Medicine

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Clinical Case Report

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Acute ischemic stroke in a 7-month-old infant,
risk factors, and diagnosis peculiarities
A case report

∗

Lorena Elena Meliţ, MD, PhDa, Cristina Oana Mărginean, MD, PhDa, , Iunius Simu, MD, PhDb,
Gabriela Bucur, MD, PhDc
Abstract
Introduction: Ischemic stroke is an extremely rare disorder in children. The timely diagnosis is essential for the outcome of these

children, but unfortunately, delays in diagnosis occur frequently.
Patient concerns: We report the case of a 7-month-old infant admitted in our clinic for limited movements of the superior and
inferior right limbs whose onset was 27 hours before with repeated clonic movements of the right hand associated with the same
manifestations in the right oral commissure lasting approximately 10 seconds.
Diagnosis: The laboratory tests revealed high D-dimers, and positive IgG anti-cardiolipin and anti-beta2 glycoproteins I antibodies,
whereas the genetic proﬁle for thrombophilia revealed heterozygote mutation in MTHFR C677T and A1298C genes. Brain imaging
established the diagnosis of left frontal ischemic stroke, frontal ischemic stroke, hypoplasia of internal carotid artery, and agenesia of
segment M1 of median cerebral artery and segment A1 of left anterior cerebral artery.
Intervention: We administered low-molecular-weight heparin, antiplatelet therapy along with vasodilators and depletive treatment,
wide-spectrum antibiotics, and anticonvulsant therapy.
Outcome: The neurological deﬁcit was greatly improved, especially in the inferior limb after 6 month from the incident of stroke, and
all laboratory parameters were within normal limits including the antibodies mentioned above.
Conclusion: Cerebral vascular malformation, excessive weight, and altered lipid proﬁles contributed to the development of acute
ischemic stroke in our patient.
Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging.
Keywords: infant, ischemic stroke, vascular malformation

Editor: N/A.

1. Introduction

Table of Contents Summary: Ischemic stroke is an extremely rare disorder in
children. The timely diagnosis is essential for the outcome of these children, but
unfortunately, delays in diagnosis occur frequently. Cerebral vascular
malformations, excessive weight, and altered lipid proﬁles are important risk
factors for both ischemic and hemorrhagic stroke independently of the age.

Stroke is deﬁned by the association between any acute neurologic
event and acute radiological abnormality with evidence of
ischemia.[1] Childhood stroke must occur between the age of 28
days and 18 years persisting for at least 24 hours.[2] The incidence
of stroke in pediatric ages is extremely low accounting for up to 3
cases in 100,000 children above 5 years of age and 8 to 13 cases
per 100,000 children with the age between 5 and 14 years.[3]
Depending on the type of stroke, the incidence may vary between
0.3 and 2.7 cases in 100,000 children.[4] Moreover, up to 90% of
the children with stroke present neurologic deﬁcits and seizures,
20% of cases present recurrences and in up to 10% is a leading
cause of death.[5,6] The reports of stroke in children are few in the
literature and most of them originate from developed countries,
this pathology remaining underdiagnosed in developing countries since data regarding this topic are nonexistent in these
areas.[7] Furthermore, there are multiple differences between
pediatric and adult stroke. Thus, in children 50% of stroke cases
are ischemic as compared to 85% of adult cases.[8] The etiology is
also particular in children because in comparison to adults where
the most frequent causes include hypertension, atherosclerosis,
and diabetes; the most commonly incriminated risk factors in
pediatric patients are cardiac diseases, infections, trauma, or
vascular/vasculitic and metabolic disorders.[1,9]
Despite the recent increasing physician’s awareness regarding
this life-threatening pathology in children, the timely diagnosis
remains a real challenge. The diagnostic and management
difﬁculties are related to the wide spectrum of risk factors in these

