Clinical Neurology and Neurosurgery 108 (2005) 52–55

Case report

Alexia without agraphia following cerebral venous thrombosis
associated with protein C and protein S deficiency
Nese Celebisoy∗ , Ayse Sagduyu, Ceyla Atac
Department of Neurology, Ege University Medical School Hospital, Bornova, 35100 Izmir, Turkey
Received 18 June 2004; received in revised form 13 September 2004; accepted 3 November 2004

Abstract
A 26-year-old right handed female was admitted to hospital with right homonymous hemianopia associated with alexia without agraphia.
Her cranial magnetic resonance imaging and magnetic resonance angiography revealed a left occipital venous infarction due to thrombosis
of the left transverse, sigmoid sinuses and the left internal jugulary vein. The underlying conditions were protein C and protein S deficiency
associated with the use of oral contraceptives. To our knowledge, alexia without agraphia has never been described due to a venous infarction
associated with hereditary thrombophilia in the literature.
© 2004 Elsevier B.V. All rights reserved.
Keywords: Alexia without agraphia; Intracranial venous thrombosis; Protein C and S deficiency

1. Introduction
Alexia without agraphia is a rare disturbance, which is
mostly caused by a stroke in the territory of the left posterior
cerebral artery, with infarction of the medial occipital lobe,
the medial temporal lobe, and often the splenium of the corpus callosum. However, the syndrome has also been reported
in CNS infections [1,2], tumors [3], multiple sclerosis [4],
eclampcia [5] and following head trauma [6], as well as with
right occipital lobe lesions in left handed patients [7]. Venous
infarction has not been mentioned as one of the etiologic factors.

2. Case Report
A 26-year-old right handed female was admitted to our
clinic with right sided visual loss. Three days before admission she had complained about occipital head pain radiating
to neck, followed by vomiting and loss of vision in both eyes
for which she had been seen in another hospital. Loss of vision
∗ Corresponding author. Tel.: +90 232 3880980; fax: +90 232 3880980.

E-mail address: celebi@med.ege.edu.tr (N. Celebisoy).
0303-8467/$ – see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.clineuro.2004.11.005

had lasted for 3 h and resolved partially leaving a right sided
hemianopia when she was taken to our clinic for further investigations. She had never experienced memory loss. Her past
medical history was insignificant other than oral contraceptive usage for 6 months. Her physical examination was normal. The neurological examination revealed right homonymous hemianopia. The visual acuities were normal on both
sides with normal fundoscopic appearance. At the time her
history was taken she had almost normal language function
but Boston Diagnostic Aphasia Examination revealed that she
was unable to read the words and had difficulty in spelling.
However, she could read the letters and the numbers and
could name visually presented objects without difficulty. Her
comprehension of oral spelling was normal. Though she was
slow, she could write orally presented words correctly and she
could name the colors. These clinical features were consistent
with alexia without agraphia. The remainder of the examination was unrevealing. Her complete blood count showed anemia with Hb levels 8.6 mg/dl and Hct 27.2. Leukocyte and
platelet counts were normal. Blood smears showed hypochromia and microcytosis. On blood biochemistry, serum iron
concentration was found to be 12 ␮g/dl (50–140) and the
iron binding capacity was 360 ␮g/dl (250–350), which were
consistent with iron deficiency anemia. The rest of the blood

N. Celebisoy et al. / Clinical Neurology and Neurosurgery 108 (2005) 52–55

Fig. 1. T2-weighted axial MRI showing a hyperintense lesion with hypointense components in it, localized at the left occipital lobe, consistent
with a haemorrhagic infarction.

biochemistry was normal. Immunologic tests including antinuclear antibody, ethanol and formalin ANCA, anti Ro, anti
La antibodies, anti dsDNA, anticardiolipin IgM and anticardiolipin IgG levels did not reveal any pathology. The activated
partial thromboplastin time, prothrombin time and fibrinogen levels were within normal limits. Protein C and protein
S concentrations measured by an automated functional clotting assay for the quantitative determination of protein C and
protein S in human plasma (IL testTM Proclot for protein C
and IL testTM protein S for protein S, Instrumentation Laboratory, Italy) were 10% (normal 70–140%) and 40% (normal 60–140%), respectively. Antithrombin III level was 96%
(normal 70–125%) by a chromogenic assay (IL testTM Antithrombin III, Instrumentation Laboratory, Italy). Factor V
Leiden mutation was negative. Cranial computed tomography (CT) without contrast performed on the day of admission showed hyperdensity of the left sigmoid sinus associated with a left occipital hypodensity. Magnetic resonance
imaging (MRI) revealed a left occipital lobe lesion with both
hypointense and hyperintense components on T1- and T2weighted images consistent with a haemorrhagic infarction
(Fig. 1). Magnetic resonance angiography (MRA) revealed
thrombosis of the left transverse, sigmoid sinuses and the left
internal jugulary vein (Fig. 2).
She was treated with intravenous heparin continued with
oral warfarin with target INR of 2.0–3.0. On the sixth day of
admission, she began to read the letters. When she left the
hospital at the end of 3 weeks, she was able to read slowly
with the right sided hemianopia still continuing.

