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Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report

Congenital Afibrinogenemia with Cerebellar and Spinal

Cord Infarction Caused by Vertebral Artery Dissection:
A Case Report
Yung-Tsai Chu, Chih-Hao Chen, Li-Kai Tsai, Sung-Chun Tang, Jiann-Shing Jeng

Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

ABSTRACT
Background: Congenital afibrinogenemia is a rare fibrinogen disorder. The typical manifestation is
bleeding tendency, including mucosal, musculoskeletal, and even intracranial bleeding. Nevertheless,
thromboembolic events could still occur. Here we report a case of congenital afibrinogenemia, who
presented with concomitant cerebellar and spinal cord infarction related to vertebral artery dissection.
Case Report: A 35-year-old woman with congenital afibrinogenemia experienced acute-onset vertigo, left
shoulder pain and subsequent left hemiparesis within one week. Initial brain imaging showed left vertebral
artery dissection and infarction of left cerebellum and cervical cord. Aspirin was administered initially but
was later changed to low-molecular-weight heparin for 3 days because of clinical deterioration. Spinal cord
magnetic resonance imaging (MRI) after one week showed hemorrhagic transformation within the infarct
area so all antithrombotic agents were withdrawn. Upon discharge, she was able to carry out most of the
activities of daily living.
Conclusion: This case highlights the importance of recognizing potential thromboembolic events in
patients with afibrinogenemia, and vertebral artery dissection related spinal cord infarction may be a unique
feature.

Keywords: congenital afibrinogenemia, spinal cord infarction, stroke, vertebral artery dissection.

Background The typical manifestation of congenital

Congenital afibrinogenemia is a rare
autosomal recessive fibrinogen disorder. The
prevalence rate is approximately 1/1,000,000. It
is caused by the mutations in one of three genes,
1
FGA, FGB, or FGG. Those genes are responsible
for the production of subunits of fibrinogen and
the mutations cause nearly total loss of functional
fibrinogen.
afibrinogenemia is bleeding tendency, including
mucosal, musculoskeletal, and even intracranial
bleeding. 1 The onset of bleeding complication
mostly is often in childhood. The diagnosis is made
by the coagulation study and the quantification of
fibrinogen level. Some patient may receive regular
fibrinogen replacement therapy for bleeding
prophylaxis.2
Nevertheless, in rare circumstances,

Corresponding author: Dr. Chih-Hao Chen, Department of Neurology, National Taiwan University Hospital, No. 7, Chung-
Shan South Road, Taipei 100, Taiwan, R.O.C.
E-mail: antonyneuro@gmail.com
DOI: 10.6318/FJS.202003_2(1).0008

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 Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report
thromboembolic events could occur. Deep venous
thromboses, arterial occlusion, pulmonary
3
embolism and ischemic strokes are reported. Here
we report a case of congenital afibrinogenemia
presented with concomitant cerebellar and spinal
cord infarction (SCI) related to vertebral artery
(VA) dissection (VAD).
Case Report
A 35-year-old woman was born to
consanguineous parents. She first presented with
easy bruising at 5 months of age. The coagulation
profile showed that her prothrombin time (> 100
seconds) and activated partial thromboplastin
time (> 200 seconds) were above upper limits,
while fibrinogen level was below detection
threshold (< 30 mg/dL). The diagnosis of congenital
afibrinogenemia was made since then.
She had several episodes of hemarthrosis in
left shoulder and right ankles and several episodes
of corpus luteum rupture with hemoperitoneum.
During those acute episodes, cryoprecipitates and
tranexamic acid were administered. At age of 26
years, she developed chronic subdural hemorrhage
with midline shift of 1.4 cm and she underwent
hematoma evacuation. No neurological sequelae
were recorded. At that time, head CT also showed
an incidentally found old insult with tissue lost in
left frontal lobe.
One week prior to this presentation, she
experienced acute-onset vertigo. Three days later,
vertigo resolved but left shoulder pain ensued.
Her husband massaged her neck and shoulders
in order to alleviate her pain. However, the pain
slowly progressed in the following 2 days and left
arm weakness developed. The next day, left leg
weakness was also noted. She was then brought to
the emergency department of our hospital.
Initial neurological examination was notable
for left Horner syndrome, left arm and leg weakness,
and hypoesthesia to pinprick and temperature over
right hemi-body. The muscle power of left arm was
only 1 on Medical Research Council (MRC) scale
and left leg was 4 on MRC scale. A high cervical
cord lesion, more on the left side, was suspected
clinically.
Head computed tomography (CT) revealed
left cerebellar infarct (Figure 1A) and CT
angiography showed dissection from the left
VA V1 to V3 segments (Figure 1B). Aspirin
was administered initially. However, her left
leg weakness worsened from 4 to 2 on MRC
scale, so aspirin was changed to low-molecular-
weight heparin for 3 days. Low-molecular-
weight heparin was shifted to clopidogrel after
stabilization of neurological status. Spinal cord
magnetic resonance imaging (MRI) after one week
(Figure 1C, 1D) demonstrated heterogeneous T2
hyperintensity in nearly whole cervical spinal cord
(C2-C7 segments) with greater involvement of left
hemi-cord. The above findings were suggestive
of cervical spinal cord infarction (SCI) with
hemorrhagic transformation within infarct area.
Her neurological status improved gradually,
and all antithrombotic agents were withdrawn
because of hemorrhagic transformation and her
bleeding diathesis. One month later, when she was
discharged from inpatient rehabilitation unit, the
muscle power of the left arm and left leg were 3
and 5 on MRC scale and she was able to carry out
most of the activities of daily living. Her modified
Rankin scale was 4 initially and improved to 2
upon discharge.
Discussion
Although intracranial hemorrhage is the
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 Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report

