□ CASE REPORT □

Cerebral Venous Thrombosis as a Complication of
Neuropsychiatric Systemic Lupus Erythematosus
Hiroshi Nishida, Kenji Wakida and Takeo Sakurai

Abstract
A 51-year-old woman undergoing steroid treatment for systemic lupus erythematosus (SLE) was admitted
to our hospital after developing a fever, consciousness disturbance and seizures, leading to a diagnosis of
SLE-induced meningoencephalitis. Although steroid therapy improved her symptoms, she complained of
post-lumbar puncture thunderclap headaches during follow-up, and cerebral venous thrombosis (CVT) was
subsequently diagnosed on magnetic resonance venography and cerebral angiography. This is a rare case of
neuropsychiatric SLE complicated by CVT during treatment for aseptic meningoencephalitis. The onset of
aseptic meningoencephalitis and administration of the lumbar puncture and steroid therapy may have induced
the development of the patient’s CVT symptoms.
Key words: neuropsychiatric SLE, cerebral venous thrombosis, thunderclap headache
(Intern Med 54: 837-841, 2015)
(DOI: 10.2169/internalmedicine.54.3079)

Introduction
Systemic lupus erythematosus (SLE) may be complicated
by a variety of neuropsychiatric symptoms during its clinical
course. The neuropsychiatric symptoms of SLE, including
peripheral nerve injury, are classified by the American
College of Rheumatology as neuropsychiatric SLE
(NPSLE) (1). Although previous studies have reported cognitive disorders and headaches as frequently observed symptoms in such patients (2, 3), a limited number of case reports have reported the rare complication of cerebral venous
thrombosis (CVT) (4-10).
We herein describe a case of SLE accompanied by
NPSLE symptoms, including convulsions, acute confusion
and aseptic meningoencephalitis, with the subsequent development of CVT associated with post-lumbar puncture thunderclap headaches.

Case Report
A 51-year-old woman was admitted to our hospital with a
fever and consciousness disturbance after a seizure. She had
a past history of encephalitis diagnosed at 36 years of age

(details unknown), secondary epilepsy as an aftereffect of
the encephalitis and SLE. She had been treated with anticonvulsants (phenytoin, 240 mg/day; valproic acid, 800 mg/
day) and low-dose corticosteroids (prednisolone, 10 mg/day)
for SLE at another hospital. She subsequently developed a
fever the day before admission to our hospital, followed by
tonic convulsions lasting approximately one minute with a
consciousness disturbance and fever on the day of admission.
Upon admission, the patient’s vital signs were as follows:
body temperature, 38℃; blood pressure, 102/56 mmHg;
pulse rate, 98 beats/min; and consciousness level according
to the Japan Coma Scale, 3. No abnormal findings were observed on cardiovascular, respiratory or abdominal examinations. A neurological examination revealed mild neck rigidity, with no other focal neurological deficits.
A complete blood cell count demonstrated the following
normal findings: white blood cells, 8,600/μL; red blood
cells, 384×104/μL; and platelets, 24×104/μL. Blood biochemistry showed an elevated C-reactive protein level and erythrocyte sedimentation rate (19 mg/dL and 58 mm/h, respectively), with a PT of 80.5% (normal, 70-130). Serology was
positive for antinuclear antibodies [1:320 (normal, <40fold)] and negative for anti-ds-DNA IgG [10 IU/mL (nor-

Department of Neurology, Gifu Prefectural General Medical Center, Japan
Received for publication April 17, 2014; Accepted for publication August 26, 2014
Correspondence to Dr. Hiroshi Nishida, 41151@gifu-hp.jp

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DOI: 10.2169/internalmedicine.54.3079

(a)

(b)

(c)

Figure 1. Brain computed tomography (CT) performed upon the appearance of symptoms (b)
demonstrated a high-density area in the right transverse sinus (arrow), leading to a suspected diagnosis of cerebral venous thrombosis. Brain CT performed on admission (a) and follow-up (c) showed no
abnormalities.

