Metab Brain Dis
DOI 10.1007/s11011-017-0106-1

ORIGINAL ARTICLE

Epileptic seizures in nonalcoholic Wernicke’s
encephalopathy: a case report and literature review
Wenjin Shang 1 & Xiuhui Chen 1 & Xunhua Li 1 & Hongbing Chen 1 & Shujin Tang 1 &
Hua Hong 1,2

Received: 13 April 2017 / Accepted: 29 August 2017
# Springer Science+Business Media, LLC 2017

Abstract Wernicke encephalopathy (WE) is characterized by
eye signs, cerebellar dysfunction, and confusion. Epileptic
seizures are rare in nonalcoholic WE. We reviewed the clinical, laboratory, radiological, and prognostic characteristics of
nonalcoholic WE accompanied by epileptic seizures. We reported 1 case and searched similar cases using PubMed, WoK,
Ovid, and Embase. WE was diagnosed according to dietary
deficiencies, clinical symptoms and brain magnetic resonance
imaging (MRI). We reviewed 13 patients (median age,
27 years; 5 men) with clear histories of thiamine deficiency
and symptoms of typical WE. The type of epileptic seizures
reported in the 13 cases reviewed was generically reported as
seizures or convulsions in 4 patients; 7 patients had generalized tonic-clonic seizures, 1 partial seizure, and 1 generalized
convulsive status epileptics. Two patients had epileptic seizures as the first symptom of WE. Laboratory tests mainly
indicated metabolic acidosis and electrolyte disturbances.
Electroencephalography may present as normal patterns, increased slow waves or epileptic discharge. Six patients had
cortical lesions on brain MRI. These lesions were usually
diffuse and band-like, and sometimes involved all lobes either

Wenjin Shang and Xiuhui Chen contributed to the work equally.
* Hua Hong
hhsums@126.com
1

Department of Neurology, First Affiliated Hospital of Sun Yat-sen
University, Zhongshan 2nd Road 58, Guangzhou, Guangdong
Province 510080, China

2

Department of Neurology, Seventh Affiliated Hospital of Sun
Yat-sen University, Zhenyuan Road 628, Shenzhen, Guangdong
Province 518017, China

symmetrically or asymmetrically, with the frontal lobe
as the most susceptible area. All cortical lesions were
accompanied by non-cortical lesions typical of WE.
Brain MRI abnormalities, after thiamine treatment,
mostly disappeared on follow-up MRIs. The patients
had good prognoses. Only 1 patient had repeated seizures, and there were no comas or deaths. Patients with
nonalcoholic WE accompanied by seizures are young
and generally have good prognoses. Most patients experienced
generalized convulsive seizures, which may have been related
to abnormal cerebral cortical metabolism due to subacute thiamine deficiency.
Keywords Wernicke encephalopathy . Nonalcoholic .
Seizure . Cortical impairment . Prognosis

Introduction
Wernicke encephalopathy (WE) is an acute or subacute neurological disorder due to thiamine deficiency and often occurs
in alcoholics (Galvin et al. 2010). It is a severe disease with
complex clinical manifestations and is often delayed in diagnosis. Typical lesions involve symmetrical alterations in the
medial thalami, mammillary bodies, tectal plate, and
periaqueductal gray matter. The classical clinical triad of signs
of WE comprise eye signs, cerebellar dysfunction, and confusion (Galvin et al. 2010; Zuccoli et al. 2009; Singh and Kumar
2007; Sechi and Serra 2007; Harper et al. 1986; Lough 2012).
Compared to alcoholic WE, nonalcoholic WE leads to a high
proportion of atypical brain lesions and a lower proportion of
classic triad symptoms. This may result in the high frequency
of undiagnosed cases of nonalcoholic WE (Galvin et al. 2010;
Zuccoli et al. 2009; Sechi and Serra 2007; Manzo et al. 2014).
Epileptic seizure is an exceedingly rare symptom of WE, even

Metab Brain Dis

in patients with WE involving the cortex (Galvin et al. 2010;
Wu et al. 2017). However, patients without cortical involvement can also have epileptic seizures (Verma et al. 2014;
Hiraki and Kikuchi 2014; Watanabe et al. 2009; FattalValevski et al. 2005; Kesler et al. 2005; Rees et al. 1997).
This highlights the complexity of WE and makes its diagnosis
more difficult. Given that thiamine administration leads to
dramatic improvements in patients with WE, and that the disease may be fatal if left untreated (Galvin et al. 2010; Wu et al.
2017; Vasconcelos et al. 1999), in-depth studies of epileptic
seizures in patients with nonalcoholic WE have clinical relevance. Here we report the case of a patient with nonalcoholic
WE with seizures and cortical lesions and review the literature
on the clinical, radiological, and prognostic features of nonalcoholic WE accompanied by epileptic seizures.

