ILLUSTRATIVE CASE

Venous Stroke and Status Epilepticus Due to Milk-Induced
Anemia in a Child
Leslie Finkel, MD, Juan Piantino, MD, Joshua Goldstein, MD, and Mark S. Wainwright, MD, PhD

A 4-year-old, previously healthy, girl presented to the ED
with status epilepticus. She complained of headache for 2 weeks

and abdominal pain for 2 days before admission. On the morning
of presentation, she had experienced onset of right arm tonicclonic activity and arrived in the ED in complex partial status
epilepticus. For acute management of seizures, the patient received 2 doses of intravenous Ativan (0.1 mg/kg) and a dose of
Fosphenytoin (20 mg/kg), followed by a 10-mg/kg dose. She
was then noted to have sustained eye deviation to the right. Her
pupils were dilated (left greater than right) and were nonreactive.
Fundoscopic examination was not documented. She did not withdraw to painful stimulus. Her toes were downgoing, clonus was
absent, and reflexes were decreased throughout. She was intubated for airway protection and began to have 4 extremity internal rotation with a rhythmic component, for which she received
2 doses of Phenobarbital (20 mg/kg, then 10 mg/kg). Head computed tomography (CT) obtained in the ED (Fig. 1A) was suspicious for subdural hemorrhage or venous sinus thrombosis.
Continuous electroencephalogram monitoring showed diffuse leftsided slowing and no ictal activity. The patient became febrile,
and a lumbar puncture was performed (Table 1). She was treated
with acyclovir and meningitic dosing of vancomycin and ceftriaxone. Magnetic resonance imaging (MRI) with venogram was performed on the same day (Fig. 1B) and showed filling defects
in the left transverse and sigmoid sinuses consistent with nonocclusive thrombus. There was also a focal area of T2 hyperintensity in the inferior and lateral left temporal lobe, consistent
with a small venous infarction (Fig. 1C).
The patient's social history was notable for a 1-year history of
pica (toilet paper), continued use of a bottle to drink, and over
1 year of ingestion of at least 1 ½ gallons of milk daily. Laboratory
studies on admission revealed a microcytic anemia (hemoglobin,
7.7 g/dL [normal range, 11.5-13.5 g/dL] and mean corpuscular
volume 54 f. [normal range, 75–87 fL]), which was attributed to
her excessive milk intake. Echocardiogram and Doppler studies
of other extremities revealed no other venous or cardiac thrombi.
Screening studies for other genetic or autoimmune factors associated with venous or arterial strokes in children (Table 2) were
negative.
She was transfused with red blood cells and treated with a
2-day course of empiric antibiotics. She had no further seizures
and was discharged on Levetiracetam 29 mg/kg per day divided
twice daily for a 5-month course of treatment. For management
of cerebral venous thrombosis, she was treated with Enoxaparin
for a 4-month course following published guidelines for treatment
of venous stroke in children.4 At 4 months follow-up, her neurologic examination was normal, and she had no further symptoms,
although the long-term sequelae of this stroke, including seizures
and impaired memory, may not yet be apparent.

From the Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program, Ann
& Robert H. Lurie Children's Hospital of Chicago, Northwestern University
Feinberg School of Medicine, Chicago IL.
Disclosure: The authors declare no conflicts of interest.
Reprints: Mark S. Wainwright, MD, PhD, Division of Neurology, No. 51, Ann &
Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Ave,
Chicago, IL 60611 (e‐mail: m-wainwright@northwestern.edu).
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0749-5161

The presenting signs and symptoms of cSVT are variable and
may include headache, decreased consciousness, cranial nerve
palsies, focal weakness, and papilledema.3 The majority of patients have an identifiable predisposing risk factor including dehydration, infection, diabetic ketoacidosis, or anemia. Our patient
presented with seizures, which is the most common presenting

Abstract: The risk factors for cerebral sinus venous thrombosis include
dehydration, infection, and anemia. The clinical presentation in children
of venous strokes associated with cerebral venous thrombosis is variable
and may include seizures. Acute management should focus on the treatment of the primary cause and anticoagulation or antiplatelet therapy if
needed. Early recognition and targeted treatment is important because survivors are at increased risk for long-term neurologic complications. We report a case of a 4-year-old girl who presented with status epilepticus and
was subsequently found to have a cerebral venous sinus thrombosis in
the transverse and sigmoid sinus, with venous infarction in the temporal
lobe. Laboratory results were significant for a microcytic anemia caused
by excessive milk intake. Although iron deficiency anemia is a common
pediatric disorder, this uncommon presentation demonstrates the potential
for neurologic complications secondary to anemia, as well as the need for a
high index of suspicion in order to identify venous stroke as a cause in children who present to the emergency department with seizures.
Key Words: anemia, cerebral sinovenous thrombosis, status epilepticus,
stroke
(Pediatr Emer Care 2015;31: 129–131)