(a)

(b)

(c)

Figure 2. A brain magnetic resonance imaging (MRI) T2*-weighted image (b) showed a low-intensity area in the right transverse sinus (arrow), and a diagnosis of transverse sinus thrombosis was
suspected. Thrombosis was subsequently detected in the superior sagittal sinus as an area with an
iso-intense signal on a brain MRI T2-weighted image (arrow) (c). A brain MRI T2-weighted image
obtained on admission (a) showed no abnormalities.

mal, !
12 IU/mL)], anti-ds-DNA IgM [2 U/mL (normal, 6
IU/mL)], anti-Sm antibodies, lupus anticoagulant [1.02 (normal, <1.3)], anticardiolipin antibody IgG [8 U/mL (normal,
<10 U/mL)] and anticardiolipin antibody IgM [5 U/mL
(normal, <8 U/mL)]. The D-dimer level was not measured.
A lumbar puncture revealed a primary pressure of 100
mm H2O, cell count of 349/3 μL (N/L=7/342), protein level
of 271 mg/dL, glucose level of 54 mg/dL, myelin basic protein level of 40 pg/mL, elevated interleukin-6 (IL-6) level of
331 pg/mL, the absence of bacteria and tuberculosis microorganisms and negative findings for herpes simplex virus
polymerase chain reaction, varicella-zoster virus polymerase
chain reaction and oligoclonal bands. Brain computed to-

mography (CT) and magnetic resonance imaging (MRI)
showed no abnormalities (Fig. 1, 2).
Although the patient received acyclovir (1,500 mg/day)
and antibiotics for aseptic meningoencephalitis, she did not
respond to the treatment. A diagnosis of aseptic meningoencephalitis as a complication of SLE was thus made based on
the pre-existing SLE and elevated IL-6 level in the spinal
fluid. Steroid treatment was administered (prednisolone, 60
mg/day), and her symptoms quickly improved on day 6.
On day 11, a repeated lumbar puncture showed improvements in the data, with a cell count of 44/3 μL, protein level
of 56 mg/dL and IL-6 level of 33 pg/mL. However, the patient suddenly developed a headache two hours after the

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DOI: 10.2169/internalmedicine.54.3079

(a)

(b)

Figure 3. A digital subtraction cerebral angiogram of the right carotid artery (venous phase) (a:
frontal view, b: lateral view) did not visualize the superior sagittal sinus (b: arrows), straight sinus (b:
arrowheads), bilateral transverse sinus (a: arrowheads) or sigmoid sinus (a: arrowheads); cerebral
venous thrombosis was diagnosed.

(a)

(b)

Figure 4. Magnetic resonance venography (MRV) performed upon the appearance of symptoms
(a) did not visualize the superior sagittal sinus (arrowheads) or straight sinus (arrows), cerebral venous thrombosis was diagnosed. MRV performed six months later (b) successfully visualized the superior sagittal sinus, transverse sinus and straight sinus; the site of cerebral venous thrombosis had
been recanalized.

lumbar puncture that immediately reached a peak in severity
(similar to a thunderclap headache). Although an analgesic
was administered, the headache was not relieved. In addition, the presence of a high-density area in the right transverse sinus on brain CT (Fig. 1) was suspicious of venous
sinus thrombosis. However, no brain lesions were detected,
such as cerebral hemorrhage. Nevertheless, an MRI T2*weighted image showed low intensity in the right transverse
sinus, and a diagnosis of transverse sinus thrombosis was
suspected. Thrombosis was subsequently detected in the superior sagittal sinus based on an iso-intense signal on a
brain MRI T2-weighted image (Fig. 2).
Digital subtraction cerebral angiography (DSA) (Fig. 3)

and MR venography (MRV) (Fig. 4) showed occlusion of
the superior sagittal sinus, straight sinus, bilateral transverse
sinus and sigmoid sinus, confirming the diagnosis of CVT.
A blood test showed elevation of the D-dimer level (5.4 μg/
mL). Anti-coagulation therapy with heparin-Na was therefore started and subsequently changed to warfarin. No complications involving the brain parenchyma, such as cerebral
hemorrhage, were observed after treatment, and the patient’s
clinical course was uneventful, including the alleviation of
her headache. Follow-up MRV (Fig. 4) showed recanalization of the venous sinus.

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Table. Reported of the Cases of Crebral Venous Thrombosis in Systemic Lupus
Erthematosis (Negative Antiphospholipid Antibodies Cases)
Reference Age Sex renal disorder APLA
Treatment
5
40 F
heparin, wafarin
7
34 F
+
steroid pulse, heparin, warfarin
7
55 F
+
steroid pulse, heparin, warfarin
8
14 F
heparin, steroid, wafarin
8
13 F
steroid
9
39 F
steroid, cyclophosphamide,anticoagulant
10
33 F
steroid
our case 51 F
steroid, anticoagulant
APLA: anti-phospholipid antibody (lupus anticoagulant and anticardiolipin antibody),
+: positive, -: negative

