YAJEM-159294; No of Pages 3
American Journal of Emergency Medicine xxx (2020) xxx

Contents lists available at ScienceDirect

American Journal of Emergency Medicine
journal homepage: www.elsevier.com/locate/ajem

Acute necrotizing encephalopathy: A case report
Evan L. Jackson a,⁎, Wesley Eilbert a, Amber M. Hathcock b
a
b

Department of Emergency Medicine, University of Illinois, College of Medicine, 1819 West Polk St. Room 469, Chicago, IL 60612, United States of America
Department of Pediatric Emergency Medicine, University of Illinois, College of Medicine, 1819 West Polk St. Room 469, Chicago, IL 60612, United States of America

a r t i c l e

i n f o

Article history:
Received 29 June 2020
Received in revised form 29 July 2020
Accepted 9 August 2020
Available online xxxx
Keywords:
Necrotizing encephalopathy
Acute necrotizing encephalopathy
Viral encephalopathy
Post-infectious encephalopathy

a b s t r a c t
Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children.
ANE is characterized by a preceding viral illness followed by seizures and rapid progressive neurologic deterioration. The diagnosis of ANE is made based on clinical presentation and characteristic multifocal brain lesions seen
on computed tomography (CT). We report a previously healthy two-year-old boy who presented to our emergency department (ED) after a seizure in the setting of fever and diarrhea. He was ultimately diagnosed with
ANE and treated with steroids and IVIG. Early identification of this high morbidity condition by its typical clinical
picture and characteristic radiologic findings is key to allow for optimal treatment.
© 2020 Elsevier Inc. All rights reserved.

1. Introduction
Acute necrotizing encephalopathy (ANE) is a recently identified, uncommon encephalopathy affecting children. ANE is characterized by a
preceding virus-associated illness followed by seizures and rapid, progressive neurologic deterioration. The diagnostic cornerstone of ANE is
the identification of symmetric, multifocal brain lesions involving bilateral thalami and possibly the cerebral white matter, brainstem, or cerebellum as seen on computed tomography (CT) [1,2].
2. Case report
A previously healthy two-year-old boy presented to the emergency
department (ED) after a 20-min “shaking episode” witnessed by his
mother at home. After a brief period of decreased responsiveness, the
child returned to his baseline after the event. His mother reported he
had experienced fever and diarrheal stools during the preceding day.
On initial physical examination, he was febrile with a temperature of
41.4 oC. He was alert and interacted with his mother and the emergency
physician in an age-appropriate manner. He appeared well-hydrated
and had no apparent neurologic deficits. The remainder of his physical
examination revealed no obvious source of the fever. Shortly after arrival to the ED, he was noted to have decreasing alertness followed by
a brief tonic clonic seizure that resolved after the administration of
0.1 mg/kg of intravenous (IV) lorazepam. His mental status did not return to the baseline after the seizure and continued to deteriorate over
the next several hours.
⁎ Corresponding author.
E-mail address: evanleighjackson@gmail.com (E.L. Jackson).

Laboratory testing performed in the ED found a serum white
blood cell count of 6200/mm3. Significant elevations in the hepatic
transaminases were noted, with an aspartate transaminase level of
16,963 IU/L (<38 IU/L) and alanine transaminase level of 8356 IU/
dL (<64 IU/L). The serum ammonia level was 55 mg/dL, which is in
the range of normal for children. The international normalized ratio
(INR) was elevated at 2.7, which precluded the performance of a
lumbar puncture in the ED. A head CT without contrast demonstrated
symmetric hypodensities in the thalami and posterior paramedian
pons suggestive of ANE (Figs. 1 and 2).
The patient was treated for presumed meningitis, and he was admitted to the intensive care unit (ICU). On arrival to the ICU he was noted to
be nonverbal with no eye opening, though had localizing withdrawal of
his extremities to pain. He was intubated two days after admission because of deteriorating mental status and transiently required peritoneal
dialysis because of renal failure. A lumbar puncture performed three
days after admission found no white blood cells and a mildly elevated
cerebrospinal fluid protein level of 45 mg/dL. Blood and cerebrospinal
fluid cultures ultimately yielded no growth, and viral polymerase
chain reaction testing was positive for parainfluenza type 1 and rhinovirus/enterovirus. The patient was treated with IV immunoglobulin and
methylprednisolone. His neurologic condition began to slowly improve
after one week. He was discharged after one month of hospitalization to
a rehabilitation facility. At the time of discharge he remained nonverbal,
though was interactive with his mother.
3. Discussion
First described in 1995, ANE is a rare disorder characterized by fever,
seizures, and rapid progression to coma within days after the onset of a

Please cite this article as: E.L. Jackson, W. Eilbert and A.M. Hathcock, Acute necrotizing encephalopathy: A case report, American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.08.026