I

ron deficiency anemia is still a significant problem in the United
States. According to the CDC data from 2003 to 2006, 14% of
children aged 1 to 2 years and 4% of children aged 3 to 5 years
have iron deficiency anemia. Feeding cow's milk to infants and
young children is strongly associated with diminished iron stores
and increased probability of iron deficiency.1,2 Initial symptoms may
be subtle and include pallor, pagophagia, and decreased activity.
Untreated anemia may result in complications including ischemic
cerebrovascular disease and adverse effects on neurodevelopment.2
The incidence of cerebral sinus venous thrombosis (cSVT) in
children is less than 1/100,000 per year and may present with protean neurologic deficits including encephalopathy and seizures.
Risk factors include infection, dehydration, and anemia.3 Guidelines for management include treatment of the primary cause
and anticoagulation or antiplatelet therapy.4
We report a case of a healthy child who presented to the
emergency department (ED) with status epilepticus due to a venous stroke. She was found to have iron deficiency anemia caused
by excess milk ingestion. This case illustrates the diverse presentations of cerebral venous thromboses in children and highlights
a preventable neurologic complication of a milk-induced anemia.

CASE

DISCUSSION

Pediatric Emergency Care • Volume 31, Number 2, February 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

www.pec-online.com

129

Pediatric Emergency Care • Volume 31, Number 2, February 2015

Finkel et al

FIGURE 1. (A) Admission CT scan (axial view) showing focal hyperattenuation in the left transverse/sigmoid sinus. (B) MR venogram (sagittal
view) showing a filling defect in the left transverse/sigmoid sinuses concerning for nonocclusive thrombus (arrow). (C) MRI brain (axial T2
weighted) showing focal signal changes in the inferior and lateral left temporal lobe consistent with small venous infarction.

symptom in many studies.3,5 Up to 50% of children with cerebral cSVT may have long-term neurologic deficits, and the risk
is increased in infants.5 Accordingly, a high index of suspicion
is needed in order to identify the thrombosis with appropriate imaging in order to begin treatment and to manage potential complications including seizures, hydrocephalus, and intracranial
hemorrhage.
The initial routine head CT obtained in the ED did not identify the presence of cSVT. When cSVT is suspected, this should be
confirmed with either MRI T2-weighted imaging with MR
venogram or CT venogram if MRI is not available.4,6 Acute management can begin in the ED by treatment of the primary disorder
using antimicrobials or hydration. Anticoagulation with either

TABLE 1. Laboratory Values
Laboratory Test

Result

WBC
Hemoglobin
Hematocrit
Platelets
MCV
RDW
Lead
D-Dimer
Coagulation profile
Fibrinogen
CRP, ESR
Lumbar puncture

22,800/μL*
7.7 g/dL*
30%*
1,082,000/μL*
54 fL*
18%*
<3 mg/dL
<1.3 μg/mL*
aPTT 21 s*, PT 11.9 s, INR 1.2
202 mg/dL
0.4 mg/dL, 7 mm/h
1 WBC, 185 RBC, protein 23,
glucose 87, cytology and
infectious studies normal
Iron 34*, TIBC 472*,
transferrin 372*, % saturation 7,
ferritin 8* → 22
351 IU/L
1.7%

Iron studies

LDH
Reticulocytes

Basic metabolic panel was within normal limits, with the exception of
glucose [data not shown].
*Abnormal values.
MCV indicates mean corpuscular volume; RDW, red cell distribution
width; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate;
TIBC, total iron binding capacity; LDH, lactate dehydrogenase.

130

www.pec-online.com

unfractionated or low molecular weight heparin is recommended
for children,4,7 although this is a class IIa recommendation. The
objective of treatment with anticoagulants is to promote recanalization of the vessel and to limit propagation of the thrombus. In
adults, there is a specific recommendation for the acute use of
weight-adjusted doses of low molecular weight heparin.6 No such
data are available to recommend a specific agent in children.
Our patient presented with microcytic anemia, which is a
recognized risk factor for cSVT. The peak prevalence of irondeficiency anemia is 4% to 8% in children between the ages of
1 and 3 years.8 Iron deficiency affects an estimated 2 billon people
worldwide.9 Children with iron-deficiency anemia or iron deficiency alone are at increased risk of cognitive impairment, particularly in mathematics, and possibly attention-deficit hyperactivity
disorder.10,11
Thrombocytosis was also a prominent laboratory abnormality in our patient, although only on the first complete blood count
and may have been an acute phase reaction. The association of
iron deficiency anemia, with thrombocytosis and venous stroke
in a child has previously been reported.12 In a more recent series
of 4 children with iron-deficiency anemia and stroke, 3 were
due to cSVT and 1 due to arterial ischemic stroke. As in our patient, 2 of these patients consumed large quantities of cows' milk
and 2 presented with focal seizures.13 In a case-control study of
children between 12 and 38 months, children with anemia were
10 times more likely to have a stroke. Of these 15 cases, 6
(40%) were venous infarcts.14

TABLE 2. Thrombophilia Evaluation
Laboratory Test
Prothrombin gene mutation PCR
Factor V Leiden
Antiphospholipid antibody panel
Lupus anticoagulant
Protein C
Protein S
Antithrombin III
Lipoprotein A
Homocysteine
Coagulation factor VIII activity

Result
Negative
Negative
Negative
Negative
86%
86%
102%
15 nmol/L
3.4 μmol/L
183%*

*Abnormal value.