Verbal and written informed consent was obtained from the patient’s mother
(legal guardian) for the publication of this case presentation.
This research was partially supported by the UEFISCDI grant: ‘The development
of an innovative diagnostic guide of obese child through genetics,
anthropometric, bioimpedance and ultrasound assessment’, project number:
8159/27.07.2017 - PN-III-P4-ID-PCE-2016-0766
All authors have no ﬁnancial relationships relevant to this article to disclose.
The authors have no conﬂicts of interest to disclose.
a

Department of Paediatrics, b Department of Radiology, George Emil Palade
University of Medicine, Pharmacy, Science, and Technology of Targu Mures,
c
Emergency County Hospital, Târgu Mureş, Romania.
∗

Correspondence: Cristina Oana Mărginean, Department of Pediatrics I, George
Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu
Mures, Gheorghe Marinescu street no 38, Târgu Mures 540136, Romania
(e-mail: marginean.oana@gmail.com).
Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
How to cite this article: Meliţ LE, Mărginean CO, Simu I, Bucur G. Acute
ischemic stroke in a 7-month-old infant, risk factors and diagnosis peculiarities.
Medicine 2019;98:46(e17864).
Received: 17 June 2019 / Received in ﬁnal form: 23 September 2019 /
Accepted: 9 October 2019
http://dx.doi.org/10.1097/MD.0000000000017864

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stimuli (no blabbing, no smiling, no sitting), paresis of the inferior
and superior right limbs, ﬂask hypotonia and reduced muscular
strength at this level, a mild cardiac murmur, and excessive
weight gain, weight 10.5 kg.

ages, atypical onset, and presentation complaints, but also the
lack of a consensus regarding the therapeutic approach in these
patients.[7] Nevertheless, in most cases, the poor outcome is
related diagnostic delays due to the lack of both community
awareness and symptoms recognition by medical health
providers.[7] Based on these striking differences, the approach
of a child with stroke is different from adults. Brain imaging is
mandatory for both the conﬁrmation of an ischemic stroke and to
exclude a hemorrhagic one.[10] Each imagistic method has its own
pros and cons. Thus, brain computed tomography (CT) presents
increased sensitivity for acute hemorrhage, but low sensitivity for
acute ischemic stroke within the ﬁrst 6 hours, being readily
available and fast. On the other hand, magnetic resonance
imaging (MRI) has high sensitivity for acute ischemia, but
presents other disadvantages, such as poor availability and the
need for general anesthesia in children for a complete and
appropriate evaluation.[10] The evaluation of a child with stroke
should also involve the identiﬁcation of potential risk factors that
might result in short-term recurrence.[10] Thus, vascular imaging
of the brain and neck, along with electrocardiogram, echocardiography, lipid proﬁles, or extended cardiac rhythm monitoring
should also be taken into account in these ages.[10]
The acute management in case of infants and children with
stroke involves appropriate oxygenation, assurance of airway
integrity and adequate hydration without administering hypotonic
ﬂuids.[10] In case of unknown source of ischemic stroke,
anticoagulant therapy with unfractionated heparin or lowmolecular-weight heparin along with antiplatelet therapy should
be initiated.[11] The recommendations regarding secondary
prevention are controversial. Nevertheless, limited data underline
that children should be administered antithrombotic agents in
order to prevent acute recurrences, but the duration of this
treatment is uncertain.[12] The outcome is closely related to
appropriateness pediatrician-child-parents relationship, and speciﬁc medical centers for children with stroke should exist also in our
country in order to avoid delays in diagnosis and management.[13]
Our aim was to underline the particularities related to the diagnosis
and management of ischemic stroke in a 7-month-old infant.
The written informed consent was obtained from the patient’s
mother prior to publication of this case.