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E.L. Jackson et al. / American Journal of Emergency Medicine xxx (2020) xxx
Table 1
Diagnostic criteria of acute necrotizing encephalopathy.
1. Acute encephalopathy following viral disease, with seizure and deterioration of
consciousness.
2. Absence of cerebrospinal fluid pleocytosis. Cerebrospinal fluid protein is commonly increased.
3. Neuroimaging findings of symmetric, multifocal brain lesions involving the
bilateral thalami, upper brain stem tegmentum, periventricular white matter,
internal capsule, putamen, and cerebellum.
4. Elevation of hepatic transaminase levels to a variable degree. No increase in
serum ammonia level.
5. Exclusion of resembling diseases.
A. Diseases that clinically resemble acute necrotizing encephalopathy: toxic
shock syndrome, hemolytic uremic syndrome, Reye's syndrome, hemorrhagic shock and encephalopathy syndrome, and heatstroke.
B. Diseases that radiologically or pathologically resemble acute necrotizing
encephalopathy: Leigh encephalopathy, glutaric acidemia, methyl malonic
aciduria, infantile bilateral strial necrosis, Wernicke encephalopathy, carbon monoxide poisoning, acute disseminated encephalomyelitis, acute
hemorrhagic leukoencephalitis, arterial or venous infarct, and hypoxic
injury.

Fig. 1. Computed tomography image showing symmetric hypodensities in the thalami
(arrows) suggestive of acute necrotizing encephalopathy.

Fig. 2. Computed tomography image showing hypodensities in the posterior paramedian
region of the pons (arrow) suggestive of acute necrotizing encephalopathy.

of cases initially reported were in East Asian countries; however, more
recent reports indicate a worldwide distribution [3].
Diagnostic criteria for ANE have been proposed (Table 1) [2,4,5].
Over 90% of children with ANE will have a preceding febrile illness,
often with symptoms of upper respiratory infection [2]. Several viral illnesses have been associated with ANE, with influenza being the most
commonly reported [6]. Neurologic dysfunction, most commonly seizure, typically occurs within three days of the illness onset, followed
by rapid decline in mental status with coma ensuing within 24 h [2].
In most cases, the diagnosis of ANE can be made on the basis of the combination of a typical clinical profile and characteristic radiologic
findings.
Imaging findings are the hallmark of ANE, with symmetric, multifocal brain lesions seen on CT. Bilateral thalamic involvement is present in virtually all cases. The majority of patients with ANE will have
some elevation of hepatic transaminases and elevated cerebrospinal
fluid protein, and a minority will have laboratory studies consistent
with disseminated intravascular coagulation (DIC) and acute renal
failure [2].
The exact pathogenesis of ANE is unknown. The most prevalent hypothesis is that ANE is the result of an exaggerated immune response to
a viral infection, with resultant elevated pro-inflammatory cytokines
[4]. This “cytokine storm” leads to liver dysfunction, acute renal failure,
and DIC. In the central nervous system, it results in alteration of vessel
wall permeability and brain injury.
While several parainfectious encephalopathies can result in a clinical
picture similar to ANE, the two that most closely resemble it are acute
disseminated encephalomyelitis and Reye's syndrome (Table 2)
[2,7,8]. No specific treatments for ANE exist, although some case reports
and small case series have suggested that administration of corticosteroids, IV immunoglobulin, and induced hypothermia may improve clinical outcomes [9-11]. The overall prognosis of ANE is poor, with over
90% of survivors left with permanent neurologic sequelae (5). Mortality
rates for ANE approach 30% (1,2).
4. Why should an emergency physician be aware of this?

viral infection [1]. It predominately afflicts children under five years of
age. The global incidence of ANE is unknown, although fewer than 300
cases have been reported in the medical literature. The vast majority

ANE is a recently identified parainfectious encephalopathy afflicting
young children. This high-morbidity condition presents with characteristic history and physical examination findings and quickly progresses

Please cite this article as: E.L. Jackson, W. Eilbert and A.M. Hathcock, Acute necrotizing encephalopathy: A case report, American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.08.026

E.L. Jackson et al. / American Journal of Emergency Medicine xxx (2020) xxx

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Table 2
Characteristics of acute necrotizing encephalopathy, acute disseminated encephalomyelitis, and Reye's syndrome
Characteristic

Acute necrotizing encephalopathy

Acute disseminated encephalomyelitis

Reye's
syndrome

Age preponderance
Seizures
Hepatic dysfunction
Coagulation disorder
Lactic acidemia
Hyperammonemia
Hypoglycemia
Increased cerebrospinal fluid protein
Cerebrospinal fluid pleocytosis
Radiologic findings

Under 5 years
Frequent
Frequent
Occasional
Occasional
Rare
Rare
Frequent
Rare
Symmetric brain lesions of the bilateral
thalami and possibly the cerebral white matter,
brain stem, or cerebellum

Over 5 years
Occasional
None
None
None
None
None
Frequent
Frequent
Asymmetric areas of inflammation and
demyelination of the cerebral white matter,
basal ganglia, brain stem, and spinal cord

Over 5 years
Occasional
Frequent
Frequent
Frequent
Frequent
Frequent
Rare
None
Diffuse cerebral edema

with rapid neurologic deterioration. Identification of ANE by its clinical
characteristics and distinctive radiologic findings is key to allow for optimal treatment.
Source of support
None.
This article has not previously been presented.
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Please cite this article as: E.L. Jackson, W. Eilbert and A.M. Hathcock, Acute necrotizing encephalopathy: A case report, American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.08.026