Journal of Clinical Neuroscience xxx (2017) xxx–xxx

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Journal of Clinical Neuroscience
journal homepage: www.elsevier.com/locate/jocn

Case report

Epileptic seizures as the first symptom of Wernicke’s encephalopathy
with cerebral cortical lesions
Kailei Fu a, Li Tian b, Weishuang Xue a, Weiyu Teng a,⇑
a
b

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
Department of Geriatrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China

a r t i c l e

i n f o

Article history:
Received 21 October 2016
Accepted 22 January 2017
Available online xxxx
Keywords:
Wernicke’s encephalopathy
Cerebral cortex
Epileptic seizures
Prognosis

a b s t r a c t
Wernicke’s encephalopathy (WE) is acute metabolic disease of the central nervous system caused by deficiency of thiamine. Typical imaging findings are bilateral and symmetric signal in mammillary bodies,
medial thalamus and periaqueductal gray. We present a 45-year-old man diagnosed for WE with two seizures and unconsciousness. The magnetic resonance imaging showed bilateral and symmetrical signal
hyper-intensities in the frontal and parietal cortex, in addition to the classical MRI findings of WE.
Cortical damage in WE is rare. The patient was improved significantly from unconsciousness to obeying
commands and answering questions after 3 days by thiamine supplementation. But the muscle strength
and conscious state did not improve after 1 year. This case report reminds us that we should take into
account the possibility of WE when imaging shows cortical damage.
Ó 2017 Published by Elsevier Ltd.

1. Introduction
Wernicke’s encephalopathy (WE) is severe metabolic disease of
the central nervous system caused by deficiency of thiamine (vitamin B1). It is classically characterized by the triad of ocular abnormalities, ataxia and changes in consciousness. Images showes
symmetrical abnormal signal in the mammillary bodies, medial
thalamus, periventricular regions around the third and fourth ventricles. Now we report a case of WE with diffuse cortical lesions
demonstrating seizure as the initial symptoml, with a long history
of heavy drinking.

2. Case report
A 45-year-old man was admitted to the emergency department
of The First Hospital of China Medical University with two generalized tonic-clonic seizures and unconsciousness, which had begun 3
hours prior to admission. The patient drunk 6–9 bottles of beer
every day and drunk for 25 years, without alcohol temperance
prior to the illness onset. The patient had a history of chronic alcoholic hepatitis and had not been treated with systemic therapy. On
neurological examination: vital sign was normal. The patient was
unconscious and the Glasgow Coma Scale score was 3. Both pupil
were round, diameter were 3.0 millimetres and light reflex was
⇑ Corresponding author.

dullness. Tendon reflex was disappeared. The Babinski sign: the left
was negative and the right was positive. The patient was unable to
cooperate with other examinations (sensation, muscle strength,
coordination and gait). Brain magnetic resonance imaging (MRI)
was performed with a Marconi 1.5-Tesla magnet within 12 hours
after the onset. On the Brain MRI, there were bilateral and symmetrical T2-Weighted (T2W) and Fluid Attenuation Inversion Recovery
(FLAIR) hyper-intensities in the frontal and parietal cortex, medial
thalamus, third ventricle edge, cerebellar vermis, and periaqueductal area (Fig. 1.x; y). The diffusion weighted imaging (DWI)
showed signal hyper-intensities in the above positions
(Fig. 1.s; t; u; v; w). The electroencephalogram (EEG) showed
extensive moderate abnormality and no attack wave. Laboratory
investigations revealed the following: aspartate aminotransferase
was 218 U/L (normal range：15–46), cerebrospinal fluid (CSF):
the pressure was 85 mmH2O, protein level of 927 mg/l, and Glucose, chloride, and cell numbers were within the normal range.
The patient was diagnosed with WE, given vitamin B1 by intramuscular injection and hepatoprotective therapy. After 3 days, he
improved significantly from unconsciousness to obeying commands and answering questions. Neurological examinations 3 days
after the onset: the patient was conscious with slurred speech.
There was spontaneous binocular horizontal nystagmus and
upward gaze palsy on the right eye. The muscle strength of right
upper limb was grade III, others were 0. The follow-up after 1 year,
there was no significant improvement in muscle strength and conscious state.

E-mail address: tengweiyucmu@126.com (W. Teng).
http://dx.doi.org/10.1016/j.jocn.2017.01.016
0967-5868/Ó 2017 Published by Elsevier Ltd.

Please cite this article in press as: Fu K et al. Epileptic seizures as the first symptom of Wernicke’s encephalopathy with cerebral cortical lesions. J Clin
Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.016

2

K. Fu et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx

Fig. 1. r Axial computed tomography (CT): no abnormal signal. stu MRI showed characteristic WE with DWI signal hyper-intensity in the mamillary bodies s. black
arrow), medial thalamus s white arrow), periaqueductal area t white arrow) and cerebellar vermis u white arrow). v DWI showed bilateral and symmetrical signal hyperintensities in the frontal cortex. wxy DWI, axial T2W and axial FLAIR images showed diffuse hyper-intensities in parietal cortex (white arrow).

