Lupus (2016) 0,

1–5

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Wernicke’s encephalopathy mimicking neuropsychiatric symptoms
in patients with systemic lupus erythematosus: a report of three
cases and literature review
S Appenzeller1, F Reis2, LT Lavras Costallat1, J Adams Pérez3, CF Saldanha4 and OA Monticielo4
1

Rheumatology Department, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), São Paulo, Brazil; 2Radiology
Department, Faculdade de Ciências Médicas, UNICAMP, São Paulo, Brazil; 3Division of Neuroradiology, Department of Radiology, Hospital de
Clı́nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil; and 4Division of Rheumatology, Department of Internal
Medicine, Hospital de Clı́nicas de Porto Alegre, UFRGS, Brazil

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs
and systems. Nervous system involvement in SLE encompasses neurological and psychiatric disorders, and remains a diagnostic and therapeutic challenge. Wernicke’s encephalopathy (WE) is a
neurological disorder that occurs as a consequence of thiamine deficiency, and its clinical presentation resembles the neuropsychiatric events attributed to SLE (NPSLE). Differentiation between
these two entities is crucial because their treatment differs greatly and can change prognosis. We
describe three cases of patients with SLE who presented with initial clinical findings suggestive of
NPSLE that, at the end of a thorough clinical investigation, were actually found to represent WE.
In all of these cases, treatment with thiamine resulted in significant improvement. WE should be
considered as a differential diagnosis in SLE patients with neuropsychiatric signs and symptoms,
especially when risk factors for thiamine deficiency are present. Lupus (2016) 0, 1–5.
Key words: Wernicke’s encephalopathy; systemic lupus erythematosus; neuropsychiatric lupus

Introduction
Systemic lupus erythematosus (SLE) is a chronic
inflammatory autoimmune disease characterized
by multisystem involvement. The injuries observed
in different organs in this condition occur as a
result of autoantibody production and immune
complex deposition.1 The polymorphic clinical
manifestations of SLE occur over a course characterized by exacerbations and periods of remission,
resulting in cumulative damage over time.
Neuropsychiatric events attributed to SLE
(NPSLE) are common, and generally represent a
diagnostic and therapeutic challenge.2
Wernicke’s encephalopathy (WE) is a rare, severe
neurological syndrome resulting from deficiency of

Correspondence to: Odirlei Andre Monticielo, Division of
Rheumatology, Hospital de Clı́nicas de Porto Alegre, UFRGS Rua
Ramiro Barcelos, 2350, room 645, ZIP Code 90035-003, Porto
Alegre, Brazil.
Email: omonticielo@yahoo.com.br
Received 14 September 2015; accepted 14 June 2016

thiamine (vitamin B1). Ophthalmoplegia, ataxia,
and mental confusion are the classic symptoms of
WE, but are present in only a minority of patients;
this can delay recognition and treatment. Untreated
WE may progress to the Korsakoff syndrome, an
irreversible disorder characterized by anterograde
and retrograde amnesia.3
Some of the clinical manifestations associated with
NPSLE and WE are similar, and both conditions
require emergency treatment, but their therapeutic
approaches are completely distinct. Delays in recognizing these conditions can cause additional morbidity to the patient. To date, there has been no
published report of WE mimicking NPSLE in the
literature. The present study describes three patients
with SLE patients who were admitted for suspicion of
NPSLE and ultimately received a diagnosis of WE.

Methods
The patients reported herein were followed at two
rheumatology centers in Brazil. Two patients were

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10.1177/0961203316658556

WE mimicking neuropsychiatric symptoms in patients with SLE
S Appenzeller et al.

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managed at Hospital de Clı́nicas de Porto Alegre
and one patient was treated at Hospital de Clı́nicas
da Universidade Estadual de Campinas. In all
patients, further investigation with magnetic resonance imaging (MRI) of the brain after initial suspicion of NPSLE was suggestive of WE, and all
experienced clinical improvement with thiamine
replacement.
A review of the literature on NPSLE and WE
was performed using the MEDLINE (via
PubMed), EMBASE, SciELO, Cochrane Library,
and BIREME databases. The following keywords
were used: ‘‘lupus erythematosus systemic,’’
‘‘Wernicke’s encephalopathy,’’ ‘‘lupus erythematosus systemic AND Wernicke’s encephalopathy,’’
‘‘Wernicke’s encephalopathy AND neuropsychiatric symptoms’’ and ‘‘Wernicke’s encephalopathy
AND neuropsychiatric lupus.’’ Articles in
Portuguese, Spanish, and English published until
2015 were included in this review.