Fig. 1. (A) Cerebellar infarct with hemorrhagic transformation on non-contrast CT. (B) Vertebral artery
dissection on contrast-CT reconstructed angiography (arrows). (C) Sagittal view of cervical spine
MRI T2 image showed long-segment hyperintensity indicating acute infarct with edema from
C2 to C6 segments. (D) Axial view of cervical spine MRI T2 image showed infarction in almost
whole spinal cord transection, with heterogeneous signal intensity in the left hemi-cord indicating
hemorrhagic transformation.

leading cause of cerebrovascular event in patients aggregation in the absence of fibrinogen.1

with coagulopathy, thromboembolism event could
occur in certain types of coagulopathy, such as
congenital afibrinogenemia in this case. The
mechanism underlying thromboembolism event
in afibrinogenemia is not fully elucidated yet. The
complex interaction between fibrinogen, thrombin,
von Willebrand factor (vWF) and platelet is
implicated. Fibrin was once called antithrombin
I for its ability to bind thrombin. Thus, lack
of fibrinogen could increase the proportion
of free thrombin, which lead to a paradoxical
prothrombotic state. 3 Moreover, there is also
evidence to suggest vWF could also trigger platelet
Based on literature review, at least 5 cases
of congenital afibrinogenemia-related ischemic
strokes have been reported and their clinical
features are summarized in Table 1.4-7 All 5 cases,
including ours, experienced ischemic stroke in
their 3rd or 4th decade. Four (80%) of them were
female, who all experienced VAD. The only case
not associated with VAD, reported by Nathoo et
al., was a patient who was diagnosed of congenital
afibrinogenemia since age of 5 and received weekly
fibrinogen concentrates infusion. 7 He suffered
from ischemic stroke in the left middle cerebral
artery territory at the age of 21, and then another

