Case Report

Deep Venous Thrombosis with Decreased Cerebral Blood Flow
to the Thalamus was Completely Restored by Factor Xa
Inhibitor
Yu Shimizu, PhD, MD, Katsuhiro Tsuchiya, PhD, MD, and
Hironori Fujisawa, PhD, MD

Background: Cerebral venous thrombosis is rare and an uncommon cause of stroke
and has diverse etiologies and varied clinical presentations. Here, we report 2 cases
of deep cerebral venous thrombosis. Case Description: A 64-year-old woman presented with cerebral venous thrombosis due to a hypercoagulable state associated
with ovarian tumor. On initial fluid-attenuated inversion recovery and diffusionweighted imaging, there was a diffuse high-intensity lesion in the bilateral thalamus. Computed tomography angiography showed occlusion of the straight sinus,
vein of Galen, and internal cerebral vein. Single-photon emission computed tomography showed decreased cerebral blood flow in the bilateral thalamus. After 3
weeks of factor Xa inhibitor therapy, the patient’s consciousness gradually
improved and eventually became clear enough to leave the hospital. She had no
neurological deficit. Another patient was a 47-year-old man who presented with
splitting headache and drowsiness. Magnetic resonance venography confirmed
deep thrombosis of the vein of Galen. He completely recovered after 4 weeks of factor Xa inhibitor therapy. Conclusions: This study reports on 2 rare cases of decreased
cerebral blood flow in the bilateral thalamus on single-photon emission computed
tomography, which improved following the administration of factor Xa inhibitor.
Key Words: Deep venous thrombosis—single-photon emission computed
tomography—cerebral blood flow—thalamus—factor xa inhibitor
© 2019 Elsevier Inc. All rights reserved.

Introduction
Acute bilateral thalamic edema may vary in clinical presentation, with symptoms such as coma, disorientation,
and confusion. Venous drainage in the thalamus occurs
via vessels that drain into the vein of Galen and straight
From the Department of Neurosurgery, Kanazawa Medical Center,
Kanazawa, Japan.
Received November 26, 2018; revision received January 12, 2019;
accepted January 22, 2019.
We used heparin to control APTT in 2-2.5 times of the normal level. We
used edoxaban 60 mg, because the weight of the patient exceeded 60 kg.
Address correspondence to Yu Shimizu, PhD, MD, Department of
Neurosurgery, Kanazawa Medical Center, Kanazawa, Japan, 1-1 Shimoishibikimachi, Kanazawa 920-8650, Japan.
E-mail: bleuler3a@yahoo.co.jp.
1052-3057/$ - see front matter
© 2019 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.01.023

sinus. We report the clinical and imaging findings of a
patient with thrombosis of the vein of Galen and straight
sinus, leading to a completely reversible thalamic edema,
and review the literature on this rare entity. No case of
deep cerebral venous thrombosis (DCVT) that presents as
decreased cerebral blood flow (CBF) to the bilateral thalamus on single-photon emission computed tomography
(SPECT) has been reported to date. Factor Xa inhibitor is
an uncommon therapy for DCVT but was very effective
in our cases.

Case Description
Case 1
A 64-year-old woman was found unconscious, requiring endotracheal intubation. On admission, neurological
examination revealed that she was stuporous, with a

Journal of Stroke and Cerebrovascular Diseases, Vol. 28, No. 5 (May), 2019: pp e39 e43

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Y. SHIMIZU ET AL.

e40

Figure 1. (A) Axial reconstruction of the CT angiography shows a filling defect on the vein of Galen and ICV. (B) Coronal section shows a filling defect of the
straight sinus. It appears like a ring that is strongly indicative of an intraluminal clot. We call it the ring sign. (C) Sagittal section shows a filling defect on the
straight sinus, vein of Galen, and ICV. (D-F) CT angiography images obtained 3 months after thrombosis show complete recanalization of the straight sinus,
vein of Galen, and ICV.

Glasgow Coma Scale score of E2V4M6. Her cranial nerves
were intact. She had no weakness, ataxia, sensory disturbance, or signs of meningeal irritation. Blood tests
revealed iron deficiency anemia (hemoglobin, 11.2 g/dL;
iron, 54 mg/dL), normal platelet counts (21 £ 103/mL),
and elevated D-dimer level (2.4 mg/mL). White blood
cell counts were within normal ranges. The C-reactive protein level was 1.22 mg/dL. The serum interleukin-6 level
was elevated at 36.7 pg/mL (reference, <4.5 pg/mL).
Results indicated that renal function, liver function, and
serum electrolyte level were normal. Her medical history
included benign ovarian tumor. Computed tomography
(CT) showed high attenuation in the straight sinus. CT
angiography revealed a filling defect in the straight sinus,
vein of Galen, and internal cerebral vein (Fig 1A-C). The
inferior sagittal sinus was dilated due to venous congestion. This was confirmed on magnetic resonance (MR)
imaging as representing a partial dural venous sinus
thrombosis with congestive thalamic edema (Fig 2). SPECT
showed decreased CBF in the bilateral thalamus (Fig 3).
Analysis of cerebrospinal fluid showed normal protein and
glucose levels. Gram staining was negative. Heparin
(15,000 U/day for 7 days) and edoxaban (60 mg/day)
were administered for therapeutic efficacy. Levels of factors, including protein C, protein S, antithrombin III, and
antiphospholipid antibodies that potentially cause a hypercoagulable state were within normal ranges. After a 3week follow-up, the patient completely recovered. Findings
on CT angiography 3 weeks after symptom onset revealed
that the bilateral internal cerebral vein and straight sinus
had regained blood flow, and SPECT findings normalized
(Fig 3). She had no intracranial or other major bleeding
complications and no recurrent thrombotic events during
the 3-year follow-up.