Patients and methods
We reviewed one patient who was diagnosed in 2016 in our
institution, as well as other patients with nonalcoholic WE
accompanied by epileptic seizures from the literature. We
searched PubMed, WoK, Ovid, and Embase using the terms
BWernicke encephalopathy^ AND Bseizure OR epilepsy OR
epileptic OR convulsion^,and reviewed the references in all of
the reports for additional cases. Searches were carried out until
January 1, 2017. We reviewed cases that met the following
four criteria: 1) consistent with the operational case definition
of WE, which requires meeting two of the following four
signs: (i) dietary deficiencies, (ii) eye signs, (iii) cerebellar
dysfunction, and (iv) either an altered mental state or mild
memory impairment; 2) presence of epileptic seizures; 3)
availability of brain magnetic resonance imaging (MRI) results; 4) nonalcoholic. Patients with comorbidities such as
stroke, cerebral arteriovenous malformation, intracranial infection, or tumor, which may cause epileptic seizures, were
excluded. We reviewed information regarding age, sex, past
history, causes of thiamine deficiency, clinical manifestations
(WE classic triad, type and number of seizures, pyramidal
signs, etc.), comorbidities, hematological and cerebrospinal
fluid examinations, electroencephalogram (EEG), MRI (location, extent, form, and follow-up of impairment; sequences of
MRI), and prognosis for each included patient.

the patient developed mild memory impairment, ataxia, dizziness, diplopia, bilateral visual and hearing loss, tinnitus, numbness of the whole body, and intractable hiccups. He was admitted to the department of gastrointestinal surgery in our hospital two weeks later. He had a history of hepatitis but no
history of alcohol abuse. Blood tests on the day of admission
indicated an anion gap of 23.57 mmol/L, amylase levels of
279 U/L, lipase levels of 1950 U/L, glutamic-pyruvic transaminase levels of 69 U/L, glutamic-oxaloacetic transaminase
levels of 50 U/L, total bilirubin levels of 26.4 μmol/L, activated partial thromboplastin time of 21.5 s, and fibrinogen levels
of 1.81 g/L. Leukocytes, erythrocytes, hemoglobin, platelets,
prothrombin time, thrombin time, international normalized ratio, sodium levels, potassium levels, calcium levels, osmolality,
and creatinine levels were normal. Brain MRI showed bilaterally symmetric lesions in the medial thalami, tectal plate, and
dorsal medulla, as well as bilaterally extensive and partially
symmetric lesions in the cortex (Fig. 1). On the second day
of admission, the patient experienced a generalized tonicclonic seizure (GTCS) which lasted 1 to 2 min. After the seizure, mental status recovered in 1–2 h. Consultation with a
neurologist revealed horizontal nystagmus, ocular muscle paralysis, Rinne test left > right, and ataxia. After the seizure, the
patient had higher leukocyte count and creatinine levels
(18.87 × 109 /L and 123 μmol/L, respectively), which returned
to normal within a few hours. Blood pH as revealed by gas
analysis, ammonia levels, and the results of a lumbar puncture
and EEG were normal. The patient was treated with thiamine
(50-100 mg once per day, intramuscular injection) and
Levetiracetam (500 mg twice per day) immediately after the
diagnosis of WE was made. His symptoms improved rapidly
following treatment. Follow-up brain MRI 2 weeks after admission indicated improvements in most of the lesions, although there were some hyperintense cortical regions on
T2WI, FLAIR imaging, and DWI (Fig. 2). Four months later,
the patient had persistent nystagmus and ataxic gait.
Literature review
We identified 12 other cases from 11 full-text reports
(Wicklund and Knopman 2013; Gregory et al. 2012; Pereira
et al. 2011; Doss et al. 2003; Verma et al. 2014; FattalValevski et al. 2005; Kesler et al. 2005; Rees et al. 1997;
Kwon 2004; Hiraki and Kikuchi 2014; Watanabe et al.
2009). There were no language restrictions.