Discussion
The present case report involves a patient who developed
a variety of neuropsychiatric symptoms, including convulsions, acute confusion and aseptic meningoencephalitis, during the clinical course of SLE. Moreover, CVT was diagnosed following the onset of a post-lumbar puncture headache.
Previous case reports have reported complication rates of
convulsions, acute confusion and meningitis, neuropsychiatric symptoms associated with SLE collectively known as
NPSLE, of 9-16%, 7% and 2%, respectively (2, 3). However, no cases of CVT have been described in previous reports, and this symptom is thus considered to be a rare complication.
Although the Virchow triad (a hypercoagulable state,
blood flow congestion and structural changes in the vascular
wall) is thought to play a role in the onset of CVT, several
other causes of this complication are suspected. Acquired
causes include infections, such as meningoencephalitis and
otitis media, brain tumors, pregnancy and puerperium, oral
contraceptive use and surgery, while hereditary causes comprise protein C and S deficiencies. However, SLE accounts
for only 1% of underlying causes of CVT (11, 12).
Although the development of CVT during the clinical
course of SLE is rare, some cases have been shown to involve anti-phospholipid antibodies (4-6), while others were
negative for anti-phospholipid antibodies, with suspected underlying causes of hypercoagulability, vasculitis and hypertrophic pachymeningitis (5, 7-10) (Table).
The present report discusses a case of CVT that occurred
after lumbar puncture. Previous reports have suggested that
lumbar puncture accounts for 1.9% of all causes of
CVT (10), possibly attributable to a reduced amount of cerebrospinal fluid. Other suspected causes of CVT include venous dilatation resulting from cerebrospinal fluid reduction
and associated decreases in the venous blood flow, increased
venous blood viscosity, stenosis and occlusion of the veins
and venous sinuses due to cerebral ptosis (13, 14). In addition, the administration of drugs, such as steroids, may promote the development of CVT after lumbar puncture (15, 16), with lumbar puncture and corticosteroid treat-

Outcome
Resolved
Resolved
Resolved
Resolved
Resolved
Resolved
Resolved
Resolved

ment likely to play a role in the onset of CVT in patients
with multiple sclerosis (17-19).
In the current case, the aseptic meningoencephalitis appeared to be a symptom of NPSLE. Moreover, the initially
elevated IL-6 level decreased following treatment with corticosteroids.
In patients with NPSLE, the CSF levels of IL-6 and IL-8
are initially elevated and subsequently decrease after successful treatment. Furthermore, analyses of the CSF cytokine levels, particularly IL-6 and IL-8, are useful for making the diagnosis and possibly in providing follow-up in patients with NPSLE (20). Hence, intrathecal immunological
inflammation plays an important role in the pathogenesis of
NPSLE (21). In this case, anti-phospholipid antibodies were
negative and not associated with anti-phospholipid antibodies. Therefore, the direct expansion of inflammation due to
meningoencephalitis and the administration of steroid therapy may have induced the development of CVT. Moreover,
the lumbar puncture was associated with the onset of the
CVT in association with a thunderclap headache.
Taken together, we conclude that the direct expansion of
inflammation resulting from aseptic meningoencephalitis and
the administration of the lumbar puncture and steroid treatment with prednisolone played a role in the onset of CVT in
the present case.
Lastly, the patient’s severe post-lumbar puncture headache
appeared suddenly, with the severity peaking immediately.
Even with the administration of an analgesic, the headache
persisted until the following day and resembled the features
of a thunderclap headache. The classic symptom of CVT is
headache, observed in approximately 90% of cases (11). In
addition, Cumurciuc et al. reported that headaches are observed as the only symptom of CVT in 14% of cases, with
thunderclap headaches in 17.5% of cases as the only symptom. It has been reported that a diagnosis of CVT should be
ruled out on MRI and/or MRV in cases of disease progression with a thunderclap headache, even if CT and spinal tap
examinations show normal findings (22). Although headache
is a common disease manifestation, CVT must be excluded
in patients exhibiting thunderclap headaches and/or progressive deterioration.
We herein reported the case of a patient who developed a
variety of neuropsychiatric symptoms, including convul-

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DOI: 10.2169/internalmedicine.54.3079

sions, acute confusion and meningoencephalitis. Although
steroid treatment successfully improved these symptoms,
CVT was ultimately diagnosed because the patient developed a thunderclap headache after undergoing lumbar puncture. While a variety of causes may have contributed to the
onset of CVT in the present case, the lumbar puncture was
likely an aggravating factor. Our findings suggest that the
risk of CVT is increased in the context of pre-existing disease and treatment requiring lumbar puncture, a relatively
common examination in daily practice in the field of neurological medicine. Therefore, careful follow-up after lumbar
puncture is warranted.
The authors state that they have no Conflict of Interest (COI).

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