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 Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report
episode of ischemic stroke in multiple locations at
the age of 36 years. The cause of infarction could
be caused by congenital afibrinogenemia per se
or viewed as an iatrogenic complication of the
fibrinogen replacement. Of the other 4 patients
with VAD, three (75%) developed SCI. The
incidence of SCI seems much higher in patients
with afibrinogenemia than those without, since two
large series of VAD in general population reported
8, 9
no accompanied SCI. Thus, afibrinogenemia
might be a unique and under-recognized risk factor
of coexistence of VAD and SCI. It was suspected
that in patients with afibrinogenemia, micro-trauma
related bleeding might easily cause intra-mural
hematoma and progressive arterial dissection,
leading to compromised hemodynamic status and
potential embolic formation.10
Among 4 cases of VAD, only ours suffered
from both cerebellar and spinal cord infarctions,
which were supplied by the vertebral artery
simultaneously. The perfusion of upper cervical
spinal cord was mostly supplied by intracranial
and extracranial VA, while the lower cerebellum
was supplied by posterior inferior cerebellar artery,
a major branch of the VA. It has been suggested
that watershed VAD-associated SCI most often
involved C3-C5 cervical cord, while embolic
VAD-associated SCI was often short-segmental
and located at the higher levels. 11 In our case,
anterior watershed infarct secondary to direct flow
compromise of dissection, combined with artery-
to-artery embolic infarcts in the cerebellar might
be the most plausible stroke mechanism.
The treatment consideration of this case
was complicated. From the standpoint of VAD,
antiplatelet or anticoagulant therapy probably hold
similar efficacy as shown in the recent Cervical
Artery Dissection in Stroke Study (CADISS) trial
which included patients with dissection of the
extracranial carotid artery or VA.12 However, in our
case, the possibility of intracranial artery dissection
of V4 segment could not be excluded due to the
lumen narrowing, as shown in Fig. 1-B. Thus,
the result of CADISS trial may not be directly
applicable to our case. In addition, the management
of infarction associated with congenital
afibrinogenemia is not standardized yet, and both
antiplatelet and anticoagulant had been tried in the
past.3 In Table 1, three out of four previous cases
had tried anticoagulant, while another one used
antiplatelet therapy. In our case, we first adopted
antiplatelet but then changed it to anticoagulation
due to clinical progression. Anticoagulation
was stopped because her neurological status
stabilized and follow-up MRI showed hemorrhagic
transformation within the infarct area.
Some experts suggested that concomitant
fibrinogen replacement therapy (FRT) may
be administered to reduce the risk of severe
hemorrhage during the use of antithrombotics.3
However, this practice is still controversial because
thrombotic complication has been reported after
FRT. A review of fibrinogen replacement therapy
showed a relatively high rate of thrombotic
complication, including deep vein thrombosis,
pulmonary embolism and emboli in the cerebral
circulation.2 Therefore, close monitor of potential
thromboembolic events is required when FRT is
administered, and simultaneous anticoagulation
might even be considered.2 In our case, we did not
choose FRT in the acute stage because she already
had significant burden of infarction, including
preceding cerebellar infarct and subsequent SCI,
and FRT may exacerbate the thromboembolic
process. Her stroke condition stabilized without
FRT, and her function recovery was also fair.
In summary, despite long-standing history of
bleeding in multiple sites, this patient suffered from
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Table 1. Clinical and imaging findings for 5 patients with adult ischemic strokes associated with congenital afibrinogenemia

Authors, year Garcia-Monco et al. Laufs et al. 20045 Bas et al. 20096 Nathoo et al. 20187 Present case
19994
Age, year 28 32 22 36 35
Sex Female Female Female Male Female
Prior cerebro-
vascular event nil nil nil Left MCA infarct Old insult in left frontal
lobe
Management before nil regular fibrinogen in nil Clopidogrel Nil
presentation menstrual cycle
Predisposing event nil nil nil nil Neck massage
Initial presentation Neck pain Neck pain, left Quadriparesis Headache, diplopia, vertigo Vertigo, left hemiparesis
hemiparesis
Infarct location Right medulla C2-C4 SCI C2-T1 SCI Bilateral cerebellum, left Left cerebellar (PICA
occipital lobe and right territory), C2-C7 SCI
parietal lobe
Associated vascular Bilateral VAD Left V2-V3 VAD Right V1–V2 VAD right superior cerebellar Left V1-V3 VAD
anomaly artery was irregular distally,
chronic occlusion of left ICA
to MCA

Diagnostic modality MRI MRI MRI, DSA CTA MRI, CTA

Treatment FR, AC FR, AC FR, AP, steroid pulse AC AP, AC
therapy
Abbreviation: AC, anticoagulation; AP, antiplatelet; CTA, computed tomography angiography; DSA, digital subtraction angiography; FR, fibrinogen replacement;
MCA, middle cerebral artery; MRI, magnetic resonance imaging; PICA, posterior inferior cerebellar artery; SCI, spinal cord infarct; TIA, transient ischemic
accident; VAD, vertebral artery dissection.
Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report
 Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report
concomitant cerebellar and spinal cord infarction
due to VAD. This case highlighted the importance
of recognizing potential thromboembolic events in
patients with afibrinogenemia. The management
should depend on the clinical judgement of the
dynamic state between thrombosis and hemorrhage
in the setting of afibrinogenemia.
Conflicts of Interest
The authors have no conflicts of interest
relevant to this article.
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 Congenital Afibrinogenemia with Cerebellar and Spinal Cord Infarction Caused by Vertebral Artery Dissection: A Case Report

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