Results
Clinical features
Case 1
A 26-year-old man experienced duodenal obstruction after surgery owing to pancreatic and duodenal injuries caused by an
abdominal knife wound. After recurrent vomiting and parenteral nutrition which was deficient of thiamine for 1.5 months,

The clinical characteristics of all 13 cases are summarized in
Table 1. Patients ranged in age from 0.4 to 71 years, with a
median age of 27 years. There were 5 men (38.5%, median
age of 23 years) and 8 women (61.5%, median age of
30.5 years).

Metab Brain Dis

Fig. 1 Fluid-attenuated inversion-recovery (FLAIR) images obtained at
onset in Case 1. Hyperintense signals were observed in the bilateral
frontal, parietal, and temporal lobes, the right insular and occipital

lobes, the bilateral medial thalamus, tectal plate, and the gray matter
around the third and fourth ventricles and the aqueduct

Six patients (46.2%, median age of 30.5 years, 2 men)
had cortical lesions. All of the patients had identified
causes of thiamine deficiency, which included gastrointestinal disease, persistent vomiting, parenteral nutrition, and
cancer. Five of the cases displayed classical WE signs.
None of the patients had epileptic seizures as the first
symptom of WE. The type of epileptic seizure was specified in 5 of the reports. Four of these cases had generalized
seizures (GTCS in 3, partial seizure evolving to generalized seizure in 1), and 1 had simple partial occipital lobe
seizures. The prognosis at the end of treatment or at
follow-up visits was reported in all 6 cases. Two patients

had an almost normal prognosis, while 4 had neurologic
sequelae, although there were no repeated seizures.
Seven patients had no cortical lesions (53.8%, median
age of 3 years, 3 male patients). All had identified causes
of thiamine deficiency, which included gastrointestinal disease, persistent vomiting, a diet deficient in thiamine, and
starvation. These patients displayed classic WE signs. Two
patients had epileptic seizures as the first symptom of WE.
The types of epileptic seizures were reported in five cases
(GTCS in 4 and generalized convulsive status epileptics in
1). The prognosis at the end of treatment or at follow-up
visits was reported for all 7 patients. Two patients had

Fig. 2 Follow-up fluid-attenuated inversion-recovery (FLAIR) imaging performed 15 days after thiamine treatment in Case 1. Compared with Fig. 1,
the high-intensity alterations have faded significantly

51 M

27 F

31 F

30 F

Gregory
et al. 2012

Pereira
et al. 2011

Kwon 2004

Doss et al.
2003

0.7 M

Fattal-Valevski 0.4 F
et al. 2005

Watanabe et al. 3 M
2009

Hiraki and
Kikuchi 2014

Non-cortex-involved
Verma
23 M
et al. 2014

71 F

26 M

Cortex-involved
Case 1

Wicklund and
Knopman
2013

A(Y)/G

Infantile autism, severe
eating disorder for
0.7 months
Thiamine-deficient
diet and vomiting
for 2–5 months

Cholecystitis,
cholecystectom and
vomiting for
1 months
Excessive intake of
isotonic drinks for
2 months

Self-induced vomiting
after meals for
6 months

Pancreatitis, parenteral
nutrition

Crohn’s disease, total
colectomy and
parenteral nutrition
for 0.5 months

NA

3.5

Low
weight

18.1

NA

NA

NA

Type of
seizure

(−)

Simple partial >1
occipital
lobe
seizures
NA
NA

E,C

C

E,C

NA

Generalized
convulsive
status
epileptics
GTCS

E,A,C GTCS

NA

NA

(−)

(−)

1

Cluster

(−)

2

(−)

(−)

(+)

(+)

(−)

>1

GTCS

1

iv

(−)

Movement disorder

(−)

(−)

(−)

(−)

(−)

(−)

(−)

Asthma

(−)

250 mg iv
bid

2.1 mg/kg
iv qd

NA

500 mg iv
tid

High-dose
iv

300 mg iv
qd

500 mg iv
tid

NA

50–100 mg
im qd

(−)