Case reports
Case 1
A 29-year-old woman with SLE (malar rash,
polyarthritis, photosensitivity, oral ulcers, and
antinuclear antibodies (ANA) titers 1:80 with
homogeneous pattern) and antiphospholipid antibody syndrome (APS) (two fetal losses after 10

weeks’ gestation and positive lupus anticoagulant
testing on two separate occasions) who had
received irregular follow-up for the preceding
10 years was admitted at 31 weeks’ gestation, in
preterm labor, with a four-week history of vomiting. She also exhibited mental confusion, reduced
sensation in the lower limbs, ataxia, diplopia, and
nystagmus, which were consistent with cerebellar
ataxia. The patient had a history of severe
depression with previous suicide attempts and
was taking chloroquine diphosphate (250 mg
daily) and aspirin (100 mg daily). Considering
the possibility that this syndrome could be attributed to NPSLE, she was started on prednisone
1 mg/kg/day while awaiting laboratory test
results. There were no other signs or symptoms
of SLE activity. Cerebrospinal fluid (CSF) analysis showed normal cellularity, glucose within
the normal range, and a slight increase in protein.
Brain MRI performed four days after admission
showed signal hyperintensity and contrast
enhancement in the tuber cinereum, mammillary
bodies, medial thalamic nuclei, tectal plate, and
pontine region on T1-weighted and diffusionweighted imaging sequences (Figure 1). The
changes described were consistent with WE.
Thus, corticosteroid treatment was discontinued
and thiamine replacement was initiated, with progressive improvement of nystagmus and confusion. However, at three-year follow-up, the
patient still exhibited mild cerebellar ataxia.

Figure 1 Brain magnetic resonance imaging of case 1. (a) There is diffuse enhancement of both mammillary bodies (red arrows)
and the tectal plate (yellow arrows). T1-weighted post-contrast axial view. (b) Diffusion-weighted imaging (DWI) at the level of the
basal ganglia shows hyperintensities consistent with diffusion restriction in the medial thalamic nuclei (red arrows). DWI, axial
view.
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WE mimicking neuropsychiatric symptoms in patients with SLE
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Case 2
A 51-year-old woman diagnosed with SLE in 2000
(malar rash, autoimmune hemolytic anemia,
lymphopenia, oral ulcers, peripheral neuropathy,
myositis, ANA titers 1:320 with a nuclear finespeckled pattern) was admitted to the emergency
department with acute confusional state, dysarthria, nausea, perioral paresthesias, and retrograde
amnesia associated with signs of SLE activity,
including low complement and leukopenia. She
had chronic diarrhea with no defined etiology, despite extensive prior investigation, and was taking
hydroxychloroquine (400 mg daily), azathioprine
(100 mg daily), and prednisone (5 mg daily).
Because of suspected NPSLE, intravenous methylprednisolone was initiated at a dose of 1 mg/kg/
day. Brain MRI performed approximately five
days after symptom onset showed fluid-attenuated
inversion recovery (FLAIR) hyperintensities in the
medial thalamus (Figure 2), frontal cortex, and
mammillary bodies, with contrast enhancement in
the latter that was highly suggestive of WE.
Lumbar puncture was not performed because of
the patient’s adverse clinical condition. Thiamine
replacement was started and the corticosteroid
dose was tapered. The patient recovered completely
from her neurological symptoms after three days of
thiamine therapy. Her SLE treatment regimen was
not modified.
Case 3
A 53-year-old woman diagnosed with SLE in 1987
(class IV lupus nephritis, serositis, lymphopenia,

autoimmune hemolytic anemia, discoid lupus, and
ANA titers 1:1280 with a thin dotted nuclear pattern) was hospitalized for lupus pericarditis and an
infected wound in the left knee. She had undergone
knee ligament stabilization surgery three months
prior to admission and, after 42 days of hospitalization, which included an intensive care unit stay
and various infectious complications, had been discharged on thalidomide (100 mg daily), hydroxychloroquine (400 mg daily), and prednisone (40 mg
daily). Her nutritional status was apparently good
and she did not need feeding devices. Two days
after discharge, she was readmitted to the emergency room with signs and symptoms of pneumonia, which was treated with a broad-spectrum
intravenous antibiotic (meropenem). On the last
day of antibiotic treatment, approximately 20
days after admission, the patient had recovered
from pneumonia, but exhibited new-onset recent
memory loss and confusion. Other neurological
functions were preserved. All medications to
which these manifestations could be attributed,
including a benzodiazepine and tricyclic antidepressant that had been started five days before symptom onset, were discontinued, but the patient did
not improve. Brain MRI performed on the fifth day
after onset of the neurological syndrome showed
free water restriction and signal hyperintensity in
the mammillary bodies on diffusion-weighted,
FLAIR, and T2 sequences, without contrast
uptake. The diffusion-weighted image sequence is
shown in Figure 3. WE was considered a strong
possibility. The patient was started on thiamine
replacement therapy, and experienced complete
resolution of neurological symptoms. CSF analysis
was never performed.