2.3. Diagnostic focus and assessment
The usual laboratory tests (complete cellular blood count,
inﬂammatory biomarkers, liver, and renal function tests)
performed on admission day were within the normal ranges.
The CT showed a left parietal hypodensity of approximately 20/
18 mm. The brain MRI conﬁrmed the presence of left ischemic
stroke. The laboratory tests performed in order to identify
potential risk factor consisted in D-dimers, anti-thrombin III,
protein C and S, anti-phospholipid, anti-cardiolipin, anti-beta2
glycoproteins I, antinuclear antibodies, and the genetic proﬁle for
thrombophilia. Nevertheless, only D-dimers, IgG anti-cardiolipin
and anti-beta2 glycoproteins I antibodies were positive, whereas
the genetic proﬁle for thrombophilia revealed heterozygote
mutation in MTHFR C677T and A1298C genes. We also
assessed the lipid proﬁle after a 9-hours fasting period and
identiﬁed hypercholesterolemia (213 mg/dl) and increased lowdensity lipoprotein cholesterol (137 mg/dl). The echocardiography showed a minor ostium secundum atrial septal defect and
aneurism of interatrial septum, while the electrocardiogram was
normal. The angio CT performed after 10 days from admission
pointed out left frontal ischemic stroke, hypoplasia of internal
carotid artery, and agenesia of segment M1 of median cerebral
artery and segment A1 of left anterior cerebral artery (Figs. 1 and
2). The electroencephalogram established the diagnosis of right
focal convulsive syndrome.
2.4. Therapeutic focus and assessment
On the 1st day of admission we initiated low-molecular-weight
heparin, antiplatelet therapy along with vasodilators and
depletive treatment in order to diminish the acute cerebral
edema. We also associated wide-spectrum antibiotics since we
were not able to rule out a former infection of the central nervous
system. According to the neurologist recommendations, we also
administered anticonvulsant therapy.

2. Case report
2.1. Presenting concerns
We report the case of a 7-month-old infant admitted in our clinic
for limited movements of the superior and inferior right limbs.
The onset was approximately 27 hours before the admission with
paroxysmal manifestations consisting in repeated clonic movements of the right hand associated with the same manifestations
in the right oral commissure lasting approximately 10 seconds
followed by the limitation of active movements in the superior
and inferior right limbs. The family history revealed that
maternal grandfather had acute myocardial infarction and
maternal great grandmother had both acute myocardial infarction and stroke. His recent personal history showed an episode of
acute otitis and rubella, 4 weeks before the admission and 3
weeks before the admission, respectively.
2.2. Clinical ﬁndings
The clinical exam at the time of admission revealed inﬂuenced
general status, right central facial paresis, the lack of reaction to

Figure 1. Angio CT, axial section.

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must also mention that our patient’s birth weight was high, 4 kg
that might have inﬂuenced his further excessive weight gain
during the ﬁrst 7 months of life. Moreover, obesity-related
inﬂammatory status was also proved in children as well as higher
lipid proﬁles.[20,21]
Delays in diagnosis are due to both the rarity of ischemic stroke
and atypical symptoms in pediatric patients. Thus, stroke mimics
in children might consist in seizures, migraine, syncope, Bell
palsy, peripheral nerve disorders, central nervous system
infection, drug intoxication, or even abdominal pain associated
with other suggestive symptoms, etc.[22–24] Certain intoxications,
such as lead poisoning should also be taken into account for the
differential diagnosis of stroke in these age groups.[25] Our
patient presented hemiparesis, seizures, and central facial paresis.
We did not experience delays in diagnosis in our case since we
established the diagnosis within the ﬁrst 24 hours after admission,
but unfortunately, the patient presented only after 27 hours from
onset.
Neuroimaging of the brain is the most important diagnostic
tool in both ischemic and hemorrhagic strokes independently of
the age. Nevertheless, the ﬁrst step in the assessment of a child
with stroke is CT since it is readily available, and it does not
require sedation. MRI and angio CT might represent 2 viable
options as further steps in the evaluation of these cases.
Nevertheless, a study performed on 26 patients with acute
stroke suggested that magnetic resonance angiography might
overestimate the stenosis in medium-sized vessels, and even miss
occlusion in distal small vessels.[26] A large meta-analysis that
focused on strokes in children, identiﬁed malformations of the
large intracranial arteries consisting in irregularities, stenosis, or
occlusion as the most common etiology for ischemic stroke in
pediatric patients.[27] In our case, the angio CT also revealed a
complex vascular malformation consisting in hypoplasia of
internal carotid artery, and agenesis of both segment M1 of
segment M1 of median cerebral artery and segment A1 of left
anterior cerebral artery.
The outcome of children with stroke depends mostly on the
timely diagnosis, but the mortality in these patients remains high.
Thus, a prospective study performed on 95 children with stroke
from Switzerland with a follow-up period of approximately 7
years showed an overall mortality of 14%, and 6% of the patient
presented a recurrent stroke. Most of the studied patients had
hemiparesis and speech impairment.[28] Nevertheless, neurological deﬁcits in children might suggest also certain genetic
disorders.[29,30] Fortunately, our patient’s outcome was very
good, with major remission of the neurological deﬁcits after 6
months from the incident of stroke.

