Neurol Med Chir (Tokyo) 41, 83¿86, 2001

Growth of Occult Arteriovenous Malformation After
Cerebral Hemorrhage Demonstrated
by Serial Magnetic Resonance Imaging
—Case Report—
Takahisa FUSE, Yuji NIWA, Masanari UMEZU, and Kazuo YAMADA*
Department of Neurosurgery, National Tohsei Hospital, Shizuoka; *Department of
Neurosurgery, Nagoya City University Medical School, Nagoya

Abstract
A 19-year-old male presented with sudden onset of right hemiparesis caused by left cerebral hemorrhage. Cerebral angiography demonstrated no vascular abnormality, and the hematoma was removed
surgically. At operation, no abnormal vascular lesion was found in the brain adjoining the hematoma.
Two years later, magnetic resonance (MR) imaging demonstrated a few foci of flow voids adjacent to the
hematoma cavity. Four years after the hemorrhage, MR imaging showed more extensive flow-void abnormalities that indicated growth of an occult arteriovenous malformation (AVM). Cerebral angiography indicated a definite AVM supplied mainly by branches of the middle cerebral artery. Total
resection of this lesion was performed. The histological diagnosis was typical AVM. Immunohistochemistry with vascular endothelial growth factor showed staining in the walls of the abnormal vessels. Serial MR imaging is very useful for the diagnosis and management of occult AVMs.
Key words: cerebral hemorrhage,
vascular endothelial growth factor

occult arteriovenous malformation,

Introduction

hemiparesis. Computed tomography showed a subcortical hematoma with ventricular extension on the
left (Fig. 1A). Carotid or vertebral angiography
showed no abnormality at that time (Fig. 1B, C). Left
front temporal craniotomy was performed, and the
hematoma was evacuated. No vascular malformation was found despite careful inspection. Cerebral
angiography was repeated on the 21st day after onset, but failed to show any vascular abnormalities.
After discharge, the patient was in good health and
had no neurological deficit.
Serial follow-up MR imaging initially was normal
except for the presence of hematoma cavity
(Fig. 2A). Two years after the hemorrhage, MR imaging demonstrated a few foci of flow voids adjacent
to the hematoma cavity (Fig. 2B). Two years later,
MR imaging showed more extensive flow-void abnormalities, indicating growth of an occult AVM not
evident at the operation 4 years earlier (Fig. 2C).
Cerebral angiography confirmed presence of an
AVM supplied mainly by branches of the middle
cerebral artery (Fig. 3). We decided to remove the
AVM to prevent additional hemorrhagic episodes.

Arteriovenous malformations (AVMs) of the brain
are generally considered to be congenital malformations that arise during the early fetal stage when
newly formed blood vessels begin to differentiate
into primitive arteries, capillaries, and veins.10)
Growth of an occult AVM and final manifestation as
cerebral hemorrhage has been reported in several
cases.2,4,5,8,12) Diagnosis has required serial conventional angiography until very recently. We describe
a case of occult AVM detected by serial magnetic
resonance (MR) imaging over 4 years following
cerebral hemorrhage.

Case Presentation
A 19-year-old male was found unconscious at home
and was transported to our hospital by ambulance.
On admission, he was semicomatose with mild right
Received
2000

August 14, 2000;

Accepted

November 27,

83

T. Fuse et al.

84

Fig. 1

Radiologic findings on the first hospital day. A: Computed tomography scan showing a subcortical hematoma with intraventricular extension on the left. B, C: Left carotid angiograms, anteroposterior (B) and lateral views (C), demonstrating no abnormal vascular lesions.

Fig. 2

Serial magnetic resonance (MR) images. A: One month after cerebral hemorrhage, T2weighted MR image showing no abnormalities except for the hematoma cavity. B: Two
years after hemorrhage, MR image showing focal areas of flow voids adjacent to the hematoma cavity, suggesting the presence of a previously occult arteriovenous malformation (AVM)
(arrow). C: Four years after hemorrhage, MR image showing more extensive flow-void abnormalities, indicating growth of the AVM (arrow).