(−)

Hepatit-is B

Complications Vitamin
B1

Sixth, ninth and tenth (−)
cranial nerve
palsies, tinnitus

Aphasia, sixth and
seventh cranial
nerve palsies,
upper limb
spasiticity

Headache

(−)

Dizziness, tinnitus
and hearing loss,
numbness,
hiccups

No. of Pyramidal Other clinical
seizures signs
manifestations

E,A,C Partial seizure 2
evolving to
generalized
seizure
A,C
GTCS
2

E,C

E,C

E,C

E,A,C GTCS

Weight WE
triad
loss
(kg)

light
Duodenal obstruction,
frequent vomiting
and parenteral
nutrition for
1.5 months
Myelofibrosis, vomiting NA
and diarrhea after
chemotherapy for
2 months
B-cell lymphoma for
NA
6 months

Inducement

Clinical manifestations and prognoses of the 13 cases of WE accompanied by seizures

Author

Table 1

(−)

(+)

(−)

(−)

(−)

(+)

(−)

(+)

(−)

(+)

Anti-epileptic
drugs

Ataxia and
mental
disturbance
sequalae

Aphasia,
tetraparesis
and upper
limb
spasticity
sequalae
Recovered

Recovered

Severe
memory
loss

Nystagmus
and ataxia
sequalae

Outcome

5 weeks

3 months

7 months

Nystagmus
and
movement
disorder
sequalae

Recovered

Mental
retardation

Recovered
Several
months

NA

25 days

14 days

NA

NA

4 months

Duration

Follow-up

Metab Brain Dis

WE Wernicke encephalopathy, E eye signs, A ataxia, C confusion, GTCS generalized tonic-clonic seizure, im intramuscular, qd once per day, NA not available, iv intravenous, tid three times per day, bid
twice per day

Nystagmus
and ataxia
sequalae
2 months
(−)
NA
(−)
(−)
(+)
1
E,A
>6.4

31 F
Rees et al. 1997

31 F

0.4 F
Kesler
et al. 2005

Hyperemesis
gravidarum for
2 months
Hyperemesis
gravidarum for
1.5–2.5 months

GTCS

E,A,C GTCS
>13.6

1

(−)

(−)

(−)

NA

(+)

11 months Oculomotor
and mental
disturbance
sequalae
3 months Memory loss
(−)
iv
(−)
(−)
(−)
NA
E,C
NA
Thiamine-deficient
diet for 4.5 months

>1

Duration

Type of
seizure
Weight WE
loss
triad
(kg)
Inducement
A(Y)/G
Author

Table 1 (continued)

No. of Pyramidal Other clinical
seizures signs
manifestations

Complications Vitamin
B1

Anti-epileptic
drugs

Follow-up

Outcome

Metab Brain Dis

almost normal prognoses, while 5 had neurologic sequelae.
One patient had repeated seizures.
Results of laboratory and auxiliary examinations
Details of laboratory and auxiliary tests for all 13 cases are
summarized in Table 2.
Of the 6 patients who had cortical involvement, thiamine
deficiency was only reported in 1 patient. Results of other
blood analyses and lumbar puncture were only reported in 3
and 2 patients respectively and they were normal. One patient
had epileptogenic activity over the left occipital region on
EEG, which is consistent with simple partial occipital seizures, and 1 case had normal EEG. MRI indicated that 5
patients had cortical lesions involving the frontal lobe, 3 had
lesions involving the temporal and occipital lobes, and 1 had
parietal lobe and insular lesions. MR images were displayed in
5 articles. Four of the MR images indicated the presence of
band-like cortical lesions, while 1 displayed limited band-like
cortical lesions. No cortical enhancement was observed in the
3 cases for which MR contrast enhancement was reported. All
of these 6 patients had non-cortical lesions, most of which
were typical WE lesions. Three patients underwent followup MRI, which indicated significant amelioration of the lesions after thiamine treatment.
Of the 7 patients without cortical lesions, thiamine deficiency was reported in 5 patients. 4 patients had metabolic
acidosis and 3 had electrolyte disturbance. The results of lumbar puncture were reported for 4 patients, 3 of whom had
increased lactic acid, while 1 had increased protein levels.
EEG results were reported for 2 patients, wherein merely diffuse slow waves were observed. One patient had normal MRI
results and 6 had non-cortical lesions in the typical areas implicated in WE. Follow-up MRI was performed in 3 patients.
The lesions had disappeared in 1 patient who had atrophy and
were significantly ameliorated in 2 patients.