Figure 2. Angio CT, coronal section.

2.5. Follow-up and outcome
The infant is discharged after approximately 3 weeks of
hospitalization with a favorable evolution and great improvements of the neurological deﬁcit, being able to express mild active
movements of both superior and inferior right limbs. After
approximately 6 month, the patient presented major improvements of the neurological deﬁcit, especially in the inferior limb,
and all above-mentioned antibodies positive at onset, turned out
within normal ranges. In addition, the lipid proﬁle was normal.
We also repeated the angio CT that conﬁrmed the presence of the
previously mentioned vascular malformation and showed
cerebral atrophy as a result of ischemic stroke. Based on the
complex cerebral vascular malformation we recommended
continuing the anticoagulant therapy lifelong.

3. Discussions
Ischemic stroke is extremely rare in children beyond the neonatal
period.[10] It is well-documented that during the neonatal period,
the incidence of stroke may vary between 1 in 4400 and 1 in 7700
live births, and it can also occur during the intrauterine life.[10,12]
Moreover, in the USA the prevalence of cerebral palsy account
for 3.1 cases in 1000 children with the age of 8 years, of which up
to 35% express unilateral spasticity.[14] Furthermore, 89% of
strokes during childhood occur in low- and middle-income
countries representing a real social burden for these nations.[15]
Similarly, our country might be considered a middle-income
nation, even though our infant was from a family with a normal
socio-economic level. The most common risk factors for stroke in
children are arteriopathy, cardiac diseases, other chronic
disorders (e.g. iron deﬁciency anemia, sickle cell anemia, different
genetic syndromes, aneurysms, autoimmune disorders, prothrombotic state, etc.), sepsis, shock, dehydration, and
others.[10,16] Of these risk factors, we identiﬁed only isolated
foramen ovale in our patient, but also a complex cerebral
vascular malformation. Despite the fact that dyslipidemia and
obesity are known as risk factors in adults, our infant was
identiﬁed with high levels of cholesterol and low-density
lipoprotein cholesterol associated with excessive weight for his
age, 10 kg at 7 months of age. According to recent studies that
focused on identifying the factors that inﬂuence neonatal
outcome, birth weight is an important predictor of further
nutritional status, with a multifactorial determinism.[17–19] We

4. Conclusions
Ischemic stroke in children is an uncommon pathology that is
often underdiagnosed leading to life-threatening complications.
Cerebral vascular malformation, excessive weight, and altered
lipid proﬁles contributed to the development of acute ischemic
stroke in our patient. The outcome of children with stroke
depends mostly on the timely diagnosis.

