Professor, Harborview Medical
Center, Box 359724, 325 Ninth Avenue, Seattle, WA 98104-2499 (e-mail:
irozet@u.washington.edu).
Copyright © 2004 by Lippincott Williams & Wilkins

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of pericardial effusion, moderate pulmonary hypertension, and
decreased global systolic function. A pulsed dose of steroids
was administered (0.5 g intravenous methylprednisolone), followed by a maintenance steroid regimen (20 mg oral prednisone daily).
Repeat head CT and magnetic resonance imaging of the
brain revealed patent venous sinuses and a small left frontal
SAH and edema. Neuroradiologic interpretation of the head
imaging suggested frontal cortical venous thrombosis, and the
patient was treated with aspirin (81 mg daily) until day 7. On
day 7, the patient developed generalized tonic-clonic seizures.
Subsequent head CT revealed an extensive new SAH within
the posterior fossa, intraventricular hemorrhage, and early
acute hydrocephalus (Fig. 1). The patient was treated with tracheal intubation and mechanical ventilation. Emergent ventriculostomy was performed for drainage of cerebrospinal
fluid and monitoring of intracranial pressure, which was 20
mm Hg. Urgent angiography revealed a 3.5 × 4-mm left posterior inferior cerebellar artery (PICA) aneurysm. On day 8, a
decompressive craniotomy of the posterior fossa was performed, followed by some mental status improvement. On day
11, the patient underwent successful clipping of left PICA aneurysm. Her postoperative course was notable for severe vasospasm of the middle cerebral and basilar arteries by transcranial Doppler ultrasonography, accompanied by deterioration of mental status. The patient received “triple H” therapy
(hypertension, hypervolemia, hemodilution), which was adjusted to the severity of vasospasm, according to institutional
protocol. Repeat head CT showed progressive cerebral swelling and the development of supratentorial and infratentorial
infarctions. The patient stayed intubated and mechanically
ventilated and developed anasarca, pericardial effusion, and
renal dysfunction manifested by oliguria and increased creatinine. On day 18, she developed an acute dilatation of the left
pupil with severe intracranial hypertension. Emergent head CT
revealed further swelling of the brain, and an emergency temporal bifrontal decompressive craniectomy was performed.
Head CT on day 19 showed global cerebral swelling and new
brain infarct zones and hemorrhages (Fig. 2). After discussion
with the family, therapy was withdrawn on day 20 and the patient died.
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FIGURE 1. Head CT scan on day 7 shows extensive subarachnoid hemorrhage within the posterior fossa (arrow).

DISCUSSION
In the United States, the incidence of SLE ranges from
15 to 50 cases per 100,000 population, with the peak between
age 15 and 40 years.1,2 SLE has a gender bias with a female:
male ratio of about 8:1, and the increased incidence of SLE in
females of reproductive age suggests estrogen as a possible
risk factor.1,3 The incidence of SLE in females from Southeast
Asia is seven times that of white females and twice that of
African American females.1,4 In this report, we present the
youngest patient with SLE reported to develop SAH and cerebral edema secondary to cerebral aneurysmal rupture.
The incidence of central nervous system (CNS) manifestations of adult and pediatric SLE ranges from 20% to 75%,5–9
and CNS manifestations are risk factors for death.10,11 The
most frequent CNS symptoms of SLE include cognitive dysfunction, headache, and seizures. SLE-associated CNS manifestations can include both global and focal features. The main
underlying mechanism of SLE-associated CNS disease is
brain ischemia secondary to progressive narrowing of small
cerebral vessels associated with antiphospholipid antibodies
and premature atherosclerosis.12 True cerebral vasculitis, with
development of cerebral aneurysms, and intracranial hemorrhage, however, are infrequent.12 The true incidence and time
course of development of cerebral aneurysms in children with
SLE are unknown. To date, the youngest reported patient with
SLE and a cerebral aneurysm was a 22-year-old woman with a
ruptured middle cerebral artery aneurysm who died on the 10th
day of admission because of brain swelling.13
The association of intracranial hemorrhage and cerebral
aneurysms in adults with SLE has been described in limited
retrospective reviews, mostly from Japan.14,15 The largest retrospective review found a 3.9% incidence of SAH in 258 patients with SLE.14 Patients with SLE and cerebral aneurysms
have a greater than 50% mortality rate, especially when the
SLE is active or when aneurysmal rupture occurs.14–16 The
© 2004 Lippincott Williams & Wilkins

Global Cerebral Edema and Subarachnoid Hemorrhage in SLE

pathophysiologic mechanism of aneurysm formation in SLE is
thought to be transmural angiitis or fibrinoid necrosis leading
to local weakness in the walls of the cerebral vessels.13 Rupture of cerebral aneurysms during active SLE is known to be a
devastating complication resulting in SAH and may be followed by global cerebral edema and multiple cerebral infarcts.14,15,17
In general, global cerebral edema following SAH is rare
and has been reported to occur in 6% to 7% of patients on
hospital admission.18,19 The incidence of cerebral edema following SLE-related SAH is unknown. Global cerebral edema
following SAH can either be acute or delayed. In a recent prospective study of 374 adults with SAH, which did not include
patients with vasculitis, the incidence of acute and delayed cerebral edema on admission was 8% and 12% (hospital days
2–16), respectively.20 Loss of consciousness at ictus, use of
vasopressors, and aneurysmal size were found to be risk factors associated with development of delayed global cerebral
edema, and the authors proposed that cerebral ischemia consequent to primary hemorrhage is a major pathophysiologic
mechanism for the development of global cerebral edema.20
We cannot confirm the exact pathophysiologic CNS
process in the present case because autopsy was refused by the
family, but the clinical scenario suggests that cerebral ischemia and cerebral edema were important contributors to mortality, with the early onset of venous infarction as diagnosed
neuroradiologically.

FIGURE 2. Head CT scan on day 19 shows: (1) global cerebral
edema, brain herniating through bilateral temporal craniectomy sites (thick arrows) and (2) supratentorial infarct zones
(thin arrows).

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Rozet et al

Prominent endothelial dysfunction with hypercoagulation plays a major role in active SLE and contributes to the
development of cerebral infarcts. Fluid therapy in patients with
acute cerebral infarction typically consists of a regimen of
maintenance intravenous fluid. However, the management of
patients with SAH and attendant vasospasm may necessitate
the administration of “triple H” therapy,21 which may aggravate cerebral edema formation in the context of the endothelial
dysfunction seen in SLE.
In combination, the inflammatory consequences of SLE
could augment and accelerate the severity and onset of cerebral
ischemia and edema after SAH, creating a vicious circle that
results in uncontrolled progressive global brain swelling and
development of cerebral infarction, hemorrhages, and herniation. These factors were significant contributors to our patient’s death. To alleviate cerebral edema, moderation of induced hypertension and hypervolemia may be warranted.

CONCLUSIONS
The purpose of this case report is not to outline a new
feature of SLE, but rather to provoke discussion on the management dilemma of SAH-induced cerebral vasospasm in the
patient with active SLE. In this report, we present an adolescent with cerebral edema associated with cerebral aneurysmal
rupture and SLE. The major learning points of this case are that
cerebral aneurysms may be present in pediatric patients with
active SLE, and SLE and the consequences of SAH can exert
synergistic pathophysiologic effects, complicating patient
management. To prevent the development of malignant cerebral edema, “triple H” therapy for vasospasm from SLErelated SAH may have to be moderated.
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