© 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Pediatric Emergency Care • Volume 31, Number 2, February 2015

Given the risk for long-term compromise of neurodevelopment resulting from iron-deficiency and iron-deficiency anemia
in infancy, the American Academy of Pediatrics recommends
7 mg per day of dietary iron for children from 1 through 3 years.15
Bottle feeding has also been associated with excessive milk intake
in observational studies, and the American Academy of Pediatrics
recommends weaning children from the bottle by 15 months.16
There is considerable regional variation in the management
of cSVT. In an international study of 84 neonates with isolated
cSVT, infants in the United States were less likely to be treated
with anticoagulation or antiplatelet therapy.17 However, anticoagulation appears to be safe for the acute treatment and may reduce propagation of the thrombus in both neonates and children.18
A recent meta-analysis also suggests that anticoagulation reduces
both mortality and the risk of sequelae in children and neonates,
although these conclusions are limited by differences in study design, endpoints, and duration of follow-up.19
Iron-deficiency anemia is common in children between the
ages of 1 and 3 years, and excess milk intake is a common cause.
This general pediatric problem is associated with a significant increase in the risk of stroke, particularly venous thrombosis. The
clinical presentation and imaging findings of cSVT may be subtle.
This case illustrates the need for a high index of suspicion to identify through appropriate imaging, examination, and laboratory
tests early signs of a treatable disorder with the potential for longterm neurologic morbidity.
REFERENCES
1. Penrod JC, Anderson K, Acosta PB. Impact on iron status of introducing
cow's milk in the second six months of life. J Pediatr Gastroenterol Nutr.
1990;10:462–467.
2. Kwiatkowski JL, West TB, Heidary N, et al. Severe iron deficiency anemia
in young children. J Pediatr. 1999;135:514–516.
3. Wasay M, Dai A, Ansari M, et al. Cerebral venous sinus thrombosis in
children: a multicenter cohort from the United States. J Child Neurol. 2008;
23:26–31.

Venous Stroke and Milk-Induced Anemia

6. Saposnik G, Barinagarrementeria F, Brown R, et al. Diagnosis and
management of cerebral venous thrombosis: a statement for healthcare
professionals from the American Heart Association/American Stroke
Association. Stroke. 2011;42:1158–1192.
7. Monagle P, Chalmers E, Chan A, et al. Antithrombotic therapy in neonates
and children: American College of Chest Physicians evidence-based
clinical practice guidelines. Chest. 2008;133:887S–968S.
8. Booth I, Aukett M. Iron deficiency anemia in infancy and early childhood.
Arch Dis Child. 1997;76:549–554.
9. Zimmerman M, Hurrell R. Nutritional iron deficiency. Lancet. 2007;370:
511–520.
10. Halterman J, Kaczorowski J, Aligne C, et al. Iron deficiency and cognitive
achievement among school-aged children and adolescents in the United
States. Pediatrics. 2001;107:1381–1386.
11. Abbas E, Valli S. Iron deficiency anaemia in children with ADHD. Arch
Dis Child. 2012;97:A93–A94.
12. Belman AL, Roque CT, Ancona R, et al. Cerebral venous thrombosis in a
child with iron deficiency anemia and thrombocytosis. Stroke. 1990;21:
488–493.
13. Munot P, De Vile C, Hemingway C, et al. Severe iron deficiency anaemia
and ischaemic stroke in children. Arch Dis Child. 2011;96:276–279.
14. Maguire JL, deVeber G, Parkin PC. Association between iron-deficiency
anemia and stroke in young children. Pediatrics. 2007;120:1053–1057.
15. Baker RD, Greer FR. Diagnosis and prevention of iron deficiency and
iron-deficiency anemia in infants and young children (0–3 years of age).
Pediatrics. 2010;126:1040–1050.
16. Maguire JL, Birken CS, Jacobson S, et al. Office-based intervention to
reduce bottle use among toddlers: TARGet Kids! Pragmatic, randomized
trial. Pediatrics. 2010;126:e343–e350.
17. Jordan LC, Rafay MF, Smith SE, et al. Antithrombotic treatment in
neonatal cerebral sinovenous thrombosis: results of the International
Pediatric Stroke Study. J Pediatr. 2010;156:704–710.

4. Roach E, Golomb M, Adams R, et al. Management of stroke in infants and
children. Stroke. 2008;39:2644–2691.

18. Moharir MD, Shroff M, Stephens D, et al. Anticoagulants in pediatric
cerebral sinovenous thrombosis: a safety and outcome study. Ann Neurol.
2010;67:590–599.

5. Sebire G, Tabarki B, Saunders D, et al. Cerebral venous sinus thrombosis in
children: risk factors, presentation, diagnosis and outcome. Brain. 2005;
128:477–489.

19. Lebas A, Chabrier S, Fluss J, et al. EPNS/SFNP guideline on the
anticoagulant treatment of cerebral sinovenous thrombosis in children and
neonates. Eur J Pediatr Neurol. 2012;16:219–228.

© 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

www.pec-online.com

131