Case 2
A 47-year-old man was admitted to the hospital with
1-week history of progressive headache and drowsiness.
On admission, a neurological examination revealed that
he was stuporous, with a Glasgow Coma Scale score of
E3V4M6. His cranial nerves were intact. He had no weakness, ataxia, sensory disturbance, or signs of meningeal
irritation. He had no past or family history of coagulation

Figure 2. (A) Diffusion-weighted image (DWI) shows bilateral thalamic
edema. (B) Axial fluid-attenuated inversion recovery (FLAIR) MRI depicting extensive bilateral thalamic and basal ganglia edema. (C, D) FLAIR and
DWI images in the 3-month follow-up show resolution of bilateral thalamic
edema and no residual parenchymal defects.

THE SPLENDID EFFECT OF FACTOR XA INHIBITOR FOR DEEP VENOUS THROMBOSIS

e41

normal.
Initial
anticoagulation
with
heparin
(15,000 U/day for 7 days) was followed by edoxaban (60
mg/day). A fluid attenuated inversion recovery image of
the brain MRI taken 1 month after the initial symptoms
showed disappearance of pre-existing edema of the thalamus. The patient completely recovered by the end of the
first month.

Discussion
Figure 3. (A) Single-photon emission computed tomography in the 3month follow-up shows hypoperfusion in the thalamic regions and basal
ganglia similar to that in MRI (CBF: right thalamus, 31 mL/100 g/min; left
thalamus, 35 mL/100 g/min; right basal ganglion, 34 mL/100 g/min; left
basal ganglion, 37 mL/100 g/min). (B) After the patient’s recovery showing
improvement of perfusion in the bilateral thalamus and basal ganglia (CBF:
right thalamus, 44 mL/100 g/min; left thalamus, 45 mL/100 g/min; right
basal ganglion, 47 mL/100 g/min; left basal ganglion, 46 mL/100 g/min).

abnormalities. The results of an initial fundoscopic examination were normal. Findings on brain CT, showed no
abnormal findings. A fluid attenuated inversion recovery
imaging study of brain MRI showed bilateral thalamic
high signal intensity, suggesting edema. MR venography
(MRV) confirmed deep thrombosis of the vein of Galen.
MR angiography was normal. MRV images are shown in
Figure 4. The results of coagulation studies, including prothrombin time, platelet count, thrombin time, partial
thromboplastin time, fibrinogen, antithrombin III, activated protein C resistance, antiphospholipid antibody,
lupus anticoagulant, and protein C and S, were all normal. The CSF protein level was slightly elevated. Other
screening investigations, including antinuclear antibodies,
anti-DNA, and antineutrophil cytoplasmic antibodies,
were normal, and tests for tumor markers were also

Figure 4. Filling defect consistent with thrombosis of the vein of Galen seen
on MR venography (arrow).