3. Discussion
Alexia without agraphia is a rare disconnection syndrome
first described by the French neurologist Dejerine in 1892
in a patient with an infarction involving the medial occipital

53

Fig. 2. MRA showing absence of flow in the left transverse and sigmoid
sinuses and the left internal jugulary vein.

lobe and the splenium of the corpus callosum. It is characterized by the loss of reading ability with retention of writing and verbal comprehension. Associated deficits include a
right hemianopia or right upper quadrant defects in nearly all
patients. Color anomia is found in 50–70% of patients [8].
There is usually no hemiparesis or sensory loss but a shortterm memory deficit may be seen due to the damage of the
medial temporal lobe [9]. Patients initially cannot read at all.
As they recover, they learn to read letter by letter. By contrast,
they can quickly understand words spelled orally to them, and
their own written spelling is intact. Dejerine claimed that the
syndrome could be explained by a severing of the tracts that
connected the left and right primary visual cortex to the left
angular gyrus. However, Geshwind and Damasio have placed
more stress on the involvement of the transhemispheral fibers
in producing the syndrome [10,11].
Cerebral venous thrombosis (CVT) accounts for less than
1% of all strokes [12]. The disease occurs in all age groups
with peak incidences in neonates and in adults in their third
decade with a female/male ratio of 1.5–5 [13]. The presenting clinical picture depends on the extension, localisation and
activity of the thrombotic process as well as on the presence
of venous collaterals [12]. Headache is the most frequent
symptom of CVT and occurs in 75–95% of all cases [13,14].
In most cases, headache precedes the development of other
neurological deficits for days. Focal neurological signs are
the most common finding. They include central motor and
sensory deficits, aphasia or hemianopia and occur 40–60%
of all cases. Our patient had a history of occipital head pain
for 3 days when she first realized bilateral visual loss which
lasted for a few hours and resolved partially leaving a right
sided homonymous hemianopia associated with alexia without agraphia, found on neurological examination. The usual
lesion for this disorder is one that destroys the visual cortex
of the left hemisphere and the splenium of the corpus callosum. However, in our patient the lesion was restricted to the

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N. Celebisoy et al. / Clinical Neurology and Neurosurgery 108 (2005) 52–55

left occipital lobe and alexia without agraphia was a transient
disorder, which seems to be due to the edema effect on the
medial structures.
The diagnosis of CVT is based on neuroimaging. CT is
usually the first investigation performed in the emergency
room [15]. The cord sign, a visualization of a hyperdense
thrombosed cortical vein and a dense triangle sign indicating
a fresh thrombus in the posterior part of the superior saggital
sinus are direct signs of CVT on unenhanced CT. Empty triangle or delta sign, a non-filling of the confluens sinuum on contrast enhanced CT is the most frequently observed direct sign.
MRI and MRA are the best tools both for the diagnosis and
follow up of CVT [16,17]. Within the first days, the thrombus appears isointense on T1-weighted and hypointense on
T2-weighted images. An absence of flow void in the form
of higher intraluminal signal intensity is observed after administration of gadolinium. In the majority of cases multiple small intraparenchymal haemorrhages surrounded by a
hypodensity, which is compatible with venous hemorrhagic
infarction is found. Pathophysiologically, venous thrombotic
occlusion increases venous and capillary pressure and thus
promotes diapedesis of erythrocytes causing haemorrhagic
infarcts in CVT [18]. MRA shows a loss of signal-due to absence of flow-of the thrombosed sinus. Unenhanced CT of
our patient showed hyperdensity of the left sigmoid sinus associated with a left occipital hypodensity. MRI revealed a left
occipital lobe lesion with both hypointense and hyperintense
components on T1- and T2-weighted images consistent with
a hemorrhagic infarction. MRA showed thrombosis of the
left transverse, sigmoid sinuses and the left internal jugulary
vein.
Underlying conditions which may cause CVT are varied
[14,15,19]. The aetiology remains unknown in up to 35%
of cases [20]. A hereditary thrombophilia will be found in
20–30% of patients [21]. Common inherited trombophilic
dispositions are the factor V Leiden mutation, 20210 G to
A mutation of the prothrombin gene, antithrombin, protein C
and protein S deficiency. Factor V Leiden mutation is detected
in 15–17% and prothrombin gene mutation in 10–12% of the
cases whereas protein C and S deficiency is rare and detected
in only 2–6% of cases. Several studies have indicated that the
combination oral contraceptives and thrombophilia greatly
increased the risk of CVT [22,23]. In addition to protein S
and C deficiency our patient was using oral contraceptives.
Available treatment data from collected trials favour the
use of anticoagulation in patients with CVT [24,25]. However, controlled data about the optimal duration of therapy
does not exist [12]. Oral anticoagulation is recommended
for 3 months in patients with idiopathic CVT and for 3–6
months if it is related to pregnancy or oral contraceptives.
In patients with hereditary thrombophilia it is used for 6–12
months or longer [12]. Anticoagulant therapy was instituted
in our patient after the diagnosis of CVT was verified. Alexia
without agraphia showed prominent regression at the end
of three weeks but right sided hemianopia was continuing.

In the current literature, this is the first case with alexia
without agraphia due to CVT associated with hereditary
thrombophilia and oral contraceptive usage.

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