Discussion
The classic triad of WE symptoms comprises eye signs, ataxia, and confusion (Galvin et al. 2010; Zuccoli et al. 2009;
Singh and Kumar 2007; Sechi and Serra 2007; Harper et al.
1986; Lough 2012). Epileptic seizure is an exceedingly rare
symptom in nonalcoholic WE. The incidence of epileptic seizure in WE was 0%–3.1% reported by Galvin et al. By
reviewing 218 WE patients diagnosed clinically and 256
WE patients diagnosed by autopsy. We reviewed the clinical,
radiological, and prognostic features of nonalcoholic WE accompanied by epileptic seizures for the first time. The results
revealed that the form of epileptic seizure is various while
GTCS is the main type, and epileptic seizure could be the first
symptom of WE. The results also showed that about half of

None

None

None

15 nM/l

Gregory
et al. 2012

Pereira
et al. 2011

Kwon 2004

Doss
et al. 2003

Non-cortex-involved
Verma
36 nM/l
et al. 2014

None

Wicklund and
Knopman 2013

None

Almost
normal

Normal

Almost
normal

NA

NA

NA

Shown in
the text

Thiamine Other blood
tests
blood
level

None

Normal

None

None

None

None

Normal

Lumbar
puncture

Slow waves

T1/T2/FLAIR

T1/T2/FLAIR/CE
(DWI on
follow-up)

MRI sequences

Non-cortex
lesions
Location

Cortex lesions

Bilaterally
symmetric
medial
thalamus,
periaqueductal

/

Bilaterally
Bilaterally
symmetric
symmetric
medial
frontal, periatal,
thalamus, tectal
and temperal
plate, and dorsal
cortex (including
medulla
precentral
gyrus), and right
occipital and
insular cortex
None
T1/T2/DWI/ CE
Bilaterally
Left precentral
symmetric
gyrus
medial thalamus
and tectal plate
Epileptogenic
NA
Bilateral temporal- Bilateral temporalactivity over
occipital
occipital cortex
the left
leptomeninges
occipital
and cavernous
lobe
sinus
None
T1/T2/FLAIR/DWI Bilaterally
Bilaterally
symmetric
symmetric
hypoglossal,
frontal cortex
abducens and
(including
facial nuclei,
precentral gyrus)
right medial
thalami,and
tectal plate
None
T1/T2/DWI
Bilaterally
Bilaterally
symmetric
symmetric
medial thalamus,
frontal cortex
tectal plate, and
(not including
periaqueductal
precentral gyrus)
gray matter
None
T1/T2/DWI
Bilaterally
Bilaterally
symmetric
asymmetric
medial
frontal cortex
thalamus and
(including
hypothalamus
precentral
gyrus) and
hippocampus

Normal

EEG

Results of the accessory examinations in the 13 cases of WE accompanied by seizures

Cortex-involved
Case 1

Author

Table 2

NA

/

/

Diffuse Band-like /

Diffuse Band-like /

/

None

15 days

7 days

None

25 days

21 days

Significantly
fading

/

/

Significantly
fading

/

/

Significantly
fading

Duration Noncortical
lesions

Follow-up MRI

Non-cortex None

Diffuse Band-like /

NA

Limited Band-like Tectum

Diffuse Band-like (−)

Range Form

CE

/

/

Disappeared

Partial fading

/

/

Significantly
fading

Cortical
lesions

Metab Brain Dis

Hyponatremia,
hypokalemia

None

None

None

None

None

Slow waves

None

EEG

NA

T1/T2

T1/T2/DWI

T1/T2

T1/T2/FLAIR

T1/T2/DWI

MRI sequences

gray matter, and
hypothalamus
Bilaterally
symmetric
caudatum and
putamina
Bilaterally
symmetric
caudatum and
putamina
Bilaterally
symmetric basal
ganglia,
mammillary
bodies, and
periaqueductal
gray matter
Bilaterally
symmetric basal
ganglia and
periaqueductal
gray matter
Gray matter around
aqueduct and
the third
ventricle
(−)

