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When the Problem Became the Solution
Ari Shemesh, Laila Al-Shafai, Timo Krings, Edward Margolin

ABSTRACT: We present a unique case where a young man developed subtle cavernous sinus thrombosis (CST) due to underlying
hypercoagulable state. He also had coexisting frontal lobe brain dural arteriovenous fistula (bdAVF). After CST developed, venous
drainage from the optic nerve was redirected into the frontal lobe which was already under high venous pressure because of preexisting
bdAVF. This caused backflow of venous blood into the optic nerve causing massive persistent optic nerve head swelling. Presumed acute
venous hypertension event within bdAVF caused frontal mass effect presenting as seizure leading to thrombosis of bdAVF.
RÉSUMÉ: Comment faire d’un problème une solution. Nous voulons présenter ici le cas unique d’un jeune homme chez qui une thrombose du sinus
caverneux s’est développée en raison d’une condition sous-jacente d’hypercoagulabilité. Ajoutons également que le lobe frontal de son cerveau donnait à
voir des fistules artério-veineuses durales. Une fois développé ce type de thrombose, on a procédé à un drainage veineux à partir du nerf optique, drainage
ensuite redirigé dans le lobe frontal, lequel faisait déjà face à des conditions de pression veineuse élevée à cause de ces fistules. Cela a entraîné le
refoulement de sang veineux dans le nerf optique, ce qui a provoqué en retour une grave et persistante enflure de la tête du nerf optique. À cet égard, on
peut présumer qu’une manifestation aigüe d’hypertension veineuse dans ces fistules a causé l’apparition de cet effet de masse du lobe frontal se
manifestant par des crises convulsives, ce qui a fini par engendrer la thrombose des fistules artério-veineuses durales.

Keywords: Brain dural arteriovenous fistula, Neuro-ophthamology, Cavernous sinus thrombosis, Antiphospholipid antibody syndrome

doi:10.1017/cjn.2019.239

Can. J. Neurol. Sci. 2019; 46: 767–769

A 25-year-old man noticed gradual worsening of vision in the
left eye over 4 weeks. Vision was 20/40 with the presence of optic
nerve head swelling on the affected side. Brain MRI reported
white matter hyperintense lesions limited to the left frontal lobe.
Lumbar puncture demonstrated normal cerebrospinal fluid composition and no oligoclonal banding. Multiple sclerosis was felt
to be a possible diagnosis and treatment with dimethyl-fumarate
commenced.
Vision continued to deteriorate and when seen 2 months later, it
was 20/200 in the left eye with the presence of brisk relative afferent
pupillary defect. Fundoscopy demonstrated massive optic nerve
head edema with surrounding hard exudates (Figure 1A). Urgent
brain and orbits MRI/MRV demonstrated hyperintense white matter
lesions in the deep left frontal lobe (Figure 1B) that seemed
microischemic and not demyelinating in nature but was otherwise
normal. Treatment with dimethyl-fumarate was stopped. Extensive
workup (testing for HIV, Lyme, Toxoplasma, Bartonella titers,
VDRL, ACE, ANA, ds-DNA, ENA, NMO, total body CT, and
gallium scan) looking for potential etiologies of severe unilateral
optic nerve head swelling was all unrevealing. Over the following 2
years, vision remained stable with remarkably persistent swelling of
the left optic nerve head. Repeated tests including repeat of previously performed serologic testing, total body CT, and lumbar
puncture were all noncontributory.
Two and a half years after the initial presentation, the patient
developed a generalized seizure. MRI of the brain was urgently
performed and demonstrated a left frontal lobe mass with surrounding edema and peripheral enhancement (Figure 1C). Brain
biopsy was performed and demonstrated macrophages surrounding blood vessels and unexpected areas of necrosis but was
deemed indeterminate. Second opinion on the results of the

