DOI: 10.5137/1019-5149.JTN.10918-14.1

Faktör V Leiden Tanılı 8 Yaşında Erkek Çocukta Eozinofilik Granülom
Rezeksiyonu Sonrası Gelişen Sağ Orta Serebral Arter İnfarktı
Ertugrul cakır1, Erhan Arslan2, Ugur Yazar1, Gokce Pinar Reıs3
1Karadeniz Technical University, School of Medicine, Department of Neurosurgery, Trabzon, Turkey
2Giresun University, School of Medicine, Department of Neurosurgery, Giresun, Turkey

3Karadeniz Technical University, School of Medicine, Department of Pediatric Hematology, Trabzon, Turkey

Corresponding Author: Erhan Arslan / E-mail: [email-masked]

ABSTRACT
Stroke in children is relatively uncommon. We describe an 8-year-old boy diagnosed with primary eosinophilic granuloma (EG) of the frontal
bone. After excision of the EG, the postoperative course was eventful. The patient had an acute right middle cerebral artery (MCA) infarct and
had been comatose with a diminished Glasgow Coma Scale (GCS) score of 5. Urgent decompressive hemicraniectomy with duraplasty was
performed. The postoperative course after the second operation was uneventful. Hematological tests revealed a diagnosis of factor V Leiden.
The patient was discharged with left hemiparesis and GCS of 15. To the best of our knowledge, no such clinical picture of MCA infarction
after EG excision has been described before. Neurosurgeons should be aware of inherited thrombophilias, such as factor V Leiden, if the
postoperative clinical course worsens because of cerebral artery thrombosis. Also, decompressive hemicraniectomy could be life saving and
should be performed urgently without any hesitation.
Keywords: Decompressive hemicraniectomy, Eosinophilic granuloma, Factor V Leiden, Middle cerebral artery stroke

ÖZ
Çocuklarda inme göreceli olarak nadirdir. Frontal kemikte primer eozinofilik granülom (EG) tanısı almış 8 yaşında erkek çocuk hastayı
sunmaktayız. EG’nin eksizyonundan sonra, postoperatif seyir beklenmedik şekilde gelişti. Hasta akut sağ orta serebral arter (OSA) infarktı
geçirip, Glasgow Koma Puanı (GKP) 5’e düşüp, koma halini aldı. Acil dekompresif hemikraniyektomi ve duraplasti yapıldı. İkinci operasyondan
sonra hastanın postoperatif seyri olağandı. Hematolojik testlerde faktör V Leiden teşhisi konuldu. Hasta GKP 15 ve sol hemiparezi ile taburcu
edildi. Bilgilerimiz ışığında, EG eksizyonu sonrası OSA infarktı olan bu şekilde bir klinik tablo henüz bildirilmemiştir. Eğer serebral arter
trombozundan dolayı postoperatif klinik gidişat kötüleşir ise, nöroşirürjiyenler faktör V Leiden gibi kalıtımsal trombofililerin de bu durumun
sebebi olabileceğinin farkında olmalıdırlar. Ayrıca dekompresif hemikraniyektomi, bu gibi inme durumlarında acilen ve tereddütsüz olarak
uygulandığında hayat kurtarıcı olabilir.
ANAHTAR SÖZCÜKLER: Dekompresif hemikraniyektomi, Eosinofilik granülom, Faktör V Leiden, Orta serebral arter inmesi

CASE ILLUSTRATION
An 8-year-old boy was referred to our outpatient clinic with
swelling in the right frontal region and headache around the
right ear. Cranial computed tomography (CT) showed a bone
defect at the right frontal bone (Figure 1a). A mass, 27x11
mm in size with typical eosinophilic granuloma, isointense
to gray matter on T1W images (Figure 1b) and slightly hyperintense to gray matter on T2W images (Figure 1c) at cranial
magnetic resonance imaging (MRI) was observed. The neurosurgery clinic was consulted. Once preoperative preparations
including bleeding and coagulation times, were completed,
the mass was resected totally, together with a sound area of
skull bone. There was no evidence of dural infiltration by the
tumor. Histopathological examination revealed eosinophilic
Turk Neurosurg 2015, Vol: 25, No: 5, 831-834