Left frontal craniotomy was performed. The abnormal vessels were identified near the premotor area,
and the nidus of the AVM was totally removed. During this procedure, the hematoma cavity was not entered. After surgery, the patient suffered a generalized convulsion, with gradual resolution of the
postictal state. The patient was discharged with no
neurological deficit. Postoperative MR imaging
showed no abnormal vascular lesion.
Histological examination of the surgical specimen
showed typical cerebral AVM (Fig. 4A). Immunostaining of the surgical specimen using antivascular endothelial growth factor (VEGF) antibody
(Oncogene Science, Cambridge, Mass., U.S.A.)
showed staining of several abnormal vessel walls
(Fig. 4B). Immunohistochemical protocol with omis-

Fig. 3

Left carotid angiograms, anteroposterior (A)
and lateral views (B), at the second admission showing the arteriovenous malformation supplied mainly by branches of the
middle cerebral artery.

Neurol Med Chir (Tokyo) 41, February, 2001

Growth of Occult AVM After Cerebral Hemorrhage

Fig. 4

85

Photomicrographs of the resected specimen. A: Typical findings of arteriovenous malformation. HE stain, original magnification ×100. B: Immunoreactivity for vascular endothelial growth factor (VEGF) is present in the abnormal blood vessel walls (arrows). The endothelium is the most reactive layer. Anti-VEGF immunostain, original magnification ×
100. C: Control section from the same region as in B, showing absence of reaction product
when the primary antibody was omitted from the immunostaining protocol. Original magnification ×100.

sion of the primary antibody showed no staining of
adjacent control sections (Fig. 4C).

Discussion
Initial failure of angiography to detect an AVM
responsible for intracerebral hemorrhage can be attributed to small size of the AVM; occlusive pressure
from the hematoma; thrombosis caused by compression from the hematoma or posthemorrhagic edema;
and vascular spasm, or regressive changes of the
vessel wall.4) In the present case, no AVM was identified shortly after cerebral bleeding.
Importantly, small AVMs are considered more
likely to grow than large ones.11) Possible mechanisms of occult AVM enlargement following hemorrhage include hemodynamic stress favoring enlargement of fistulous shunts and poorly differentiated
vessels; repeated ``silent'' hemorrhage resulting
progressive vascular dilation; and space available
for AVM enlargement in the hematoma cavity.10) In

Neurol Med Chir (Tokyo) 41, February, 2001

our patient, MR imaging 2 years after intracranial
hemorrhage demonstrated a few patent abnormal
vessels. Repeated silent hemorrhagic episodes are
unlikely as a mechanism of growth in this case
because serial MR imaging demonstrated no new
hemorrhagic change. Therefore, we suspect that a
small AVM initially present caused the subcortical
hemorrhage and then disappeared, possibly because
of thrombosis related to the hematoma. Subsequent
ongoing hemodynamic stress at the site of the lesion
resulted in regrowth of the AVM. The presence of
the residual cavity from the hematoma might also
have encouraged expansion of the AVM.
Histological abnormalities characterized by increased vascularity have recently been linked to the
angiogenic trophic factor VEGF.6) Immunohistochemistry in the surgical specimen of our case
demonstrated vessel wall staining with VEGF, suggesting a contribution to growth of this occult
AVM. VEGF and VEGF messenger ribonucleic acid
are upregulated in the cells of brain parenchyma

T. Fuse et al.

86

adjacent to AVMs and in the AVMs.1) VEGF was
expressed in four recurrent pediatric AVMs,9) and
30 of 34 cases of AVMs were reactive to VEGF antibody and the endothelium was the most reactive
layer of the AVM vessels.3) These recent observations indicate the involvement of angiogenic factor
VEGF in the pathogenesis of AVM. The AVM wall
may have a biologically changing molecular structure because of continuing angiogenesis, which
may be part of the natural history of AVMs.3) Further investigation is necessary to understand how
VEGF may induce growth of an occult AVM.
Conventional cerebral angiography remains the
gold standard for the diagnosis of AVM.7) However,
cerebral angiography is associated with an incidence of neurological complications of approximately 0.5% to 1%.7) MR imaging is safe and noninvasive, and can demonstrate a patent AVM as a
flow-void signal abnormality. Unfortunately, single
MR imaging examination performed for the diagnosis of AVM detects only about 80% of cases.7)
Follow-up examination using serial MR imaging
is important in young patients with cerebral hemorrhage of unknown origin, even if angiography following hematoma evacuation demonstrates no vascular lesion. We believe that serial MR imaging can
accurately demonstrate patency and enlargement of
a suspected occult AVM.

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Address reprint requests to: T. Fuse, M.D., Department of
Neurosurgery, National Tohsei Hospital, 762–1
Nagasawa, Shimizu–cho, Suntoh–gun, Shizuoka
411–8511, Japan.

Neurol Med Chir (Tokyo) 41, February, 2001