biopsy reported findings inconsistent with both demyelination
and arterial infarct. Cerebral angiography was performed and
demonstrated unusual left hemispheric cortical veins without
arteriovenous shunting. After consulting with pulmonary, rheumatological, and neuroradiological services, neurosarcoidosis
was felt to be a unifying diagnosis. After receiving 3 days of
1 g of intravenous methylprednisolone, treatment with oral
mycophenolate mofetil commenced. MRI of the brain performed
2 months later demonstrated dramatic resolution of left frontal
lobe lesion.
While satisfied with radiological improvement, the case was
reexamined and the diagnosis of neurosarcoidosis was challenged. Cerebral angiogram was meticulously reexamined.
Unusual tortuous cortical veins in the left hemisphere were
noticed and felt to be compatible with “pseudophlebitic” pattern
seen in brain dural arteriovenous fistulas (bdAVF) (Figure 1D).1
Enlarged left anterior falcine artery was also demonstrated
(Figure 1E). Review of the literature on the pathological findings
seen in bdAVFs yielded one published retrospective study of
spinal dural AVFs biopsies that were performed because the
lesion resembled a neoplasm radiologically. Their reported tissue
findings were the presence of thick-hyalinized vessels in all cases,
hemosiderin-laden macrophages in 71%, and necrosis in 29%.2

THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES

767

https://doi.org/10.1017/cjn.2019.239 Published online by Cambridge University Press

From the Department of Ophthalmology and Vision Sciences, University of Toronto,
Toronto, Ontario, Canada (AS, EM); Department of Medical Imaging, University of
Toronto, Toronto, Ontario, Canada (LA-S, TK)
RECEIVED DECEMBER 24, 2018. FINAL REVISIONS SUBMITTED JUNE 24, 2019. DATE OF
ACCEPTANCE JUNE 29, 2019.
Correspondence to: Edward Margolin, Department of Ophthalmology and Visual
Sciences, Department of Medicine, Division of Neurology, Chief of Service, NeuroOphthalmology, University of Toronto, 801 Eglinton Ave West, Suite 301, Toronto,
Ontario M5N 1E3, Canada. Email: edward.margolin@uhn.ca

THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES

Figure 1: (A) Fundus photo of the left eye demonstrating massive optic nerve head swelling with surrounding hard exudates. (B) MRI. Corontal T2
sequence demonstrating hyperintense lesions deep in the left frontal lobe (blue arrow). (C) MRI. Axial T1 with gadolinium demonstrating left frontal
mass lesion with peripheral enhancement. (D) Left lateral internal carotid angiogram demonstrating "pseudophlebitic pattern" in the left frontal
lobe. (E) Left lateral internal carotid angiogram demonstrating enlarged left anterior falcine artery (white arrow). (F) Frontal lobe biopsy
specimen. Hematoxylin and eosin (H&E) and Prussian blue stain demonstrating perivascular macrophages (yellow arrows). (G) Right and left
lateral carotid angiograms demonstrating decreased left cavernous perfusion. (H) MRI. Coronal FLAIR demonstrating left hyperintense signal in
the left cavernous sinus corresponding to cavernous sinus thrombosis.

Third review of brain biopsy was thus requested and reported the
presence of thick-hyalinized vessels, hemosiderin-laden macrophages, and areas of necrosis in our case that were all compatible
with chronic venous congestion (Figure 1F).
A decision was made to perform a second cerebral angiogram
as the presence of previously not identified bdAVF was felt to be
the most likely diagnosis; however, it also failed to demonstrate
it.1 Detailed review of both angiographies was undertaken and
revealed unusual tortuous cortical veins in the left frontal lobe
consistent with “pseudophlebitic” pattern seen in bdAVFs.1 It
was previously reported that in small number of patients bdAVFs
can spontaneously close off during an acute venous hypertensive
event and thus cannot be demonstrated on follow-up cerebral
angiograms.3 We believe that this is what happened in our
patient, and spontaneous closure of his bdAVF explained the
resolution of the left frontal mass lesion on follow-up MRI after
brain edema has resorbed. It was also noticed that there was definite
decreased perfusion of the left cavernous sinus on both angiographies (Figure 1G). When all imaging was reexamined, subtle left
cavernous sinus thrombosis (CST) was seen in all previous studies

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https://doi.org/10.1017/cjn.2019.239 Published online by Cambridge University Press

