(2022) 16:452
Karimi et al. Journal of Medical Case Reports
https://doi.org/10.1186/s13256-022-03672-5

Open Access

CASE REPORT

Cerebrovascular accident in a child
with precursor B‑cell acute lymphoblastic
leukemia and coronavirus disease 2019: a case
report
Hanie Karimi1, Roham Sarmadian2, Abolfazl Gilani3, Poorya salajegheh4, Habibe Nejad Biglari5 and
Mahsa Gholizadeh1*   

Abstract
Background: Coronavirus disease 2019 can lead to rare but severe and life-threatening diseases in susceptible highrisk populations, including patients with immunodeficiency. A rare event in this report is stroke following COVID-19
disease in a patient with an immunocompromised background due to leukemia and anti-cancer treatments.
Case presentation: A 6-year-old iranian girl with precursor B-cell leukemia receiving vincristine therapy presented
with fever and absolute neutrophil count < 500. Her severe acute respiratory syndrome coronavirus 2 polymerase
chain reaction test was positive. During hospitalization, she had abrupt onset tachypnea, reduced O
­ 2 saturation, and
generalized tonic–clonic seizures treated with phenytoin and levetiracetam. Right parietal lobe ischemia was found
on a brain computed tomography scan, and the cerebrospinal fluid polymerase chain reaction test was positive for
severe acute respiratory syndrome coronavirus 2. Several days later, she developed lower extremity paralysis and
speech impairment, so speech therapy and physiotherapy were initiated. The patient also received dexamethasone,
mannitol, heparin, and remdesivir. She was discharged with enoxaparin and levetiracetam. Chemotherapy resumed
2 weeks following discharge. Her speech and walking improved after 10 months of follow-up, and bone marrow
aspiration showed total remission.
Conclusion: Owing to the link between coronavirus disease 2019 and hematologic cancers with hypercoagulopathy
and the tendency of patients with leukemia to have coronavirus disease 2019 complications, children with leukemia
as well as suspected coronavirus disease 2019 must be hospitalized to prevent blood clot formation.
Keywords: COVID-19, SARS-CoV-2, Pre-B-cell leukemia, Cerebrovascular accident, Brain ischemia
Introduction
The coronavirus disease 2019 (COVID-19), first reported
in Wuhan, China, was caused by severe acute respiratory
syndrome coronavirus (SARS-CoV-2). It then became
a pandemic, leading to high morbidity and mortality
*Correspondence: Mahsagholizadeh11@yahoo.com
1
Alumna of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Full list of author information is available at the end of the article

worldwide [1–3]. Although all ages can be affected,
COVID-19 has a lower clinical impact, milder course,
and better clinical outcomes in children than in adults [4].
Common symptoms of COVID-19 are fever, cough, and
dyspnea. In addition, it can affect other organs, resulting
in hematological, neurological, cardiac, and renal complications [5, 6]. Owing to the detection of SARS-CoV-2
in cerebrospinal fluid (CSF) and brain tissue during the
autopsy, several studies have suggested that the virus
may be neuroinvasive [7–9]. The neurological symptoms

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Karimi et al. Journal of Medical Case Reports

(2022) 16:452

include encephalitis, encephalopathy, Guillain–Barré
syndrome, epileptic seizures, and stroke [10]. In a retrospective study on 214 patients in Wuhan, China, neurological complications were observed in 36.4% of patients
with COVID-19 [11]. During the COVID-19 pandemic,
the incidence of ischemic stroke has been approximately
5%. Patients infected with COVID-19 who experience a
stroke are more likely to be elderly and have hypertension [12]. Despite annual incidence estimates of 1.3–1.72
instances per 100,000 children in Europe and North
America, little is known regarding the occurrence of
ischemic stroke in pediatric COVID-19 [13, 14].
Immunocompromised populations, such as patients
with hematological cancers, appear to be at higher risk
of severe COVID-19-related illnesses, such as cerebrovascular disorders, than the general population [15–17].
Moreover, children with acute lymphoblastic leukemia
were found to have the highest risk of both ischemic
stroke and intracerebral hemorrhage [18, 19]. Therefore,
COVID-19 infection raises the risk of stroke in children
with acute lymphoblastic leukemia (ALL) owing to their
immunodeficiency and hypercoagulability. We present
the case of a 6-year-old girl with pre-B-cell ALL who was
hospitalized with the diagnosis of COVID-19 and experienced a cerebrovascular accident during hospitalization.