3. Discussion
Wernicke’s encephalopathy is severe metabolic disease of the
central nervous system caused by deficiency of thiamine (vitamin
B1) because of a variety of reasons. Typical imaging findings are
bilateral and symmetric signal in mammillary bodies, medial thalamus and periaqueductal gray. Cortical damage is very rare [1–
3]. The previous studies showed that WE with cerebral cortical
lesions (WEc) usually occurs in nonalcoholic’s. Zuccoli G. et al.
[3] reported only one nonalcoholics WEc patient in 56 patients
with WE, they speculated that alcohol may have a protective effect
on the brain areas that show atypical lesions in WE. Keita Sakurai
et al. [4] reported and literature review revealed that 30% of WEc
was Alcoholic. The present case report is a WE patient with chronic
alcoholic addiction, which MRI showed diffuse frontal and parietal
increased signals in the T2W, FLARI and DWI (Fig. 1.v; w; x; y).
The mechanisms underlying the development of WE had not been
completely elucidated, the possible mechanisms according to the
existing researches are as follows. thiamine acts as a co-factor for
various enzymes (transketolase, pyruvate dehydrogenase, aketoglutarate dehydrogenase complex) of glycometabolism.
Chronic alcohol intake leads to the malabsorption of thiamine
[2]. The thiamine, which stored in the liver, was exhausted within
3–4 weeks. Thiamine deficiency reduced efficiency of the tricarboxylic acid cycle, resulting in ATP insufficiency in the vulnerable
parts of brain, and reduced the efficiency of sodium potassium
pump so that it can not maintain the osmotic gradient on both
sides of the cell membrane. In this state, coupled with the high alanine, lactic acid and glutamic, resulted in the development of cytotoxic edema and eventual neuronal necrosis in the vulnerable
regions [1,3]. This may explain the cytotoxic edema that was suggested by restricted diffusion in DWI. Ocular abnormalities, ataxia
and changes in consciousness was classic manifestations of WE.
however, this classical triad can be seen in just one-third of
patients. Except ophthalmoplegia, spontaneous nystagmus, and
mental status changes, Epileptic seizures and quadriplegia were
the characteristic manifestations of our patient. Sakurai Keita
et al. [4] reported that 30% of the WEc were presented seizure,
and 83% with muscular weakness (including tetraplegia). Epileptic

seizures and mechanism were rare reported [5,6]. The mechanism
of epileptic seizure was not clear, we speculated that it is closely
related with glutamate, which is a kind of excitatory neurotransmitters produced in the arrested tricarboxylic acid cycle. The thiamine
deficiency
reduced
activity
of
a-ketoglutarate
dehydrogenase. a-ketoglutarate generated large amounts of glutamate by transamination, which was stored in the cytosol of neurons instead. As action potentials reach presynaptic terminals,
the resulting depolarization opens voltage-gated calcium channels
within the presynaptic membrane, leading to an influx of calcium.
This, in turn, causes docked small synaptic vesicles (SVs) to fuse
with the active zone membrane, via exocytic SNARE proteins. As
SVs fuse, glutamate is released into the synaptic cleft and then acts
on the postsynaptic cell through the opening of neurotransmittergated ion channels. The resulting depolarization of postsynaptic
membrane generate excitatory postsynaptic potential (EPSP).
when a sufficient number of neurons are engaged in sustained
bursting, further excitatory phenomena ensue, thereby resulting
in seizure [7]. Sakurai Keita et al.[4]reported that muscular weakness of all extremities may be the core symptoms of WEc, but the
specific mechanism is still not clear. We hypothesize that this is
associated with damage of bilateral cerebral motor cortex. The
prognosis of WEc is still the focus of controversy. Fei G.q. et al.
[8] concluded that cortical involvement in patients with nonalcoholic WE may be indicative of irreversible lesions and a poor prognosis. Kril J.J’s [9] study showed that chronic alcoholism led to the
loss of cortical neurons, and such deficits were unlikely to be reversible. Guler Ayse et al. [10] reported a case of WEc with good prognosis. Our patient had no significant improvement in
consciousness and muscle strength after 1 month. We believe that
the prognosis of WEc is closely related to the vitamin B1 supplementation in time. In clinical, we should consider the possibility
of WE and take brain MRI to confirm the diagnosis as early as possible, when the patient with the atypical manifestations (seizure,
muscular weakness et al.) and inducements (aocohol intoxication
and malnutrition). In addition to the classical MRI findings, We
should take into account the atypical MRI findings of WE such as
cortex, basal ganglia, cerebellar vermis and callosum [4]. Bearing
in mind that a negative MRI does not allow the diagnosis of WE

Please cite this article in press as: Fu K et al. Epileptic seizures as the first symptom of Wernicke’s encephalopathy with cerebral cortical lesions. J Clin
Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.016

K. Fu et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx

to be excluded. For patients who were definitely diagnosed or
highly suspected of WE, thiamine supplementation promptly
may stop progression and improve the prognosis.

Grant/Fund Support
This work was supported by Science project of Shenyang (Grant
No. F16-206-9-03) and Science and technology project of Liaoning
Province (Grant No. 2014226033), China.

Conflict of interest
No potential conflict of interest relevant to this article was
reported.

Acknowledgments
This work was supported by Science project of Shenyang (Grant
No. F16-206-9-03) and Science and technology project of Liaoning
Province (Grant No. 2014226033), China.

3

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Please cite this article in press as: Fu K et al. Epileptic seizures as the first symptom of Wernicke’s encephalopathy with cerebral cortical lesions. J Clin
Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.01.016