Author contributions
Conceptualization: Lorena Elena Meliţ , Cristina Oana Marginean.
Data curation: Cristina Oana Marginean.
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[14] Christensen D, Van Naarden Braun K, Doernberg NS, et al. Prevalence of
cerebral palsy, co-occurring autism spectrum disorders, and motor
functioning - Autism and Developmental Disabilities Monitoring
Network, USA, 2008. Dev Med Child Neurol 2014;56:59–65.
[15] Feigin VL, Forouzanfar MH, Krishnamurthi R, et al. Global and regional
burden of stroke during 1990-2010: ﬁndings from the Global Burden of
Disease Study 2010. Lancet 2014;383:245–54.
[16] Meliţ LE, Mărginean CO, Georgescu A, et al. Complications of sepsis in
infant. A case report. J Crit Care Med (Targu Mures) 2016;2:96–9.
[17] Mărginean C, Mărginean CO, Iancu M, et al. The role of TGF-(1 869
T>C and PPAR (2 34 C>G polymorphisms, fat mass, and anthropometric characteristics in predicting childhood obesity at birth: a crosssectional study according the parental characteristics and newborn’s risk
for child obesity (the newborns obesity’s risk) NOR study. Medicine
(Baltimore) 2016;95:e4265.
[18] Mărginean CO, Mărginean C, Bănescu C, et al. The relationship between
MMP9 and ADRA2A gene polymorphisms and mothers-newborns’
nutritional status: an exploratory path model (STROBE compliant
article). Pediatr Res 2019.
[19] Mărginean C, Bănescu CV, Mărginean CO, et al. Glutathione Stransferase (GSTM1, GSTT1) gene polymorphisms, maternal gestational
weight gain, bioimpedance factors and their relationship with birth
weight: a cross-sectional study in Romanian mothers and their
newborns. Rom J Morphol Embryol 2017;58:1285–93.
[20] Mărginean C, Meliţ L, Ghiga D, et al. Early inﬂammatory status related
to pediatric obesity (STROBE compliant article). Front Pediatr 2019;7.
[21] Ma?rginean CO, Ma?rginean C, Meliţ LE. New insights regarding
genetic aspects of childhood obesity: a minireview. Front Pediatr
2018;6:271.
[22] Mackay MT, Chua ZK, Lee M, et al. Stroke and nonstroke brain attacks
in children. Neurology 2014;82:1434–40.
[23] Meliţ LE, Mărginean CO, Mocanu S, et al. A rare case of iron-pill
induced gastritis in a female teenager: a case report and a review of the
literature. Medicine (Baltimore) 2017;96:e7550.
[24] Mărginean MO, Mărginean CO, Meliţ LE, et al. The impact of host’s
genetic susceptibility on Helicobacter pylori infection in children.
Medicine (Baltimore) 2017;96:e7612.
[25] Mărginean CO, Meliţ LE, Moldovan H, et al. Lead poisoning in a 16year-old girl: a case report and a review of the literature (CARE
compliant). Medicine (Baltimore) 2016;95:e4916.
[26] Husson B, Rodesch G, Lasjaunias P, et al. Magnetic resonance
angiography in childhood arterial brain infarcts: a comparative study
with contrast angiography. Stroke 2002;33:1280–5.
[27] Gumer LB, Del Vecchio M, Aronoff S. Strokes in children: a systematic
review. Pediatr Emerg Care 2014;30:660–4.
[28] Goeggel Simonetti B, Cavelti A, Arnold M, et al. Long-term outcome
after arterial ischemic stroke in children and young adults. Neurology
2015;84:1941–7.
[29] Groselj U, Tansek MZ, Smon A, et al. Newborn screening in
southeastern Europe. Mol Genet Metab 2014;113:42–5.
[30] Zerjav Tansek M, Groselj U, Angelkova N, et al. Phenylketonuria
screening and management in southeastern Europe - survey results from
11 countries. Orphanet J Rare Dis 2015;10:68.

Formal analysis: Lorena Elena Meliţ , Gabriela Bucur.
Investigation: Lorena Elena Meliţ , Iunius Simu, Gabriela Bucur.
Methodology: Lorena Elena Meliţ , Gabriela Bucur.
Supervision: Cristina Oana Marginean.
Validation: Cristina Oana Marginean, Gabriela Bucur.
Writing – original draft: Lorena Elena Meliţ , Cristina Oana
Marginean, Gabriela Bucur.
Writing – review & editing: Lorena Elena Meliţ , Cristina Oana
Marginean, Iunius Simu.

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