Thrombosis of the deep cerebral veins develops very
rarely, and approximately 6% of patients with cerebral
venous thrombosis develop deep cerebral venous thrombosis.1 DCVT often leads to death or major long-term
sequelae.2 It is an uncommon disease, arising from various causes, including infection, connective tissue disease,
anemia, inflammatory diseases, and trauma.3 Women are
affected 3 times more often than men.4 Clinical manifestations of DCVT, including headache, nausea, vomiting,
focal neurologic deficits, hemiparesis, aphasia, seizures,
coma, and death, are complex and nonspecific. In CT
scans, direct and indirect signs of CVT, including the cord
sign in the superior sagittal sinus or cortical vein and the
empty delta sign in CT scans with contrast, are well documented. They are often not primarily identified.5 CT
angiogram, MRI, and MRV are valid techniques in CVT
diagnosis and follow-up. Thrombosis appears as an
absence of flow void on spin-echo images and lack of signal in angiographic techniques.5 We found bilateral
hyperintensities in diffusion-weighted imaging and fluidattenuated inversion recovery sequences in the thalamus
and basal ganglia.
Edema observed on imaging in cases of venous infarction is vasogenic in nature due to reduced venous drainage.6 An imaging study of our patient shows congestive
thalamic edema and DCVT and decreased CBF in the thalamus and basal ganglia. We believe that because of the
persistence of high venous and capillary pressures, ischemic change occurred in the thalamus. Like in arterial
infarction, if this state continues, it might lead to complete
stroke.
Of 23 patients reported in the literature (Table 1), 5 presented with mild symptoms, 7 with neurologic deficits,
and 11 with decline of consciousness or seizure. In all
patients with DCVT, signal intensity changes were limited
to one thalamus (n = 7) or both thalami (n = 16). Of all
patients, 5 had mild symptoms, 17 completely recovered,
and 1 had persistent deficits. In 7 patients with focal neurologic symptoms, 3 recovered almost completely. Finally,
of 11 patients with impairment of consciousness or coma,
1 had persistent deficits. In 22 of 23 patients treated with
heparin and warfarin, 1 patient was treated with factor Xa
inhibitor (edoxaban). The patients had no relevant
complications or recurrent thrombotic events. Factor
Xa inhibitor was an uncommon therapy for deep
venous infarction but safe and effective in our case

e42

Table 1. Patients with cerebral deep venous sinus thrombosis
Case no.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23

Author [reference]
Spearman et al

7

Gladstone et al8
M. von Mering et al9

Herrmann et al10
Prochazka et al11
Rossetti et al12
Wada et al13
Won Chung et al14
Kochanski et al15
Taniguchi et al16
Soda et al17
Wieshmann et al18
Haug et al19
Bezerra et al20
Amemiya et al21

Age/Sex

Symptoms

Thrombosed vein

Risk

Location

Treatment

Outcome (mRS)

18/M
24/F
24/F
15/M
56/M
24/F
65/F
21/F
15/F
43/F
47F
24/F
18/F
57/M
36/F
58/M
52/F
69/F
14/F
12/M
18/F
49/F
53/M

Headache, Paresis
Headache, Paresis
Headache
Headache, Paresis
Coma
Headache
Coma, Paresis
Coma, Headache, Seizure
Coma, Paresis
Coma, Headache, Seizure
Headache,Paresis
Coma, Headache, Seizure
Coma, Headache, Seizure
Coma, Paresis, Headache
Paresis
Coma
Coma
Coma
Headache, Paresis
Paresis
Headache
Headache
Headache

ICV,Galen,SS
ICV,Galen,SS
ICV
ICV,Galen,IPS,SS,TS
ICV,Galen,IPS,SS
ICV,Galen,IPS,SS
ICV, SS
Galen, SS, TS
ICV, Galen, SS
Galen,SS
ICV
Galen, TS
Galen
SS,SSS
ICV
SS
SS
Galen, SS
ICV
Galen, SS
Galen, SS
Galen, SS
ICV, ISS, Galen

Unknown
Unknown
Unknown
Unknown
Unknown
ProteinC resistance
Hormonal medication
Hormonal medication
ProteinC resistance
Hormonal medication
Unknown
Unknown
Hormonal medication
Unknown
Unknown
Unknown
Unknown
Cancer
Factor V Leiden.
Unknown
Unknown
Unknown
Unknown

BT
UT,BG
BT
BT
BT,BG
BT
BT,BG
BT
BT
BT
UT
UT
BT
UT
UT
BT
BT
BT
UT
UT
BT
BT
BT

H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/W
H/E

1
1
0
0
0
0
3
0
0
0
0
0
0
0
1
0
0
0
1
0
0
1
0

BG, basal ganglia; BT, bilateral thalamus; H/E, heparin/edoxaban; H/W, heparin/warfarin; ICV, internal cerebral vein; IPS, inferior petrosal sinus; ISS, inferior saggital sinus; SS, straight sinus;
TS, transverse sinus; UT, unilateral thalamus.
Y. SHIMIZU ET AL.

THE SPLENDID EFFECT OF FACTOR XA INHIBITOR FOR DEEP VENOUS THROMBOSIS

and review case. Even in DCVT, edoxaban might be a
desirable treatment alternative to vitamin K antagonists because of its known application and metabolism
benefits.

Conclusions
Symptoms from bilateral thalamic edema caused by
increased venous hypertension can be reversed with appropriate management of the inciting vascular lesion. This case
demonstrates a rare patient with decreased CBF in the thalamus in SPECT and completely recovered after factor Xa
inhibitor administration. If a patient presents with focal
neurological deficits, headache, and neuropsychological
symptoms such as somnolence, DCVT might be the underlying condition. As in DCVT in other locations, early recognition of this clinical entity and treatment are prerequisites
for a favorable outcome.22 Although this is a case report,
factor Xa inhibitor may show a similar clinical benefit as
vitamin K antagonist in the treatment of DCVT. Further
systematic prospective evaluation is warranted.

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