Pediatric Neurology 50 (2014) 652e654

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Pediatric Neurology
journal homepage: www.elsevier.com/locate/pnu

Clinical Observations

Postictal Subcortical Restricted Diffusion in a Child With Focal
Symptomatic Epilepsy
Kenneth A. Myers MD, PhD a, *, Mehmet S. Albayram MD b, Aleksandra Mineyko MD a
a
Section of Neurology, Department of Pediatrics, Alberta Children’s Hospital, University of Calgary Faculty of Medicine, Calgary,
Alberta, Canada
b
Division of Radiology, Department of Pediatrics, Alberta Children’s Hospital, University of Calgary Faculty of Medicine, Calgary,
Alberta, Canada

abstract
BACKGROUND: Diffusion abnormalities on MRI are well described after prolonged seizures. However, isolated, focal,
subcortical restricted diffusion is uncommon. PATIENT: A girl of Kurdish descent experienced focal-onset epilepsy

secondary to a left thalamic infarction at age 3 years. At age 6 years, she developed status epilepticus in the context
of a febrile illness. RESULTS: Four days after the seizure, she had neurological deterioration including involuntary
posturing movements and irritability. A brain MRI revealed left hemisphere subcortical restricted diffusion, predominantly in the frontal and occipital regions. She experienced persistent right hemiparesis for 2 months after
the initial seizure. CONCLUSIONS: This presentation is reminiscent of acute encephalopathy with biphasic seizures
and late reduced diffusion, a syndrome thus far reported almost exclusively in Japan. This represents one of the few
documented examples of acute encephalopathy with biphasic seizures and late reduced diffusion in an individual
not of east Asian descent.
Keywords: magnetic resonance imaging, epilepsy, acute encephalopathy with biphasic seizures and late reduced diffusion,
hemiparesis, status epilepticus

Pediatr Neurol 2014; 50: 652-654
Ó 2014 Elsevier Inc. All rights reserved.

Introduction

Patient description

Diffusion abnormalities on magnetic resonance imaging
(MRI) are well described after a prolonged seizure.1,2
However, isolated, focal, subcortical restricted diffusion is
uncommon.3 For reasons that are not clear, this radiologic
pattern is primarily observed in pediatric patients with
seizures occurring in the context of febrile illness.4 We
present a child with focal status epilepticus who subsequently developed persistent neurological deficits and
subcortical restricted diffusion on MRI.

At age 3 years, this girl suffered a left thalamic infarction secondary to
cerebral venous sinus thrombosis, possibly related to severe anemia. She
subsequently developed focal epilepsy with seizures characterized by
clonic movements of the right face and arm. Her seizures were generally
well controlled on levetiracetam; however, she continued to have
infrequent episodes of focal status epilepticus associated with postictal
weakness. One episode required intensive care unit admission and
intubation.
She had previously exhibited left hand preference and moderate
global developmental delay. Her physical examination was significant for
bilateral microphthalmia and congenital cataracts. Her parents were first
cousins, both from the region of Kurdistan. The family history was significant for a brother who also had microphthalmia and cataracts, as well
as two brothers with congenital ichythosis, and multiple individuals
with carnitine transport deficiency. Although there was a high index of
suspicion that the patient had an underlying genetic or metabolic disorder, thorough testing did not yield a diagnosis.
At age 6 years, she presented with generalized tonic-clonic status
epilepticus during a febrile illness. She was intubated upon arrival at the
hospital and required multiple antiepileptic medications including lorazepam, fosphenytoin, and a midazolam infusion. The total duration of

Article History:
Received December 16, 2013; Accepted in final form February 13, 2014
* Communications should be addressed to: Dr. Myers; Section of
Neurology; Department of Pediatrics; Alberta Children’s Hospital; University of Calgary Faculty of Medicine; 2888 Shaganappi Dr. NW; Calgary, Alberta T3B 6A8, Canada.
E-mail address: kmyers@ucalgary.ca
0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.pediatrneurol.2014.02.010