granuloma with typical Langherhans cells and eosinophilic
infiltration. Postoperative course was eventful. At the 5th hour
postoperatively, the patient suffered a focal seizure with shaking of the left lips and jaw. In the postictal period, the patient
was unconscious with a left hemiparesis (grade 2 on the muscle strength test) and Glasgow Coma Scale (GCS) score was
9. The pediatric neurology department was immediately consulted. Bolus infusion of phenytoin sodium at 20 mg/kg/h for
30 minutes was performed. Phenytoin sodium was continued
at 5 mg/kg qid. Dexamethasone 0.25 mg/kg qid and furosemide 1 mg/kg bid were also added to the medical therapy. As
the dura was not opened during surgery, Todd’s paralysis after seizure attack was suspected and electroencephalography
(EEG) was performed. Cranial CT on the same day was consistent with slight cerebral edema (Figure 2a). The patient’s

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Case Illustration

A Right Middle Cerebral Artery Infarct After Frontal
Eosinophilic Granuloma Resection in an 8-Year-Old
Boy with Factor V Leiden

Cakir E. et al: Cerebral Infarct with Factor V Leiden

left motor weakness progressively increased to hemiplegia,
and GCS decreased to 7. Urgent cranial MRI was performed.
Cranial MRI with diffusion weighted images revealed an acute
cerebral infarct in the water shedding area of the right middle
cerebral artery (MCA) and ventricular shifting towards the left
side (Figures 2 b,c). Digital substraction angiography (DSA)
was immediately performed. This revealed severe stenosis of
the right internal carotid artery (ICA) just before the bifurcation, and occluded right MCA from the point of origin. Blood
flow in the left ICA was normal. No filling of the right ICA and
MCA by the way of the anterior communicating artery (AcomA) was observed (Figure 2d). The patient was transferred
to the intensive care unit (ICU). Information about the patient’s clinical course was given to the parents, during which
we obtained further details regarding his familial history. We
learned that the patient’s sister, who was 3 years older than
him, also had cerebral infarct after a minor head trauma. She
had experienced a left upper extremity monoparesis. The patient was examined by the pediatric hematology department.
Anticoagulant (enoxaparin sodium) at 100 U/kg bid was started, and 70 mg/day acetylsalicylic acid was added. Blood levels
of protein C, protein S, homocysteine, lipoprotein (a) and factor VIII, and prothrombin time (PT) and partial thromboplastin
time (PTT) were normal. Blood tests using SNaPshot revealed
no prothrombin G20210A mutation. However, the patient
was heterozygous for factor V Leiden, and heterozygous for
methylenetetrahydrofolate reductase (MTHFR) C677T mutation. His sister’s and parents’ blood were also analyzed. His sister was homozygous for the MTHFR C677T mutation, and the
father and mother were heterozygous for the MTHFR C677T
mutation. The patient’s ECHO cardiogram and Doppler ultrasonography revealed no other thrombus in the cardiovascular
system. His clinical condition worsened, and GCS decreased
to 5. We performed urgent right fronto-temporoparietal decompressive craniectomy with duraplasty (Figure 3a). The patient was observed in the ICU in an intubated state. The post-

A

b

operative course after decompressive hemicraniectomy was
uneventful. The patient was extubated on the 15th day postoperatively. At neurological examination, GCS was 14 with
left hemiplegia. Passive exercises were started in the ICU. On
the 20th day postoperatively, the patient was transferred to a
bed in the neurosurgery clinic. On the 45th day postoperatively, the removed skull bone was replaced on the cranial defect (Figure 3b). The patient was transferred to physical therapy and rehabilitation clinic 2 months after the first operation
with left hemiparesis (grade 2 on the lower extremity muscle strength test and grade 1 on the upper extremity muscle
strength test). The patient showed improvements in motor
power. By the 6th month after the first operation, he had grade
4 muscle strength in the left lower extremity and grade 3
muscle strength in the left upper extremity. On discharge, the
patient was able to walk without assistance.
Eosinophilic granuloma (EG) is considered a benign histiocytosis of unknown etiology. It is characterized by single or
multiple skeletal lesions. It predominantly affects children,
adolescents and young adults, although it may be encountered at all ages. Solitary lesions are more common than multiple ones. The more common sites for EG include the skull,
mandible, spine, ribs and long bones (1). The usual treatment
of solitary EG of the skull consists of a craniectomy, or curettage if necessary, followed by local radiation therapy (1). As
the usual treatment of solitary EG is resection of the mass, we
excised the frontal EG using craniectomy in our patient. The
patient’s preoperative hematological tests, including PT and
PTT, were within normal limits. The patient suffered an unexpected arterial ischemic stroke on the first postoperative day.
Stroke in children is a heterogeneous disorder. Multiple
risk factors for stroke have been reported, and genetic
predisposition to stroke has been confirmed (5). The incidence
of stroke in children is estimated at between 2.6 and 6.4 per
100,000 per year, with a higher frequency in the current

