Case Report | Neuroimaging and Head and Neck
http://dx.doi.org/10.3348/kjr.2013.14.2.324
pISSN 1229-6929 · eISSN 2005-8330

Korean J Radiol 2013;14(2):324-328

Acute Hepatic Encephalopathy Presenting as Cortical
Laminar Necrosis: Case Report
Jong Mun Choi, MD1, Yoon Hee Kim, MD1, Sook Young Roh, MD2
Departments of 1Radiology and 2Neurology, Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam 463-774, Korea

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis
showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal
changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and
occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals
on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We
suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.
Index terms: Acute hepatic encephalopathy; Cortical laminar necrosis; Cirrhosis; Magnetic resonance imaging

INTRODUCTION
Hepatic encephalopathy, also known as portosystemic
encephalopathy, indicates a spectrum of neuropsychiatric
changes in patients with impaired liver function, after
an exclusion of other known brain disease. In a patient
with chronic liver disease, acute attacks are frequently
precipitated by an intercurrent problem, such as
gastrointestinal bleeding, acute superimposed hepatitis,
concomitant infection, drugs, or constipation, which
leads to an elevation of blood ammonia level. Prolonged
hyperammonemia results significant brain injury and longterm sequelae, such as intellectual impairment by the
primary toxic effects of ammonia on the brain parenchyma.
Received January 13, 2012; accepted after revision May 10, 2012.
Corresponding author: Yoon Hee Kim, MD, Department of
Radiology, Bundang Jesaeng General Hospital, Daejin Medical
Center, 255-2 Seohyeon-dong, Bundang-gu, Seongnam 463-774,
Korea.
• Tel: (8231) 779-0037 • Fax: (8231) 779-0062
• E-mail: janet@dmc.or.kr
This is an Open Access article distributed under the terms of
the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/3.0) which permits
unrestricted non-commercial use, distribution, and reproduction in
any medium, provided the original work is properly cited.

324

Hepatic encephalopathy is reversible with treatment.
Therefore, recognition and correction of hyperammonemia is
essential to avoid the complications, as mentioned before (1,
2).
The most common cause of hyperammonemic
encephalopathy is acute hepatic dysfunction, and other
etiologies include portosystemic shunt surgery, drugs (e.g.,
sodium valproate, asparaginase therapy, or chemotherapy),
infection, hypothyroidism, multiple myeloma, and post-lung
or bone marrow transplantation (3).
Although the imaging findings of acute hyperammonemic
encephalopathy are well described in children with inborn
errors of metabolism (4), the radiologic findings of acute
hyperammonemic encephalopathy in adults are less well
described. We report a serial MRI of a patient with acute
hepatic encephalopathy, who showed cortical laminar
necrosis, not reported previously as a consequence of acute
hepatic encephalopathy.

CASE REPORT
A 55-year-old man was admitted to the emergency
room with generalized tonic-clonic seizures and stuporous
mentality, without regaining consciousness for two hours.
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Acute Hepatic Encephalopathy Presenting as Cortical Laminar Necrosis

He was a chronic alcoholic with alcoholic liver cirrhosis.
The initial blood ammonia level was 1002 µmol/L (normal
range 12-47 µmol/L), and the liver function test results
were mildly deranged (bilirubin, 0.91 mg/dL; aspartate
aminotransferase, 63 IU/L; alanine aminotransferase, 30
IU/L; pulmonary trunks 1.30 international normalized
ratio). Other serum electrolytes and blood glucose
levels were within normal ranges (glucose, 113 mg/dL).
Anticonvulsant was initially administered intravenously, and
the seizures immediately disappeared. Lactulose enema was
administered to decrease the patient’s blood ammonia level.
Electroencephalography performed 3 days after the onset of
symptoms showed continuous generalized slowing without
epileptiform discharges, suggesting a moderate diffuse of
cerebral dysfunction. No hypotensive or hypoxemic episode

was observed during the admission days.
Diffusion-weighted imaging (DWI) (b = 1000), 5 hours
after the onset of seizures, showed relatively symmetric
bilateral high signals in both temporo-fronto-parietal
cortex, including insular and cingulate cortex, with
restricted diffusion on the apparent diffusion coefficient
(ADC) map (Fig. 1A). The initial differential diagnosis was
acute hepatic encephalopathy, hypoxic ischemic change,
and other metabolic encephalopathy.
On the fourth day, MRI was performed at 3.0 tesla
(Achieva; Philips Medical Systems, Best, the Netherlands),
with T2-weighted (TR, 3000 ms; TE, 80 ms), fluidattenuated inversion recovery images (FLAIR) (TR, 11000
ms; TE, 125 ms; TI, 2800 ms), and T1-weighted inversion
recovery (TR, 2000 ms; TE, 10 ms) and intravenous contrast-

A
Fig. 1. Serial MRI on 5 hours, 4th and 37th days.