K.A. Myers et al. / Pediatric Neurology 50 (2014) 652e654
seizure activity was estimated at 90 minutes. Computed tomography
scan performed 4 hours after seizure onset revealed no acute change.
Evaluation for infection later revealed an enterovirus and/or rhinovirus
upper respiratory tract infection, enterococcus urinary tract infection,
and a suspected atypical pneumonia. An electroencephalography
approximately 10 hours after the seizure revealed diffuse nonspecific
slowing.
She was extubated after <12 hours and appeared to return to her
baseline level of consciousness within 2 days. She did, however, have
persistent right hemiparesis. Four days after the seizure, she was still
remained hemiparetic and developed involuntary posturing movements
of her right arm and leg. She also had an episode of headache with irritability that parents felt was very abnormal. With these new features, a
repeated electroencephalography was performed and revealed frequent
bifrontal epileptiform discharges, with a background still slightly slow
for age.
MRI of the brain under general anesthetic was performed on day 4
after the seizure and revealed T2 hyperintensity in the left hemisphere,
primarily in the occipital and frontal regions. These same areas were
associated with restricted diffusion in the subcortical white matter
including U fibers, with sparing of the cortex (Fig 1). Vascular imaging
was normal and no abnormal enhancement was observed with gadolinium. A repeat MRI 2 months later revealed resolution of these changes
with interval atrophy of the left cerebral hemisphere (Fig 2). The patient
continued to have gradual improvement of the right hemiparesis, but
still had persistent weakness at 2-month follow-up.

Discussion

We present a child with epilepsy who presented with
status epilepticus in the context of a febrile illness. After a
relatively lucid interval, her neurological function deteriorated and an MRI demonstrating subcortical cytotoxic
edema. A similar clinical pattern has been described as
acute encephalopathy with biphasic seizures and late
reduced diffusion (AESD), a syndrome thus far recognized
almost exclusively in Japan.5
The classic AESD clinical phenotype involves a prolonged
seizure in the context of a febrile illness.5 Immediately after
the seizure, patients have a normal MRI and a lucid interval
of several days before again developing seizures and encephalopathy. MRI at this time reveals subcortical restricted
diffusion. Follow-up MRI reveals resolution of the diffusion
abnormalities but often demonstrates cerebral atrophy.
Patients with the same radiologic findings, without the

FIGURE 1.
Axial apparent diffusion coefficient (A) and diffusion weighted imaging (B)
images from a study 4 days after the initial seizure. Subcortical cytotoxic
edema is observed in the left hemisphere, primarily in the frontal and
occipital regions (arrows).

653

FIGURE 2.
Coronal T2-weighted images taken 4 days after the initial seizure (A) and at
follow-up 2 months later (B), illustrating interval atrophy of the left cerebral hemisphere. Both images also demonstrate the left thalamic encephalomalacia secondary to the remote venous sinus thrombosis infarction
(arrow).

biphasic course, are considered to have acute encephalopathy with subcortical restricted diffusion.5
This girl’s clinical presentation fits within the spectrum
of acute encephalopathy with subcortical restricted diffusion, with some features that have not been previously
described. She had prolonged hemiplegia, well beyond
what is considered normal for a simple postictal paresis,
and clinical deterioration 4 days after the initial seizure. The
precise mechanism for her late deterioration is not clear;
however, late seizures could explain the brief periods of
irritability and involuntary right arm movements. Her
initial computed tomography scan did not reveal white
matter abnormalities, suggesting that the cytotoxic edema
may have appeared after some delay. Our patient illustrates
that the acute encephalopathy with subcortical restricted
diffusion pattern can be observed in patients with symptomatic epilepsy. Additionally, if this child’s presentation
can be accepted as within the sphere of AESD this would be
only the second reported patient outside of Asia and one of
the few in a non-Japanese individual.5,6
The pathophysiology of postictal subcortical restricted
diffusion remains poorly understood. Biomarker studies
have demonstrated differences in cerebrospinal fluid between AESD and febrile status, specifically that levels of
visinin-like protein-1, tau protein, and S100B are elevated
in AESD.7-9 The precise significance of these differences is
unclear; however, the pattern suggests increased
neuronal damage, which could explain why patients with
AESD develop atrophy and persistent neurological
impairment.
Given the seemingly high prevalence of AESD in Japanese
individuals, an underlying genetic or metabolic disorder is
likely a contributing factor in cases of postictal subcortical
restricted diffusion. This hypothesis is further supported by
the reports of similar postictal radiologic patterns in a
number of genetic and/or metabolic diseases including nonketotic hyperglycemia,10,11 incontinentia pigmenti,12 and
Dravet syndrome.13 Our patient’s suspected underlying
genetic and/or metabolic disorder likely played a role in her
presentation; however, the exact contribution is difficult to
determine given the lack of a precise diagnosis.

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K.A. Myers et al. / Pediatric Neurology 50 (2014) 652e654

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We can never really be prepared for that which is wholly new. We have to adjust ourselves, and every radical adjustment is a
crisis in self-esteem: we undergo a test, we have to prove ourselves. It needs inordinate self-confidence to face drastic change
without inner trembling.
Eric Hoffer