c

Figure 1: a) Axial computed CT scan showing an osteolytic lesion in the right frontal bone on the right side. b) Axial T1W MRI scan
showing a lesion isointense to gray matter, c) axial T2W MRI scan showing a lesion slightly hyperintense to gray matter in the right
frontal bone.

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Turk Neurosurg 2015, Vol: 25, No: 5, 831-834

Cakir E. et al: Cerebral Infarct with Factor V Leiden

literature (2). In children up to age 14, the incidence of stroke
ranges from 2 to 8 per 100,000 (3). The most frequently reported
risk factors for stroke are congenital heart malformations,
hemolytic anemias, collagen vascular diseases and some rare
congenital metabolic disorders. Trauma, infectious diseases,
and thrombophilias are also included among the risk factors
(5). In up to 30% of children, risk factor cannot be established,
despite extensive investigations (5).
The well-established inherited thrombophilic risk factors are
deficiency of antithrombin, protein C, and protein S, factor V
Leiden and factor II G20210A (5). Several studies have reported

A

c

A

Turk Neurosurg 2015, Vol: 25, No: 5, 831-834

an increased frequency of factor V Leiden in childhood
arterial ischemic stroke (5). Kenet et al. (2) reported that metaanalysis showed a significant association between arterial
ischemic stroke and FV Leiden and PT G20210A. Our case had
an inherited thrombophilic risk factor (factor V Leiden). The
first operation (excision of EG) was also another risk factor for
arterial thrombosis. Both of these thrombophilic factors may
have led to MCA thrombosis in this child. Stroke in children
results in significant morbidity and mortality. Brain swelling
and subsequent cerebral herniation is the usual cause of early
death after acute stroke. Medical treatments may help to

b

d

b

Figure 2: a) Axial CT scan taken on the first
postoperative day showing the right frontal
bone defect and slight hypointensity and
effacement of sulci in the right frontoparietal
region. b) Axial T2W MRI scan demonstrating
hyperintensity in the area of the right middle
cerebral artery (MCA). c) Apparent Diffusion
Coefficient (ADC) showing hyperintensity in
the area of the right MCA due to acute cerebral
infarct. d) A frontal view of the right carotid
angiogram showing thrombus formation within
the right internal carotid artery (ICA) just before
it bifurcates, and excessive stenosis in this
segment (arrow). Note that there is no blood
flow in the right MCA, due to thrombosis.

Figure 3: a) Axial computed CT scan after
decompressive hemicraniectomy showing
the right cerebral infarct with ventricular
midline shifting. Note the swollen cerebral
parenchyma extending through the cranial
defect. b) Computed CT scan after replacement
of the removed skull bone showing the right
frontoparietal chronic infarct with pulling of the
right lateral ventricle to this encephalomalacic
site.

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Cakir E. et al: Cerebral Infarct with Factor V Leiden

control intracranial hypertension. However, failure of medical
therapy and progressive worsening of clinical condition, as
in our patient, necessitate surgical decompression. Optimal
timing of decompressive craniectomy remains controversial
(4). If signs of herniation and midline shift appear at cranial
CT or MRI, surgery should be considered. Recent studies have
reported that if decompressive craniectomy is performed
early the procedure reduces mortality and also improves
functional outcomes (4). The potential life saving benefit of
decompressive craniectomy has been shown in the literature
and in our experience with our patient.
We report an 8-year-old boy undergoing EG excision from
the skull and decompressive hemicraniectomy for right MCA
infarct due to factor V Leiden. The lesson we have learned from
this patient is familial history must be taken from the parents
with great care, and only this may prevent postoperative
morbidity and mortality. Inherited thrombophilias (e.g,
factor V Leiden and MTHFR mutations) must be kept in
mind if cerebral arterial thrombosis occurs in a child. We
would also emphasize the importance of decompressive
hemicraniectomy. This can be life-saving if performed in
patients with life-threatening brain swelling refractory to
medical treatment.

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