A. Diffusion-weighted imaging (DWI) 5 hours after onset of seizures in 55-year-old man. DWI (b = 1000) obtained 5 hours after onset of seizures
showed bilateral relatively symmetric high signals in both temporo-fronto-parietal cortex, including insular and cingulate cortex, with restricted
diffusion on apparent diffusion coefficient map.

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Choi et al.

B

C
Fig. 1. Serial MRI on 5 hours, 4th and 37th days.

B. MRI on fourth day after onset of seizures. fluid-attenuated inversion recovery images shows interval increase in extent of brain cortical edema
in both cerebral hemispheres, while showing unique sparing of occipital cortex and perirolandic regions. It also shows symmetric high signals in
both medial thalami, basal ganglia, periventricular and cerebellar white matter. Basal ganglia shows subtle high signal on T1-weighted image in
both globus pallidus. C. Follow-up MRI 37 days after onset of seizures. T1-weighted images show diffuse cortical atrophy in both temporo-frontoparietal lobe and curvilinear form high signals on T1-weighted image, particularly temporal lobes (obvious on sagittal T1-weighted image).
In addition, obvious T1 high signals appear in lower portion of both basal ganglia. These findings were considered cortical laminar necrosis,
presumably consequence of extreme toxic effect of ammonia.

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Acute Hepatic Encephalopathy Presenting as Cortical Laminar Necrosis

enhanced images. An interval increase in the extent of brain
cortical edema was noted in both cerebral hemispheres,
while the occipital cortex and perirolandic regions were
uniquely spared. Symmetric high signals were observed
in both the medial thalami, basal ganglia, periventricular
and cerebellar white matter on the T2-weighted and FLAIR
images. Basal ganglia showed subtle high signal on the
T1-weighted image in both globus pallidus (Fig. 1B). No
pathologic contrast enhancement was seen.
After one month of medical treatment and supportive
care, the patient’s blood ammonia level decreased to 49
µmol/L, and his seizure attack did not recur. But the
patient’s intellectual function was impaired. Follow up
brain MRI revealed a diffused cortical atrophy in both
temporo-fronto-parietal lobe and curvilinear, gyriform high
signals on the T1-weighted image in both temporal cortex.
In addition, bilateral basal ganglia showed obvious high
signals on the T1-weighted image (Fig. 1C). These findings
were considered as a cortical laminar necrosis, presumably,
the consequence of extreme toxic effect of ammonia.

DISCUSSION
The basic physiology of acute hepatic encephalopathy
involves the increased levels of CNS glutamine, as a
result of elevated CNS ammonia levels. As CNS ammonia
levels increase, glutamine, which is a potent osmolyte,
accumulates and leads to numerous consequences, such as
astrocyte swelling, oxidative/nitrosative damage, disruption
of glucose metabolism, defective neurotransmitter synthesis
(such as gamma-aminobutyric acid), and increased bloodbrain barrier permeability. As CNS ammonia levels rise
with systemic hyperammonemia, the direct toxic effects
of ammonia may take hold; thus, increasing CNS ammonia
concentrations have been shown to disrupt neuronal
function, and glutamine levels have been shown to correlate
with the severity of hepatic encephalopathy. These changes
collectively contribute to the astrocyte swelling, cytotoxic
brain edema, intracranial hypertension and cerebral
hypoperfusion, as well as decreased consciousness, which
may be seen in an acute hepatic encephalopathy (4, 5).
MRI can show cytotoxic brain edema as extensive cortical
signal changes, with associated restricted diffusion (3).
Similarly, our patient also showed relatively symmetrical,
bilateral high signals, in both temporo-fronto-parietal
cortex, including the insular and cingulate cortex on the
DWI, with restricted diffusion on the ADC map.
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Korean J Radiol 14(2), Mar/Apr 2013