Discussion

Figure 2 Brain magnetic resonance imaging of case 2, showing signal hyperintensity in the medial thalamic area. Fluidattenuated inversion recovery (FLAIR) sequence, axial view.

WE is a disease caused by thiamine deficiency. Its
frequency is low in the general population, but
reaches 12.5% in alcoholic individuals.4,5 Besides
chronic alcohol intake, other risk factors for WE
include hyperemesis gravidarum,6 parenteral nutrition,7 malignancies,8 gastrointestinal tract diseases
or procedures, hemodialysis, malnutrition, and psychiatric disorders such as anorexia and schizophrenia.9 In nonalcoholic patients, the prevalence of
WE ranges from 0.04% to 0.13%.4
However, an autopsy-based study found a higher
incidence (approximately 20%) of characteristic
WE lesions in nonalcoholic individuals with no
clinical symptoms. This suggests WE is an
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WE mimicking neuropsychiatric symptoms in patients with SLE
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Figure 3 Brain magnetic resonance imaging of case 3, showing signal hyperintensity in the mammillary bodies. Diffusionweighted imaging (DWI), axial view.

underdiagnosed condition.4,5 To date, WE had not
been described as a mimic of NPSLE. Here, we
describe three patients with SLE who had acute
onset of a neuropsychiatric syndrome suggesting
NPSLE. In all three cases, brain MRI findings
were suggestive of WE and the patients improved
after thiamine replacement. Hyperemesis gravidarum, chronic diarrhea, and impaired nutritional
status after prolonged hospitalization were, respectively, the risk factors for WE occurrence identified
in our patients.
Confusion, ophthalmoplegia, and ataxia make
up the classic triad of WE, but are found in only
one-third of cases.10 The main symptom is confusion, which can range from spatial disorientation
and memory impairment to coma. The most
common ocular sign is horizontal nystagmus, but
a delayed pupillary response to light, papilledema,
anisocoria, ptosis, extraocular muscle palsy, and
diplopia may be present. Peripheral polyneuropathy, dysarthria, and gait and balance disorder
may also be found. Finally, hypotension, tachycardia, nausea, abdominal pain, and convulsions are
also part of this highly diverse clinical syndrome.10
The main diagnostic modality for WE is brain
MRI, owing to the high specificity of its findings.
Typical findings include bilateral and symmetrical
signal hyperintensity in the thalamus, mammillary
bodies, tectal plate, and periaqueductal area on
T2-weighted and FLAIR sequences.3 Changes in
the mammillary bodies may be the only findings,
and are present in up to 40% of cases. All three
cases reported herein had mammillary body
changes. In these locations, cell membrane

gradients are strictly related to thiamine levels.
Other signal intensity changes in the pons, cerebellar dentate nucleus, red nucleus, substantia nigra,
corpus callosum, caudate nucleus, parietal cortex,
and fornices may be found concomitant with the
typical findings described previously.11
In patients with SLE, the neurological symptoms
of WE make diagnostic differentiation between this
condition and NPSLE particularly challenging. In
the cases described, the presence of symptoms and
risk factors both for NPSLE and WE made the
distinction even more complex. Based on some of
these symptoms, empiric corticosteroid therapy at
immunosuppressive doses was started until MRI
could be performed. The treatment of WE consists
of thiamine replacement, first intravenously and
subsequently orally if possible. The low rate of
complications of this therapy justifies empiric thiamine replacement whenever WE is suspected in
patients with risk factors for its development.4

Conclusion
During evaluation of SLE patients with neuropsychiatric manifestations, WE should be considered in the differential diagnosis, especially in
cases with known risk factors. This approach
would allow appropriate treatment, prevent excessive use of corticosteroids, and improve the odds of
clinical improvement and resolution of the neuropsychiatric disorder.

Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or
publication of this article.

Funding
The authors disclosed receipt of the following
financial support for the research, authorship,
and/or publication of this article: This study was
supported by grants from the Research Incentive
Fund (Fundo de Incentivo à Pesquisa e Eventos,
FIPE) of Hospital de Clı́nicas de Porto Alegre,
the Coordination for the Improvement of Higher
Education
Personnel
(Coordenação
de
Aperfeiçoamento de Pessoal de Nivel Superior,
CAPES), and the National Council for Scientific
and Technological Development (Conselho

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WE mimicking neuropsychiatric symptoms in patients with SLE
S Appenzeller et al.

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Nacional de Desenvolvimento
Tecnológico, CNPq).

Cientı́fico

e

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