Non-cortex
lesions

/

/

/

/

/

/

Location

Cortex lesions

/

/

/

/

/

/

/

/

/

/

/

/

Range Form

/

/

/

/

/

/

CE

None

None

None

5 weeks

None

2 months

/

/

/

Significantly
fading

/

Disappeared
and
atrophy

Duration Noncortical
lesions

Follow-up MRI

/

/

/

/

/

/

Cortical
lesions

WE Wernicke encephalopathy, EEG electroencephalogram, MRI magnetic resonance imaging, CE contrast enhancement, NA not available, T1 T1-weighted imaging, T2 T2-weighted imaging, FLAIR fluid
attenuated inversion recovery, DWI diffusion-weighted imaging, BE base excess, Lac lactic acid, Glu glucose, TPPE thiamine pyrophosphate effect, normal values range from 0% to 15%, a value of
>15%indicates thiamine deficiency

None

Protein,
Hypocalcemia,
1.3 g/dl
hypomagnesemia

None

Lac,
4.7 mmol/l

Rees et al. 1997

Lac, 6.6 mmol/l

TPPE
>15%

Lac,
6.9 mmol/l

Lac,
4.8 mmol/l

None

Lumbar
puncture

Kesler
et al. 2005

Fattal-Valevski
et al. 2005

<5 ng/ml

Watanabe
et al. 2009

pH 7.45;BE,
−6.2 mmol/l;

Lac, 7.2 mmol/l;
Glu,
22.2 mmol/l;
hyponatremia
TPPE>15% Lac, 5.9 mmol/l

8 ng/ml

Thiamine Other blood
blood
tests
level

Hiraki and
Kikuchi 2014

Author

Table 2 (continued)

Metab Brain Dis

Metab Brain Dis

these patients didn’t have cortical lesions on brain MRI, and
their prognoses were good.
Our review indicates that the main type of epileptic seizures
observed in nonalcoholic WE is generalized seizure, and especially GTCS. However, the exact cause of seizures in nonalcoholic WE has not been clarified yet. Our review included
6 patients with cortical alterations. Five of these patients had
bilateral lesions, while Case 1 had bilateral cortical lesions on
brain MRI before the seizure. Among the 7 patients without
cortical alterations, 3 had electrolyte disturbances, which
might evoke epileptic seizures (Rees et al. 1997), and 4 had
metabolic acidosis, which might inhibit epileptic seizures
(Ziemann et al. 2008). The EEG results were variable, and
included normal, epileptic discharge, and slow waves. The last
pattern may also be found in the later periods of WE in the
absence of epileptic seizures (Sechi and Serra 2007).
Meanwhile, epileptic seizures stopped as the WE symptoms
improved. Thus, we hypothesized that epileptic seizures might
be associated with cortical damage and pathophysiological
changes after thiamine deficiency. These changes include impaired energy metabolism, glutamate-mediated excitotoxicity,
impaired synthesis of glucose-derived neurotransmitter
gamma-aminobutyric acid, oxidative stress, and inflammation
(Manzo et al. 2014; Jhala and Hazell 2011; Jung et al. 2012;
Sechi et al. 2016).
Generally, epileptic seizures are not the first symptoms of
nonalcoholic WE. However, among patients in our review, 1
patient had ocular movement and mental status disorder after
status epilepticus (Hiraki and Kikuchi 2014), and 1 patient had
epileptic seizure after 6 weeks of hyperemesis gravidarum,
which was followed by ocular movement disorders and ataxia
4 weeks later (Rees et al. 1997). In addition, one study revealed that only 16% of patients had the classical clinical triad
and that 19% had no documented clinical signs (Harper et al.
1986). This suggests that the presentations and onset of nonalcoholic WE may be more complex than the current cognition. Epileptic seizures may be the first symptoms of nonalcoholic WE, although usually one or more symptoms may appear later in the course of WE (Sechi and Serra 2007).
Brain MRI impairments of nonalcoholic WE with epileptic
seizure could involve the cortex or not. The non-cortical impairments were located in typical areas of WE (Zuccoli et al.
2009; Zuccoli et al. 2010; Zuccoli and Pipitone 2009; Manzo
et al. 2014). And we found some features of the cortical impairments. First, all of the brain lobes could be involved, with
the frontal lobe (usually including the precentral gyrus) the
most susceptible area, followed by the temporal and occipital
lobes. Second, cortical impairments were usually diffuse and
band-like. Third, in contrast to typical lesions of WE, cortical
impairments might be asymmetric or unilateral. Fourth, all
cortical impairments were accompanied by non-cortical impairments. The cortical impairments of nonalcoholic WE
without epileptic seizure described by Wu et al. (2017) are