(Figure 1H). Full hypercoagulability workup revealed significantly
elevated titers of anticardiolipin IgG antibodies (46 CU, normal
<20), which were even higher on repeat testing performed 1 month
later. Hypercoagulable state due to anticardiolipin antibody syndrome was felt to be the most likely cause of long-standing left
CST. Treatment with oral steroids was discontinued; and at the last
follow-up 4 years after presentation, visual acuity was hand motions
in the affected eye with the atrophic-looking optic nerve. There
were no new brain lesions on follow-up neuroimaging.
BdAVFs account for 10%–15% of all intracranial arteriovenous malformations. They represent an abnormal communication
between an artery and small veins in the dura mater.1 Venous
drainage of bdAVF dictates their clinical presentation: frontal
bdAVFs draining toward the cavernous sinus exhibit features of
orbital congestion4 but bdAVFs draining anteriorly have aggressive natural history with annual event rate of 15%.1 Absence of
dural sinus in the anterior cranial fossa causes venous drainage to
flow directly into the intracranial cortical veins with retrograde
venous reflux into brain parenchyma,4 seen radiologically as
“pseudophlebitic” pattern.

LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES

The most sensitive test for localizing arteriovenous shunting is
cerebral angiography. However, its false negative rate is 10%;
and in 7% of cases, fistulas can spontaneously thrombose during
an acute venous hypertensive event thus no arteriovenous shunting can be demonstrated.1,3
We hypothesize that in our case there was a long-standing left
frontal lobe bdAVF based on the presence of indirect neuroimaging findings: enlarged anterior falcine artery (branch of anterior
ethmoid artery which is the most commonly reported feeder
vessel in frontal bdAVFs) on cerebral angiogram plus a unique
pattern of venous drainage seen in the left frontal lobe.5 Both
brain MRI and cerebral angiogram demonstrated “pseudophlebitic” pattern implying the presence of retrograde leptomeningeal
venous reflux. We believe that hyperintense white matter lesions
limited to the left frontal lobe were a consequence of microischemic injury which has been reported in bdAVF.6 While
hypercoagulable state due to elevated plasma titers of anticardiolipin’s antibodies was likely the cause of CVT in our case
(the presence of anticardiolipin antibodies has been well described to be associated with CVT), it is unclear whether bdAVF
predisposes to CVT or whether bdAVF results from CVT.7,8
We hypothesize that the left frontal lobe bdAVF drained both
posteriorly toward the cavernous sinus and anteriorly toward the
frontal lobe. A hypercoagulable state conferred by the presence
of very elevated anticardiolipin antibody titers likely led to the
formation of left CST. This in turn resulted in an optic neuropathy by diverting venous drainage from the left optic nerve
sheath that was destined to flow back into the cavernous sinus to
instead flow toward the left frontal lobe, which was coincidentally chronically under high venous pressure because of the
presence of bdAVF. This led to the continuous optic nerve
leakage and caused massive optic nerve head edema. We
hypothesize that no other signs of orbital congestion were seen
because of the compartmentalization of cavernous sinus that
resulted in subtle CST that affected only venous drainage from
the left optic nerve sheath.
Two and a half years after the onset of left optic neuropathy,
the patient had a presumed acute venous hypertensive event
(clinically manifesting as a seizure) in the area supplied by
bdAVF. Coincidentally, elevated titers of anticardiolipin antibodies conferred a prothrombotic state causing spontaneous

Volume 46, No. 6 – November 2019
https://doi.org/10.1017/cjn.2019.239 Published online by Cambridge University Press

clotting of the bdAVF during the acute event; thus, no shunting
of bdAVF was demonstrated on two cerebral angiograms. Closure of bdAVF then led to the resorption of brain edema and
dramatic resolution of frontal lobe lesion.
This unique case demonstrates how interaction between
hypercoagulable state and the presence of bdAVF in the same
patient led to monocular visual loss but serendipitously caused
spontaneous resolution of bdAVF.
DISCLOSURES
The authors have no conflicts of interest to declare.
STATEMENT OF AUTHORSHIP
All authors contributed equally to the preparation of the
manuscript.
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