Case presentation
A 6-year-old iranian girl with a history of pre-B-cell acute
lymphoblastic leukemia (pre-B-cell ALL) was admitted to
the hospital. Her leukemia was identified 8 months prior
to her hospitalization with the 46XX blast cell karyotype,
positive for terminal deoxynucleotidyl transferase (TdT),
CD10, CD34, CD19, Human Leukocyte Antigen-DR
isotype (HLA-DR), and cytoplasmic immunoglobulin
M (CyIgM), placing her in the standard-risk group. The
patient was at the beginning of the maintenance treatment, which included vincristine injections and examinations every 35 days. Her family resided in a rural area and
had a lower-middle-class income. Family medical history
had no evidence of any cancerous or hematologic diseases. Patient was not exposed to any dangerous factors
(radiation and chemicals) during her life or fetal period.
She was the firstborn child and the mother’s first pregnancy. Her weight at birth was 3000 g. Mother’s age at
birth was 20 years of age and the father’s was 27 years of
age.
Three days before admission, the child experienced a
rapid onset of fever with no other symptoms. With the
onset of fever, the patient received supportive treatment and acetaminophen syrup 6 cc/kg/8 h, which had
no effect on improving the patient’s fever. At the beginning of admission the hospital, vital signs were: temperature (T) 39.8 °C, pulse rate (PR) 86 beats per minute,

Page 2 of 6

respiratory rate (RR) 13 breaths per minute, blood pressure (BP) 100/70 mmHg, and O2 saturation 97%. Physical examination revealed pale skin and splenomegaly.
Lymphadenopathy, hepatomegaly, and the presence of a
central nervous system (CNS) disorder/leukemia were
not observed. The neurological examination, including
all cranial and peripheral nerve examinations, was normal. She was admitted for additional examination, and
the initiation of antibiotic treatment after a laboratory
test revealed that her absolute neutrophil count (ANC)
was lower than 500/µl. She was treated empirically with
intravenous vancomycin 500 mg and meropenem 500 mg
three times daily. The blood culture was negative after
48 h with a normal chest X-ray (Fig. 1) The patient’s laboratory test results were as follows: red blood cell count
(RBC) 4600, white blood cell count (WBC) 1700/µl,
ANC 1100/µl, Hemoglobin 9.3 gr/dl, Platelets 47,000/µl,
PT 16s, International normalized ratio 1.1, Prothrombin
time test 24s, Alanine transaminase 12, Aspartate aminotransferase 14, Alkaline phosphatase 20, Blood Urea
Nitrogen 11, Creatinine 0.8, Erythrocyte sedimentation rate 35, C-Reactive Protein 1+; urine analysis: WBC
2–3, RBC 0; epithelial cell: 1–2; crystals: not seen; cast:
not seen; bacteria: not seen; and the other test results
were normal.
On the third day of hospitalization, which corresponded to the sixth day of the onset of fever, the patient
developed sudden-onset tachypnea and lowered oxygen
saturation to 88% in ambient air, which increased to 94%

Fig. 1 Chest X-ray taken on the second day of hospitalization,
showing normal field of both lungs

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(2022) 16:452

when using a reservoir oxygen mask. After partial stabilization, the patient’s oxygen saturation reached 90%, and
generalized tonic–clonic seizures commenced concurrently. Despite receiving IV midazolam 5 mg twice, the
seizure persisted.
The patient was immediately transferred to the pediatric intensive care unit (PICU) and was intubated.
According to the patient’s symptoms, a cerebrovascular
accident (CVA) was suspected; therefore, she underwent a brain computed tomography (CT) scan without contrast, which revealed an ischemic CVA in the
right parietal lobe, resulting in edema and midline shift
of the brain. (Fig. 2) Therefore, treatment procedures,
including intravenous dexamethasone 4 mg daily and
mannitol 12 g, were started for the patient.
The patient’s seizure was controlled by administering intravenous phenytoin 500 mg and levetiracetam
1 g. Owing to the patient’s low platelet count, heparin
was administered at a therapeutic dose of 1800 units to
prevent thrombosis development, and the infusion was
continued at a dose of 700 units per hour for 24 h. In
consultation with the neurosurgery service, supportive treatment and the following tests were requested
to rule out potential thrombosis causes: C, S protein, antithrombin3, and factor V Leiden, all of which
were normal. Owing to the patient’s fever, a polymerase chain reaction (PCR) test for SARS-COV-2 was
requested, and the result was positive. Supportive care
with anticonvulsants and heparin administration was
continued. Following the patient’s relative stability, a
lumbar puncture (LP) was performed, which revealed
normal pressure, clear cerebrospinal fluid (CSF), and

Fig. 2 Brain computed tomography scan showing right parietal lobe
ischemia (black arrow)