band-like and asymmetric in some cases, which was consistent with our observation. However, in Wu’s review, all lesions were bilateral with the frontal and parietal lobes as the
most susceptible areas.
The median age of nonalcoholic WE patients with epileptic
seizure and cortical impairments was 31 years (range, 26–
71 years), which was significantly younger than that of nonalcoholic WE patients with cortical impairments but without
epileptic seizure reviewed by Wu et al. (2017) (median age,
53 years; range, 13–81 years). The nonalcoholic WE patients
with epileptic seizure but without cortical impairments was
even younger (median age, 3 years; range, 0.4–31 years) and
3 of them were infants. Therefore, young patients and infants
may be more sensitive to these changes induced by thiamine
deficiency, which would in turn makes them more prone to
epileptic seizures, especially in the absence of cortical lesions.
Patients in our review had better prognoses than other WE
patients reported in previous studies. Among the 13 patients, 4
had almost normal outcomes, 5 had persistent mental or memory disturbances, 6 had persistent eye signs and/or ataxia, and
only 1 had repeated seizures. There was no cases of coma or
death. The mortality rate of WE has been reported to be 14.3–
20% in previous studies (Sechi and Serra 2007; Lough 2012;
Manzo et al. 2014), and may be as high as 26.1% in those with
cortical lesions (Wu et al. 2017). About 80% of patients who
survived from WE developed Korsakoff’s syndrome, which is
a severe memory disorder (Sechi and Serra 2007; Victor et al.
1971). Our results indicate that these patients with atypical
WE respond well to thiamine and antiepileptic drugs, and that
epileptic seizures do not lead to poor prognosis in WE.
Our review has following limitations. First, some data was
insufficient in those cases, and we couldn’t make a stricter
description and explanation on some results like blood tests,
lumbar puncture and electroencephalogram. Second, the effectiveness and route of administration of antiepileptic drugs
for these patients were not clear. Antiepileptic drug use was
only reported in 4 cases, and we were unable to determine
whether antiepileptic drugs were used in the other 10 cases.
Only 1 case report that did not mention the use of antiepileptic
drugs indicated repeated seizures in follow-up. Therefore, the
method required to control epileptic seizures (thiamine vs.
antiepileptic drugs), and how long anti-epileptic drugs should
be used require further study.

Conclusions
Epileptic seizures are very rare in nonalcoholic WE. Patients
with nonalcoholic WE accompanied by epileptic seizures are
usually younger than those reported in previous studies.
Epileptic seizures may be the first symptoms of WE, and the
most common type of epileptic seizures in WE is GTCS. The
mechanisms underlying these epileptic seizures are as yet not

Metab Brain Dis

clear, but may be related to cortical lesions and abnormal
metabolism owing to thiamine deficiency. The cortical lesions
on brain MRI are mostly diffuse and band-like, and may involve all lobes either symmetrically or asymmetrically. The
frontal lobe is the most susceptible area, followed by the temporal and occipital lobes. In addition to cortical lesions, brain
MRI lesions typical for WE are usually present. The prognosis
for nonalcoholic WE is good and seizures rarely recur.
Acknowledgements This review was supported by the grant from the
National Key Clinical Department and Key Discipline of Neurology, the
Guangdong Provincial Key Laboratory for Diagnosis and Treatment of
Major Neurological Diseases (No. 2014B030301035). We thank the patient and his family for giving us permission to publish his case. We also
thank Qiuxin Lv for her assistance in translation of literatures in Japanese
and Shen Tao (Zhongshan Ophthalmic Center, Sun Yat-sen University)
for his assistance in translation of literature in Korean.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflicts of
interest.
Informed consent Informed consent was obtained from the one case
included in the study.

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