Some researches reported the vulnerable or resistant
area of the brain in hyperammonemic encephalopathy
patients. U-King-Im et al. (3) reported that symmetric
involvement of the cingulate gyrus and insular cortex
is the striking common imaging finding in adult acute
hyperammonemic encephalopathy, while additional cortical
involvement is more asymmetric and variable. They suggest
that these cortical changes appear to be early imaging
finding, and potentially, reversible if aggressive treatment
is instituted. They postulate that subcortical white matter,
basal ganglia, thalami, and brain stem involvement can
also be seen in cases with more severe injury. Several
case reports have revealed sparing of the perirolandic and
occipital cortex, with early involvement of the cingulate
gyrus and the insular cortex in both adults and children
patients (4, 6). Thus, the cingulate gyrus and insular cortex
appear to be particularly vulnerable to hyperammonemichyperglutaminergic encephalopathy, while the perirolandic
and occipital cortex seem relatively resistant. However, the
pathophysiologic mechanism of regional vulnerability in
hyperammonemic encephalopathy is not clearly proved.
McKinney et al. (5) reported abnormalities in the thalami,
posterior limb of internal capsule, periventricular white
matter, and dorsal brain stem, as well as the diffused
cortical involvement on FLAIR and DWI in acute hepatic
encephalopathy patients, which can be reversible. The
MRI extent on FLAIR and DWI strongly correlates with
the maximal plasma ammonia level, and plasma ammonia
level correlates well with the clinical outcome. However
MRI severity correlates only moderately with the clinical
outcome. Our patient showed a periventricular and
cerebellar white matter abnormalities, in addition to the
diffusede extensive involvement of the cerebral cortex, both
basal ganglia, and medial thalami. After 1 month treatment,
he showed intellectual impairment, these seem to be caused
by extremely high ammonia level on admission. The direct
correlation between MRI and clinical outcome has not yet
been entirely determined, and it should be explored further
in a prospective study.
A follow up brain MRI, in our patient, showed a diffused
cortical atrophy in both temporo-fronto-parietal cortex
and cortical laminar necrosis in both of the temporal
cortex. Cortical laminar necrosis has been described as a
consequence of hypoxic encephalopathy, but also in some
cases of electrolyte imbalance and diffuse encephalitis.
Distinguishing a feature between hypoxic encephalopathy
and metabolic encephalopathy is the distribution of the
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cortical signal changes. Cortical laminar necrosis of hypoxic
brain damage is predominant in the watershed zones or
the parieto-occipital regions, which possibly reflects the
haemodynamic factors (6-8). In our patient, there was no
hypotensive or hypoxemic episode during the admission
days. Furthermore, the cortical signal change and cortical
atrophy were more diffused and generalized in both
temporo-fronto-parietal lobes and cortical laminar necrosis
were predominant in both temporal cortex. We, therefore,
suggest that the cortical laminar necrosis in our case
represent an extreme toxic effect of ammonia.
The bilateral basal ganglia of T1 high signal intensity
changes have been described in patients with chronic liver
disease (1, 9). In our patient, the basal ganglia showed
subtle T1 high signal in both globus pallidus on the
fourth day after the onset of seizures. This finding can be
interpreted as chronic lesions, due to longstanding cirrhosis.
On the 37th days after the onset of seizures, a follow up
brain MRI showed obvious T1 high signals in the lower
portion of both basal ganglia, rather than globus pallidus.
It is known that the T1 high signals in the basal ganglia or
caudate nucleus can be seen with cortical laminar necrosis
in patients of hypoxic-ischemic encephalopathy (10). We
suspect the obvious T1 high signals in the lower portion of
both basal ganglia by extreme toxic effect of ammonia, as
in the cortical laminar necrosis.
In conclusion, extensive cortical edema, including deep
gray matter, with sparing of the perirolandic and occipital
cortex, appears to be a unique imaging feature, particularly
in patients with an extremely high blood ammonia level. In
addition, the diffused cortical atrophy with T1 high signals
in both basal ganglia and temporal lobe cortex representing
cortical laminar necrosis can appear on a follow up brain
MRI in such cases. Therefore, we suggest that the brain
lesions in our case represent a consequence of toxic
effect of ammonia. Acute hepatic or hyperammonemic
encephalopathy can be considered as one of the causes in

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the differential diagnosis of cortical laminar necrosis.

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