Page 3 of 6

normal culture, analysis, and serology; however, the
CSF PCR test was positive for SARS-COV-2.
Remdesivir was added to the patient’s treatments at
a dose of 100 mg daily for 5 days, with no dose reductions. Oral vitamin C at a dose of 500 mg every 12 h,
a single dose of intramuscular vitamin D at 300,000
units, and intramuscular vitamin A at 50,000 units were
also administered according to the national protocol for
COVID-19.
After 3 days, the patient was weaned off the ventilator,
the seizure was under control, and the CT scan showed
no signs of the progression of the thrombotic lesion.
However, the patient developed paralysis of the left lower
extremities and speech impairment; hence, physiotherapy was initiated for the patient.
After discharge from the PICU, the patient developed
recurrent coughs and moderate fever, and a chest CT
scan was performed since pneumonia was suspected.
Mild bilateral ground glass opacities were detected in the
periphery of both lungs on the CT scan image. In addition to supportive therapy for COVID-19, the patient was
administered intravenous ceftriaxone 500 mg two times
daily and azithromycin syrup 100 mg, 10 ml daily. Owing
to the improvement of symptoms and negative blood
culture, the patient’s antibiotic treatment was discontinued. The patient was discharged with a prescription for
subcutaneous enoxaparin 15 mg twice daily for 2 months
and levetiracetam 500 mg twice daily. Two weeks after
discharge, the chemotherapy maintenance phase was
resumed.
During 3-month post-discharge follow-ups, the patient
could walk and speak properly with physiotherapy and
speech therapy assistance. After a 10-month follow-up,
the patient’s ability to speak and walk had fully recovered, and bone marrow aspiration revealed the complete
remission phase.

Discussion
In the current report, we have demonstrated a known
case of patient with pre-B-cell ALL who experienced
CVA following the COVID-19 infection.
Patients with ALL are a subset of the immunocompromised population, putting them at increased risk for
complicated diseases such as COVID-19. Owing to the
highly immunosuppressive treatment regimen and prolonged treatment duration, the risk of COVID-19-related complications and life-threatening diseases may be
higher in these patients than in the general population
[15, 20, 21]. Fung and Babik demonstrated that immunocompromised patients with COVID-19 may be at a
higher risk for severe diseases and poor outcomes [22].
A Chinese cohort of confirmed patients with COVID19 found that the fatality rate of COVID-19 in patients

Karimi et al. Journal of Medical Case Reports

(2022) 16:452

with cancer is estimated to be 5.6%. Also, the severity of
COVID-19 in cancer is 3.5 times higher than in the general population [23]. Furthermore, it is stated that more
than 80% of hematologic patients require hospitalization,
with about 15% requiring intensive care unit admission
[24, 25]. Dai et al. demonstrated that patients with hematologic cancers infected with COVID-19 had the highest
severity and mortality rate (33%) compared with patients
with other malignancies [26]. Several other studies confirm the greater mortality rate among patients infected
with COVID with hematologic cancers compared with
those with solid tumors [27–29]. Infection with COVID19 in children with hematologic malignancies appears to
carry a low mortality risk. However, children with hematologic cancer have a higher mortality risk than those
with solid organ malignancies [30].
CVA is a frequent consequence of COVID-19 and
hematologic cancers. In children with cancer, stroke is
a significant consequence that increases morbidity and
mortality and necessitates higher levels of critical care
[31]. Noje et al. showed that children with leukemia and
brain tumors have the highest risk for stroke [19]. Parasole et al. predicted a prevalence of 1.97% for stroke in
children treated for ALL [32]. Strokes in patients with
cancer can be hemorrhagic or ischemic [33]. During the
first 6 months after a cancer diagnosis, the risk of a hemorrhagic stroke is greater than that of an ischemic stroke
in patients with cancer, which is also true for patients
with leukemia [34]. The mechanisms of stroke in patients
with cancer are multifactorial and may be directly related
to cancer, consequences of cancer such as infections and
hypercoagulability, or therapeutic and diagnostic interventions [35]. Infection, particularly brain infection, is
one of the important risk factors for stroke. Owing to
anti-cancer therapy, patients with cancer are immunocompromised; therefore, infections can easily spread
throughout the body. Sepsis and its combination with
disseminated intravascular coagulation (DIC) can induce
septic cerebral infarction [36]. COVID-19 has been one
of the most widespread diseases worldwide over the past
2 years, and is known to raise the risk of stroke. The risk
of ischemic stroke in COVID-19 is reported to be 5%. In
COVID-19, hemorrhagic stroke is uncommon but has
occurred in a few cases. The mechanisms of ischemic
stroke in COVID‐19 are hypercoagulopathy, vasculitis,
and cardiomyopathy. A hemorrhagic stroke in COVID19 may result from the following probable causes: the
inflammatory response, or cytokine storm, that occurs
alongside the infection, and the angiotensin-converting
enzyme 2 (ACE-2) receptors that are expressed in intracranial arteries, which permit the SARS-CoV-2 virus
to damage the arteries and lead to rupture of the vessel wall [12, 37]. Another study revealed the following

Page 4 of 6

reasons underlying the occurrence of stroke in COVID19: (1) Susceptibility of a group of patients to hypoxemiainduced cerebrovascular damage, (2) Sepsis-induced
coagulopathy, which is widespread in patients with
COVID-19 with high D-dimer and fibrinogen levels, and
(3) ACE-2 receptors and cytokine storm. Cytokine storm
is an adverse effect of immunity to COVID-19, defined
by uncontrolled hyperactivation of the immune system.
These excessive cytokines can cause plaque rupture and
superimposed thrombosis [38].
Given that both the COVID-19 infection and underlying cancer can raise the patient’s risk of stroke, the presence of both conditions may raise the risk of stroke [39].
However, there are still some debates about the synergy
between these two in thrombosis [40]. Owing to this controversy, additional research is required on these populations before a conclusion can be reached.
Owing to the rarity of this case, one of the limits of the
disease’s management was the lack of a defined treatment
protocol at the time of the patient’s treatment and the
partial implementation of preventative measures at the
beginning of the patient’s treatment. On the other hand,
because of the presence of multiple factors in the occurrence of stroke in children with COVID-19 who have a
history of leukemia, it is impossible to completely prevent this occurrence. However, this case provides useful
information for the management of future patients.

Conclusion
Owing to the association between COVID-19 and leukemia with hypercoagulopathy, as well as the susceptibility of children with leukemia to severe complications
of COVID-19, children with leukemia and suspected
COVID-19 must be hospitalized and given special care.
Additionally, proper measures should be taken to prevent
the formation of blood clots to reduce the risk of consequences such as stroke. Moreover, In the presence of
stroke-suspicious symptoms, physicians should initiate
essential evaluations as well as cardioembolism prevention or treatment.
Abbreviations
COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory
syndrome coronavirus; ANC: Absolute neutrophil count; CT: Computed
tomography; PICU: Pediatric intensive care unit; CVA: Cerebrovascular accident; ACE-2: Angiotensin‐converting enzyme 2; ALL: Acute lymphoblastic
leukemia; Pre-B-cell ALL: Precursor B-cell acute lymphoblastic leukemia; TdT:
Terminal deoxynucleotidyl transferase; HLA-DR: Human Leukocyte Antigen-DR
isotype; CyIgM: Cytoplasmic immunoglobulin M; CSF: Clear cerebrospinal fluid;
ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline
phosphatase; PCR: Polymerase chain reaction; DIC: Disseminated intravascular
coagulation.
Acknowledgements
Not applicable.

Karimi et al. Journal of Medical Case Reports

(2022) 16:452

Author contributions
HK was the principal investigator. HK and MG were included in preparing the
concept and design. AG, RS, PS, and HB revisited the manuscript and critically
evaluated the intellectual contents. All authors participated in preparing the
final draft of the manuscript, revised the manuscript, and critically evaluated
the intellectual contents. All authors have read and approved the manuscript’s
content and confirmed the accuracy or integrity of any part of the work. All
authors read and approved the final manuscript.
Funding
There is no funding.

Page 5 of 6

11.
12.

13.

Availability of data and materials
Not applicable.
14.

Declarations
Ethics approval and consent to participate
The content of this manuscript are in accordance with the declaration of Helsinki for Ethics. No committee approval was required. Oral and written consent
to participate was granted by the parents.
Consent for publication
Written informed consent was obtained from the patient’s legal guardian for
publication of this case report and any accompanying images. A copy of the
written consent is available for review by the Editor-in-Chief of the journal.
Competing interests
The authors declare that they have no competing financial interests and nothing to disclose.
Author details
1
Alumna of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2
Department of Infectious Disease, Arak University of Medical Sciences, Arak,
Iran. 3 Department of Pediatric Surgery, Tehran University of Medical Sciences,
Tehran, Iran. 4 Department of Pediatric Oncology, Kerman University of Medical
Sciences, Kerman, Iran. 5 Department of Pediatric Neurology, Kerman University of Medical Sciences, Kerman, Iran.
Received: 27 June 2022 Accepted: 7 November 2022

15

16.
17.
18.

19.
20.

21.
22.
23.

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